1

What are the causes of nausea? Which antipsychotic antiemetics are the most
Meds and toxic substances sedating?
Labyrinthitis (inner ear infection) Levomepromazine and chlorpromazine
Vestibular disorders
Motion sickness Which drugs can cause severe acute dystonic
Gut irritation reactions, especially in children?
Metabolic disturbances Group 3 phenothiazines antipsychotics-antiemetics:
Bowel obstruction Perphenazine, trifluoperazine, prochlorperazine
Gastroparesis anxiety
anticipatory N/V" How is nausea in pregnancy treated?
Higher stimuli (sights, smells and emotions) 1st trimester: mild - no drug treatment required
Severe vomiting - short term antihistamine e.g. 1.
What causes nausea and vomting? promethazine
Nausea and vomting occurs when the vomiting centre Prochlorperazine, metoclopramide
inside the brain is activated by input from the If symptoms do not settle after 24-38hrs seek
chemoreceptor trigger zone (CTZ). specialist options
The chemoreceptor trigger zone is located in the
medulla oblongata of the brainstem and contains What is hyperemesis gravidarum?
dopamine, serotonin, histamine and muscarinic Excessive vomiting during pregnancy
receptors
How is hyperemesis agravidarum treated?
How do antiemetics work? Regular antiemetics
Antagonising receptors in the CTZ IV fluids and electrolyte replacement
Sometimes supplements are needed e.g. thiamine to
State the types of antiemetics reduce the risk of wernickes encephalopathy
*Dopamine agonists*
Metoclopromide What are the risk factors for PONV?
Domperidone (drug of choice in Parkinson's disease) Anaesthetic used, type and duration of surgery,
*Prochlorperazine (as buccal tablet in migraine, post- females, non-smokers, previous history, motion
operative) sickness, opioid use
*Perphenazine, trifluoperazine, chlorpromazine (post-
operative) What is the treatment for post operative nausea and
*Haloperidol, Levopromazine (palliative care) vomiting?
Droperidol (post-operative) Antiemetic prevention: 5HT3 receptor antagonists,
*Antipsychotics droperidol, dexamethasone, phenothiazine,
*Anthistamines* antipsychotics e.g. prochlorperazine and
For vertigo & motion sickness: Cinnarizine, antihistamine e.g. cyclizine
cyclizine, promethazine teoclate (preferred if sedative High risk of PONV or if PONV poses danger:
effect required) Combination of 2 or more antiemetics with from
*Antimuscarinics* different drug classes
Hyoscine hydrobromide (most effective in motion
sickness) What is the mechanism of action of metoclopromide?
*5HT3 antagonists* Antagonises D2 receptors in chemoreceptor trigger
For chemotherapy or PONV: zone. Also acts directly on the gut to promote gastric
Granisetron, ondansetron, palonosetron emptying; pro kinetic effect.
*Others*
Dexamethasone (cancer chemotherapy, post What is the indication for use of metoclopramide?
operative) Prevention of nausea and vomiting:
Nabilone (synthetic cannabinoid, used in Post-operation, radiotherapy-induced, delay
chemotherapy unresponsive to other anti-emetics) chemotherapy
Aprepitant fosaprepitant rolapitant (chemotherapy. Symptomatic treatment of nausea and vomting:
Given with dexamethasone and 5HT3) e.g. acute migraine, also used to improve absorption
of oral analgesics
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What are the restrictions associated with use of What is the indication for use of domperidone?
metoclopramide? Symptomatic relief of nausea and vomiting
Maximum use 5 days 10mg TDS, (max Choice antiemetic in Parkinson's disease;
500mcg/kg/day) domperidone does not cause extrapyramadial side
18+ effect
Only for the treatment of postoperative nausea and
vomiting, radio-therapy induced nausea and vomiting, What are the restrictions associated with use of
delayed (but not acute) chemotherapy-induced domperidone?
nausea and vomiting, and symptomatic treatment of For symptomatic relief of nausea and vomitting
nausea and vomiting, including that associated with Lowest effective dose for shortest possible duration
migraine (where it may also be used to improve (Usually max 1 week)
absorption of oral analgesics) Recommended dose for Adult/12+ and over 35kg:
IV bolus doses should be administered slowly over at 10mg up to TDS
least 3 minutes Children under 35kg: 250mcg/kg up to TDS
All liquid formulations should be given via a syringe to Oral liquid formulations should be given via syringe to
ensure dose accuracy ensure dose accuracy
This advice does not apply to unlicensed uses of This advise does not apply to unlicensed uses of
metoclopramide e.g. palliative care domperidone e.g. palliative care

How does metoclopramide improve absorption of oral What are the side effects of domperidone?
analgesics during a migraine attack? Risk of cardiac side effects (e.g. QT prolongation,
The small intestines are where drugs are primarily ventricular arrhythmias, sudden death) therefore
absorbed into systemic circulation MHRA has restricted indication, new
During migraines gastric emptying in the small contraindications, reduced dose and duration
intestine is delayed > Report signs of arrhythmias: syncope, palpitations
Slows the rate of absorption of oral analgesics and
explains why they may not be as effective during a What are the contra-indications for use of
migraine attack domperidone?
The use of a pro kinetic drug e.g. metoclopramide Impaired cardiac conduction (or possible impaired
increases gastric emptying and improves absorption cardiac conduction), cardiac disease, severe liver
of oral analgesics impairment, administered concomitantly with drugs
that prolong the QT interval or potent CYP3A4
What are the side effects of metoclopramide? inhibitors
Risk of neurological adverse effects - restricted dose (Domperidone is heavily metabolised by the liver so in
and duration of use liver impairment less would be metabolised, leading
Acute dystonic reactions to an increased risk of QT prolongation)
> Facial and skeletal muscle spasms and oculogyric
crises What are the interactions for use of domperidone?
> More common in young, especially girl and young Potent CYP3A4 inhibitor which will prevent
women and very old domperidone metabolism and lead to increasing
> Procyclidine (anti-parkinsonian drug) aborts dystonic concentrations and higher risk of QT prolongation e.g.
attacks amiodarone, ketoconazole, erthromycin
Drugs causing QT prolongation e.g. amiodarone, SSRIs,
What are the interactions with metoclopramide? quinolone
Antipsychotics: increased extrapyramidal side effects
Parkinson's disease: exacerbates condition What is mechanism of action of 5-HT3 receptor
antagonists?
What is the mechanism of action of domperidone? Block 5-HT3 receptors in the chemoreceptor trigger
Antagonises D2 receptors in chemoreceptor trigger zone and GI tract. 5-HT is a key neurotransmitter
zone. Also acts directly on gut to promote gastric released by the gut in response to emetogenic stimuli
emptying; pro kinetic effect. State examples of 5HT3 receptor antagonists
Does not cross the BBB therefore does not cause Granisetron
EPSE/ or other central effects such as sedation Ondansetron
Palonosetron
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What is the indication for use of 5HT-3 receptors? dopamine)

Granisetron and ondansetron for symptomatic relief Ergot derived, fibrotic reactions - NOT RECOMMENED:
of: Bromocriptine
Post-operative nausea vomiting Cabergoline
Chemotherapy-induced nausea vomiting Pergolide
Palonosetron: prevention of N&V associated with Non-ergot derived:
moderately or highly emetogenic cytotoxic Pramipexole
chemotherapy) Ropinirole
They are not useful in vestibular causes of vomiting Rotigotine
e.g. motion sickness because serotonin is not in Amantadine (weak dopamine agonist)
communication between vestibular system and Apomorphine (Advanced disease for unpredictable
vomiting centre "off periods")
MAO-B INHIBITORS (prevents degradation of
What are the side effects of 5HT3 receptor dopamine)
antagonists? Selegiline (drugs and driving - metabolised to
QT interval prolongation amphetamine)
Rasagiline
What are the interactions for 5HT3 receptor COMT INHIBITORS (prevents degradation of
antagonists? dopamine)
Increased risk of tornado de pointes with Used as an adjust to levodopa for end of dose motor
hypOkalaemia fluctuations
> Loop/thiazide diuretics, corticosteroid, beta-agonists Entacapone (colours urine)
e.g. salbutamol, theophylline, stimulant laxatives Tolcapone (hepatotoxic)
abuse amphoteracin B
Increased risk of QT interval prolongation: What is the treatment for Parkinson's disease?
Amiodarone, clarithromycin, quinine, sumatriptan, If motor symptoms decrease quality of life
lithium, antipsychotic 1: Levodopa (with benserazide/carbidopa)
Serotonin syndrome: 5HT1a agonists e.g. sumatriptan, If motor symptoms do not affect quality of life
MAOIs, SSRIs Levodopa (with carbidopa/benserazide)
Non-ergot derived dopamine receptor agonists
What is Parkinson's disease? MAO-B inhibitors
Movement disorder caused by the death of cells that Adjuvant therapy
generate dopamine in the basal ganglia and Dyskinesia & motor fluctuations with levodopa
substantial nigra (nigrostriatal pathway) Non-ergot derived dopamine receptor agonists
What are the symptoms of Parkinson's disease? MAO-B inhibitors
Motor symptoms: COMT inhibitors
Hypokinesia Ergot derived dopamine receptor agonist if
Bradykinesia inadequate response with non-ergot derived
Rigidity dopamine receptor agonists
Resting tremor Amantadine if dyskinesia not adequately managed by
Postural instability modifying therapy
Non-motor symptoms: Advanced Parkinson's disease:
Dementia > Apomorphine (SC intermittent injections/continuous
Depression infusion) for refractory motor fluctuations "OFF"
Sleep disturbances episodes
Speech and language change > Levodopa-carbidopa intestinal gel for advanced levodopa-
Swallowing problems responsive Parkinson's disease with severe motor
Weight loss fluctuations, hyperkinesia or dyskinesia)
> Deep brain stimulation only if symptoms are not
adequately controlled with the best drug treatment
State the dopaminergic drugs
Physiotherapy if patient has balance and motor function
LEVODOPA (dopamine precursor) difficulties
Co-beneldopa (levodopa + benserazide) SALT if patient had communication, swallowing difficulties,
Co-careldopa (levodopa + carbidopa) saliva problems
> Associated with more motor complications Occupational therapy if patient has problems with their day
DOPAMINE RECEPTOR AGONIST (mimics action of to days activities
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What is levodopa? What is the indication for dopamine receptor

The amino acid precursor of dopamine and acts by agonists?
replenishing depleted dopamine levels in the brain Non-ergot derived dopamine receptor agonists are
> Used for 1st line treatment in Parkinson's disease as one of the first-line option in patients with motor
overall improvement in motor performance is more symptoms that do not affect quality of life OR as an
noticeable with levodopa than with dopamine- adjunct to levodopa
receptor agonists
What are the side effects of dopamine receptor
Name the peripheral dopa-decarboxylase inhibitors agonists?
and why are they given with levodopa? Associated with more hallucinations, excessive
Carbidopa and benserazide - they are given with sleepiness and impulse control disorders than with
levodopa to prevent its breakdown to dopamine in levodopa
the periphery. Once levodopa is broken down to Psychotic symptoms e.g. hallucinations, delusions
dopamine in the periphery it cannot enter the BBB as Can cause hypotensive reactions in the first few days
it is too solubl. Levodopa enters the BBB through a > Warning: driving or operating machinery, advise
transporter. Also decreases side effects of nausea, patient to take at night
vomiting and cardiovascular effects and a lower dose Ergot derived:
of carbidopa is required for therapeutic effect Fibrotic reactions
> Pulmonary (dyspnoea, persistent cough)
Why is levodopa taken at specific times of the day? > Retroperitoneal (abdominal pain and tenderness)
To avoid "off" periods > Pericardial (cardiac failure)

What are the side effects of levodopa? Name examples of MAOB inhibitors
1. Impulse control disorders Rasagiline
e.g. compulsive gambling, hyper sexuality, binge Selegiline (metabolises to amfetamine; driving
eating, obsessive shopping offence)
2. Excessive sleepiness and sudden onset of sleep
> Warning: driving or operating machinery What is the mechanism of actions of MAOB
3. Motor complications inhibitors?
Dyskinesia: involuntary muscle movements Inhibits monoamine oxidase B enzymes which are
Response fluctuation: large variations with "ON" responsible for the breakdown of monoamines; e.g
period = normal function and "OFF" period = dopamine
weakness and restricted mobility
4. End of dose deterioration with shorter length of What is the indication for MAOB inhibitors?
benefit (wearing off) Used alone in Parkinson's disease in patients with
> Modified-release preparations may help motor symptoms that do not affect quality of life OR
as an adjunct to levodopa
Name examples of dopamine receptor agonists
Non-ergot derived: What are the side effects of MAOB inhibitors?
Pramipexole Hypertensive crises
Ropinirole
Rotigotine What are the interactions of MAOB inhibitors?
Hypertensive crises can occur with sympathomimetics
Ergot-derived: (drugs that increase blood pressure);
Bromocriptine pseudoephedrine, phenylephrine, xylometazoline,
Carbergoline oxymetazoline, adrenaline, noradrenaline,
Pergolide methylphenidate, amphetamines, B2 agonists (OTC
Apomorphine interactions: nasal decongestants)
Amantadine
Name examples of COMT inhibitors
How do dopamine receptor agonists work? Entacapone
(Parkinson's meds)
Direct action on dopamine D2 receptors in striatum
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What is the mechanism of action of COMT inhibitors? How are non-motor symptoms of Parkinson's disease
Prevents the peripheral breakdown of levodopa, by managed?
inhibiting catechol-O-methyltransferase, allowing 1. Dementia
more levodopa to reach the brain. 2. Depression
Catechol-O-methyltransferase is one of the enzymes 3. Psychotic symptoms
that degrade catecholamines, dopamine, adrenaline 1. Reminence therapy, rivastigmine
and noradrenaline 2. CBT, SSRI
3. Review Parkinson's meds, atypical antipsychotics if
What is the indication for use of COMT inhibitors? needed
Used as an adjunct to levodopa

What are the side effects of COMT inhibitors?

Entacapone: colours urine reddish-brown
Tolcapone: hepatotoxicity
> Report signs of liver toxicity e.g. anorexia, nausea,
vomiting, abdominal pain, dark urine, pruritus

What are the interactions of COMT inhibitors?

Increased cardiovascular effects (sympathomimetic
effects)
Adrenaline, noradrenaline, MAOIs e.g.
tranycypromine (catecholamines)

What are the side effects associated with abrupt

withdrawal of antiparkinson meds?
Acute kinesia
Neuroleptic malignant syndrome

What are the DVLA requirements for Parkinson's

disease patient?
Notify DVLA and car insurer

What are the side effects of apomorphine?

Nausea, vomiting: Start domperidone two days before
apomorphine treatment and discontinue ASAP (both
cause QT prolongation = serious risk of arrhythmias )

QT interval prolongation, arrhythmias, postural

hypotension, hallucination, pronounced sleepiness

What are the monitoring requirements for

apomorphine?
ECG

What are the interactions for apomorphine?

Drugs that prolong the QT interval:
Macrolides, amiodarone, antipsychotics,

What are the options for treating nausea and

vomitting in Parkinson's disease patients?
Domperidone
DO NOT give metoclopramide - causes acute dystonia
and antagonises the effect of antiparkinsons meds