UEA Revision Tool 21-22

2021/2022 REVISION TOOL
Short Guides for Key Therapeutic Areas
Acknowledgment for Victoria Bowles (Rotational Pharmacist, Cambridge University Hospitals) for writing the content
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CONTENTS
Cardiovascular System 2 • Corticosteroids 35

• Cardiovascular Disease 2 • Osteoporosis: Bisphosphonates 36
• Cardiovascular Disease Treatment 3 • Thyroid Disorder 37
Nervous System 5 • Diabetes Insipidus 38
• Epilepsy 5 Infection 39
• Depression 9 • Antibiotics 39
• Lithium 12 • Tuberculosis 43
• Antipsychotics 14 • Antifungals 44
o Antipsychotics - Side Effects 15 Genito-Urinary Tract System 45
• Clozapine 16 • Genitourinary Medicine 45
• Dementia 17 • Contraception 46
• Parkinson’s Disease 18 Gastro-Intestinal System 48
• Benzodiazepines 20 • Constipation 48
• Nausea and Vomiting 21 • Diarrhoea 50
• Pain 22 • Inflammatory Bowel Disease 51
o Opioids 22 • Crohn’s Disease 54
o Neuropathic Pain & Lower Back Pain 24 • Ulcerative Colitis 56
Respiratory 25 • H. Pylori 58
• Asthma 25 Immune System and Malignant Disease 59
• COPD 28 • Cytotoxic Drugs 59
Endocrine System 30 • Immunotherapy 63
• Diabetes Overview 30 • Oncological Emergencies 64
o Diabetes Treatment 32 • Breast Cancer 65
o Antidiabetic Agents 33 • Lung Cancer 66
• Prostate Cancer 67
Please note: This revision guide is intended for use only as an aide memoire. Please use with caution as the content may not go into the depth of learning required for the GPhC assessment.
Copyright of UEA (2022)
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CARDIOVASCULAR SYSTEM – CARDIOVASCULAR DISEASE
HYPERTENSION
HEART FAILURE
First-line treatment: ATRIAL FIBRILLATION
HT with T2DM – any age/ethnicity: (Most common type of arrhythmia)
First-line treatment:
• ACEi or ARB
• ACE I/ARB + BB
Rate control:
HT – no T2DM: • BB – ‘start low go slow’
• First-line: Beta-blocker
• < 55yrs & not African/ • Second-line: rate-limiting CCB
• MRA – Spironolactone
Caribbean – CCB /eplerenone
• Note: digoxin only effective for controlling ventricular
• > 55 yrs - CCB rate at rest (use as monotherapy in sedentary patients • Loop diuretic – “acute
• African/ Caribbean any age – only) phase” or symptom control
CCB with fluid overload
Rhythm control (pharmacological) Add on options:
T1 DM – ACEi or ARB • First-line: Beta-blocker • Ivabradine
• Second-line: dronedarone/amiodarone/other • Hydralazine + nitrate
Targets (clinic): antiarrhythmic agent • Digoxin
• <80 yrs 140/90 mmHg Rhythm control (electrical cardioversion) • Sacubitril + valsartan
• >80 yrs 150/90 mmHg • Preferred if AF >48hrs • SGLT2i (specialist use)
• In Type 1 diabetes aim • Anticoagulate for 3 weeks before and at least 4 weeks Symptoms:
for<135/85 (or <130/80 if after • Fatigue, dyspnoea,
other risk factors). Type 2 DM Stoke risk- assessment tools orthopnoea, pink frothy
same as non-diabetic • CHA2DS2VASc of 1+ in males and 2+ in females sputum, nocturnal cough,
requires anticoagulation weight loss…
• ORBIT score for assessing bleeding risk (replaced BNP= marker of ventricle stretching
HASBLED in 2021 NICE AF guidelines)
STABLE ANGINA • Use to consider risk vs. benefit of anticoagulation
Acute attacks: PRIMARY / SECONDARY

• S/L GTN spray PREVENTION
Long-term management: STROKE For primary prevention offer

• First-line: BB or CCB atorvastatin 20mg to people who have
• Second-line: BB+CCB or long- Thrombolysis – alteplase within 4.5hrs of symptom onset a 10% or greater 10-year risk of
acting nitrate, ivabradine, Aspirin 300mg for 2 weeks (initiated 24hrs after thrombolysis), developing CVD (QRISK2/3)
ranolazine or nicorandil then, long-term treatment with clopidogrel 75mg OD (or
(nicorandil last resort due to For secondary prevention offer
anticoagulant if AF)
risk of ulceration) atorvastatin 80mg OD to people with
TIA -> clopidogrel 75mg OD as long-term prevention CVD and aim for a 40% reduction in
Nicorandil – can cause ulceration
LDL-C regardless of baseline.
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CARDIOVASCULAR SYSTEM – CARDIOVASCULAR DISEASE TREATMENT & PREVENTION
ACS PROTOCOL ANTICOAGULANTS

Initial management of STEMI/NSTEMI Warfarin
• Oxygen if hypoxic • Takes approx. 5 days to become therapeutic (unless loading dose used)
• Nitrates – to relieve ischaemic pain • AF – slow loading with no bridging appropriate
• Opioids – for ischaemic pain • DVT/PE – bridging required with LMWH/UFH
• Antiemetic – to prevent opioid-induced N&V • Target INR usually 2.5
• Aspirin • Target of 3.5 for recurrent VTE whilst on anticoagulation and mitral valve
• Clopidogrel (ticagrelor + prasugrel = alternatives) replacement
• Food interactions: maintain constant levels of dietary vitamin K and avoid
Long-term management cranberry juice
• Aspirin (+ clopidogrel/ticagrelor/prasugrel for 12 months)
(ticagrelor 60mg bd after 12 months for further 3 years in DOACs
high-risk patients) • Contraindicated with prosthetic heart valves (see MHRA warning)
• Beta blocker (titrate up as able) • Caution in renal impairment (dose based on creatinine clearance)
• ACE inhibitor (titrate up as able) • Bridging not required as fast onset of action, except: edoxaban & dabigatran
• Nitrates – if angina present (all patients prn GTN) for DVT treatment/prevention (apixaban and rivaroxaban have initial loading
• Spironolactone/Eplerenone – if HF present doses for DVT/PE treatment)
• Atorvastatin 80mg OD for secondary prevention • No need for INR but bloods still required (FBC, LFTs, U&Es) + weight check
LMWHs/UFH
• S/E: haemorrhage, HIT (more common with UFH) and hyperkalaemia
• UFH – administered as a continuous infusion requiring APTT monitoring
• Pregnancy – LMWHs preferred as do not cross placenta and have less risk of
HIT
AMIODARONE
Loading – 200mg TDS 1 week; 200mg BD 1 week; 200mg OD
thereafter (alternative unlicensed fast loading 400mg tds 3 days
then 200mg od thereafter)
Adverse effects: pulmonary toxicity, thyroid dysfunction, DIGOXIN
hepatotoxicity, peripheral neuropathy, corneal microdeposits,
Take levels at least 6 hours post-dose (or pre-dose) once reach steady state reached (7-
phototoxicity
14 days)
Monitoring: TFTs, LFTs, CXR, serum K+, ECG, ophthalmic exam
Signs of toxicity – nausea, blurred /yellow vision, bradycardia
Long half-life therefore potential for drug interactions for months Increased risk of toxicity – hypercalcaemia, hypokalaemia, hypoxia hypomagnesaemia, renal
after cessation impairment. Interaction with amiodarone => reduce digoxin dose by 50%
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CARDIOVASCULAR SYSTEM – CARDIOVASCULAR DISEASE TREATMENT & PREVENTION
BETA BLOCKERS DIURETICS
Heart Failure Loop diuretics

• ‘Start low go slow’ • Potent diuretics, act within 1 hour and complete diuresis within 6 hours.
• Bisoprolol, carvedilol and nebivolol licensed in HF First line for CCF.
• IV furosemide maximum 4mg/min due to risk of ototoxicity
Contraindications • Monitor weight loss (from fluid loss), maximum 1-2 kg a week
• 2nd and 3rd-degree AV block, bradycardia
Thiazide diuretics
Caution • Produce a weaker diuresis within 1-2hrs and diuresis is complete within
• COPD/asthma (cardio selective BB frequently used with 12-24hrs
caution e.g., bisoprolol) • Ineffective if CrCL <30ml/min
• Chlortalidone and indapamide (thiazide-like) used in hypertension
Side effects • Metolazone produces a profound diuresis (atypical thiazide – only used in
• Bradycardia, bronchospasm, cold extremities, fatigue, CCF in combination with LOOP diuretic). Often given twice weekly as
hyperglycaemia very potent.
• May mask symptoms of hypoglycaemia
• Nightmares (more common in lipid soluble e.g., Both loop and thiazide diuretics can cause hyperglycaemia (LOOPs less),
propranolol) exacerbation of gout (due to ↑ uric acid) and potassium loss
Other uses: Potassium-sparing diuretics First line for CCF. Step 4 for HT.
• Anxiety, thyrotoxicosis, migraine prophylaxis, glaucoma • Contraindicated in Addison’s disease, anuria, and hyperkalaemia
NITRATES
STATINS
1o prevention: Atorvastatin 20mg OD & 2o prevention: Atorvastatin S/E – flushing, throbbing headache, dizziness, postural hypotension
80mg OD (lower dose if CKD or frailty).
High intensity statin – ‘the dose at which a reduction in LDL-C of Tolerance – remove patch for 8-12hrs per day, take BD plain tablets morning and
>40% is achieved: early afternoon and take MR formulations 8 hours apart (instead of 12-hourly) or
• Atorvastatin 20-80mg; rosuvastatin 10-40mg; simvastatin preferably once daily to ensure “nitrate-free period”
80mg
S/E: headache, nausea, myopathy & rhabdomyolysis; hepatic GTN tablets – supply in glass containers, closed with foil-lined cap containing no
disorders (only stop if>3xULN). cotton wool and discard after 8 weeks (N.B. spray more commonly used)
Simvastatin + pravastatin requires doses at night
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NERVOUS SYSTEM - EPILEPSY
Overview of management Considerations Driving
When monotherapy with a 1st-line AED Antiepileptic hypersensitivity syndrome Drivers must inform the DVLA and stop
has failed, monotherapy with another 1st driving immediately if they have a seizure
• Rare (5 in 10,000 patients) and potentially
or 2nd-line drug should be tried
fatal
• Symptoms occur 1-8 weeks after exposure Single unprovoked seizure: Can reapply
When changing from one drug to for license after 12 months (6 months if
(fever, rash, lymphadenopathy, multiorgan
another, slow cross tapering should low risk for recurrence).
failure)
occur – slowly withdraw the first drug
once the new regimen has been • Drug should be withdrawn immediately
Established epilepsy: Must be seizure
established free for >12 months (6 months if due to
Minor blood dyscrasias
change in AED) or >3 years if only having
A single AED should be used whenever • Normally mild and no action required
seizures while asleep
possible • E.g., carbamazepine → Leucopenia,
valproate → thrombocytopenia DVLA advises not to drive during
• Severe blood dyscrasias in 6 in 10,000 AED changes or withdrawal periods
patients
Different regulations apply for other types
Brand-specific prescribing Suicidal thoughts and behaviour of licence e.g., lorry
• MHRA warning – all AEDs associated with
3 risk-based categories: risk
• Can occur as early as 1 week after starting
1 – Should always be prescribed by • Advise patients to seek medical advice
brand (phenytoin, carbamazepine,
Breastfeeding
phenobarbital, primidone) Interactions
• +++ (particularly with older generation AEDs) Monotherapy – should generally be
2 – Need for brand-specific prescribing • Carbamazepine, oxcarbazepine, encouraged in BF
should be based on clinical judgement phenobarbital, phenytoin, topiramate (at Combination therapy – specialist advice
(e.g., sodium valproate, lamotrigine, >200mg daily) = enzyme inducers
clobazam, topiramate, oxcarbazepine,
• Sodium valproate = enzyme inhibitor Monitor infants for sedation, feeding
clonazepam)
difficulties, adequate weight gain
Withdrawal
3 – Not usually necessary to prescribe
• Avoid abrupt withdrawal Phenobarbital & lamotrigine may
by brand (levetiracetam, lacosamide,
gabapentin, pregabalin) • Should be a gradual reduction in dose accumulate in infant therefore monitor
(months) closely for s/e
• If on multiple AEDs, withdraw one at a time
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Pregnancy Hormonal Contraceptive Advice

Sodium Valproate and Pregnancy
MHRA – Valproate Use by Women and Girls
Increased risk of teratogenicity associated Enzyme inducing AEDs that reduce
with the use of AEDs depends on the the effect of the combined oral
Associated with significant risk of birth defects and
type, number, and dose of AEDs. contraceptive pill:
developmental disorders (4 in 10 risk of developmental
disorders and 1 in 10 risk of birth defects) • Primidone (metabolised to
The highest risk is with sodium valproate phenobarbital)
(see right) Valproate must no longer be used in any women/girl of • Phenobarbital
childbearing potential without a pregnancy prevention • Phenytoin
There is also an increased risk with programme in place. • Carbamazepine
phenytoin, phenobarbital, and (HCPs must ensure patients are enrolled on this – use of • Oxcarbazepine
topiramate. highly effective contraception, signed annual risk • High dose topiramate
acknowledgement form, annual review with a specialist) Breakthrough bleeding, spotting and
Lamotrigine or carbamazepine unplanned pregnancy can occur.
monotherapy at lower doses are thought Urgently refer patient to specialist in event of unplanned
to be safer (limited evidence). Although pregnancy or where patient is planning pregnancy. Advice: CHC (pill/patch/vaginal ring),
carbamazepine can cause cleft palate. Valproate is contraindicated for use during pregnancy POP, Progestogen implant not
except for treatment of epilepsy when there is no suitable recommended.
General advice -Effective contraception to alternative treatment option. CHC monophasic pill may be used if
avoid unplanned pregnancy at least 50mcg ethinylestradiol per
Valproate should be dispensed in the original packaging day and continuous/tricycling regime.
-If planning pregnancy, need referral to as it displays a warning. Patches/rings not recommended.
specialist and 5mg folic acid daily A patient card, patient booklet, booklet for HCPs and a
valproate annual risk acknowledgement form is available EHC – 1st line = copper IUD.
-Unplanned pregnancy: usually too late to here: https://www.gov.uk/guidance/valproate-use-by- If Cu-IUD is unacceptable/impractical
make changes to medication; do not stop women-and-girls prescribe double-dose levonorgestrel
AEDs unless advised by specialist; folic 3 mg stat (2 x levonorgestrel 1500
acid 5mg daily advised during 1st trimester micrograms tablet) as possible and
(to reduce risk of neural tube defects) within 72 hours of unprotected sexual
intercourse. Ulipristal acetate is not
-Routine injection of vitamin K at birth recommended.
minimises risk of neonatal haemorrhage
in women taking enzyme inducing AEDs See: Stockley’s Drug
Interactions/FSRH for more
information
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SODIUM VALPROATE PHENYTOIN
Indications – all forms of epilepsy; migraine prophylaxis; BPAD Indications – tonic clonic seizures, focal seizures (which are not controlled by
(generally valproic acid used due to licensing) other 1st line AEDs), prevention/treatment of seizures following head
injury/neurosurgery – now rarely used.
Brands – Epival, Episenta, Epilim Status epilepticus (adults) – loading dose of 20mg/kg (IV) then 100mg (IV/PO)
every 6-8hrs
Safety Information – as per MHRA guidance above Conversions – phenytoin sodium is not equivalent to phenytoin base
(100mg phenytoin sodium = 92mg phenytoin base)
CIs – acute porphyria’s; personal/family hx of severe hepatic Safety information – ‘risk of death and severe harm with injectable phenytoin’
dysfunction, mitochondrial disorders Patient Safety Alert due to risk of error
Caution – MHRA advises Vitamin D supplementation in patients Cautions – enteral feeding: interrupt feed for 2 hours before and after dose.
who are immobilised for long periods/have inadequate sun With IV use: hypotension, respiratory depression, HF (resuscitation facilities must
exposure/ reduced dietary intake of calcium due to reduced BMD be available); formulation is irritant therefore given via central line using a filter.
s/e. SLE Vitamin D supplementation as with sodium valproate. Highly protein bound
Liver toxicity has occurred, especially in patients <3yrs. therefore, caution in patients with low albumin e.g., hepatic impairment
Discontinue treatment if abnormally prolonged prothrombin time.
Raised liver enzymes are usually transient. S/E – acne, hirsutism, coarsening of facial appearance, gingival hypertrophy, and
tenderness (maintain good oral hygiene), bone marrow disorders and blood
Monitoring – LFTs, FBC dyscrasias. Discontinue and cautiously re-introduce if rash occurs; discontinue
immediately if recurrence.
S/E – transient hair loss, weight gain, nystagmus, blood disorders Overdose signs: nystagmus; diplopia; slurred speech; confusion;
(thrombocytopenia) and bone marrow suppression, hepatic hyperglycaemia; ataxia
dysfunction, pancreatitis, tremor
Monitoring – pre-treatment screening in Han Chinese and Thai patients
Counselling – PPP as per MHRA warning; withdraw treatment (HLAB*1502 allele increases risk of SJS); HR and BP during IV administration;
and seek medical attention if signs of blood disorders, hepatic LFTs, FBC; TDM: 10-20mg/L = target. In pregnancy, the elderly, and certain
dysfunction or pancreatitis develop e.g., abdominal pain, jaundice disease states where protein binding may be reduced, careful interpretation of
total plasma-phenytoin concentration is necessary
Interactions – carbapenems decrease the concentration of Counselling –recognising blood and skin disorders → seek immediate medical
sodium valproate (increasing the dose does not counteract this attention; maintain good oral hygiene; signs of toxicity → seek immediate medical
interaction), lamotrigine, phenytoin, topiramate and primidone. attention
Interactions – enzyme inducer, number of interactions
PO vs IV – when switching between oral and IV therapy, no Pharmacokinetics – zero order – small increase in dose can result in large
conversion required (dosage is the same) increase in plasma drug concentration
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LAMOTRIGINE
CARBAMAZEPINE
Indications – for many seizure types
Indications – many seizure types; trigeminal neuralgia; prophylaxis of
BPAD unresponsive to lithium (unlicensed, not recommended by NICE); Titration – dose must be increased very slowly (e.g., every 1-2 weeks)
adjunct in acute alcohol withdrawal (unlicensed); diabetic neuropathy due to risk of skin reactions (slower when used as adjunctive treatment)
If a patient misses lamotrigine for 5 half-lives (dependent on
Formulations – MR tablet, tablet suppository (dose equivalents are concomitant AEDs), dose titration needs to be repeated.
noted in BNF), oral suspension (note – no injectable formulation)
Cautions – may exacerbate Parkinson’s Disease; may exacerbate
Contra indications - Acute porphyria’s ; AV conduction abnormalities myoclonic seizures.
(unless paced); history of bone-marrow depression
Skin reactions – serious skin reactions, including SJS, have occurred
Cautions – cardiac disease, skin reactions, vitamin D supplementation especially in children and usually occur in the first 8 weeks. The risk is
as per valproate/ phenytoin. Blood, hepatic, and skin disorders – increased with concomitant use of valproate and following rapid dose
withdraw immediately. Can aggravate absence or myoclonic seizures. escalation.
S/E – Dose related s/e: headache, ataxia, drowsiness, N&V, blurred Counselling –recognising signs and symptoms of blood and skin
vision, dizziness, unsteadiness, allergic skin reactions (can offer MR disorders → seek immediate medical attention,
preparations, as per NICE recommendation). Serious s/e: blood Interactions – increased levels with valproate; reduced levels with
disorders, SJS, hepatic impairment, cardiac conduction disorders carbamazepine; reduces efficacy of COC
Monitoring – TDM 4-12mg/L measured after 1-2 weeks. This is to
measure for optimum response but is not usually used unless compliance
is an issue. Blood counts; hepatic function; renal function; Pre-treatment
screening for Han Chinese and Thai patients (HLA-B*1502 allele LEVETIRACETAM
increases risk of SJS). U&Es – can rarely cause hyponatremia due to
SIADH. Indications – many types of seizures
Interactions – a potent enzyme inducer (reduces effect of combined PO vs IV – when switching between oral and IV therapy, no conversion is
contraceptive and warfarin); concurrent use of MAOIs is contraindicated; required (dosage is the same)
macrolides may increase carbamazepine concentration (increased risk of
toxicity) S/E- can cause anxiety and irritability; rarely causes blood disorders and
Pharmacokinetics – exhibits autoinduction – needs to start with low skin disorders, depression (more acceptable ADR profile compared to
dose and titrate slowly over 4 weeks other AEDs), suicidal thoughts and behaviour
No monitoring required! No important interactions!
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NERVOUS SYSTEM - DEPRESSION
Overview Switching Antidepressants

Monitoring Therapy
Antidepressant drugs are useful for Evidence for switching between or
moderate to severe depression and within classes is weak.
If side effects develop:
dysthymia (low grade, chronic
depression). Initially switch to a different SSRI or
• Can stop the antidepressant a better tolerated newer-generation
They should not be used for mild • Can switch to a different antidepressant antidepressant
depression (psychological therapy first • Can consider short-term treatment with a
line; could be tried if psychological benzodiazepine if anxiety, agitation and/or insomnia Subsequently, switch to an
therapy ineffective) are problematic (can occur in first couple of weeks) antidepressant of a different class
however this should be limited to 2 weeks to prevent that may be less well tolerated (e.g.,
First-line is usually an SSRI dependence venlafaxine, TCA, MAOI)
Antidepressants work gradually not
immediately therefore patients must be No improvement in symptoms: Switching can usually be achieved in
counselled on taking the medication 1 week for drugs with shorter half-
continuously for 3-4 weeks If response is absent/minimal after 3-4 weeks: lives, however, consider the
• Consider increasing the dose following:
Antidepressants may be associated • Switching to another antidepressant
with discontinuation symptoms Fluoxetine to other drugs – caution
If there is some improvement at 4 weeks: due to long half-life of fluoxetine
Augmentation is the term used when a • Continue treatment for another 2-4 weeks
non-antidepressant drug is used in • Consider above if response still inadequate Fluoxetine/paroxetine to TCAs –
combination with an antidepressant to caution as both of these inhibit the
enhance its effects. Examples include Monitoring for increased risk of suicide: metabolism of TCAs (start with a
lithium, aripiprazole, olanzapine, lower dose of TCA)
quetiapine, risperidone (specialist use There is an increased risk of suicide when treatment with an
only) antidepressant is started, particularly for patients <30yrs. Switching to an MAOI – caution
because of the risk of serotonin
Patients should continue treatment For patients at high risk, see within 1 week of starting therapy syndrome
with antidepressants for at least 6
months after remission to prevent For patients at lower risk, see within 2 weeks of starting MAOI to another antidepressant –
relapse (for at least 2 years if they are therapy a 2 week wash out period is
at high risk of relapse or have a history required (3 weeks if starting
of recurrent depression) clomipramine/imipramine)
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Serotonin Syndrome SSRIs
An uncommon ADR caused by too much central and peripheral Recommended first-line for depression in adults due to being as effective
serotonin. as other agents with less side effects.
Symptoms can occur within hours to days following the initiation, dose Common s/e include – GI symptoms (more common at the start of
increase or overdose of a serotonergic drug, switching between treatment); anxiety (more common at start of treatment); insomnia and
serotonergic drugs or the addition of a new serotonergic drug. sexual side effects. SSRIs also increase the risk of GI bleeding.
3 categories of symptoms: All antidepressants can cause hyponatraemia however, this is most
common with the SSRIs.
1 – Neuromuscular hyperactivity
• Tremor Drug specific points:
• Hyperreflexia
• Clonus and myoclonus Citalopram – risk of QTc prolongation; has fewer drug interactions
• Rigidity compared to other SSRIs
2 – Autonomic dysfunction Escitalopram – S enantiomer of citalopram therefore also causes QTc

• Tachycardia prolongation and has fewer drug interactions
• BP changes
Fluoxetine – more drug interactions compared to other SSRIs, long half-
• Hyperthermia
life; only antidepressant licensed for children
• Shivering
• Diarrhoea Paroxetine – more drug interactions compared to other SSRIs; short
half-life therefore risk of withdrawal symptoms upon stopping (withdraw
3 – Altered mental state slowly)
• Agitation
• Confusion Sertraline – few drug interactions; antidepressant of choice for patients
• Mania who have a history of MI / unstable angina
Treatment – withdrawal of the drug; supportive care; specialist support Interactions to bear in mind – NSAIDs, anticoagulants, antiplatelets,
triptans
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TCAs MAOIs
MOA – block the reuptake of 5HT and NA to different extents depending Used much less frequently than TCAs, SSRIs and SNRIs due to the
on the drug dangers of dietary and drug interactions.
Sedating TCAs vs Non-sedating TCAs
• Sedative: better for agitated and anxious patients (e.g., Irreversible (e.g., phenelzine) vs reversible (e.g., moclobemide MAO-a
clomipramine, amitriptyline, trazadone, trimipramine) selective). Irreversible should be reserved for specialist use only.
• Non-sedative: better for withdrawn and apathetic patients (e.g.,
lofepramine, nortriptyline, imipramine) Food interactions - MAOIs can potentiate the pressor effect of tyramine,
S/E – antimuscarinic (dry mouth, blurred vision, constipation, urinary causing a hypertensive crisis (first sign is a throbbing headache) therefore
retention) and cardiotoxic in overdose counsel patients on the need to avoid foods high in tyramine (mature
• Lofepramine: lower incidence of s/e, less dangerous in overdose cheese, game, Bovril, Oxo, Marmite) and to avoid alcohol and foods
but can be hepatotoxic suspected of ‘going off’.
• Imipramine – more marked antimuscarinic s/e
• Amitriptyline + dosulepin: particularly dangerous in overdose, Drug interactions – Lots! e.g., inhibit the metabolism of indirect-acting
not recommended in depression sympathomimetic contained in many cough and cold medicines (e.g.,
Dosulepin should not be prescribed pseudoephedrine) → hypertensive crisis
TCAs are not recommended first line due to potential harm in overdose
Danger of interactions persists for up to 2 weeks after an MAOI is
withdrawn therefore a 2 week wash out period is required when switching
from a non-reversible MAOI to another antidepressant.
SNRIs
S/E – similar to SSRIs, particularly GI related. Can also cause sweating, Mirtazapine
headaches, BP changes and palpitations.
MOA – a presynaptic alpha2-antagonist; increases central NA and 5HT
Venlafaxine – marginally more effective than SSRIs; BP monitoring transmission
required; short half-life therefore slow withdrawal required. Higher doses
may exacerbate cardiac arrhythmias. Significant toxicity in overdose. S/E – sedation (useful for patients with insomnia); oedema; increased
appetite (useful for patients with reduced appetite) and weight gain. Can also
Duloxetine – licensed for depression, diabetic neuropathy, and moderate- cause blood disorders (rare)
severe stress urinary incontinence in women. Lower doses used for
depression. Counselling – counsel patients on how to recognise signs of blood
disorders
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NERVOUS SYSTEM - LITHIUM
Indications Monitoring
• Treatment and prophylaxis of mania • RFTs (95% renally excreted) and U&Es (Na+ affects lithium
• Treatment and prophylaxis of bipolar affective disorder (BPAD) clearance and electrolyte disturbances will predispose to QT
• Treatment and prophylaxis of aggressive behaviour or prolongation/arrhythmias) (3/12ly)
intentional self-harm
• Treatment and prophylaxis of recurrent depression • TFTs (can affect thyroid function) (6/12ly)
Brands • Body weight/BMI (can cause weight gain) (12/12ly)
• Brand specific prescribing- wide variability in bioavailability e.g., • FBC (12/12ly)

Priadel, Camcolit, Liskonum
• Cardiac function (can cause arrhythmias) (12/12ly)
• Different salt forms have different bioavailability’s (carbonate vs
citrate) • Calcium (can cause hypercalcaemia) (12/12ly)
Side Effects
TDM (3/12ly)
• GI disturbances (particularly at initiation)
• Take a level 12 hours post dose (therefore dosing at night for
• Metallic taste in mouth level in the morning)
• Below 0.4mmol/L is usually thought not to work for most people,
• Weight gain although some people still seem to do well on very low doses
• 0.4-0.6mmol/L – may have lower side effects but is probably
• Ankle oedema slightly less effective than the higher levels
• 0.6-0.8mmol/L – the usual effective range, although side effects
• Polyuria and polydipsia (due to inhibition of ADH) will increase with increased levels
• 0.8-1.2mmol/L – usually only needed for people for whom mania
• Neurotoxicity (can occur at therapeutic levels [paraesthesia, or hypomania is more of a problem
ataxia, tremor, cognitive impairment) • 1.2 and above – generally thought to be the toxic or dangerous
levels. These are higher levels than needed in most people, with
• Tremor more risk of worse side effects.
• Take a level weekly at initiation and after each dose change until
• QT interval prolongation, arrhythmias stable
• Take a level every 3 months once stable for the first year
13
NERVOUS SYSTEM - LITHIUM
Lithium Toxicity
Usually due to dehydration, reduced renal function, infection, treatment with interacting medicines (e.g., diuretics and NSAIDs)
Early Signs Following signs Severe signs
• Non-specific • Vomiting • Convulsions

• Restlessness • Diarrhoea • Coma
• Apathy • Ataxia • Renal failure
• Confusion • Weakness • Electrolyte imbalance
• Drowsiness • Dysarthria • Hypotension
• Muscle twitching • Cardiac arrhythmias
• Tremor
• Visual disturbances
• Polyuria, incontinence
Interactions Patient Counselling
Rise in lithium levels • Importance of adherence and monitoring

• ACEIs and ARBs
• Diuretics • Avoid dehydration and big changes to the level of salt in your diet
• NSAIDs
• Importance of effective contraception (inform doctor immediately if unplanned
Drugs that prolong the QT-interval pregnancy / planning pregnancy)
• Phenothiazines
• Citalopram • Inform pharmacist before buying OTC products (e.g., ibuprofen / aspirin)
• Clarithromycin
• Antiarrhythmics • Seek medical advice if you experience diarrhoea and vomiting (→ dehydration →
increased risk of lithium toxicity)
Sodium (e.g., antacids)
• Increased Na+ intake decreases lithium levels • How to recognise signs of toxicity, hypothyroidism, renal dysfunction, and benign
• Decreased Na+ intake increases lithium levels intracranial hypertension
• See Stockley’s Drug Interactions for explanation
14
NERVOUS SYSTEM - ANTIPSYCHOTICS
Symptoms of Psychosis & Schizophrenia

Positive Negative First Generation (typical) APDs
Hallucinations Emotional blunting
Delusions Reduced speech Phenothiazine derivatives Butyrophenones
Disordered behaviour, Loss of motivation 1 – Chlorpromazine, levomepromazine, • Benperidol and haloperidol
speech and/or thoughts Self-neglect promazine • Same clinical properties as group 3
Social withdrawal • Pronounced sedative effects phenothiazines
• Moderate antimuscarinic and EPS
Thioxanthenes
2 – Pericyazine
• Flupentixol and zuclopenthixol
• Moderate sedative effects
• Moderate sedative, antimuscarinic and EPS
Second Generation (atypical) APDs • Fewer EPS than groups 1 and 3
3 – Fluphenazine, perphenazine, Diphenylbutylpiperidines
Risperidone These are generally prochlorperazine, trifluoperazine • Pimozide – reduced sedative, antimuscarinic
Olanzapine better for treating the • Fewer sedative and antimuscarinic and EPS
Quetiapine negative symptoms effects
Clozapine Substituted benzamides
of schizophrenia • More pronounced EPS than
Aripiprazole • Sulpiride – reduced sedative, antimuscarinic
compared to the 1st groups 1 and 2
Paliperidone and EPS
generation
Lurasidone
Extrapyramidal S/E (EPS)

Antipsychotic Drugs (APDs)
Most common with group 3 phenothiazines, the butyrophenones and the first-generation depots.
1st generation VS 2nd generation
Parkinsonian symptoms
Includes tremor, which may appear gradually. Can be treated with antimuscarinic drugs e.g., procyclidine
1st generation – predominantly block D2
receptors in the brain and are not selective for Dystonia
any of the 4 dopamine pathways, therefore Abnormal face and body movements.
cause a range of side effects Occur more commonly in children and young adults and can appear after a few doses
Akathisia
2nd generation – act on a range of different
Restlessness, which occurs after large initial doses.
receptors. Less likely to cause extrapyramidal
side effects but increased risk of weight gain, Tardive dyskinesia
hyperprolactinaemia and glucose intolerance. Rhythmic, involuntary movements of the tongue, face, and jaw. Usually develops on long-term therapy or
with high doses. This is the most serious manifestation of EPS and may be irreversible on drug withdrawal.
15
NERVOUS SYSTEM - ANTIPSYCHOTICS SIDE EFFECTS
Hyperprolactinaemia Sexual Dysfunction APD Monitoring
Occurs with all APDs to some One of the main causes of non-adherence FBC, U&Es, LFTs – start and then
extent apart from aripiprazole, Mechanisms causing sexual dysfunction: annually
which reduces prolactin due to its • Decreased dopamine transmission and hyperprolactinaemia lead
partial dopamine-receptor to decreased libido Blood lipids and weight – start, 3
agonist effects. • Antimuscarinic effects lead to disorders of arousal months and then yearly
• Alpha1-adrenoceptor antagonist properties can lead to erection
Clinical symptoms of high and ejaculation problems Fasting blood glucose – start, 6
prolactin: months and then yearly
• Sexual dysfunction
• Reduced bone mineral ECG and BP – start and during dose
density Hyperglycaemia and Weight Gain titration
• Menstrual disturbances
• Breast enlargement Less likely with first generation APDs Prolactin – start, 6 months then where
Hyperglycaemia and sometimes DM can occur with APDs – clozapine,
• Galactorrhoea clinically indicated, annually for known
olanzapine, quetiapine, and risperidone = most common prolactin elevating APDs
All APDs can cause weight gain but to different extents (clozapine and
olanzapine = most)
Other Uses of APDs

Cardiovascular S/E Hypotension and Interference with Temperature Regulation
Nausea and vomiting
Include: These are dose-related side effects, which can cause falls and
hypo/hyperthermia in the elderly. Chorea (abnormal involuntary
• Tachycardia movement disorder)
• Arrhythmias Postural hypotension may be associated with syncope.
• Hypotension Motor tics
Intractable hiccup
QT-prolongation is a particular
concern with: Neuroleptic Malignant Syndrome Deviant antisocial sexual behaviour
Symptoms – hyperthermia, fluctuating levels of consciousness, muscle Psychomotor agitation
• Haloperidol
rigidity, autonomic dysfunction, tachycardia, labile BP, sweating, urinary
• Pimozide Severe agitation and restlessness in
incontinence, elevated creatine kinase levels.
• Any IV preparation Requires immediate withdrawal and admission to hospital the elderly
16
NERVOUS SYSTEM - CLOZAPINE
Overview Blood Tests Additional Points
2nd generation APD Clozapine can cause neutropenia (2%), agranulocytosis (0.8%) and eosinophilia. Initiation
(Dopamine D1, dopamine D2, Therefore, FBC monitoring is required. Slow dose titration is
5-HT2A, alpha1-adrenoceptor, need upon initiation with
and muscarinic-receptor FBC monitoring requirements: close monitoring
antagonist). • Newly started: weekly for 18 weeks
• 18-52 weeks of treatment: fortnightly Missed Doses
Used for treatment-resistant
schizophrenia (only APD • >52 weeks of treatment: monthly If doses have been
licensed for this and with Fasting blood glucose: missed for >48hrs, the
Blood lipids and weight:
proven efficacy), 30-60% of • Baseline dose will need to be re-
• Baseline titrated.
patients will respond. • After 1 month
• 3 months for the first year
• Then every 4-6 months
All patients treated with • Yearly If >72hrs missed, FBC
clozapine must be registered monitoring frequency
with an approved clozapine Maximum quantity of clozapine that can be supplied: may need to be altered
monitoring service. • Weekly FBCs = 10 days
• Fortnightly FBCs = 21 days Smoking
• Monthly FBCs = 42 days
Dose adjustment needed
in smoking cessation and
Clozapine drug history Other Monitoring
increase/decrease in
taking As for other APDs above.
smoking habits (dose
related effect). Levels not
What brand and dose? Clozapine blood level monitoring is recommended in certain clinical situations: smoking
cessation, switching to an e-cigarette, concomitant medicines that may interact with affected by nicotine
The current frequency of FBC replacement therapy.
clozapine, pneumonia, or other serious infection, if reduced clozapine metabolism is
tests and when the last one suspected, or if toxicity is suspected.
was Due to enzyme induction.
An ECG before treatment is vital due to risk of myocarditis and cardiomyopathy. Persistent
Patient’s adherence – have Particular care needed
tachycardia, particularly in the first 2 months should prompt observation for indicators of
they missed any doses? during transfers of care
myocarditis and cardiomyopathy.
When did they last take a
dose? Other indications
Frequent monitoring of BP, pulse and temperature during initiation and slow dose titration
Who supplies the clozapine? required due to risk of BP changes, tachycardia, and pyrexia. Clozapine is also
indicated for psychosis in
Have they brought a supply Patients should be monitored for constipation due to the risk of potentially fatal intestinal Parkinson’s Disease
into hospital with them? obstruction, faecal impaction, and paralytic ileus
17
NERVOUS SYSTEM - DEMENTIA
Overview Memantine
Acetylcholinesterase Inhibitors (AChEI)
Several conditions cause the A glutamate (NMDA) receptor
Donepezil, galantamine and rivastigmine
symptoms of dementia: Alzheimer’s antagonist
disease, vascular dementia, dementia
Reversible inhibitors of acetylcholinesterase (increase the Side effects:
with lewy bodies…
concentration of acetylcholine) • Balance disorders, constipation,
Cognitive symptoms dizziness/drowsiness
Recommended for the treatment of cognitive symptoms of mild
to moderate dementia to due Alzheimer’s Disease Can be used as monotherapy or in
Consider cholinergic burden and combination with AChEIs in
review drugs that have anticholinergic moderate/severe disease (Alzheimer’s
General side effects:
side-effects. or Lewy body dementia).
• GI – diarrhoea, GI discomfort, nausea
Drugs used to treat the cognitive • Syncope Higher doses used to treat Oscillopsia
symptoms of dementia are not • Urinary incontinence in Multiple Sclerosis (MS).
recommended for vascular dementia. • Sleep disturbance
Treatment should be assessed on a • Skin reactions (with rivastigmine patches)
regular basis and only be continued
when it is having a worthwhile effect Donepezil
on symptoms. • Initial dose titration needed Treatment of aggression, violence,
• Recommended to take at bedtime and extreme agitation
Non-cognitive symptoms • Can cause bradycardia (monitor pulse)
An antipsychotic drug or a
e.g., delusions, anxiety, aggression, Galantamine benzodiazepine can be given (high
and agitation. • Severe cutaneous adverse reactions (SCARs), doses / combinations should be
including SJS can occur, so treatment must be avoided) e.g., = lorazepam or
Pharmacological treatment should discontinued at the first appearance of a rash risperidone (licensed)
only be offered if the symptoms cause Rivastigmine
severe distress or if there is immediate If IM administration is required, options
• Slow dose titration needed on initiation include:
risk of harm to the patient or to others. • Available as a transdermal patch – less likely to cause
The MHRA reports a clear increased • Lorazepam
GI side effects (conversion from oral form available)
risk of stroke when antipsychotics are • Haloperidol
• Rotate patch site daily and do not use same patch site
used in elderly patients with dementia
location for 14 days Avoid antipsychotics where possible in
therefore risk: benefit ratio must be
• Also indicated in dementia of Parkinson’s Disease lewy body or Parkinson’s dementia
assessed.
due to risk of severe adverse effects.
18
NERVOUS SYSTEM - PARKINSON’S DISEASE
Overview
Drug Treatment
PD occurs due to the degeneration of
dopaminergic neurons, resulting in a Levodopa – gold standard treatment – most effective oral symptomatic treatment
deficiency of dopamine within the basal
ganglia. Cannot use dopamine replacement as dopamine does not cross the blood brain barrier however its
Classical symptoms of motor symptoms: precursor, levodopa, does.
• Bradykinesia
Levodopa is converted to dopamine via the enzyme dopamine decarboxylase, which would not be ideal
• Rigidity
in the periphery due to side effects (e.g., nausea, tachycardia, postural hypotension) therefore a
• Tremor – approx. 70% of patients
dopamine decarboxylase inhibitor is combined with levodopa (carbidopa/ benserazide).
have a resting tremor
• Postural instability (stooping) Carbidopa and benserazide do not cross the blood brain barrier therefore they prevent the conversion to
Non-motor symptoms dopamine in the periphery but not within the brain – allows lower dose of levodopa to be administered.
• Sleep disturbances Levodopa usually improves symptoms for 6-18 months and then after approx. 2yrs, a slow decline
• Hallucinations occurs. Patient may want to wait to start to get maximal benefit at a time of their choosing.
• Dementia
Dyskinesias – develop in 30-40% of patients after 4–6 years of treatment.
• Restless legs
• REM sleep behaviour disorder
Motor fluctuations – occur in due course and cause ‘on/off’ symptoms (fluctuations between symptom
• Depression control and flares)
Visual and olfactory disturbances
End of dose deterioration (‘wearing off’) – the effects of levodopa wear off before the next dose is
Dysphagia, which can contribute to due.
mortality from pneumonia; sialorrhoea
Autonomic dysfunction MR preparations have a limited role in preventing or reducing wearing off but does have important
therapeutic role in managing night-time akinesia and simplifying dosing regimens.
• CV disorders (postural
hypotension)
Dispersible tablets are often used first thing in the morning for their fast onset of action to help the patient
• Impaired sweating
get up from bed
• Constipation
• Bladder disturbance Side effects: Nausea (can take with food initially), postural hypotension, somnolence, urine discoloration.
All dopaminergic drugs are associated with the risk of impulse control disorders (ICDs – see dopamine
Haloperidol, metoclopramide and agonists).
prochlorperazine must not be given as they
are dopamine antagonists.
19
NERVOUS SYSTEM - PARKINSON’S DISEASE
Monoamine oxidase type B inhibitors (MAOI-B) – useful mild symptomatic

Dopamine Agonists – less effective at controlling motor symptoms
effect in early disease, and levodopa-sparing effect in later disease
than levodopa
Selegeline (may cause insomnia due to amphetamine-like metabolites),
Ergot derivatives – rarely used due to risk of fibrotic reactions (not
rasagiline, safinamide
recommended by NICE)
• Bromocriptine, cabergoline, pergolide MOA – selectively inhibit the oxidative metabolism of levodopa and dopamine
and therefore potentiate the effects of levodopa, allowing for levodopa dose
Non-ergot derivatives reduction
• Pramipexole, ropinirole, rotigotine (transdermal patch) Interactions – hypertension is predicted to occur when high-doses of selegiline
are taken with tyramine-rich foods; caution with SSRIs – may precipitate
Can be added to levodopa therapy to increase the ‘on’ time or they can serotonin syndrome.
be used as monotherapy, particularly in younger patients whose QoL is S/E – increased levodopa side effects, therefore, reduce levodopa dose
not affected to delay the use of levodopa.
Side effects
• Sudden onset of sleep
Catechol-O-Methyltransferase (COMT) Inhibitors
• Hypotensive reactions, oedema, hallucinations
• Impulse control disorders (e.g., pathological gambling, hyper- Entacapone – Prevents the peripheral breakdown of levodopa, allowing more to
sexuality, punding, binge eating, excessive shopping) – strong enter the brain. May colour the urine reddish-brown.
association with dopamine agonists – risk factors: young age, Tolcapone – more potent than entacapone (rarely used, can cause hepatotoxicity)
alcohol abuse, smoker, past history of mental health disorder – Needs to be taken 2-3 hrs apart from iron preparations.
adjust dose or discontinue drug.
Apomorphine
• Potent dopamine agonist (not an opioid) Antimuscarinics
• Specialist use and monitoring only
• Used in advanced disease for unpredictable ‘off’ periods Trihexyphenidyl, procyclidine, orphenadrine
• S/C injection or continuous infusion pump
• Once treatment is established, other PD medication may be MOA – restore the cholinergic-dopamine balance
able to be reduced/withdrawn
• High incidence of N&V therefore it is important to establish a Useful in drug-induced PD but are of little benefit in idiopathic PD (no longer
patient on domperidone (a peripheral D2 blocker) at least 2 days recommended by NICE – increased risk of cognitive impairment)
prior to commencement.
May be useful in controlling excessive saliva
20
NERVOUS SYSTEM - BENZODIAZEPINES
Overview
Withdrawal of BZDs
BZDs are the most used anxiolytics and hypnotics
BZD withdrawal syndrome
Dependence occurs, leading to difficulty withdrawing the drug, particularly if
taken regularly for more than a few weeks May develop at any time up to 3 weeks after stopping a long-acting BZD
BZDs are indicated for short-term relief (2-4 weeks) of anxiety that is and within 1 day of stopping a short-acting BZD. May continue for
severe, disabling or causing the patient unacceptable distress. weeks/months after stopping the BZD
It is inappropriate to use a BZD to treat short-term ‘mild’ anxiety Features:

• Insomnia and agitation
BZDs should be used to treat insomnia only when it is severe, disabling or • Loss of appetite and loss of body weight
causing the patient extreme distress • Tremor
• Perspiration
Z-drugs are benzodiazepine-like but are not BZD’s e.g., zopiclone, • Tinnitus
zolpidem. They are often used to treat short-term insomnia. • Perceptual disturbances
For short term use of 2-4 weeks, withdrawal can occur over 2-4 weeks
however after long-term use, withdrawal may take longer than several
months
Side Effects
Protocol for withdrawing:
General • Transfer the patient to an equivalent daily dose of diazepam
• Drowsiness • Reduce the dose by 1-2mg every 2-4 weeks
• Confusion • If uncomfortable withdrawal symptoms occur, maintain this dose
• Dependence until symptoms lessen
• Muscle weakness • Reduce the diazepam dose in smaller steps of 500mcg towards
• Increased falls risk the end of withdrawal
• The addition of beta blockers, antidepressants, and antipsychotics
Paradoxical effects to treat withdrawal symptoms should be avoided where possible
• A paradoxical increase in hostility and aggression may occur
• Increased anxiety and perceptual disorders can also occur Regular review and follow-up is essential to the success of BZD
• Effects range from talkativeness and excitement to aggressive and withdrawal.
antisocial acts
• Adjustment of the dose sometimes attenuates the impulses
21
NERVOUS SYSTEM - NAUSEA AND VOMITING
Antihistamines
D2 antagonists
MOA – D2 antagonists
E.g., cyclizine 50mg TDS
Metoclopramide
S/E – drowsiness and antimuscarinic side effects
• Crosses the BBB therefore not suitable in PD
Available OTC but risk of abuse as can give a ‘high’ • MHRA warning – neurological s/e such as extrapyramidal symptoms
and tardive dyskinesia; max 5 days (can use for longer in palliative
care)
• Prokinetic effects
Phenothiazines and Other Antipsychotics
Domperidone
• Does not cross the BBB therefore safe in PD
E.g., prochlorperazine, chlorpromazine, haloperidol, levomepromazine
• MHRA warning – risk of cardiac s/e; max 7 days
MOA – dopamine receptor antagonists • Prokinetic effects
• Not for use in under 12’s or those < 35kg (see MHRA warning)
S/E – extrapyramidal and anticholinergic side effects, drowsiness
Prochlorperazine can be administered as a 3mg buccal tablet (dissolved

between upper lip and gum)
5HT3 antagonists
E.g., ondansetron, granisetron
Caution – prolong the QT interval

Corticosteroids
S/E - constipation
E.g., dexamethasone
Used for N&V associated with cancer chemotherapy

Neurokinin1 receptor antagonists
Can be used alone or in combination with other antiemetics
E.g., aprepitant, fosaprepitant, rolapitant
Also has use in reducing intracranial pressure due to tumours
Used for chemotherapy-induced nausea and vomiting
22
NERVOUS SYSTEM - PAIN: OPIOIDS
Opioids Overview Opioid Side Effects

Mostly used for analgesia but can also be used as cough suppressants, to reduce Respiratory
intestinal motility and opioid dependence e.g., pholcodine. • Bronchoconstriction due to opioid-induced histamine release
(asthmatic patients are particularly prone)
Generally, they are full agonists at opioid receptors, but some have mixed agonist- • Respiratory depression – rare but serious
antagonist activity e.g., buprenorphine and pentazocine.
Skin
Tramadol also has noradrenergic and serotonergic properties.
• Pruritis – due to cutaneous release of histamine
• Flushing – due to histamine-stimulated dilation of cutaneous
Opioids are suitable for moderate-severe pain.
blood vessels (increased risk with epidural opioids)
• Little evidence to support use of antihistamines
Other
• Urinary retention – increased with epidural opioids
Opioid Side Effects • Miosis (pinpoint pupils are characteristic of opioid toxicity)
Gastrointestinal
• N&V occur very commonly – this often diminishes as tolerance develops
• Constipation – due to reduced peristalsis and increased anal sphincter tone.
For long-term use, the combination of an osmotic and stimulant laxative Special Precautions for Transdermal Patches
should be used. A bulk-forming laxative is not appropriate as it increases the
risk of faecal impaction These points are particularly important if around children:
• Dry mouth • Store out of reach and sight of children
• Affix the patch securely & rotate patch site regularly
CNS & Psychiatric • Do not apply after warm bath/shower
• Drowsiness + sedation – dose dependent effects which often diminish when • Do not shave to remove hair before application (increased
tolerance develops absorption potential)
• Confusion, delirium, dizziness • Follow the PIL for disposal instructions (may require folding
• Mood changes – euphoria and dysphoria the patch back on itself) and discard so that it cannot be
• Hyperalgesia – increased sensitivity to pain can occur with long-term use retrieved by a child or a pet
• Be alert of opioid side effects in children and get medical
Cardiovascular help if contact is suspected
• Postural hypotension • Monitor use in patients with cognitive deficit; they may
• Vasodilation due to opioid-induced histamine release remove patches and place elsewhere
23
NERVOUS SYSTEM - PAIN: OPIOIDS
Dependence and Withdrawal

Strong Opioids
Dependence can be psychological and physical Morphine
• Most valuable opioid for severe pain
Withdrawal symptoms: • Standard for which other opioids are compared
• Nausea, vomiting, diarrhoea • Can be given 4-hourly as standard release or 12/24-hourly as
• Sweating, anxiety, agitation modified release
• Restlessness, yawning, insomnia
• Dilated pupils, increased tear production, rhinorrhoea Buprenorphine
• Bone and muscle pain, abdominal cramps • Agonist-antagonist activity therefore can precipitate withdrawal
• Gooseflesh (pimply state of skin with erect hairs) • Much longer duration of action compared to morphine
• Available as patches and SL
To treat withdrawal, switch to a long-acting opioid (buprenorphine/methadone) Diamorphine
and very slowly reduce the dose over time.
• Less N&V and hypotension compared to morphine
• Greater solubility that morphine so useful in palliative care as it
Note that buprenorphine can provoke withdrawal reactions in those still under the
can be injected in a smaller volume in emaciated patients
influence of opioid drugs or those dependent on high doses due to its agonist-
antagonist activity. To prevent this reaction, the first dose of buprenorphine Fentanyl
should coincide with the appearance of withdrawal effects. • Available as a 72-hourly TD patch
• Very potent opioid, often seen in cancer-care
Methadone
• Less sedating than morphine and has a longer duration of
Weak Opioids action
Codeine Oxycodone
• Codeine is a pro-drug, metabolised to morphine by CYP2D6 – poor • Metabolite is not active and therefore used in renal impairment
metabolisers will not get sufficient analgesia from codeine and rapid instead of morphine (morphine’s metabolites are active and
metabolisers are at risk of toxicity. accumulate in renal impairment)
• Not safe during breastfeeding
Tramadol
Dihydrocodeine • Noradrenergic and serotonergic activity
• Analgesic efficacy similar to codeine • Fewer typical opioid s/e but psychiatric reactions have been
reported
Meptazinol • Monitor for serotonergic withdrawal symptoms when stopping
• Claimed to have lower incidence of respiratory depression • Serotonin syndrome risk if used with other serotonergic drugs
• Weak opioid of choice in renal impairment
24
NERVOUS SYSTEM - PAIN: NEUROPATHIC PAIN & LOWER BACK PAIN
Neuropathic Pain Overview

Lower Back Pain and Sciatica
Can be due to several causes:
Non-drug treatments (e.g., exercise programs, psychological therapies) should be
• Phantom limb pain
offered for people with lower back pain with or without sciatica
• Compression neuropathies
• Peripheral neuropathies (e.g., diabetic peripheral Paracetamol alone is ineffective for managing low back pain
neuropathy, chemotherapy) A NSAID should be considered for managing acute, low back pain
• Trauma
• Central pain (e.g., spinal cord injury) A weak opioid may be combined with paracetamol to manage acute low back pain
• Post-herpetic neuralgia only if an NSAID is contraindicated, not tolerated or ineffective
• Trigeminal neuralgia For chronic low back pain, NSAIDs should be offered first-line if non-drug treatments
are ineffective. Opioids should be the last treatment option.
Management (except trigeminal neuralgia)
• First-line: offer a choice of amitriptyline, duloxetine, NSAIDs and CV events
gabapentin or pregabalin • All NSAIDs can be associated with a small increased risk of thrombotic events,
• Second-line: offer one of the 3 remaining drugs and independent of baseline CV risk
consider switching again if this is ineffective • Greatest risk in high dose, long-term therapy
• Tramadol – only consider if acute rescue therapy is • COX-2 inhibitors (CI in IHD, HF, stroke), diclofenac 150mg/day + ibuprofen
needed (not long term unless under specialist advice) 2.4g/day have an increased risk
• Capsaicin cream – can be considered for localised • Naproxen 1g/day has a lower risk
neuropathic pain in people who cannot tolerate oral • Low dose ibuprofen 1.2g/day has not been associated with an increased risk
treatment
NSAIDs and GI events
• All NSAIDs are associated with GI toxicity (higher risk in elderly)
• Selective COX-2 inhibitors have a lower risk compared to non-selective NSAIDs
Trigeminal Neuralgia • Highest risk: piroxicam, ketoprofen, ketorolac trometamol
• Intermediate risk: diclofenac, naproxen, indomethacin
TN is severe, episodic facial pain, in the distribution of one or • Lowest risk: ibuprofen
more branches of the 5th cranial nerve (the trigeminal nerve). • Consider gastroprotection with a proton pump inhibitor (PPI)
Offer carbamazepine 100mg BD and titrate by 100-200mg every NSAIDs and hepatic impairment
2 weeks until pain is relieved. Once pain is relieved, the dose • Caution – increased risk of GI bleeding and fluid retention
should be reduced to the lowest maintenance dose for controlling
pain. Caution for drug interactions.
25
RESPIRATORY MEDICINE - ASTHMA
Overview Diagnosis – Spirometry

Asthma is a disease with many variations (phenotypes),
usually characterised by chronic airway inflammation. All patients with suspected asthma should undergo objective testing including
Described as “A chronic, inflammatory disorder of the Spirometry (evidence of obstruction and reversibility) and peak flow monitoring (evidence of
airways, which causes an increase in airway hyper- variability).
responsiveness that leads to recurrent episodes of
wheezing, breathlessness, chest tightness and coughing.” The 3 most important spirometric measures for the assessment of asthma:
Causes
No single cause but there are several environmental and 1) Forced vital capacity (FVC) – total volume expelled by forced exhalation after a
genetic risk factors: maximal inhalation
- Family history of asthma or other atopy (e.g., 2) Forced expiratory volume in 1 second (FEV1) – the volume exhaled in the first
eczema, allergic rhinitis), potentially corroborated by second of an FVC
a previous record of raised allergen-specific IgE 3) FEV1/FVC ratio – the proportion of FVC that can be expelled during the first second of
levels, positive skin-prick tests to aeroallergens or expiration (normally at least 70%. <70% suggests airway obstruction)
blood eosinophilia.
- Having bronchiolitis as a child Peak expiratory flow (PEF) – Is a useful way of monitoring variability in asthma. It may be
- Being exposed to tobacco smoke as a child used to aid diagnosis in those unable to perform spirometry or in monitoring asthma control.
- Being born prematurely
- Being born with low birth weight If an obstruction is found, a patient should be tested again to establish whether the obstruction
is reversible – i.e., after an inhaled bronchodilator or a trial of inhaled corticosteroids. A change
Signs & Symptoms in FEV1 of >12% and 200ml confirms reversibility and supports an asthma diagnosis. Testing
- Wheezing may need to be repeated during symptoms, in the early morning, or after withholding
- Short of breath (SOB) bronchodilator medications.
- Coughing – particularly at night and early morning
- Chest tightness Asthma Treatment Aims:
People with asthma generally have >one of these symptoms.
The symptoms occur variably over time and vary in intensity 1) No daytime symptoms
2) No night-time awakening due to asthma
Triggers 3) No need for rescue medication
- Airbourne irritants (cigarette smoke, chemical 4) No asthma attacks
fumes) 5) No limitations on activity, including exercise
- Allergens (pollen, house dust mites, animal dander) 6) Normal lung function (FEV1 and/or PEF >80% of predicted)
- Respiratory tract infections (RTIs) 7) Minimal side effects from medication
- Weather conditions (e.g., cold air)
- Foods containing sulphites (beer, wine, shrimp) Before initiating new drug therapy, check adherence and inhaler technique. Whenever
- Emotion (stress, laughter) possible do not mix MDIs and DPIs as they require different inhaler techniques (slow and
- Exercise steady - MDI vs quick and deep - DPI). All inhalers should also be prescribed by brand.
- Medicines (NSAIDs, beta-blockers (BBs))
26
Asthma Treatment – Stepwise Approach

BTS vs NICE guidelines
Asthma is an inflammatory condition and recent guidelines have highlighted the need to treat all individuals symptomatic of asthma with inhaled corticosteroids. The practice of using a
short acting bronchodilator (SABA) as monotherapy is now outdated and reports such as the National Review of Asthma Deaths (NRAD) have highlighted the potential dangers of this
practice with underuse of inhaled corticosteroids and over reliance on beta-agonists a contributory factor in a number of deaths.
BTS/SIGN (2019) NICE (2017)

prn SABA at each stage unless using MART.
Low dose inhaled corticosteroid (ICS)

Inhaled SABA prn (e.g., salbutamol / terbutaline)
E.g., Clenil MDI 100 2 doses BD
Move down to lowest controlling therapy
Initial add- on therapy:

Low dose ICS
Low dose ICS + LABA
Move up to improve control
E.g., Clenil MDI 100 2 doses BD

E.g., Seretide MDI 50 2 doses BD
Additional controller therapies:
Low dose ICS + Montelukast 10mg ON
Option 1 – increase ICS (as part of ICS / LABA) to medium dose
Option 2 – add in LRTA (montelukast) to ICS
Low dose ICS + LABA (with / without Montelukast)
Specialist therapies: refer patient for specialist input

Consider MART* regime
High dose ICS – e.g., Seretide MDI “250” 2 doses BD, or: add LTRA; or: add
Increase ICS dose →
tiotropium or: add a theophylline Increase ICS dose to moderate
Moderate dose ICS + LABA +/-
(Spiriva (tiotropium) Respimat® = only LAMA licensed in asthma) Continue MART* regime
LRTA
Continuous oral steroids at lowest effective dose (patient should be under
Option 1- Increase ICS to high dose
specialist care)
Option 2- Trial theophylline/ LAMA
Maintain high dose ICS, but:
Consider referral to a respiratory specialist
Think about – bone prophylaxis, risk of diabetes, lipids, BP control
*MART = maintenance and reliever therapy – ICS + LABA (fast acting e.g., formoterol) - Fostair MDI 100/6 - 1 dose BD + 1 dose prn max 8 doses per day
Note – for children under 5 years, NICE recommends the following: Note – for children aged 5-16 years, NICE recommends the following:
1) SABA prn 1) SABA prn
2) Paediatric low dose ICS 2) Paediatric low dose ICS
3) Low dose ICS + montelukast for children 3) Paediatric low dose ICS + LRTA (review in 4-8 weeks)
Refer to a specialist if not adequately controlled at step 3 4) Paediatric lose dose ICS + LABA (stop LRTA)
5) MART regimen with paediatric low maintenance ICS
6) MART + Paediatric moderate ICS
7) Increase ICS to paediatric high maintenance or trial theophylline
27
ICS Equivalence
Historically potency described in relation to Long-acting beta agonists (LABA)
beclometasone dipropionate (BDP). Now see table for Formoterol – rapid onset of action within 5 minutes, Salmeterol slower onset of 15-20
comparison of doses: minutes. Both effects last >12hrs.
https://www.nice.org.uk/guidance/ng80/resources/inhale Formoterol is licensed for symptomatic relief as well as maintenance due to its rapid onset.
d-corticosteroid-doses-pdf-4731528781 or: NB: LABAs MUST be prescribed as a combination product with ICS to obviate the risk of
https://www.brit-thoracic.org.uk/quality- patients inadvertently taking the LABA as monotherapy, which has been associated with
improvement/guidelines/asthma/ increased risk of mortality.
If no benefit is seen with a LABA, it should be discontinued as there is a possible increased
Qvar (beclomethasone) and Fostair (beclomethasone + risk of respiratory-related, asthma-related deaths
formoterol) have extra fine particles so should be S/E – as for SABAs
prescribed as approximately half the dose as other BDP
inhalers Theophylline (a methylxanthine)
Brand specific prescribing – e.g., Uniphyllin Continus
Fluticasone furoate (Relvar®) and fluticasone propionate TDM required - Therapeutic range – 10-20mg/L (sometimes 5-15mg/L is effective)
are more potent than BDP inhalers Plasma concentration…
• Increased in: congestive HF, hepatic impairment, viral infections, drugs p450
Ciclesonide is the only once daily ICS (without a inhibitors
combined LABA) • Decreased in: smokers and by alcohol consumption → care and monitoring
required during smoking cessation, drugs p450 inducers
Cautions – HT, arrhythmias, CVD, hyperthyroidism

Overdose – (think caffeine/coffee): vomiting, agitation, restlessness, dilated pupils,
Short-acting beta agonists (SABAs) tachycardia, hyperglycaemia
Salbutamol and terbutaline

Montelukast (Leukotriene-receptor antagonist)
Onset of action within 5 mins and a peak effect at 4-6hrs Achieves bronchodilation within 2 hour of administration, anti-inflammatory effect seen
within 4 weeks
Should only be used PRN as do not improve outcomes Taken ON
and monitoring SABA use is a good indicator of asthma S/E – GI disturbances, MHRA reminder of the risk of neuropsychiatric reactions
control (September 2019) Healthcare professionals are advised to be alert for neuropsychiatric
reactions, including speech impairment and obsessive-compulsive symptoms, in adults,
S/E – arrhythmias (due to effect on beta receptors on adolescents, and children taking montelukast.
cardiac tissue), fine tremor, hyperglycaemia, Formulations – tablets, chewable tablets, and granules (good for paediatric population)
hypokalaemia (more common with nebulised/IV therapy),
muscle cramps
28
RESPIRATORY MEDICINE - COPD
Overview Medical Research Council (MCR) Dyspnoea Scale

Airflow obstruction, which is progressive, not fully reversible and does not
change markedly over several months 1 Not troubled by breathlessness except during strenuous exercise
2 Short of breath when hurrying or walking up a slight hill
Similar symptoms to asthma, however the symptoms in COPD are constant
(as opposed to intermittent in asthma). In most patients, COPD is associated 3 Walked slower than contemporaries on the level because of breathlessness, or
with significant concomitant chronic disease, which increase its morbidity and has to stop for breath when walking at own pace
mortality. 4 Stops for breath after walking about 100m or after a few minutes on the level
Risk Factors 5 Too breathless to leave the house, or breathless when dressing or undressing
• Smoking (pack years = no. cigarettes smoked x number of years you
have smoked / 20) Diagnosis
• Air pollution/occupational exposure (e.g., dust, chemicals, gases, Post-bronchodilator FEV1/FVC ratio of <0.7 indicates airflow obstruction
particles) Stage 1 – mild. FEV1 80% predicted or higher
• Genetics – e.g., alpha1 antitrypsin deficiency Stage 2 – moderate. FEV1 50-79% of predicted
Stage 3 – severe. FEV1 30-49% of predicted
Symptoms Stage 4 – very severe. FEV1 <30% of predicted
• Dyspnoea
• Chronic cough Diagnosis of an acute exacerbation of COPD
• Sputum: change in volume and/or colour may indicate exacerbation
• Wheeze Defined as a sustained worsening of a person’s symptoms from their usual stable state,
• Chest tightness which is beyond normal day-to-day variations and is acute in onset.
• Fatigue
COPD or Asthma? Commonly reported symptoms: Other symptoms:
• Increased breathlessness • Increased wheeze and chest
• Increased cough tightness
• Increased sputum production • Upper respiratory tract
• Change in sputum colour symptoms e.g., sore throat
• Reduced exercise tolerance
• Ankle swelling
• Increased fatigue
• Acute confusion
Treatment for an acute exacerbation of COPD

• Prednisolone 30mg for 5 days (for asthma dose is 40mg)
• Antibiotics if infective cause of exacerbation
o Amoxicillin 500mg TDS for 5 days
o Doxycycline 200mg stat then 100mg OD to complete 5 days
o Clarithromycin 500mg BD for 5 days
29
RESPIRATORY MEDICINE - COPD
Treatment of COPD – NICE guideline NG115 (2019) Antimuscarinic Drugs

Overview
Block cholinergic nerves in the airways therefore prevent
bronchoconstriction (known as bronchodilators)
Short Acting Muscarinic Antagonist (SAMAs)

• Ipratropium – maximal effects between 30-60mins. It has a
slower onset of action to short-acting beta agonists (SABA).
Duration of action = 3-6 hours.
Long-Acting Muscarinic Antagonists (LAMAs)

• Tiotropium – Spiriva Respimat - 2p OM - (MDI)
• Aclidinium – Eklira Genuair - 1p BD - (DPI)
• Glycopyrronium – Seebri Breezhaler - 1p OM - (DPI)
• Umeclidinium – Incruse Ellipta 1p OM - (DPI)
(n.b., SAMAs not to be used with LAMAs, hold the LAMA acutely)
Cautions
• Prostatic hyperplasia and bladder outflow obstruction –
worsened urinary retention reported
• CKD stage 3+ - risk of drug toxicity
• Angle-closure glaucoma – nebulised mist can precipitate/worsen.
Use a mouthpiece rather than a mask
• Spiriva Respimat – caution in patients with arrhythmias
S/E
• Nasal congestion, nasal dryness, dry mouth, abnormal taste
Combination Inhalers
LAMA + LABA
• Umeclidinium / vilanterol – Anoro Ellipta - 1p OM – (DPI)
• Tiotropium / olodaterol – Spiolto Respimat – 2p OM – (MDI)
ICS + LABA
• Budesonide / formoterol – DuoResp Spiromax 1p BD – (DPI)
• Beclomethasone / formoterol – Fostair 2p BD – (MDI)
LAMA + LABA + ICS
• Fluticasone / vilanterol / umeclidinium – Trelegy Ellipta -
1p OM (DPI)
• Beclomethasone / formoterol / glycopyrronium – Trimbow –
2p BD - (MDI)
(List is not exhaustive; choice should be based on most suitable device for
the patient. Check inhaler technique. https://www.rightbreathe.com )
30
ENDOCRINE SYSTEM – DIABETES OVERVIEW
TARGETS DRIVING RULES

• 5-7mmol/L on waking/fasting HYPOGLYCAEMIA
• 4-7mmol/L before meals Check blood glucose before driving
• 5-9mmol/L 90mins after eating Blood glucose <4mmol/L – ‘4 is the floor’ (within 2 hours) and every 2 hours.
• > 5mmol/L when driving
Requires fast-acting form of glucose e.g.:
• HbA1c <48mmol/mol (<6.5%), Blood glucose must be >5 to drive
• Fruit juice
or < 53mmol/mol in T2DM on
treatment associated with • Non-diet soda drink If hypo when driving, pull over,
hypoglycaemia • Dextrose tablets or sugary sweets e.g., Jelly babies switch off the engine, remove the
• 40% Glucose gel (Hypostop, Glucogel) keys from ignition and move from the
driver’s seat. Take a fast-acting
Or if decreased level of consciousness: carbohydrate and wait for 45mins
DKA • IM glucagon (don’t repeat: give IV glucose) after BG has returned to normal
• IV glucose 20%, 100ml over 15 minutes
Involves hyperglycaemia, acidosis, Recheck blood glucose and repeat above until in range. Keep fast-acting carbohydrates
and ketosis. Sometimes can occur available in easy reach in the car and
without hyperglycaemia Once above 4mmol/l, have long-acting carbohydrate e.g., slice keep snacks for longer journeys.
of toast, or a meal.
1 - Fixed rate intravenous insulin
infusion (0.1units/kg/hr) – suppresses Beta blockers can mask the symptoms of hypoglycaemia
ketogenesis, reduces blood glucose
Repeated hypoglycaemic episodes can reduce awareness COMPLICATIONS
2 – Fluid replacement –Starting with (awareness of hypo’s can be measured using the Clarke
0.9% Sodium Chloride (with K+ to score or Gold score). To restore the warning signs, episodes • Retinopathy
maintain K+ in range, corrects of hypoglycaemia need to be reduced.
• Neuropathy
electrolyte disturbances) • Nephropathy
Causes of hypoglycaemia:
• Cardiovascular disease (MI,
3 – IV glucose 10% - once blood • Too much insulin
stroke, PVD)
glucose <14mmol/L – to prevent • Sulphonylureas, (glinides)
hypoglycaemia whilst insulin is still • Skipping meals/eating less carbohydrates than usual
• Infections that can lead to
amputations
running and to clear ketones • Exercise
Cardiovascular disease – offer
• Alcohol (binge drinking) atorvastatin 20mg in T1DM if aged
If patient is established on a long- • Self-harm over 40yrs or diagnosis of T1DM for
acting insulin, continue this as normal
alongside FRIII. >10yrs. Offer atorvastatin 20mg in
T2DM based on QRISK2.
31
ENDOCRINE SYSTEM – DIABETES OVERVIEW
BLOOD GLUCOSE TESTING PRESENTATION

INSULIN TYPES
At least 4 times a day advised in T1DM; • Polyuria
Rapid acting
increased in periods of illness and • Polydipsia
during long drives • Novorapid (insulin aspart), Humalog (insulin lispro) and
Apidra (insulin glulisine)
• Given immediately before a meal (within 10 mins) More commonly in T1DM: lethargy,
Equipment: meter (from DM clinic) with stupor, acetone breath, nausea,
• Onset 5-15mins; peak 0.5-1.5hrs; duration 3-5hrs
test strips and lancets (FP10) or vomiting, abdominal pain, weight loss
• Fiasp = extra fast acting (within 2mins)
continuous glucose monitor; sharps bin
Short acting/soluble
• Actrapid and Humulin S (soluble insulin)
• Administered 15-30mins prior to a meal
SICK DAY RULES • Onset 30mins; peak 2-4hrs; duration 6-8hrs ADDITIONAL MONITORING
• Actrapid used in a VRIII – immediate onset
Do not stop insulin therapy – dose Annual foot check and eye check
Isophane insulin/intermediate acting
may need to be altered according to
• Insulatard, Humulin I and Insuman basal BP: target 135/85 adults <80 years old
BG levels
• Protamine slows down the onset of action and increases the 145/85 adults >80 years old
duration of action
Monitor BG more frequently, including 130/80 in CKD
• Onset 2- 4 hours, peak 4-8 hrs, duration 14-16hrs
throughout the night • Given OD or BD
Cholesterol: if diagnosed with T1DM
Consider ketone monitoring (blood / Long acting for 10yrs+ commence atorvastatin
urine) • Lantus, Abasaglar, Toujeo (insulin glargine – once or twice 20mg OD. If T2DM, use QRISK2 to
daily) calculate CV risk.
Aim to maintain normal meal pattern • Levemir (insulin detemir – once or twice daily)
even if appetite is reduced (could • Onset 0-2hrs; duration 18-42hrs; no peak Kidney function: measure ACR and
replace with carbohydrate containing • Tresiba (insulin degludec): extra-long acting, available in 2 CrCL. Start an ACE I in adults with
drinks) strengths confirmed nephropathy
Mixed insulins BMI: aim for 18.5-24.9 (18.5-22.9 in
Aim to drink at least 3L of fluid to
• Humulin M3; Novomix; Humalog mix; Insuman Comb patients of Asian ethnicity)
prevent dehydration • Mixture of an intermediate acting insulin with a rapid acting
or a soluble insulin
Seek urgent medical attention if Thyroid: check TSH annually in T1DM
violently sick, unable to keep fluids Xultophy (increased risk of other autoimmune
down or if drowsy. • Insulin degludec with liraglutide diseases)
32
ENDOCRINE SYSTEM – DIABETES TREATMENTS
INSULIN REGIMENS T2DM TREATMENT
1 – Basal bolus regimen See NICE guide NG 28: Algorithm for blood glucose lowering therapy in
• 1st-line therapy in T1DM adults with type 2 diabetes:
• Long-acting insulin with rapid acting insulin at mealtimes Overview | Type 2 diabetes in adults: management | Guidance | NICE
• E.g., BD Levemir with mealtime Novorapid or OD Tresiba with
mealtime Fiasp
• Advantages: better glucose control and allows for mealtime If HbA1c rises to 48mmol/mol on lifestyle interventions
flexibility • Offer standard-release metformin
• Disadvantages: multiple daily injections • If standard release metformin not tolerated, trial M/R preparation
2 – Continuous glucose infusion First intensification: if HbA1c rises to 58mmol/mol, consider dual therapy adding one of
• Used with continuous glucose monitoring the following (treatment choice is based on presence of cardiovascular disease, heart
failure, renal disease or need for glucose control):
• T1DM only
• GLP-1, SGLT-2 inhibitor, DPP-4 inhibitor, sulphonylurea or pioglitazone
3 – Twice daily biphasic regimen
Second intensification: if HbA1c rises to 58mmol/mol, consider triple therapy with
• Can be used in T1DM if basal bolus not suitable
metformin + DPP-4I + SU; or + pioglitazone + SU; + pioglitazone/SU + SGLT-2i
• Can be used in T2DM also
• 1st-line is soluble mixed – Humulin M3 Or consider insulin-based treatment (intermediate or basal only regimen)
• 2nd-line is rapid-acting mixed – Novomix 30
• Advantages: fewer injections compared to basal-bolus regimen If triple therapy is ineffective, not tolerated or contraindicated consider:
• Disadvantages: does not allow for mealtime flexibility • Reassess patient for compliance
• Consider weight management and exercise levels
4 – Intermediate acting/basal only regimens • Be aware of clinical inertia – are we choosing the best therapy for this patient
• Only used in T2DM when considering their co-morbidities?
• 1st step of insulin treatment in T2DM • Consider metformin + SU + GLP-1 (see NICE ng 28 for additional info.)
• NICE recommends using an intermediate acting insulin such as
once or twice-daily Insulatard If HbA1c rises to 48mmol/mol on lifestyle interventions and metformin
contraindicated or not tolerated
Remember that insulin should be prescribed by brand! • Consider 1 of: DPP-4i, pioglitazone or SU; or SGLT-2i instead of a DPP-4i if
SU or pioglitazone not appropriate
Be aware of high strength insulin. Most insulin devices contain
100units/ml. High strength insulins are defined as insulin products First intensification: if HbA1c rises to 58mmol/mol, consider dual therapy with: a DPP-4i
that contain more than 100units/ml (e.g., Toujeo 300units/ml or +pioglitazone; OR: a DPP-4i + SU; OR pioglitazone +SU
Tresiba 200units/ml). This creates an increased risk of error
Second intensification: if HbA1c rises to 58mmol/mol, consider insulin-based treatment
Aim for HbA1c: 53 mmol/mol
33
ENDOCRINE SYSTEM – ANTIDIABETIC AGENTS
METFORMIN PIOGLITAZONE DPP-4 INHIBITORS
MOA: increases insulin sensitivity; Alogliptin, linagliptin, saxagliptin,

MOA: a PPAR agonist – increases insulin sensitivity and
inhibits gluconeogenesis and sitagliptin, vildagliptin
reduces hepatic glucose output
glycogenolysis
S/Es: Weight gain (fluid retention), bladder cancer, HF, MOA: DPP-4 usually breaks down
Dose: 500mg OD with breakfast for 1 GLP-1 (which stimulates insulin
week; 500mg BD with breakfast and increased risk of bone fractures, LF (rare)
release and lowers glucagon
dinner for 1 week; 500mg TDS with secretion). By inhibiting DPP-4, GLP-
breakfast, lunch, and dinner thereafter. CV safety: incidence of HF is increased when combined with
1 activity increases
This reduces the risk of GI s/e. If GI s/e insulin therapy. Closely monitor for signs of HF and discontinue
are still problematic, MR preparations treatment if any deterioration in cardiac status occurs
can be used. DPP-4
CI: Heart failure; previous or active bladder cancer; GLP-1
S/E: GI disturbances (very common); inactivates
uninvestigated macroscopic haematuria.
lactic acidosis (rare, increased risk of GLP-1
renal impairment); decreased absorption Review safety and efficacy after 3-6 months and stop treatment
of vitamin B12 (rare) in patients who do not receive any benefit. Advise patients to
promptly report haematuria, dysuria, or urinary urgency during
CI: CrCL <30, metabolic acidosis
treatment.
Weight neutral; does not cause hypos
Stimulates
Interactions: contrast media (increased insulin
risk of AKI) secretion and
SULPHONYLUREAS suppresses
glucagon
Gliclazide, tolbutamide, glipizide, glimepiride secretion
ACARBOSE
MOA: stimulate insulin secretion therefore taken with or
Very rarely used after meals. Note that glibenclamide is a long-acting agent
MOA: inhibits alpha glucosidases thereby delays therefore has an increased risk of hypoglycaemia, No weight gain: less hypoglycaemia
starch and sucrose absorption (must use especially at night. compared to sulphonylureas
glucose to treat hypos)
S/E: hypoglycaemia, weight gain. S/E: pancreatitis – discontinue if
S/E: GI disturbances; liver failure (rare) symptoms occur.
Note that gliclazide is principally metabolised in the liver Vildagliptin – discontinue if signs of
Take directly before meal/with 1st mouthful liver toxicity
therefore can be used with caution in renal impairment
34
ENDOCRINE SYSTEM – ANTIDIABETIC AGENTS
MEGLITINIDES GLP-1 AGONISTS

SGLT-2 INHIBITORS
Nateglinide; repaglinide More widely used now due to CVD benefits
Canagliflozin, dapagliflozin, empagliflozin
Rarely used Liraglutide, dulaglutide, semaglutide,
Excellent evidence for reducing HF and CVD. Canagliflozin exenatide, lixisenatide
MOA: have a rapid onset of has evidence for preventing deterioration in renal function and
action and short duration of can be initiated if eGFR >30ml/min. It can be continued in MOA: bind to GLP-1 receptor to increase
action. They work similarly to patients already on it if their eGFR drops below this. insulin secretion and suppress glucagon
sulphonylureas in that they secretion. They also delay gastric emptying.
stimulate insulin secretion MOA: inhibit sodium-glucose co-transporter-2 in the proximal Can help with weight loss – sometimes
convoluted tubule in the nephron to reduce glucose significantly
Administration: 1-30 minutes reabsorption and increase urinary glucose excretion
before meals. Omit dose if Initiation: in patients on insulin the insulin
omit meal. Cautions: elderly (risk of hypotension); hypotension; correct dose should be reduced but blood glucose
hypovolaemia before treatment levels monitored closely to prevent DKA or
S/E: hypoglycaemia, pruritis, hypoglycaemia
rash, urticaria Risk of DKA: DKA can present atypically with raised ketones
but only moderately raised BG (these agents cause glucose to Administration: subcutaneous injection.
These agents can be used be excreted in the urine but not ketones). Counsel patients on Some formulations must be given before
flexibly around mealtimes signs and symptoms of DKA and to seek immediate medical meals
however they are generally attention if these occur. Discontinue and do not restart if DKA
less preferred than occurs with no other identified cause. Exenatide – antibiotics and GR
sulphonylureas formulations should be taken at least 1 hour
Risk of lower limb amputation (mainly toes) and reports of before or 4 hours after exenatide.
Fournier’s gangrene.
CI: severe GI disease
S/E: polyurea, polydipsia, genital infection, UTI, dehydration,
dysuria, hypotension, hypovolaemia S/E: pancreatitis (discontinue permanently if
this develops); GI side effects
Monitoring: renal function before treatment and then annually
35
ENDOCRINE SYSTEM – CORTICOSTEROIDS
USES OTHER POINTS TO NOTE

• IBD MINERALCORTICOID SIDE EFFECTS
• Rheumatoid arthritis Infections – long courses of steroids
• Oncology • Anxiety, osteoporosis, peptic ulceration increase infection risk and infection
• Pain/symptoms due to nerve compression • Hypertension, impaired healing severity
• Respiratory tract infections • Na+ and water retention, most marked with
Chickenpox – immunisation required for
• Replacement – e.g., Addison’s disease fludrocortisone (therefore can be used for
patients who have been exposed to
• Asthma postural hypotension) chickenpox and whom are not already
• And many others • K+ and Ca2+ loss immune
• Psychiatric disorders
• Negligible with dexamethasone Measles – particular care required to
avoid exposure
TREATMENT CESSATION GLUCOCORTICOID SIDE EFFECTS
Psychiatric reactions – advise patients
Gradual withdrawal is required in the • Diabetes mellitus, muscle wasting to seek medical advice if they experience
following circumstances: • Osteoporosis, avascular necrosis of the psychiatric symptoms (rare possibility on
withdrawal of treatment also)
femoral head (high doses)
More than 40mg prednisolone daily (or
equivalent) for more than 1 week • Peptic ulceration, electrolyte imbalance Adrenal suppression/ non-functional –
• Headache, impaired healing adrenal atrophy can develop during
Repeat doses of steroids in the evening • Skin reactions, Cushing’s syndrome prolonged therapy. For patients on long-
• Psychiatric reactions, anxiety term steroids (including inhaled), acute
More than 3 weeks treatment • High potency glucocorticoids include illness, trauma or surgery requires a
dexamethasone and betamethasone temporary increase in dose. Patients
Recently received repeated courses may need a hydrocortisone emergency
MHRA/CHM ADVICE – CORTICOSTEROIDS IM injection kit to prevent adrenal crisis
A short course within 1 year of stopping
long-term therapy Growth restriction – in paediatric
• Rare risk of central serous chorioretinopathy patients, less likely with recommended
If patient has other possible causes of • Patients should report any blurred vision or doses of inhaled therapy (initial growth
adrenal suppression other visual disturbances with corticosteroid velocity may be reduced however).
treatment given by any route
Note that abrupt withdrawal can cause Steroid card – for patients on long-term
acute adrenal insufficiency, hypotension treatment
and even death August 2020: Steroid Emergency Card – to
support early recognition of adrenal crisis in
adults
36
ENDOCRINE SYSTEM – OSTEOPOROSIS: BISPHOSPHONATES
USES ALENDRONIC ACID

MHRA/CHM ADVICE – ALL BISPHOSPHONATES
Prophylaxis and treatment of Dose: 10mg daily or 70mg weekly
osteoporosis (including post- Atypical femoral fractures
menopausal and corticosteroid-induced) • Reported rarely, mainly in patients receiving long- CIs: abnormalities of the oesophagus;
hypocalcaemia, delayed gastric emptying
term treatment for osteoporosis
Treatment of Paget’s disease, • Re-evaluate use based on risk vs benefit after 5 Cautions: dysphagia; surgery of the
hypercalcaemia of malignancy and in years of use upper GI tract; GI disorders (e.g., ulcers,
bone metastases in breast cancer • Advise patients to report thigh, hip, or groin pain gastritis, bleeding) especially in elderly
patients – STOPP criteria
Osteonecrosis of the jaw Correct vitamin D deficiency or
• Higher risk in patients receiving IV therapy for the hypocalcaemia before initiating
DRUGS treatment of cancer
• Risk factors: potency of drug (zoledronate highest), S/E: GI s/e are common
Alendronic acid – most commonly route of admin, cumulative dose, duration and type
seen; oral agent Oesophageal reactions have been
of malignant disease, concomitant treatment, reported and patients should stop taking
smoking, history of dental disease and seek advice if they develop
Zoledronic acid – intravenous • Dental check-up required before treatment dysphagia, new or worsening heartburn
infusion
• Patients should maintain good oral hygiene and or retrosternal pain
Risedronate sodium – oral agent receive regular routine dental check ups
Renal: avoid if CrCL <35ml/min
• Patients should report any dental mobility, pain or
Ibandronic acid – intravenous swelling, non-healing sores or discharge Counselling: for all PO bisphosphonates
infusion and oral • Ensure dentures fit correctly
• Patients should be given a patient reminder card if Tablets should be swallowed whole with
Pamidronate disodium – intravenous receiving IV bisphosphonates plenty of water whilst sitting or standing
infusion on an empty stomach at least 30mins
before breakfast or other medication.
Osteonecrosis of the external auditory canal Remain upright for at least 30mins.
Denosumab, teriparatide and • Reported very rarely, mainly in patients receiving
raloxifene are non-bisphosphonate long-term therapy (>2 years) Interactions:
alternatives Al3+, Ca2+, Mg2+, Zn2+ containing
• Risk factors: steroid use, chemotherapy, infection,
medicines - take 30mins apart.
ear operation, cotton-bud use Gastric irritants
• Advise patients to report any ear pain, discharge, or
ear infections
37
ENDOCRINE SYSTEM – THYROID DISORDERS
HYPOTHYROIDISM HYPERTHYROIDISM
Blood results: Blood results:

Low T3, low T4 and raised TSH High T3, high T4 and low TSH
Signs and symptoms: Signs and Symptoms:

Fatigue, cold intolerance, weight gain, arthralgia, myalgia, constipation, Breathlessness, neck pressure, heat intolerance, increased sweating,
depression, coarse dry hair and skin, goitre, mood changes increase appetite, weight loss, diarrhoea, agitation, mood changes, fine
tremor, goitre, bulging eyes (exophthalmous).
Treatment: Can lead to AF and HF
Levothyroxine
• Adults 18-49yrs – 50-100mcg OD (adjusted by 25-50mcg every 3-4 Thyroid storm - rare
weeks) Emergency situation with tachycardia, fever, D&V, high BP
• Adults 50yrs+, with cardiac disease or severe hypothyroidism – 25-50mcg Treatment includes – IV fluids, IV propranolol, IV hydrocortisone, oral
OD (adjusted by 25mcg every 4 weeks) iodine and carbimazole/propylthiouracil
• Maintenance 50-200mcg OD – can be higher in pregnancy
Long-term therapy
• Caution in CV disorders (baseline ECG valuable) Carbimazole
• Used alone or in blocking-replacement regimen
• May 2021 MHRA safety update: new prescribing advice for patients
• Safety info – can cause neutropenia and agranulocytosis.
experiencing symptoms on switching between levothyroxine products:
Counsel patients on recognising signs/symptoms such as a sore
• MHRA Drug Safety Update May 2021: PSNC Main site
throat and to seek urgent medical help
• Take at least 30mins before breakfast, caffeine-containing liquids, or other • Rashes and pruritis are also common (use antihistamines)
medication Propylthiouracil
• Reserved for those intolerant of carbimazole and in 1st trimester
• S/E: if dose is too high, may cause signs of hyperthyroidism (see right) of pregnancy (switch to carbimazole in 2nd)
• Can cause hepatotoxicity (including liver failure resulting in
Liothyronine transplantation) – counsel patients to report anorexia, nausea,
• For severe hypothyroid states when a rapid response is required (e.g., vomiting, abdominal pain, dark urine
hypothyroid coma)
• Given IV Curative treatment options:
• Rapid effect that lasts 24-48hrs • Surgery
• Note: if switching from levothyroxine to liothyronine, dosage is not equivalent (20- • Radioactive iodine
25mcg of liothyronine is approx. equivalent to 100mcg of levothyroxine)
38
ENDOCRINE SYSTEM – DIABETES INSIPIDUS
DIABETES INSIPIDUS
Signs and Symptoms:

Passing of large volumes (>3L/24hrs) of dilute urine (polyuria),
nocturia and thirst
Treatment:
Maintain fluid intake
Desmopressin (vasopressin analogue) PO, SL, intranasal or SC, IV
or IM injection
Cautions:
Fluid overload, cardiovascular disease, heart failure, hypertension
Monitoring:
• Serum sodium levels
• Urine output
• Fluid balance
Interactions:
Chlorpromazine, lamotrigine, and medications that increase the risk
of hyponatraemia
Side effects:
Hyponatraemia, especially if fluid intake is not restricted
NB – Risk of severe harm or death when desmopressin is

omitted or delayed in patients with cranial diabetes insipidus;
can happen within hours, MHRA Alert 2016.
39
INFECTION - ANTIBIOTICS
GLYCOPEPTIDES
START SMART THEN FOCUS AMINOGLYCOSIDES
Vancomycin and Teicoplanin
Start smart: Bactericidal, activity against many gram-negative (including Pseudomonas
aeruginosa) and some gram-positive infections Broad spectrum against gram positive
Do not start antimicrobial therapy
only (cannot penetrate porins of
unless clear evidence of infection Not absorbed from the GI tract therefore given IV or topically gram-negative organisms)
Check allergies S/E: Active against MRSA
• Nephrotoxicity – more common in renal impairment. Therefore, Vancomycin – infusion
Sepsis – ‘golden hour’ dosage interval should be increased in pts with renal impairment Teicoplanin -bolus
(more time for drug to be excreted)
Comply with local antimicrobial • Ototoxicity S/E
guidelines • Hypocalcaemia, hypokalaemia, hypomagnesaemia • Red man syndrome (if
• May impair neuromuscular transmission (therefore CI in infused too fast)
myasthenia gravis) • Nephrotoxicity
Then focus:
• Ototoxicity
Gentamicin
Stop abx if no evidence of
• Not active against anaerobes therefore when used for empirical Vancomycin
infection
therapy, it is often used in combination with a penicillin or IV usually give a loading dose and
metronidazole then 12hrly dosing (less frequently
Switch from IV to oral route
• Usual dose 3-7mg/kg/day (ideal body weight used to calculate to and at reduced dose in renal
avoid excessive doses in obese patients (aminoglycosides are impairment)
Change abx to a narrower
hydrophilic). Dosage interval extended in pts with renal impairment
spectrum (or broad spectrum if
from 24 hourly to 36 or 48 hourly Pre-dose trough level should be 10-
required)
15mg/L (15-20mg/L in more
TDM: severe/deep seated infections e.g.,
Continue and document new
review or stop date • For once daily dose regimens pre-dose trough <1mg/L or monitor endocarditis, osteomyelitis)
again a gentamicin nomogram (see individual Trust guidelines)
OPAT – outpatient parenteral • For multiple daily dose regimens 1 hour peak 5-10mg/L (3-5mg/L Used PO for C. diff 125mg QDS for
abx therapy in endocarditis) and trough levels <2mg/L (<1mg/L in endocarditis) 10-14 days. Dose can be increased in
severe C. diff
More info: Start Smart- Then Tobramycin

Focus Antimicrobial Stewardship • Can be nebulised – often used for 28-day cycles in cystic fibrosis
Toolkit for English Hospitals
40
CARBAPENEMS CEPHALOSPORINS
Beta-lactam antibiotics (caution if penicillin allergy) therefore inhibitors of cell Beta-lactam antibiotics (caution if penicillin allergy) therefore inhibitors of
wall synthesis cell wall synthesis
Broad spectrum – gram positive, negative and anaerobes Approx. 0.5-6.5% of penicillin-sensitive patients will also be allergic to
cephalosporins.
Meropenem and Imipenem – active against Pseudomonas aeruginosa
1st generation – e.g., cefalexin (often used in UTI, safe in pregnancy)
Meropenem is least likely to induce seizures (therefore used for CNS
infections). Higher doses in CNS infections to ensure reaches CSF. 2nd generation – e.g., cefuroxime (more activity against gram negative
bacteria)
Ertapenem – Once daily - not active against Pseudomonas aeruginosa
3rd generation – e.g., ceftriaxone and ceftazidime (ceftazidime active
Interactions – carbapenems decrease the concentration of sodium valproate against pseudomonas)
to as low as 10%. Increasing the dose of sodium valproate does not counteract
this interaction 4th generation – e.g., cefepime (broad spectrum)
QUINOLONES
Ciprofloxacin – only oral agent active against Pseudomonas aeruginosa; may MACROLIDES
decrease phenytoin levels
Similar spectrum to penicillins therefore can be used in penicillin allergy
Safety information: https://www.gov.uk/drug-safety-update/fluoroquinolone-antibiotics-new- and often used to cover atypical organisms. Good bioavailability so should
restrictions-and-precautions-for-use-due-to-very-rare-reports-of-disabling-and-potentially-long-lasting- be given orally where possible
or-irreversible-side-effects
Erythromycin has more GI side effects compared to clarithromycin

Tendon damage and rupture has been reported rarely therefore CI if hx of
tendon disorders following quinolone use. Concomitant use of corticosteroids Erythromycin = QDS Clarithromycin = BD
increases the risk
Interactions – inhibitors of CYP3A4 therefore can increase the
Convulsions may be induced & taking NSAIDs at same time increases risk concentration of statins, warfarin, CCBs, apixaban, ciclosporin and digoxin
Cautions Cautions – can prolong the QT interval
QT-interval prolongation; can cause arthropathy in children; hx of epilepsy;
avoid excessive exposure to sunlight
41
PENICILLINS
Overview
• Inhibitors of bacterial cell wall synthesis; bactericidal

• Allergic reactions occur in 1-10%; anaphylaxis occurs in <0.05%
Benzylpenicillin (Pen G) & phenoxymethylpenicillin (Pen V)
• Penicillin G – inactivated by gastric acid therefore given parenterally

• Penicillin V – similar spectrum but less active than pen G; active orally; should be taken on an empty stomach
Penicillinase-resistant penicillins
• Flucloxacillin –used to treat skin and soft tissue infections caused by Staphylococcus aureus; not inactivated by penicillinases therefore active
against penicillin-resistant staphylococci; must be taken on an empty stomach; QDS dosing
• Temocillin – active against beta-lactamase-producing gram-negative bacteria
Broad-spectrum penicillins
Should not be used for the blind treatment of sore throats as often cause a maculopapular rash in people with glandular fever
• Ampicillin – active against gram-positive and gram-negative but inactivated by penicillinases (if used in hospital, should check sensitivity first)
• Amoxicillin – better absorbed PO compared to ampicillin
• Co-amoxiclav – amoxicillin plus clavulanic acid therefore active against beta-lactamase producing organisms (reduce dose of IV in renal impairment)
Anti-pseudomonal penicillins
• Piperacillin + tazobactam (tazocin) – usual dosage 4.5g TDS (reduce in renal impairment)
• Synergistic effect when combined with an aminoglycoside
Tip – it is worth learning amoxicillin doses in paediatric patients (age banded)
42
TRIMETHOPRIM / CO-TRIMOXAZOLE LINEZOLID METRONIDAZOLE
Serious Interaction – with MTX (folate antagonist) Monitoring – Can cause myelosuppression. MOA – a pro-drug whereby the nitro-group
FBC (including platelets); blood disorders must be reduced (can only be achieved by
Trimethoprim more likely if treatment >10-14 days anaerobes – therefore spectrum limited to
• Most commonly used for UTIs 200mg BD anaerobes)
• Sometimes 100mg ON for UTI prophylaxis Safety information – can cause optic
• Contra-indicated if blood disorders present neuropathy so patients should report any Dose – 400 TDS (oral), 500mg TDS (IV). Good
visual disturbances bioavailability so give by oral route if available
Co-trimoxazole
• Trimethoprim + sulfamethoxazole Interaction - can cause serotonin syndrome Counselling – take with food; avoid alcohol
with the co-administration of linezolid and during treatment and for 48hrs after; may
• Treatment/prevention of PCP
serotonergic agents, including darken the urine
• Prophylactic dose often MON/WED/FRI
• Caution in sulphonamide allergy antidepressants such as selective serotonin
reuptake inhibitors (SSRIs). Check
• Monitor for blood disorders (leucopenia,
interactions closely
thrombocytopenia, anaemia) and rash (SJS, TEN)
TETRACYCLINES
Broad spectrum; active against MRSA
NITROFURANTOIN CI - <12yrs due to deposition in teeth and bones
MOA – requires excretion into the urine for effect against UTI therefore may be ineffective if CrCL <45ml/min Counselling – swallow whole with plenty of
water whilst sitting or standing; take during
Dose – IR 50-100mg QDS; MR 100mg BD meals; avoid exposure to sunlight / sunlamps
Counselling – may turn urine yellow-brown Dose – doxycycline usually 200mg STAT
Safety Information- risk of peripheral neuropathy. Acute, subacute, and chronic pulmonary reactions have followed by 100mg OD
been observed in patients treated with nitrofurantoin. If these reactions occur, nitrofurantoin should be
discontinued immediately.
CHLORAMPHENICOL CLINDAMYCIN
Use – broad spectrum; used IV for life-threatening infections S/E – associated with antibiotic-associated colitis, which could be fatal (more
common than with other abx). D/C treatment if this occurs
Infants – can cause ‘grey-baby syndrome’ (avoid in pregnancy)
S/E – can cause blood disorders, optic neuritis, peripheral neuropathy, stomatitis
43
INFECTION - TUBERCULOSIS
TREATMENT OVERVIEW TYPES OF TB

Latent vs Active
Treated in two phases Latent
Initial phase (usually 2 months) • Dormant infection: more likely to progress to active in patients who
• To eradicate bacteria as quickly as possible and reduce the are HIV positive, immunocompromised, and elderly
chance of resistance emerging • The Mantoux skin test can be used to test for latent TB and if
• 4 drugs – isoniazid, rifampicin, ethambutol, pyrazinamide (Rifater positive, a CXR can be used to rule out active TB
+ ethambutol) • Offer chemoprophylaxis to patients with latent TB if they are
healthcare workers, close contacts of a person with active TB,
Continuation phase (usually 4 months) immunocompromised (6 months isoniazid or 3 months isoniazid +
• Isoniazid + rifampicin (Rifinah) rifampicin)
• Longer duration required for TB meningitis and for resistant Active
strains • Active infection, usually affecting the lungs but it can affect many
other body systems
Two choices of regimen • Treated in 2 phases (see box to left)
Unsupervised
• Daily treatment
• For patients who are likely to be compliant
RIFAMPICIN
Supervised (DOT – directly observed therapy)
• For patients who cannot comply reliably Interactions – potent enzyme inducer (warfarin, COCs)
• Important they are treated effectively to stop spread of the
infection Counselling – discolours soft contact lenses, turns secretions orange-red,
report sx of hepatic disorders (abdominal pain, nausea, vomiting)
• If daily supervision not appropriate, can have 3 x weekly
Monitoring – renal function; liver function; blood counts
ISONIAZID
PYRAZINAMIDE S/E – peripheral neuropathy (increased risk in DM, renal impairment, alcohol
dependence, malnourished pts, uraemic pts, pregnancy, HIV – give
Monitoring – liver and renal function (can cause hepatoxicity) prophylactic pyridoxine)
ETHAMBUTOL Monitoring – acetylator status (slow = increased risk of peripheral

neuropathy); renal function; liver function
Monitoring – visual acuity (can cause ocular toxicity), renal function
Counselling – tyramine + histamine rich foods can cause tachycardia,
Counselling – d/c treatment immediately and seek medical attention if visual hypotension, flushing, headache, dizziness; report sx of hepatic disorders
disturbances occur
44
INFECTION - ANTIFUNGALS
TRIAZOLES POLYENES
Fluconazole, itraconazole, posaconazole, voriconazole Amphotericin B

• Highly protein bound
Fluconazole • Toxic and commonly causes s/e (abnormal liver function, anaemia,
• Can purchase OTC for candida infection arrhythmias, blood disorders, hypoK+ and hypoMg2+
• Can cause QT-interval prolongation • Lipid formulations reduce toxicity (e.g., Ambisome, Abelcet, Fungizone)
• Less commonly associated with liver damage • Serious harm and fatal overdoses have occurred following confusion
• Interactions mostly relate to prolonged treatment (enzyme between liposomal, pegylated-liposomal, lipid-complex, and conventional
inhibition) formulations of the same drug substance. These formulations are NOT
interchangeable.
Itraconazole • Test dose required before first dose and patient should be observed for
• Liver damage – avoid in patients with liver disease 30mins for anaphylaxis
• Can be used to treat pityriasis versicolor • Infused slowly as rapid infusion can cause arrhythmias
• High doses and long treatment durations are associated
with HF (avoid in patients with a history of HF) Monitoring
• Capsules – take with food • Liver and renal function
• Solution – take on an empty stomach • Blood counts
• K+ and Mg2+
Posaconazole
• Used for invasive fungal infections unresponsive to other
treatments Nystatin
• Used for oral infections – swirled around the mouth and swallowed
Voriconazole
• Used for invasive fungal infections, in possible life-
threatening infections
• IV and oral
• Lots of interactions IMIDAZOLES ECHINOCANDINS
• Non-linear pharmacokinetics
• Monitor LFTs Clotrimazole, miconazole, econazole, Caspofungin, Micafungin
• Associated with phototoxicity ketoconazole
• IV only. Not effective against
Mainly topical treatments e.g., ketoconazole fungal CNS infections. Only
shampoo; clotrimazole pessary active against Aspergillus and
Candida
Miconazole oral gel – interacts with warfarin
(can increase INR)
45
GENITO-URINARY MEDICINE
Urinary Frequency Urinary Retention
Anticholinergic Drugs Antimuscarinics, tricyclic antidepressants and sympathomimetics may

Increase bladder capacity and decrease symptoms of urgency and urge contribute to urinary retention
incontinence. Their use should be reviewed at 4 weeks and 12 weeks for
efficacy then every 6 (age>75) to 12 months. Start lowest dose and titrate Urinary retention and benign prostatic hyperplasia
• Alpha blocker = treatment of choice: relaxes smooth muscle
Contraindications and produces an increase in urinary flow rate
• Angle-closure glaucoma, GI obstruction; paralytic ileus; toxic • 5a-reductase inhibitor = considered when there is raised
megacolon; severe UC, Urinary retention; bladder outflow prostate specific antigen and a high risk of progression
obstruction • Both can be combined if symptoms remain problematic
Cautions Alpha blockers

• CVD (MI, HF, CAD, HTN), Susceptibility to angle-closure • Doxazosin – 1mg OD, can be increased to 8mg OD
glaucoma, UC, elderly • Tamsulosin – 400micrograms OD
S/E • Contraindications – postural hypotension
• ‘Can’t spit, can’t see, can’t poo, can’t pee’ – dry mouth, vision
disorders, constipation, urinary retention 5a-reductase inhibitors for BPH related retention
• Dizzy, drowsy – affect driving, tachycardia • Dutasteride – 500micrograms OD
• Finasteride – 5mg OD. MHRA warning: reports of depression
Oxybutynin and suicidal thoughts
• MR preparations may reduce side effects
• Available as a transdermal patch • S/E – breast enlargement, breast tenderness, decreased
• Dose 5-20mg per day libido, ejaculation disorders, impotence
• Cases of male breast cancer have been reported – patients
Darifenacin should report any lumps, tenderness, or nipple discharge
• 7.5-15mg per day (max 5mg If CYP3A4 inhibitors prescribed) • Women of childbearing age should avoid handling
• Condoms recommended if woman is pregnant or could
Tolterodine become pregnant
• 1-2mg BD or 4mgMR OD
• Can cause peripheral oedema Combination drug of Alpha blocker and 5a-reductase inhibitors
available
Beta3 Agonist – Mirabegron 50mg OD (if above CI)
• Common side effect – tachycardia and UTI
46
GENITO-URINARY MEDICINE - CONTRACEPTION
Combined Oral Contraceptive Pill (COC) Combined Oral Contraceptive Pill (COC)
MOA – prevent ovulation, cause thickening of the mucus in the womb and A missed pill is defined as >24hrs late
thin the endometrium. Contain an oestrogen and a progesterone.
One Missed Pill
Minor S/E – mood changes, nausea, breast tenderness, headaches • Take the pill as soon as you remember, even if it means taking
2 pills at the same time
Major S/E (rare) – VTE, cervical cancer • Carry on taking the rest of the pack as normal
• Take your 7-day PFI as normal (unless you have the everyday
1 – Monophasic 21-day pills pill)
• Each pill has the same content of hormone • No extra contraception required
• Take one pill OD for 21 days, followed by a 7-day pill-free interval
(PFI) Two or more missed pills
• E.g., microgynon, gedarel, yasmin, rigevidon • This is 48hrs or more without a pill
• Take the last pill missed as soon as you remember, even if
2 – Multiphasic 21-day pills this means taking 2 at the same time
• One pill OD for 21 days, following by a 7-day PFI • Leave any earlier missed pills
• Pills must be taken in the correct order as they contain differing • Carry on the rest of the pack like normal
hormone contents • Use extra contraception for next 7 days
• E.g., logynon • If there are 7 or more pills left in the pack after the last missed
pill, finish the pack and take your 7-day PFI as normal (or
3 – Everyday pills inactive pills if everyday pill)
• 21 active pills and 7 placebo pills (different appearance) • If there are <7 pills left in the pack after the missed pill, finish
• Pills must be taken in the correct order the pack and start a new pack the next day (i.e., miss the 7-
• E.g., logynon ED day PFI or miss the inactive pills in the everyday pill)
Who should not take the COC? – see BNF for full list Vomiting and Diarrhoea
• 35yrs + and a smoker (or stopped smoking <1yr ago) • If you vomit within 3hrs of taking, take another pill straight
• Overweight – BMI 35+ away
• Previous VTE or family history of VTE at <45yrs old • If you continue to vomit, use extra protection for 7-days after
• Previous stroke, history IHD, Hypertension the vomiting has stopped
• Diabetes with microvascular disease • Severe diarrhoea for >24hrs – use extra protection for 2-days
• Severe migraines, especially with aura after the diarrhoea has finished
• History of breast cancer
47
GENITO-URINARY MEDICINE - CONTRACEPTION
COC – interactions
Progestogen-Only Pill (POP)
Rifampicin or rifabutin
• Reduces contraceptive effect (potent enzyme inducers) MOA – thicken the mucus in the cervix; if desogestrel-containing, also
stop ovulation.
Antiepileptics
• Carbamazepine, Oxcarbazepine, Phenytoin, Phenobarbital + How to take
primidone, Topiramate - These reduce the contraceptive effect (See ‘3-hour POP’ – must be taken within 3hrs of the same time each day
Stockley’s for management advice)
Others ’12-hour POP’ – contains desogestrel. Must be taken within 12-hours
• St John’s Wort of the same time each day
• Griseofulvin
A pack contains 28 days, one must be taken each day. There is no
break between packs
If the pill is started on days 1-5 of the menstrual cycle, it will work
immediately, and no additional contraception will be required.
Advantages of COC
If started on any other day, additional contraception will be required for
• Reliable and reversible 48hrs
• Reduced dysmenorrhoea and menorrhagia Missed Pills – i.e., 3 hours or 12 hours late
• Take the pill as soon as you remember
• Reduced incidence of pre-menstrual tension • Take the next pill at the usual time (may mean taking 2 on the
same day)
• Less fibroids and ovarian cysts • Carry on taking remaining pills as normal
• Use extra contraception for 48hrs
• Less benign breast disease
Side Effects
• Reduced risk of colorectal, ovarian, and endometrial cancer • Breast tenderness and enlargement
• Ovarian cysts, Menstrual irregularities
• Reduced risk of pelvis inflammatory disease
• Increased / decreased libido
NOTE – should be discontinued 4 weeks before major elective surgery and • Mood changes
restarted 2 weeks after full remobilisation (due to clot risk) • Headache
• Weight gain
48
GASTROENTEROLOGY - CONSTIPATION
Self-Help Advice for Constipation Management of short-term constipation
Diet Rule out secondary causes and review drug regime

• Healthy, balanced diet with regular meals First-line: lifestyle measures (see left). If these are ineffective, offer laxatives in a stepped
• Whole grains approach as follows:
• Fruits high in sorbitol (apples, apricots, grapes, 1 – Bulk-forming laxative: e.g., ispaghula. Provide advice on adequate fluid intake
peaches)
2 – Osmotic laxative: e.g., macrogol. Should be substituted or added if stools remain
• Vegetables
hard/difficult to pass. Lactulose is second line to macrogol
• Gradually increase soluble fibre (minimise flatulence
and bloating) – adults should aim for 30g/day
3 – Stimulant laxative: e.g., senna. If stools are soft but difficult to pass or if there is a sensation
of inadequate emptying, add a stimulant.
Fluid
• Adequate fluid intake, especially if risk of For opioid-induced constipation: offer an osmotic + a stimulant laxative (or docusate). Do not
dehydration offer a bulk-forming laxative due to risk of faecal impaction – naloxegol if not effective
Exercise Laxative use should be gradually reduced and stopped once the person is producing soft stools
• Increase exercise activity to 30mins 5 x per week without straining at least 3 x per week
Helpful toileting routines
• Regular, unhurried toilet routine, giving time to fully
defecate
• Respond immediately to the sensation of needing to Faecal Impaction
defecate
• Ensure access to supported seating if the person is This is a solid, immobile mass of faeces that can develop in the rectum due to chronic constipation
unsteady on the toilet
1 – High dose oral macrogol if stools are hard
Red flag symptoms
• New onset >50 years old with below symptoms 2 – If there are soft stools or stools remain hard after a few days, add an oral stimulant laxative
• Unexplained weight loss 3 – If response is still inadequate or too slow, consider prescribing a suppository (e.g., bisacodyl
• Abdominal pain for soft stools or glycerol with/without bisacodyl for hard stools) or a mini enema (e.g., docusate
• Rectal bleeding or sodium citrate)
4 – If response is still inadequate, consider prescribing sodium phosphate or arachis oil
retention enema (remember latter contains peanut oil)
49
GASTROENTEROLOGY - CONSTIPATION
Types of Laxatives Contra-indications to laxatives
Bulk-forming laxatives • Intestinal obstruction or perforation

• Contain soluble fibre • Paralytic ileus
• Act by retaining fluid within the stool and increasing • Colonic atony or faecal impaction – bulk-forming laxatives
faecal mass • Crohn’s disease or Ulcerative Colitis
• Also, stimulant peristalsis • Toxic megacolon
• E.g., ispaghula, methylcellulose, sterculia • Severe dehydration – bisacodyl
Osmotic Laxatives • Galactosaemia – lactulose
• Increase amount of fluid in the large intestine producing • History of hypersensitivity to peanuts – arachis oil enema
distension, which leads to the stimulation of peristalsis
• Lactulose and macrogols have stool softening
properties Cautions for the prescribing of laxatives
• E.g., lactulose, macrogols (polyethylene glycols),
phosphate and sodium citrate enemas • Fluid and electrolyte disturbances
Stimulant Laxatives • History of prolonged use – risk of electrolyte imbalance e.g., hypoK+
• Stimulate colonic nerves (senna) or colonic and rectal • CVD – do not prescribe >2 sachets of full-strength macrogol compound oral
nerves (bisacodyl, sodium picosulfate) to cause powder in any one hour
peristalsis • Lactose intolerance – lactulose may cause diarrhoea
• E.g., senna, bisacodyl, docusate
• Docusate is a surface wetting agent, which reduces
surface tension of the stool, allowing water to penetrate
and soften it
Naloxegol is used in opioid-induced constipation Constipation in Pregnancy
• PEGylated derivative of the mu-opioid receptor
antagonist naloxone, it works as a peripheral receptor • First-line: lifestyle measures
antagonist without diminishing the analgesic effects of
opioids. • Second-line: bulk-forming laxative
For use where treatment failure with at least two different laxatives
from different classes at highest tolerated recommended dose for • Third line: osmotic laxative – add or switch
at least six months and where invasive treatment is being
considered:
Prokinetic Laxatives • If stools are soft but difficult to pass or there is a sensation of incomplete
emptying, consider a stimulant laxative (short course)
• Prucalopride – a selective 5HT4 receptor agonist, which
stimulates intestinal motility
• Fifth line: docusate or glycerol suppository
50
GASTROENTEROLOGY - DIARRHOEA
Overview
Clostridium Difficile Infection
Definition: The abnormal passing of stools with
increased frequency, increased volume, or both. Risk factors: >65yrs; antibiotic treatment (most common: clindamycin, cephalosporins,
Acute <14 days ciprofloxacin, norfloxacin, co-amoxiclav, ampicillin, amoxicillin); long duration of antibiotic
treatment; previous abdominal surgery; cancer; chronic renal disease; tube feeding; PPI or H 2-
Causes: drugs, IBD, infection, altered intestinal receptor antagonist use
motility
Severity
Red flag symptoms: unexplained weight loss, rectal Mild – not associated with an increase in WCC. <3 episodes of loose stools/day
bleeding, persistent diarrhoea, systemic illness, Moderate – increase in WCC (<15 x 109/L). 3-5 loose stools per day
recent antibiotic treatment, following foreign travel, Severe – increased WCC (>15 x 109)/L) or increased serum creatinine (>50% above baseline)
recent hospital treatment, blood/pus in stool, or temperature >38.5, evidence of severe colitis. Number of stools may be a less reliable
dehydration, nocturnal symptoms indicator at this stage
Life-threatening – hypotension, partial or complete ileus, toxic megacolon, or CT evidence of
Treatment: most episodes of acute diarrhoea settle severe disease
spontaneously without treatment. Attempt to
determine underlying cause Treatment
Stop antibiotic if appropriate, where not appropriate review to narrow spectrum and seek
• Oral rehydration therapy (disodium specialist advice
hydrogen citrate with glucose, KCl and NaCl; First episode of mild-moderate
KCl with NaCl; KCl with rice powder) • Oral vancomycin 10 days – 125-500mg QDS
• Fidaxomicin 10 days – 200mg BD
• If severe dehydration – immediate
admission to hospital and IV fluid Relapse (within 12 weeks) = Fidaxomicin
replacement required Recurrence (after 12 weeks) = Vancomycin or Fidaxomicin
• Loperamide – standard treatment when rapid Infection not responding to vancomycin or fidaxomicin / life-threatening infection / ileus present
control of symptoms required. It is also first • Oral vancomycin + IV metronidazole 10-14 days – 125-500mg QDS and 500mg
line for faecal incontinence. TDS
• Dose 4mg initially followed by 2mg after each Note – vancomycin injection can be given orally
loose stool, max. 16mg per day
Avoid giving antimotility drugs such as loperamide and ensure hygiene measures in place.
Consider impact of diarrhoea/dehydration on Review other medications with GI activity e.g., iron, laxatives, proton pump inhibitors
medicines (e.g., lithium, diuretics, contraception)
51
GASTROENTEROLOGY – INFLAMMATORY BOWEL DISEASE
Aminosalicylates
Azathioprine
Mesalazine, sulfasalazine, olsalazine, balsalazide
MOA –Azathioprine (AZA) is broken down enzymatically to 6-mercaptopurine, which
Sulfasalazine antagonises purine metabolism, thereby inhibits synthesis of DNA, RNA, and proteins.
• Broken down by colonic enzymes to 5- The mechanism of therapeutic effect however is largely unknown.
aminosalicylic acid (5-ASA) and therapeutically
inactive sulfapyridine Pre-treatment screening – thiopurine methyltransferase (TPMT)
• Sulfapyridine causes systemic side effects • This enzyme metabolises thiopurine drugs
• May stain soft contact lenses, yellow • Patients with diminished TPMT activity are at an increased risk of
discolouration of body fluids myelosuppressive side effects
• Formulations: tablets, GR tablets, oral • Azathioprine is contraindicated when TPMT activity if absent or very low and it is
suspension, suppository cautioned in reduced TPMT activity
• Patients are also screen for TB and vaccination status is confirmed
Mesalazine Some patients metabolise azathioprine in such a way that efficacy of treatment is
• Free 5-ASA only reduced, whilst the risk of side-effects is higher. In these patients you may see allopurinol
• Medicines which lower stool pH (e.g., lactulose) prescribed concomitantly, with a reduced dose of azathioprine (25-33% lower dose)
might prevent the release of GR/MR preparations
• Formulations: MR tablets, GR tablets, prolonged Side Effects
release granules, enemas, rectal foams. Delivery Hypersensitivity reactions – may include malaise, dizziness, vomiting, diarrhoea, fever,
characteristics may vary with different brands rigors, myalgia, arthralgia, rash, hypotension, renal dysfunction. Immediate withdrawal
required
Side Effects of Aminosalicylates Neutropenia & thrombocytopenia – neutropenia = dose-dependent side effect. If these
Common - Leucopenia, GI side-effects, pruritis, headache occur, monitoring and dose adjustment necessary
Uncommon - Alopecia, dyspnoea, photosensitivity, Nausea – this is common at the start of therapy and usually resolves after a few weeks.
thrombocytopenia Nausea can be reduced by dividing the daily dose, taking the dose after food or with the
Rare - Agranulocytosis, bone marrow disorders, use of antiemetics.
neutropenia, pancreatitis, renal impairment
Monitoring – FBC, creatinine clearance/eGFR, LFTs
Counselling – report any unexplained bleeding, bruising, Weekly for 4-8 weeks then at least every 12 weeks. (More frequent monitoring is
purpura, sore throat, fever, or malaise appropriate in patients at higher risk of toxicity). Dose increases: Every 2 weeks until
dose is stable for 6 weeks, then revert to previous schedule
Monitoring – FBC, Creatinine clearance/eGFR, LFTs.
Haematological abnormalities occur usually in the first 3- Counselling – Report signs or symptoms of bone marrow suppression – unexplained
6 months of treatment—discontinue if these occur. bruising / bleeding and infection
52
Methotrexate
Dose in Crohn’s Disease– up to 25mg weekly MOA in Crohn’s unclear
Important Safety information

• Advise patient the dose is a weekly dose
• Explain the rationale for taking folic acid alongside MTX (decreases mucosal and GI effects of methotrexate and may prevent hepatotoxicity. Usually taken on a
different day of the week, or up to 6 days weekly if side-effects experienced)
• Only one strength of MTX tablets should be dispensed (2.5mg usually)
Contraindications
• Active infection: significant pleural effusion, ascites (accumulates in fluid – drain first); immunodeficiency syndromes
Cautions
• Blood Count – bone marrow suppression can occur; increased age, renal impairment and the addition of other anti-folate drugs increase the risk (NOT TO BE
GIVEN WITH TRIMETHOPRIM); if a clinically significant drop in WCC or platelets occurs, immediately withdraw MTX and commence supportive therapy
• GI toxicity – if stomatitis occurs, withdraw treatment immediately as this could be the first sign of GI toxicity
• Liver toxicity – liver cirrhosis reported. Do not start treatment / stop treatment if abnormal LFTs or liver biopsy
• Pulmonary toxicity – may be a particular problem in rheumatoid arthritis; discontinue if pneumonitis suspected
Monitoring
• FBC, renal function, LFTs every 1-2 weeks until a stabilised then every 2-3 months. More frequent monitoring is appropriate in patients at higher risk of toxicity.
Dose increases: Every 2 weeks until dose is stable for 6 weeks, then revert to previous schedule. (Monthly monitoring should continue if used in combination with
leflunomide).
Counselling
• Report immediately signs of blood disorders (sore throat, bruising, mouth ulcers), liver toxicity (nausea, vomiting, abdominal pain, dark urine), respiratory effects
(shortness of breath)
• Purple treatment booklet.
• Avoid self-medication with aspirin or ibuprofen
• Read treatment booklet – available here for extra revision: https://www.sps.nhs.uk/wp-content/uploads/2018/02/2006-NRLS-0267-Oral-
methotrexaosage-record-2006-v1.pdf
53
Ciclosporin
Unlicensed use, last line in steroid-resistant UC (usually in an attempt to prevent surgery). Ciclosporin inhibits production and release of lymphokines =
suppression of cell-mediated immune response.
MHRA alert - Brands – patients should be stabilised on one brand of oral ciclosporin as switching between brands may lead to important changes in blood-
ciclosporin levels
Contraindications (in non-transplant indications)

• Abnormal baseline renal function
• Malignancy
• Uncontrolled hypertension and uncontrolled infections
Cautions
• Elderly (monitor renal function)
• Hyperuricaemia
• Malignancies
Food interactions
• Pomelo/grapefruit juice is predicted to increase ciclosporin exposure and purple grape juice decreases ciclosporin exposure
Side Effects
• Electrolyte imbalance, gingival hyperplasia, hepatic disorders,
• Hyperglycaemia, hyperlipidaemia, hypertension, hyperuricaemia,
• Leucopenia, paraesthesia, peptic ulcer, renal impairment
TDM – Monitor whole blood ciclosporin concentration (trough) – target level is dependent on the indication
Other monitoring
• Liver function and renal function, FBC, blood glucose and BP – discontinue if hypertension develops that cannot be controlled by antihypertensives.
Ciclosporin levels weekly until dose is stable for 6 weeks, then monthly. People who have been stable for 12 months can be considered for reduced
monitoring frequency (every 3 months) on an individual basis. More frequent monitoring is appropriate in patients at higher risk of toxicity.
• Serum K+/Mg2+and blood lipids at baseline – risk of seizures with hypomagnesemia, and toxicity with cholesterol <3mmol/L
Dose increases: Every 2 weeks until dose is stable for 6 weeks, then revert to previous schedule.
54
Crohn’s Management
Add-on treatment
Acute exacerbation – Monotherapy
2 or more inflammatory exacerbations in a 12-month period or
1st presentation or a single inflammatory exacerbation in 12-months
the glucocorticoid cannot be tapered
1st line Glucocorticosteroid Glucocorticosteroid (or budesonide) + azathioprine or
mercaptopurine
• Prednisolone • Assess TPMT activity before
• Methylprednisolone • Do not offer if this is very low or absent
• IV hydrocortisone • Consider using lower dose if TPMT below normal (but not
deficient)
Consider enteral nutrition as an alternative to above to induce • Monitor for neutropenia
remission for children in whom there is concern about growth or
s/e and young people in whom there is concern about growth Consider adding methotrexate
• In people who cannot tolerate azathioprine or MP
2nd line Budesonide – if above CI, decline or not tolerated • In people who have deficient TPMT activity
• Less effective
• Less s/e Adalimumab or infliximab (Anti-TNF monoclonal antibody)
Do not offer for severe presentations/exacerbations • Under specialist supervision
• If inadequate response to conventional therapies or
3rd line 5-ASA intolerance or C
• If above declined, not tolerated or CI Vedolizumab (α4β7 integrin monoclonal antibody)
• Fewer s/e • Treatment option for moderate-severe active Crohn’s when
• Less effective adalimumab or infliximab is unsuccessful, CI or not
Do not offer for severe presentations/exacerbations tolerated
Do not offer azathioprine, MP or MTX as monotherapy to induce remission
55
Active Fistulating Crohn’s Disease

Metronidazole and/or ciprofloxacin
• Metronidazole – usually given for 1 month (maximum 3 months due to risk of peripheral neuropathy)
Abx
• Ciprofloxacin - unlicensed
• Or as guided by Microbiology
Azathioprine or MP
Immuno-
suppressants
• To control inflammation
• Continued for maintenance for at least 1 year
For patients with active, fistulating Crohn’s disease:
• Who have not responded to conventional therapy (abx, drainage and immunosuppressants)
Infliximab
• Who are intolerant of or have CIs
• For 12 months or until treatment failure – whichever is first
Maintenance of Remission – Crohn’s Disease

• As monotherapy
Azathioprine
• Can be used when previously used with a corticosteroid to induce remission
or MP
• Can also be used in patients who have not previously received these drugs
• Only in patients who required MTX to induce remission
MTX
• Or patients intolerant of or are not suitable for AZA or MP for maintenance
Maintaining Remission After Surgery
Consider Azathioprine or MP to maintain remission after surgery in people with adverse prognostic factors e.g. More than one resection OR
previously complicated or debilitating disease
Other treatments
Loperamide
• To manage diarrhoea in those who do not have colitis
or codeine
Colestyramine • Relief of diarrhoea associated with Crohn’s disease
56
Ulcerative Colitis - Acute Exacerbations

Step 1 Step 1 Step 1 Step 1
Mild-moderate - proctitis Mild-moderate proctosigmoiditis or Extensive disease Acute Severe UC
left-sided disease (Person admitted to hospital)
1st • Topical aminosalicylate 1st • Topical aminosalicylate 1st • Topical aminosalicylate 1st • Give IV corticosteroids
line (suppository or enema) line line and high-dose oral line
aminosalicylate
2nd If a topical aminosalicylate 2nd • If topical treatment is 2nd • Where aminosalicylates 2nd • Consider IV ciclosporin or
line is declined line declined, consider: line are not tolerated offer a line surgery for people who
• Consider oral • High-dose oral time-limited course of decline, cannot tolerate,
aminosalicylate – not as aminosalicylate alone – not corticosteroids or have CI to IV
effective as effective corticosteroids
rd
3 If cannot tolerate 3rd If aminosalicylates are CI, not
line aminosalicylates: line tolerated or declined:
• Consider a time-limited • Give topical or oral
course of topical or oral corticosteroid
corticosteroid
Step 2 Step 2 Step 2 Step 2
If there is no improvement within 4 If there is no improvement within 4 1st If no response, worsening or
If admission not achieved within 4 weeks of starting step 1 weeks, stop topical line little improvement
weeks aminosalicylate therapy or if aminosalicylates and offer a high- within 72hrs of starting IV
• Consider adding oral symptoms worsen despite treatment: dose oral aminosalicylates with a corticosteroids
aminosalicylate or a time- • Consider adding a high-dose oral time-limited course of an oral • Add IV ciclosporin to
limited course of oral or aminosalicylate or corticosteroid IV corticosteroids
topical corticosteroid where • Switching to a high-dose oral or consider surgery
oral aminosalicylate is used aminosalicylate and a time-limited
as 1st line therapy 2nd If ciclosporin is CI or
course of a topical corticosteroids
line inappropriate:
Step 3 Infliximab is recommended
If further treatment required, add
a time-limited course of a topical
or oral corticosteroid (where not
already prescribed)
57
Maintenance of Remission- Ulcerative Colitis
Maintaining Remission All extents of disease

Proctitis and Proctosigmoiditis (after mild-moderate exacerbation) Maintaining remission after a single episode of acute-severe UC
1st line • Topical aminosalicylate (daily or intermittent) 1st line • Oral azathioprine or MP
In people who cannot tolerate, have CIs, or decline

• Topical aminosalicylate + oral aminosalicylate (daily or nd
nd
2 line 2 line azathioprine or MP:
intermittent)
• Oral aminosalicylates
Disease refractory to immunomodulatory therapy despite dose

3rd line • Oral aminosalicylate alone – not as effective
optimization or where conventional treatment is not tolerated or CI
Maintaining remission - All extents of disease

After 2 or more exacerbations in 12 months that require treatment Infliximab, adalimumab or golimumab (choice made on
1st line
with systemic corticosteroids individual basis)
Or if remission is not maintained with aminosalicylates
1st line • Azathioprine or MP 2nd line Vedolizumab
Tofacitinib (where conventional therapy or a biological agent

Maintaining remission
3rd line cannot be tolerated, or disease response is inadequate/has
Left-sided and Extensive UC (after mild-moderate exacerbation)
been lost)
1st line • Low maintenance dose of an oral aminosalicylate
• Consider OD dosing regimen (although no difference in
efficacy vs divided dosing and can result in more s/e)
58
GASTROENTEROLOGY – HELICOBACTER PYLORI
Description
• One of the most common causes of peptic ulcer disease, associated with 95% of duodenal and 70–80% of gastric ulcers.
• There is an additive risk of peptic ulceration where non-steroidal anti-inflammatory drugs (NSAIDs) are used in patients with co-existent H. pylori infection.
• H. pylori is also associated with acute and chronic gastritis, gastric cancer, and gastric mucosa associated lymphoid tissue (MALT) lymphoma.
Aims of treatment
To eradicate H. pylori, reduce the risk of peptic ulcer disease, ulcer bleeding and gastric malignancy, and the recurrence of gastritis and peptic ulcers.
Testing for H. pylori

• Testing by the urea (13C) breath test, Stool Helicobacter Antigen Test (SAT), or laboratory-based serology
- NB: 13C test and SAT should not be performed within 2 weeks of treatment with a proton pump inhibitor (PPI), or within 4 weeks of antibacterial
treatment (as this can lead to false negatives)
Who to treat
• Patients with uncomplicated dyspepsia, and no alarm symptoms who are unresponsive to lifestyle changes and antacids, following a single 1-month
treatment course with a PPI
• Those at high risk (older people, those of North African ethnicity or those living in a high-risk area) should be tested before trial of PPI
• Previously untested patients with a history of peptic ulcers or bleeds, prior to initiating NSAIDs in patients with a prior history of peptic ulcers or bleeds,
unexplained iron-deficiency anaemia after endoscopic investigation has excluded malignancy, and other causes have been investigated
Drug treatment
• Usually involves triple therapy comprising a PPI and 2 antibacterial agents (choice of regimen should consider the patient’s antibacterial treatment history
and consideration to resistance)
Example regimens (these will vary depending on local guidance):
No penicillin allergy (Oral 1st line for 7 days) True penicillin allergy (Oral 1st line for 7 days)
PPI BD + amoxicillin 1g BD + (clarithromycin 500mg BD or metronidazole 400mg BD) PPI BD + clarithromycin 500mg BD + metronidazole 400mg BD
PPI medication: lansoprazole 30mg BD, omeprazole 20-40mg BD, pantoprazole 40mg BD, esomeprazole 20mg BD, rabeprazole 20mg BD
If diarrhoea develops, consider Clostridium difficile and review need for treatment
See guidance PHE publications gateway number: GW-684 for 2nd and 3rd line treatment and when to retest.
59
IMMUNE SYSTEM AND MALIGNANT DISEASE - CYTOTOXIC DRUGS
Alkylating Agents Anti-tumour antibiotics
Alkylating agents work transferring an alkyl group to the purine Anthracyclines: doxorubicin, daunorubicin, epirubicin, idarubicin
bases of DNA (adenine and guanine) which results in the formation
of cross links within the DNA chain. This ultimately leads to Specific mechanism of action is unclear but have several effects:
apoptosis. • Act on signal transduction
• Generate free radicals
These agents are non-specific and will therefore act on all rapidly • Target topoisomerase II which leads to DNA strand breaks and cell death
dividing cells. There are several dose-limiting acute toxicities:
• Myelosuppression
Side effects: anaemia, pancytopenia, amenorrhea, mucosal • Mucositis
damage, alopecia, increased risk of malignancy. • Alopecia
N.B. these side effects are due to the non-specific action of alkylating agents.
• Cumulative cardiotoxicity – due to generation of free radicals in the heart.
ECHO required before treatment with anthracyclines and periodically during
Melphalan: derivative of nitrogen mustard and the amino acid
treatment to check heart function. Due to this risk, lifetime cumulative doses
phenylalanine which make it more likely to be taken up by rapidly
cannot be exceeded.
dividing cells resulting in some selectivity.
Dactinomycin: binds to DNA and inhibits the synthesis of RNA and proteins.
Cyclophosphamide: extensively used.
Ifosfamide: isomer of cyclophosphamide - Major toxicities of both
Mitomycin: toxicity includes myelosuppression, especially thrombocytopenia.
include bone marrow suppression, alopecia, nausea, and vomiting.
Both can cause haemorrhagic cystitis, which can be overcome
by the co-administration of mesna which combines with the
metabolite responsible for causing this toxicity.
Plant Alkaloids
Cyclophosphamide and ifosfamide are pro-dugs which are
activated through cytochrome P450 enzymes. These are tubulin-interactive agents that act by binding to tubulin (protein that forms
cellular microtubules used cell division – specifically metaphase)
Chlorambucil: a well absorbed derivative of nitrogen mustard
Vinka alkaloids: Vinblastine, vincristine, vinorelbine
Carmustime: a small lipophilic molecule used in CNS tumours and Cause neurotoxicity, extravasation, myelosuppression
haematological malignancies (multiple myeloma and lymphoma). Must not be given intrathecally – can cause severe neurotoxicity, which is usually fatal
Licenced for use as intralesional implants for treatment of recurrent
glioblastoma and malignant glioma Taxanes: Docetaxel, paclitaxel, cabazitaxel
Can cause severe hypersensitivity reactions therefore may require steroids and
antihistamines pre-treatment
60
Antimetabolites
Antimetabolites are structurally related to natural compounds. They interfere with cell metabolism of nucleic acids which are necessary for DNA, RNA, and protein
synthesis. They specially act within the S-phase of the cell cycle.
Methotrexate: inhibits folate metabolism thereby inhibiting the synthesis Cytarabine: a cytosine analogue which competes with cytosine for
of purines and pyrimidines required for DNA and RNA synthesis. incorporation into RNA and DNA
Common toxicities include mucositis, myelosuppression, and Toxicities include vomiting, myelosuppression, and alopecia.
nephrotoxicity. “Rescue” folinic acid is administered after high dose MTX
to promote clearance and reduce toxicities. Due to its rapid clearance, cytarabine acts more effectively when given as
a continuous infusion.
Fluorouracil: pro-drug which is activated within the cell. Metabolites act
by inhibiting pyrimidine synthesis. It has a relatively short half-life with Gemcitabine: also, a cytosine analogue. It has better cell permeation and
significant hepatic, renal and lung clearance. affinity than cytarabine.
Toxicities include myelosuppression, stomatitis, cardiotoxicity,
Toxicities include myelosuppression, oedema, flu-like symptoms, and
neurotoxicity, and diarrhoea. Prolonged infusion can result in hand-foot
nephrotoxicity
syndrome.
Can be administered over longer periods of time (e.g., 48 hours or over 1 Fludarabine: an adenosine analogue which competes with adenosine for
week) via an infusion pump. incorporation into RNA and DNA. Before incorporation, it is
phosphorylated.
Capecitabine: orally administered pro-drug of fluorouracil which is
activated within the tumour itself and in the liver. It can potentially be used Toxicities include myelosuppression and haemolytic anaemia.
to replace prolonged and continuous infusion of fluorouracil. Dose limiting
diarrhoea can affect treatment and can result in dosage reductions or Hydroxycarbamide: reduced the availability of nucleotides by inhibiting
treatment cessation. Also get Hand and Foot Syndrome. the enzyme ribonucleotide reductase
Pemetrexed: an anti-purine which acts as an antagonist against enzymes Toxicities include myelosuppression, GI toxicity and hyperpigmentation of
involved in folate dependent pathways which result in a decrease of the skin.
intracellular purines
Toxicity is reduced by co-administration of B12 and folate supplements.
61
Topoisomerase inhibitors
Platinum complexes
Topoisomerase enzymes are involved in the regulation of the winding of
Platinum agents interfere with and disrupt the structure of the DNA DNA. In eukaryotic cells there are two types:
double helix. They also form cross links which are similar to those of • Topoisomerase I cleaves apart the double strand of DNA. These
alkylating agents. Electrolyte imbalances are caused, particularly low relaxed strands are then used for replication, transcription, and
magnesium. recombination.
• Topoisomerase II cuts both strands of DNA simultaneously
Cisplatin: bind directly to DNA and forms cross links within the strands allowing another strand of double helix DNA to pass through the
which ultimately inhibits DNA synthesis by altering its structure. cut thereby stopping tangles.
Toxicity includes dose dependent nephrotoxicity, peripheral neuropathy,
and ototoxicity. It is also highly emetogenic. Topoisomerase I inhibitors
Irinotecan and Topotecan: both block the action of Topoisomerase I
Initial clearance of cisplatin is fast followed by a reduced rate which is whose action is increased in cancer cells
due to plasma binding. Renal impairment affects clearance.
Toxicities include neutropenia, diarrhoea, nausea, vomiting, anaemia,
Carboplatin: is an analogue of cisplatin thrombocytopenia, and alopecia
Toxicities include thrombocytopenia, nephrotoxicity, ototoxicity, Topoisomerase I inhibitors

neurotoxicity, alopecia and nausea and vomiting. Carboplatin is Etoposide and Teniposide: both inhibit the action of Topoisomerase II
considered less toxic compared to cisplatin (other than higher rates of through various mechanisms:
thrombocytopenia). • Preventing the enzyme from regulating cleaved DNA
Clearance is dependent on renal function and therefore dosage is • Generating large amounts of DNA with a high number of DNA
dependent on creatinine clearance. breaks
• Creating irreversible double stranded breaks
Oxaliplatin: platinum analogue differing from carboplatin and cisplatin • Causing inconceivable recombination
(has a broader spectrum of activity). • Apoptosis
Can cause dose limiting peripheral neuropathy which can reverse upon Toxicities include blood pressure changes (related to the infusion),
withdrawal of oxaliplatin. Other toxicities experienced include diarrhoea, neutropenia, alopecia, mucositis, and hypersensitivity reactions. They
nausea, vomiting, bone marrow suppression and ototoxicity. are both heavily protein bound which leads to higher toxicities in those
with low serum concentrations of albumin.
62
IMMUNE SYSTEM AND MALIGNANT DISEASE - CYTOTOXIC DRUGS (SIDE EFFECTS)
Side effects of cytotoxic medications

Oral mucositis Alopecia
• Commonly caused by anthracyclines, fluorouracil, and • Usually occurs 3 – 6 weeks after first dose of chemotherapy
methotrexate • Reversible hair loss is common
• Also effect of radiotherapy to head and neck area • No pharmacological methods available for prevention/treatment
• Prevention: good oral hygiene, use of soft toothbrush, sucking ice • Cold caps can be worn during treatment to minimise
chips during infusion (reduced blood flow to mouth due to concentration of cytotoxic drug reaching hair follicles through
vasoconstriction meaning less drug will travel to the area), using vasoconstriction
artificial saliva mouth washed and gels.
• Treatment: anti-inflammatory mouthwashes (e.g., Benzydamine),
saline mouthwashes, palifermin (human keratinocyte growth factor),
pain medications (such as paracetamol, codeine, and morphine)
• Poor oral hygiene can cause fungal infections and also lead to
system infections
Nausea and vomiting

• Acute: within 24 hours of treatment
• Delayed: occurs 24 hours after treatment has finished
• Anticipatory: occurs prior to treatment (treatment includes use of an
anxiolytic agent e.g., lorazepam)
• Prophylaxis vital in reducing symptoms experienced – steroid
commonly used prior to treatment for this reason
• Different cytotoxic medications have different emetogenic
properties – treatment based upon this
• Common anti-emetic agents used: metoclopramide, ondansetron,
dexamethasone, aprepitant, cyclizine and domperidone
Pregnancy and reproduction

• Most cytotoxic drugs are teratogenic
• Effective contraception is required both during and after treatment
• Alkylating agents affect fertility to the greatest extent – can cause
permanent male sterility
• Women are affected less than men however their reproductive life
span may be reduced due to early menopause
63
IMMUNE SYSTEM AND MALIGNANT DISEASE – IMMUNOTHERAPY
Background
Immunotherapy toxicities
Immunotherapy uses a person’s own immune system Skin toxicity
to fight cancer. Immunotherapy works by: • Most commonly caused by ipilimumab, nivolumab and pembrolizumab
• Training the immune system to recognise and • Can cause rash, pruritus, and vitiligo and rarely alopecia, stomatitis, dry skin, and
attack cancer cells photosensitivity
• Boost person’s immune system to fight cancer • Management: topical emollients, oral antihistamines, and topical corticosteroids.
• Provide a person with additional components Systemic steroids to be used to high severity rash
to enhance the immune response to cancer
Thyroid toxicity
• Some treatments help the immune system to
• Take baseline TFTs prior to treatment
slow down or stop the growth of cancer
• Hyperthyroid disorders more common than hyperthyroid disorders
• Others help the immune system to destroy
cancer cells to stop it from metastasising • Management: thyroid hormone for hypothyroidism. Beta-blockers, carbimazole or
steroids can be used for hyperthyroidism
Immunotherapy allows for more targeted treatment. Hepatotoxicity
• Can occur in those being treated with ipilimumab, nivolumab and pembrolizumab
Monoclonal antibodies
• All patients should have serum transaminases and bilirubin measured prior to
• E.g., ipilimumab, nivolumab, pembrolizumab,
treatment to assess for presence of hepatotoxicity
atezolizumab, avelumab
• Management for moderate hepatotoxicity includes withholding immunotherapy.
• Can be used to block activity of abnormal
Steroids may be required for persistent toxicity. If no response to steroids,
proteins that are produced by cancer cells
mycophenolate mofetil can be used
• target a cancer’s specific genes, proteins, or
the tissue environment Gastrointestinal toxicity
• some are checkpoint inhibitors which work by • Diarrhoea is the most common immunotherapy related toxicity
stopping the ability of cancer cells to bypass • Management: non-severe diarrhoea should be treated with antidiarrheals, fluid and
an immune response electrolyte supplementation. Severe diarrhoea would require immunotherapy
treatment cessation and systemic steroids. Infliximab can be used in those who do
Other types of immunotherapy include: not respond to steroids
• Oncolytic virus therapy
• T-cell therapy Pneumonitis
• Cancer vaccines • Patients who are being treated with immunotherapy that present with pulmonary
symptoms, such as an upper respiratory infection, new cough, shortness of breath or
Immunotherapy does not work for everyone and can hypoxia should be assessed for presence of pneumonitis
cause some very severe toxicities • Management: steroids and antibiotics if signs of infection. If not response to steroids,
infliximab, mycophenolate mofetil or cyclophosphamide can be used
64
IMMUNE SYSTEM AND MALIGNANT DISEASE – ONCOLOGICAL EMERGENCIES
Oncological Emergencies
Hypercalcaemia Spinal cord compression
• Most common metabolic complication of malignancy • Causes include vertebral tumour, collapse of vertebra or spinal
• Common in multiple myeloma and solid tumours cord tumour
• Majority of cases due to the production of parathyroid hormone • Diagnosis confirmed through urgent MRI scan
related peptide (PTHrP) by tumours which will act on bone, • Signs and symptoms include vertebral pain, sensory changes,
kidney, and the GI tract to increase serum calcium levels motor weakness, numbness
• Also due to the reabsorption of bone by osteoclasts • Patient should immediately be started on high dose steroids (e.g.,
• Treatment: rehydration, bisphosphonates (e.g., pamidronate, oral dexamethasone 8mg BD)
zoledronic acid), calcitonin, octreotide • Treatment can also involve radiotherapy or surgery
• Patients should be advised to lie flat and rest whilst investigations
Tumour lysis syndrome are taking place
• Caused by the rapid destruction of malignant cells resulting in the
release of cellular contents into the blood stream Superior vena cava (SVC) obstruction
• Most commonly associated with lymphomas and leukaemias • Most commonly occurs with lung cancer
• Signs: hyperuricaemia, hyperphosphataemia, hyperkalaemia, • Signs and symptoms include headaches, skin discolouration,
hypocalcaemia, hypomagnesaemia, acute renal failure, and oedema and distended neck and arm veins.
metabolic acidosis • Patient should be sat upright and given oxygen therapy for
• Prevention: rasburicase for high-risk patients, allopurinol for breathlessness
intermediate/low risk patients • Treatment includes opioids for pain and high dose steroids to
• Treatment: rasburicase reduce oedema
• Optimal treatment is stenting of the SVC and radiotherapy
Bone marrow suppression/neutropenic sepsis
• Caused by all cytotoxics apart from vincristine and bleomycin Syndrome of inappropriate antidiuresis
• Blood counts required before each treatment • Diagnosis is based in plasma osmolarity, plasma sodium, urine
• Neutropenia is a neutrophil count of < 0.5 x 109/L osmolarity, urinary sodium
• Fever in a neutropenic patient = immediate broad-spectrum • Treatment includes fluid restriction, hypertonic saline (if symptoms
antibiotics severe or rapid in onset), demeclocycline
• Treatment of neutropenia can also include use of filgrastim • Loop diuretics can correct hyponatraemia but should be used in
(GCSF) caution
65
IMMUNE SYSTEM AND MALIGNANT DISEASE – BREAST CANCER
Background
Hormone Treatment
The most frequent cancer in women and the Trastuzumab (Herceptin)
commonest cause of death in women aged 35-54 years • For HER2+ breast cancer
in England • Can cause cardiotoxicity – cardiac function must be monitored before and during treatment
• Should not be given with anthracycline-containing regimens due to risk of cardiotoxicity
Both genetic and hormonal factors are involved in the Luteinising hormone releasing hormone (LHRH) analogues
aetiology of BC • E.g., Goserelin, leuprorelin, buserelin
• Used to induce chemical castration in females (oestrogen and progesterone) and males
Hormonal risk factors – prolonged exposure to (testosterone) via continuous stimulation of the pituitary gland
oestrogen (e.g., early menarche, late menopause, late • Initial treatment can cause a tumour flare
first pregnancy), combined contraceptive pill, HRT • Required in pre-menopausal women (not required in post-menopausal women as they no longer
produce oestrogen)
Clinical presentation involves: • Side effects – breast abnormalities, gynaecomastia, hot flushes, altered mood, sexual
• Mass in breast or underarm area dysfunction, vulvovaginal dryness
• Nipple discharge
Selective oestrogen receptor modulators (SERMs)
• Skin discolouration or changes in texture
• E.g., tamoxifen, raloxifene
Staging based on TNM • Partial agonists at oestrogen receptors
• Can be used in both pre- and post-menopausal women
• Tumour size, location
• Side effects – endometrial changes (hyperplasia, polyps, uterine sarcoma → prompt
• Lymph nodal involvement
investigation if abnormal vaginal bleeding), increased risk of VTE, vaginal dryness, hot flushes,
• Metastases – most common areas are bone, mood changes
lung, liver, pleura, adrenal glands, skin, and • Tamoxifen = pro-drug, which requires activation by CYP2D6 therefore interaction with SSRIs
brain (inhibitors of CYP2D6)
Treatment options include: Selective oestrogen receptor down-regulators (SERDs)

• Surgery and adjuvant radiotherapy • E.g., fulvestrant
• Surgery and adjuvant hormonal therapy (for • Block the ER as well as downregulate it
tumours that express the oestrogen receptor • Side effects – hot flushes, VTE
[ER+]) Aromatase Inhibitors (AIs)
• Surgery and adjuvant chemotherapy (for • E.g., anastrozole, letrozole, exemestane
patients at high risk of recurrence) • Aromatase is the enzyme which facilitates the conversion of androgens into oestrogens
• AIs inhibit this conversion, thus reducing levels of oestrogen
• Used in post-menopausal women (contra-indicated in pre-menopausal women)
• Side effects – hot flushes, vulvovaginal dryness, osteoporosis, vaginal haemorrhage
66
IMMUNE SYSTEM AND MALIGNANT DISEASE – LUNG CANCER
Treatment
Background
Lung cancer is the most common worldwide cancer with most patients over 65 years. Small cell lung cancer
Despite government initiatives to reduce smoking, lung cancer remains the highest death • Surgery has a limited role and chemotherapy
caused by cancer in both the UK and USA. required
• Etoposide with carboplatin or cisplatin
Risk factors:
Non-small cell lung cancer
• Smoking (most significant risk factor)
• Treatment depends on staging
• Previous radiotherapy to the chest
• Stages 1, 2 and 3a – curative surgery to remove
• Occupational exposure to chemicals such as asbestos primary tumour with adjuvant chemotherapy
• Hereditary risk factors • Stages 3b and 4 – inoperable and chemotherapy
is used. Double therapy with carboplatin or
Small cell lung cancer (SCLC): cisplatin with gemcitabine or vinorelbine.
• Treated as an emergency and requires immediate treatment • Second line- docetaxel
• Cancer in the larger airways which presents as systemic disease and frequently
metastasises (commonly to the liver, bones, bone marrow, brain, and adrenal EGFR tyrosine kinase inhibitors
glands) • E.g., gefitinib, erlotinib
• EGFR is over mutated and overexpressed in
Non-small cell lung cancers (NSCLC):
cancer cells (especially in NSCLC)
• All other lung cancers classified as non-small cell
• Inhibit the epidermal growth factor receptor
• Arise from epithelial cells from the bronchi and alveoli (EGFR) pathway which prevents cancer cell
• Divided into three main types: growth
o Squamous cell – present as obstruction to the bronchus and tend to grow • Side effects – diarrhoea, rash (acne-like)
slowly, spreading locally
o Adenocarcinoma – occurs in bronchial mucosal glands. Can originate from Radiotherapy
scar tissue and have a high risk of metastasising
• Aims to shrink the size of the tumour
o Large cell carcinoma – presents as large mass that grow rapidly and
• Often given during chemotherapy treatment to
metastasise early
make tumour more susceptible to chemotherapy
Clinical presentation involves: • Radical radiotherapy used to actively treat the
cancer
• Chronic cough
• Palliative radiotherapy given to help manage
• Chest pain
symptoms of lung cancer (e.g., chest pain, cough,
• Haemoptysis airway obstruction)
• Breathlessness
• Recurrent chest infections
67
IMMUNE SYSTEM AND MALIGNANT DISEASE – PROSTATE CANCER
Background
Treatment
Prostate cancer is the most common cancer in men in
the UK. The incidence increases with age with more Early-stage disease (T1, T2)
than 60% of cases in men over the age of 70 years.
Watchful waiting
Risk factors: Varies from waiting until patient presents with symptoms to more active follow ups with
• Family history regular PSA testing. It is the best option for men with low-grade tumours with a life
expectancy of <10yrs
• Inherited mutations (BRCA 1 and BRCA 2)
• Ethnicity
Radical radiotherapy
• Diet Most common treatment in the UK. May cause damage to adjacent organs, acute diarrhoea,
chronic proctitis.
Clinical presentation involves:
• Many asymptomatic Radical prostatectomy
• Locally advanced disease presents with urinary For younger patients, surgery is a better option but may cause complete incontinence and
frequency, poor urine flow or difficulty starting or impotence.
stopping urination
• There may also be bone pain (due to metastatic Locally advanced disease (T3, T4) & Metastatic Disease
disease), lethargy and weight loss
Treated with hormonal therapies – LHRH analogues with/without antiandrogens
Screening:
• Men over 50 years can choose to have a PSA LHRH analogues
(prostate specific antigen) test • e.g., Leuprorelin, goserelin
o A raised PSA can indicate PC, but it can • cause a chemical castration (orchidectomy) via testosterone production.
also indicate a UTI, prostatitis or an • Side effects - hot flushes, sexual dysfunction, and impotence.
enlarged prostate, therefore it is not • LHRH analogues can cause an initial tumour flare in the first 1-2 weeks, leading to.
specific Spinal cord compression, ureteric obstruction or increasing bone pain.
• Rectal examination
• Survey for focal bone tenderness Antiandrogens
• X-ray of chest and any sites of bone pain • e.g., bicalutamide, flutamide, cyproterone
• Transrectal ultrasound • are started 3-7 days prior to therapy to prevent the tumour flare
• Bone scan • side effects - breast tenderness, gynaecomastia, haematuria, sexual dysfunction

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2021/2022 REVISION TOOL

Short Guides for Key Therapeutic Areas

Cardiovascular System 2 • Corticosteroids 35

CARDIOVASCULAR SYSTEM – CARDIOVASCULAR DISEASE

Acute attacks: PRIMARY / SECONDARY

Long-term management: STROKE For primary prevention offer

CARDIOVASCULAR SYSTEM – CARDIOVASCULAR DISEASE TREATMENT & PREVENTION

ACS PROTOCOL ANTICOAGULANTS

CARDIOVASCULAR SYSTEM – CARDIOVASCULAR DISEASE TREATMENT & PREVENTION

BETA BLOCKERS DIURETICS

Heart Failure Loop diuretics

NERVOUS SYSTEM - EPILEPSY

Overview of management Considerations Driving

NERVOUS SYSTEM - EPILEPSY

Pregnancy Hormonal Contraceptive Advice

NERVOUS SYSTEM - EPILEPSY

SODIUM VALPROATE PHENYTOIN

NERVOUS SYSTEM - EPILEPSY

No monitoring required! No important interactions!

NERVOUS SYSTEM - DEPRESSION

Overview Switching Antidepressants

NERVOUS SYSTEM - DEPRESSION

Serotonin Syndrome SSRIs

2 – Autonomic dysfunction Escitalopram – S enantiomer of citalopram therefore also causes QTc

NERVOUS SYSTEM - DEPRESSION

NERVOUS SYSTEM - LITHIUM

Brands • Body weight/BMI (can cause weight gain) (12/12ly)

• Brand specific prescribing- wide variability in bioavailability e.g., • FBC (12/12ly)

NERVOUS SYSTEM - LITHIUM

Early Signs Following signs Severe signs

• Non-specific • Vomiting • Convulsions

Interactions Patient Counselling

Rise in lithium levels • Importance of adherence and monitoring

NERVOUS SYSTEM - ANTIPSYCHOTICS

Symptoms of Psychosis & Schizophrenia

Extrapyramidal S/E (EPS)

NERVOUS SYSTEM - ANTIPSYCHOTICS SIDE EFFECTS

Hyperprolactinaemia Sexual Dysfunction APD Monitoring

Other Uses of APDs

NERVOUS SYSTEM - CLOZAPINE

Overview Blood Tests Additional Points

NERVOUS SYSTEM - DEMENTIA

NERVOUS SYSTEM - PARKINSON’S DISEASE

NERVOUS SYSTEM - PARKINSON’S DISEASE

Monoamine oxidase type B inhibitors (MAOI-B) – useful mild symptomatic

NERVOUS SYSTEM - BENZODIAZEPINES

It is inappropriate to use a BZD to treat short-term ‘mild’ anxiety Features:

NERVOUS SYSTEM - NAUSEA AND VOMITING

Prochlorperazine can be administered as a 3mg buccal tablet (dissolved

E.g., ondansetron, granisetron

Caution – prolong the QT interval

Used for N&V associated with cancer chemotherapy

NERVOUS SYSTEM - PAIN: OPIOIDS

Opioids Overview Opioid Side Effects

NERVOUS SYSTEM - PAIN: OPIOIDS

Dependence and Withdrawal

NERVOUS SYSTEM - PAIN: NEUROPATHIC PAIN & LOWER BACK PAIN

Neuropathic Pain Overview

RESPIRATORY MEDICINE - ASTHMA

Overview Diagnosis – Spirometry