Preface

Agam is a group of budding medicos, who are currently doing their under graduation in
various Medical Colleges across Tamil Nadu and Pondicherry. The group was initiated on 18th
November 2017, in the vision of uniting medicos for various social and professional causes.

We feel delighted to present you Agam pharmacology notes prepared by Agam Divide and
Rule 2019 Team to guide our fellow medicos to prepare for university examinations.

This is a reference work of 2017 batch medical students from various colleges. The team
took effort to refer many books and make them into simple notes. We are not the authors of the
following work. The images used in the documents are not copyrighted by us and is obtained from
various sources.

Dear readers, we request you to use this material as a reference note, or revision note, or
recall notes. Please do not learn the topics for the 1st time from this material, as this contain just the
required points, for revision.
Acknowledgement

On behalf of the team, Agam would like to thank all the doctors who taught us Pharmacology.
Agam would like to whole heartedly appreciate and thank everyone who contributed towards the
making of this material. A special thanks to Kareeshmaa H C, who took the responsibility of leading
the team. The following are the name list of the team who worked together, to bring out the
material in good form.

• Taher Hussain
• Mustansir Aziz Kitabi
• Jeyabharathi T A
• Kareeshmaa H C
• Shree Vardhan G M
• Yokesh Kanna C
• Snehaa S
• Nandhinee A
• Sri Vishnu Prasath T
• Rishikkesh Ramana G
• Bala Diwakar T
• Hemamalini S
 INDEX

Chapter 1: Cholinergic Drugs

Essay
1. Anticholinesterase..………………..………………………. 1

Short Notes
2. Cholinoreceptors.…………………………………………… 4
3. Anticholinesterase poisoning..……………………….. 6

Short Answers
4. Cholinergic crisis………….…………..…………………… 7
5. Sialogogue……………………………………………………. 7
6. Edrophonium test…………….………………………….. 7
7. Chronic Organophosphate Poisoning……………. 7
 1

1. Anticholinesterase

a. Classification
b. Mechanism of action
c. Pharmacological action
d. Uses

Classification

Mechanism of action

The carbamates and phosphates respectively carbamylate and phosphorylate the

esteratic site of the enzyme. The active region of AChE contains an anionic site (near
glutamate 334) and an esteratic site formed by serine 203 and histidine 447.
➢ ACh binds to anionic and esteratic sites of cholinesterase
➢ The enzyme is acetylated
➢ Rapid hydrolysis occurs
➢ Which results in release of acetate and free enzyme.
Carbamates
➢ Carbamates (except edrophonium) binds to both the sites of cholinesterases.
The enzyme is carbamoylated resulting in slow hydrolysis.
➢ Reversible method

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Organophosphates:
• Forms strong covalent bonds at esteratic site, half-life of reactivation is more
than the regeneration time.
• Note: aging of receptors occurs in organophosphates.
• Irreversible method

Pharmacological actions
o Lipid soluble: have better effects on CNS, GIT, muscarinic effect, less marked
effect on skeletal muscle.
o Lipid insoluble: better effect on skeletal muscle, less effects on CNS and GIT.
(does not cross BBB)
 Effects on ganglia
Partly increases ganglionic stimulation, by direct effects on muscarinic
receptors. high dose will cause persistent depolarization and will result in ganglionic
blockade.
 Effects on CVS
Bradycardia and increase in BP (ganglionic effect >effect on heart) with most
moderate doses of anti CHE.
 Effects on muscle
In normal person: increased twitching and fasciculation.
In partially curarized and myasthenic patients, force of contraction increased.

 Effects on CNS
Generalised alerting response, improves cognitive function in Alzheimer’s.

 Git: increased motility-diarrhoea

Eye: miotic, decreases intraocular pressure in glaucoma by contracting ciliary
muscles.
 Urinary bladder: voiding of urine - contraction of detrusors.
 Lungs: bronchoconstriction
 Increases salivary secretions.

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Uses

Miotic
▪ Due to contraction of ciliary muscle and sphincter papillae (miotic)
▪ increases trabecular meshwork area – facilitates drainage of aqueous
humour.
Myasthenia gravis
▪ neostigmine DOC - used to restore muscle strength
Post operative paralytic ileus
Post operative decurarization
▪ Reverses muscle paralysis induced by competitive neuromuscular blockers.
Belladonna poisoning: pyridostigmine
Cobra bite
Alzheimer’s disease
Glaucoma
To prevent iridocyclitis

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2. Cholinoceptors
 Classification
 Subtypes
 Location
 Function
Cholinoceptors:
They are receptors for acetylcholine.
Types

• g protien couple receptors

muscarinic • (+) muscarine
• (-) atropine

• ligand gated cation channel

nicotinic • (+) nicotine
• (-) tubocurarine or hexamethonium

MUSCARINIC RECEPTORS
MUSCARINIC LOCATION FUNCTION
SUBTYPES
MAJOR
M1 Ganglionic cells, enteric  Mediate gastric secretion.
neurons, central neurons.  Relaxation of LES.
 Learning, memory and motor functions.
M2 Cardiac and smooth  Mediate vagal bradycardia.
muscles  LES contraction.
M3 Smooth muscle  Contraction.
 Glandular secretion.
 Vasodilatation.
MINOR
M4 Brain  Facilitate or inhibit certain areas of brain.

M5 Brain  Dilates cerebral arterioles.

 Facilitates dopamine release.
 Mediates reward centre.

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NICOTINIC RECEPTORS
LOCATION FUNCTION
Nm Skeletal muscle ➢ Contraction.

Nn Ganglionic cells, ➢ Facilitates or inhibits

Adrenal medullary cells, transmitter release.
Spinal cord,
Certain areas of brain.

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3. Anticholinesterase poisoning

 They are most commonly used as agricultural and household insecticide;

accidental or suicidal poisoning is more common.
 Local manifestation at the site of infection (skin, eyes) occurs rapidly followed
by systemic effect.
 Irritation of eye, lacrimation, salivation, sweeting, miosis, blurring of vision,
bronchospasms, breathlessness.
 Fall in BP. Bradycardia, tachycardia, arrhythmias, respiratory failure.
 Death is usually due to respiratory failure.
Treatment:
o Fresh air to be provided
o Wash the skin and mucous membrane with soap and water
o Gastric lavage according to need
o Maintain airway, BP, control of convulsions with diazepam
o Specific antidotes
▪ Atropine - 2 mg i.v. repeated every 10 minutes till dryness of
mouth or other signs of atropinization appear.
▪ Cholinesterase reactivators like oximes (pralidoxime…). They are
used to restore neuromuscular transmission only in case of
organophosphate anti-ChE poisoning.

pralidoxime is ineffective as an antidote to carbamate anti-ChE poisoning. It is

contraindicated.

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4. Cholinergic crisis
Cholinergic crisis is a clinical condition that develops as a result of
overstimulation of nicotinic and muscarinic receptors at the neuromuscular junctions
and synapses. This is usually secondary to the inactivation or inhibition AChE, the
enzyme responsible for the degradation of ACh. Excessive accumulation of ACh at the
neuromuscular junctions and synapses causes symptoms of both muscarinic and
nicotinic toxicity.

5. Sialogogue
Sialogogue are substances that increases the salivary secretions. These are
useful in treatment of Xerostomia.
Ex: Pilocarpine

6. Edrophonium test
▪ Edrophonium test is used to differentiate myasthenia crisis and cholinergic
crisis.
▪ This test is done by injecting edrophonium (2mg I.V). If there is an
improvement in the weakness then it is myasthenia crisis, if there is no
improvement or worsening occurs then it is due to cholinergic crisis.

7. Chronic Organophosphate poisoning

• Repeated exposure to certain fluorine containing and triaryl
organophosphates results in polyneuritis and demyelination after a latent
period of days to weeks.
• Sensory disturbances occur first followed by muscle weakness, tenderness and
depressed tendon reflexes—lower motor neuron paralysis.
• In second phase, spasticity and upper motor neuron paralysis gradually occurs.
Recovery may take years. It is due to inhibition of ChE; there is no specific
treatment.

ANS Agam Pharmacology

 INDEX

Chapter 2: Anticholinergic Drugs

Essay
1. Anticholinergic Drugs..………………..…………………. 8

Short Notes
2. Atropine Substitutes.……………………………………… 11
3. Belladonna Poisoning…………...……………………….. 13

Short Answers
4. Mydriatic………….……………………..…………………… 15
5. Vasoselective Agents……………………………………. 15
6. Smoking Cessation..………….………………………….. 15
 8

1. Anti cholinergic drugs

Pharmacological actions:
(Atropine as prototype)
1. CNS:
• Stimulant action.
• It stimulates medullary centres - Vagal, respiratory, and vasomotor.
• Depresses vestibular excitation and has anti-motion sickness property.

2. CVS:
• Heart- Tachycardia
• BP- No marked effect in BP
• Tachycardia and vasomotor centre stimulation tend to raise BP, while
Histamine release and direct vasodilator action tend to lower BP.

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3. Eye:
• Topical instillation of atropine causes mydriasis, abolition of light reflex and
cycloplegia lasting 7 to 10 days.
• Causes photophobia and blurring of near vision.
• Intraocular tension tends to rise especially in narrow angle glaucoma.

4. Smooth muscles:
• Smooth muscles receiving parasympathetic motor innervation is relaxed by
atropine.
• Tone is reduced.
• Constipation may occur.
• Causes bronchodilatation, reduces airway resistance in COPD and asthma
patients.
• Relaxant effect on ureter and urinary bladder.

5. Glands:
• Decreases sweat, salivary, tracheobronchial and lacrimal secretion.
• Decreases secretion of acid, pepsin and mucus in stomach.
• Intestinal and pancreatic secretions are not significantly reduced.
• Bile secretion not affected.

6. Body temperature:
• Rise in temperature at higher doses due to both stimulation of sweating as well
as stimulation of temperature regulatory centers.
• Children are susceptible to atropine fever.

7. Local anaesthetic:
• Mild anaesthetic action on cornea
• Sensitivity to atropine varies and can be graded as-
Saliva, sweat, bronchial secretion > eye, bronchial muscle, heart > smooth
muscle of intestine, bladder > gastric glands and smooth muscle

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Pharmacokinetics:
➢ Rapidly absorbed from g.i.t.
➢ Applied to eyes, freely penetrate to cornea.
➢ Passage through BBB is restricted.
➢ 50% metabolised in liver and rest excreted in urine.

Uses:
❖ Used as pre anaesthetic medications.
❖ Reduced pulmonary secretions, thus employed in pulmonary embolism
❖ As mydriatic and cycloplegic – used in treating iritis, iridocyclitis, choroiditis,
keratitis and corneal ulcer.
❖ Used in counteracting sinus bradycardia and partial heart block in selected
patients where increased vagal tone is responsible.
❖ It is the specific antidote for anti ChE and early mushroom poisoning.

Side effects and Toxicity:

Belladonna poisoning

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2. ATROPINE SUBSTITUTES
Many semi synthetic derivatives of belladonna alkaloids and a large number of
synthetic compounds have been introduced with the aim of producing more selective
action on certain functions. Most of these differ only marginally from the natural
alkaloids, but some recent ones appear promising.

Quaternary compounds
These have certain common features—
• Incomplete oral absorption.
• Poor penetration in brain and eye; central and ocular effects are not seen after
parenteral/oral administration.
• Elimination is generally slower; majority are longer acting than atropine.
• Have higher nicotinic blocking property. Some Ganglionic blockade may occur at
clinical doses resulting in postural hypotension and impotence as additional side
effects.
• At high doses some degree of neuromuscular blockade may also occur.
Drugs in this category and their uses:
1. Hyoscine butyl bromide: Less potent and longer acting than atropine; used for
oesophageal and gastrointestinal spastic conditions.
2. Atropine methonitrate: for abdominal colics and hyperacidity.
3. Ipratropium bromide: it acts selectively on bronchial muscle without altering
volume or consistency of respiratory secretions.
o Another desirable feature is that in contrast to atropine, it does not depress
muco-ciliary clearance by bronchial epithelium.
o It has a gradual onset and late peak (at 40–60 min) of bronchodilator effect in
comparison to inhaled sympathomimetics.
o Thus, it is more suitable for regular prophylactic use rather than for rapid
symptomatic relief during an attack. Action lasts 4–6 hours.
o It acts on receptors located mainly in the larger central airways contrast
sympathomimetics *whose primary site of action is peripheral bronchioles*.
o The parasympathetic tone is the major reversible factor in chronic obstructive
pulmonary disease (COPD).

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Therefore, ipratropium is more effective in COPD than in bronchial asthma.

o Transient local side effects like dryness of mouth, scratching sensation in
trachea, cough, bad taste and nervousness are reported in 20–30% patients,
but systemic effects are rare because of poor absorption from the lungs and
g.i.t.
4. Tiotropium bromide: A newer congener of ipratropium bromide which binds very
tightly to bronchial M1/M3 Muscarinic receptors producing long lasting
Bronchodilatation.
Like ipratropium, it is not absorbed from respiratory and G.I. mucosa and has
exhibited high bronchial selectivity of action.
5. Propantheline: it was a popular anticholinergic drug used for peptic ulcer and
gastritis. Use has declined due to availability of H2 blockers and proton pump
inhibitors.
6. Oxyphenonium: similar to Propantheline, recommended for peptic ulcer and
gastrointestinal hypermotility.
7. Clidinium: This antisecretory-antispasmodic has been used in combination with
benzodiazepines for nervous dyspepsia, gastritis, irritable bowel syndrome, colic,
peptic ulcer, etc.
9. Isopropamide: Indicated in hyperacidity, nervous dyspepsia, irritable bowel and
other gastrointestinal problems, especially when associated with emotional/mental
disorders.
10. Glycopyrrolate: Potent and rapidly acting antimuscarinic lacking central effects.
Used as preanaesthetic medication and during anaesthesia.

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3. Belladonna poisoning
Occurs due to drug overdose or excess consumption of seeds and berries of
belladonna or Datura plant.

Symptoms:
→ Dry mouth, difficulty in swallowing and talking.
→ Dry, flushed and hot skin, fever, difficulty in micturition, decreased bowel
sounds. A scarlet rash may appear.
→ Dilated pupil, photophobia, blurring of near vision, palpitation.
→ Excitement, psychotic behaviour, ataxia, delirium, dreadful visual hallucinations.
→ Hypotension, weak and rapid pulse, cardiovascular collapse with respiratory
depression.
→ Convulsions and coma occur in severe poisoning.

Diagnosis:
Methacholine 5mg or neostigmine 1mg s.c. fails to induce typical Muscarinic effects.

Treatment:
If the poison has been ingested following steps are to be done.
✓ Gastric lavage should be done with tannic acid.
✓ The patient should be kept in dark quiet room.
✓ Cold sponging or ice bags are applied to reduce body temperature.
✓ Physostigmine 1-3mg s.c. or i.v. antagonizes both central and
peripheral effects, but have been found to produce Hypotension and
arrhythmias in some cases. As such it is generally not recommended.
Neostigmine does not antagonize central effects. Therefore, most
cases are just treated symptomatically.

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✓ Other general measures (maintenance of blood volume, assisted

respiration, diazepam to control convulsions) should be taken as
appropriate.

Contraindications:
Atropinic drugs are absolutely contraindicated in individuals with
▪ A narrow iridocorneal angle— may precipitate acute congestive glaucoma.
However, marked rise in intraocular tension is rare in patients with wide angle
glaucoma.
▪ Caution is advocated in elderly males with prostatic hypertrophy— urinary
retention can occur.

Interaction:
1. Absorption of most of the drugs is slowed because atropine delays gastric
emptying. Greater peripheral degradation of levodopa and increased absorption of
digoxin and tetracycline.

2. Antacids interfere with absorption of anticholinergics.

3. Antihistamines, tricyclic antidepressants, disopyramide and pethidine have

anticholinergic property - additive side effects.

4. MAO inhibitors interfere neither metabolism of anticholinergic anti parkinsonian

drugs - delerium may occur.

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4. Mydriatic
• Atropine
• Homatropine
• Cyclopentolate
• Tropicamide

5. Vasicoselective agents
• Oxybutynin
• Tolterodine
• Flavoxate
• Darifenacin
• Solifenacin
• Drotaverine

6. Smoking cessation
• Nicotine transdermal
• Nicotine chewing gum
• Varenicline
• Bupropion

ANS Agam Pharmacology

 INDEX

Chapter 3: Adrenergic Drugs

Essay
1. Sympathomimetics..………………..…………….………. 16

Short Notes
2. Adrenergic Receptors……………..……………………… 19
 16

1. SYMPATHOMIMETICS

ACTIONS- mediated through alpha and beta receptors:

Alpha actions Beta actions

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Blood vessels contraction relaxation

Heart Little action; high ↑rate, force,
doses – arrhythmia conduction and
velocity.
Bronchioles - Dilatation
Eye – aqueous Decreased Increased
secretion
Intestine Relaxation Relaxation
Urinary bladder Trigone – contraction Detrusor- relaxation
Uterus Contraction Relaxation
Splenic capsule Contraction Relaxation
NM transmission ↑Ach release tremors
Insulin &glucagon Inhibited Secreted
Liver - Glycogenolysis
Kidney - Renin release
Male sex organ Ejaculation -
Salivary gland K+ and water Ptylin secretion
secretion
Posterior pituitary - ADH secretion
Nicitating membrane Contraction -

THERAPEUTIC USES:

1. Vascular:

a) Used in shock
➢ Dopamine- increases cardiac contractility without significant
tachycardia, improves renal blood flow, may help to raise blood
pressure.

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➢ Ephedrine/ mephentermine – causes vasoconstriction and also

counteracts as well as counteract bradycardia..

➢ Adrenaline - drug of choice in Anaphylaxis (0.5mg i.m.)

• It raises blood pressure
• Counteracts Bronchospasm and laryngeal edema that may
accompany.

b) Postural hypotension

c) Adjuvant in local anesthetic – adrenaline is used

d) Control of local bleeding

o Adrenaline can be used
o Phenylephrine – 1% soaked in cotton can control arteriolar and
capillary bleeding
o Noradrenaline – 8mg in 100- 200 ml of saline put in stomach
through a tube can control bleeding from gastric erosions and
stress ulcers.

e) Nasal decongestant

2. Cardiac:

• Cardiac arrest- Adrenaline

• AV block- Isoprenaline
• Congestive heart failure-Dopamine / Dobutamine
• Cardiac stress test- Dobutamine

3. Bronchial asthma and COPD: Adrenergic β2 stimulants.

4. Allergic disorders: Adrenaline- antagonizes histamine

5. Ocular uses:
• Phenylephrine- dilates pupil
• Dipivefrine- adjunctive in open angle glaucoma
• Apraclonidine and brimonidine- 2nd line add on drugs fir glaucoma

6. Central uses:

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• ADHD – amphetamines, methylphenidate.

• Narcolepsy – amphetamines.

7. Uterine relaxant:
Isoxsuprine- threatened abortion and dysmenorrhoea.

8. Insulin hypoglycemia:
Adrenaline rapidly reverses Insulin hypoglycemia.

2. Adrenergic receptors

Α1(GQ)
Location Function
Bladder smooth muscle Smooth muscle contraction
Pylomotor smooth muscle Vasoconstriction
Vascular smooth muscle Gland - secretion
Prostatic smooth muscle Gut – relaxation
Papillary dilator muscle

Α₂(GI)
Location Function
Fat cells Vasoconstriction
Platelets Decreased sympathetic flow
Nerve cells Decreased insulin release
Pancreatic β cells Platelet aggregation
Inhibit transmitter release

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Β₁(GS)
Location Function
Heart Increase ionotrophy, dromotrophy, chronotrophy
in heart
Kidney (JG cells) Increase BP (Renin release)

Β₂(GS)
Location Function
Bronchial smooth muscle Decrease BP (vasodilator)
Bladder smooth muscle Bronchodilation
Uterus Intestine, Uterus, Splenic capsule relaxation
GIT smooth muscle
Vascular smooth muscle

Β 3 ( G S)
Location Function
Adipose tissue Lipolysis
Detrusor of bladder Detrusor relaxation

ANS Agam Pharmacology

 INDEX

Chapter 4: Antiadrenergic Drugs

Essay
1. Beta-Blockers..………………..…………….…………..…. 21
2. Glaucoma……………………………………………………… 26

Short Notes
3. Alpha Adrenergic Blockers……...……………………… 29
4. Alpha and Beta Adrenergic Blockers……………….. 31
5. Angled Closure Glaucoma……………………………….. 33

Short Answers
6. CardioSelective Beta Blockers....…………………… 34
7. 1st Generation beta Blockers…………………………. 34
8. Drugs for BPH………..………….………………………….. 34
9. Advantages of Topical Beta Blockers
over Miotics………………………………………………….. 34
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1. ß - BLOCKERS
INTRODUCTION
• ß blockers are group of drugs which inhibit adrenergic response mediated
through ß receptors.
• All ß blockers are competitive antagonists.
• Its prodrug Propranolol blocks ß1 and ß2 receptors but has weak ß3 activity.
It is also an inverse agonist.

PROPRANOLOL
Introduced in 1963, it became the prodrug for ß blockers

PHARMACOLOGICAL ACTIONS
1) Cardiovascular system
a) Heart
• Decreases heart rate , force of contraction , cardiac output and
retarding conduction thus prolonging systole
• CHF may be precipitated

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• Cardiac work and O2 consumption are reduced as the product of heart

rate and aortic pressure decreases
• Total coronary blood flow is reduced due to blockade of vasodilatory ß
receptors
• In anginal patients there is an improvement of O2 supply and exercise
tolerance
• Abbreviates refractory period of myocardial fibres and thus slows A-V
conduction
• At high doses, a direct depressant and membrane stabilizing action is
exerted which contributes to its anti-arrhythmic action.
b) Blood Vessel
• Blocks vasodilation and fall of BP by isoprenaline and enhances rise of
BP by Adr.
• On prolong administration, BP gradually falls in hypertensive subjects
• Total peripheral resistance(t.p.r) is increased initially but with chronic
use resistance vessels gradually adapt to chronically low C.O so that
t.p.r decreases and both systolic and diastolic BP fall
• Reduced NA releases
• Decreased renin release
• Central action reducing sympathetic outflow
• These factors contribute to its anti-hypertensive action.
2) Respiratory Tract
• Increases Bronchial resistance
• Precipitates severe asthma
3) Central Nervous System
• No overt central effects produced
• Mild behavioural changes, forgetfulness, increased dreaming and
nightmares are observed in some individuals.
4) Local anaesthetic
• Has membrane stabilizing and is a potent local anaesthetic but not used
due to its irritant activity.
• Ocular irritation and corneal anaesthesia occurs and hence ocular use is
terminated.

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5) Metabolic
• Blocks adrenergically activated lipolysis and consequent increase in
plasma free fatty acids
• Plasma triglyceride levels and LDL/HDL-CH ratio increase
• Glycogenolysis in heart, skeletal muscle and liver that occurs due to
symapathetic stimulation is attenuated.
• Delayed recovery from insulin hypoglycaemia
6) Skeletal muscle
• Inhibits adrenergically provoked tremor
• Reduce exercise capacity by attenuating ß2 mediated increase in blood
flow and limiting glycogenolysis and lipolysis.
7) Eye
• Reduces secretion of aqueous humor.
8) Uterus
• Relaxation of uterus due to isoprenaline and selective ß2 agonists is blocked.

PHARMACOKINETICS
• Well absorbed orally
• Low bioavailability due to high first pass metabolism in liver
• Lipophilic and penetrates the brain easily
• Metabolism dependent on hepatic blood flow. Chronic use of
propranolol itself decreases hepatic blood flow and thus increases
bioavailability and t1/2
• Bioavailability is increased when taken with meals as it reduces first pass
metabolism
• Hydroxylated metabolite is responsible for ß blocking activity.
• Excreted through urine as glucuronides
• 90% of propranolol is plasma protein bound.

INTERACTIONS

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• Additive depression of sinus node and A-V conduction with digitalis and
verapamil and hence used always with nifedipine – cardiac arrest can
occur.
• Delays recovery from hypoglycaemia due to insulin and oral antidiabetics.
Warning signs of hypoglycaemia are suppressed.
• Phenylephrine, ephedrine and α agonists cause marked rise in BP due to
blockade of sympathetic vasodilatation.
• Indomethacin attenuates anti-hypertensive action.
• Retards lignocaine metabolism by reducing hepatic blood flow.

USES
• Hypertension
• Angina pectoris
• Cardiac arrythmias
• Secondary prophylaxis of MI
• Congestive cardiac failure.
• Thyrotoxicosis(controls sympathetic symptoms , inhibits conversion of T4
to T3)
• Chronic prophylaxis of Migraine
• Anti-Anxiety drug
• Hypertrophic cardiomyopathy.
• Glaucoma
• Dissecting aortic aneurysm.
• Pheochromocytoma.

ADVERSE DRUG REACTIONS

• Accentuate MI insufficiency and precipitates CHF by blocking sympathetic
support to the heart.
• Bradycardia (60 beats/min).
• Worsens COPD and precipitates asthma – CONTRAINDICATED IN ASTHMA.
• Exacerbates vasospastic angina due to unopposed α mediated coronary
constriction.
• Risk of hypoglycaemic episodes and thus avoided in diabetics.
• Plasma lipid profile is altered with triglyceride increase and HDL decrease

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• Withdrawal after chronic use should be gradual else rebound hypertension,

worsening of angina and even sudden death can occur.
• Contraindicated in partial / complete block
• Tiredness and reduced exercise capacity.
• Cold hand and feet during winter due to blockade of vasodilatory ß2
receptors.
• GI upset, lack of drive, nightmares, forgetfulness.

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2. GLAUCOMA

Glaucoma is a group of diseases characterized by a progressive form of optic

nerve damage. This is generally but not necessarily, associated with raised
Intraocular tension (>21 mmHg).

Glaucoma is of two types:

A. Open angle (wide angle, chronic simple) glaucoma

B. Angle closure (narrow angle, acute congestive) glaucoma.

Classification:

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Prostaglandin analogues:

→ Latanoprost
→ Travoprost
→ Bimatoprost

Mechanism of action:
Lower concentration of PGF2α was found to lower I.O.T without inducing
ocular inflammation. It acts by increasing uveoscleral outflow, possibly by increasing
permeability of tissues in ciliary muscle.

Because of good efficacy, once daily application and no systemic complications –they
are used the 1st choice of drugs for open angle glaucoma.

Latanoprost
• Efficacy similar to timolol
• It reduces i.o.t in normal pressure glaucoma also.
• Though ocular pain and irritation are relatively frequent, no systemic side effects
is noted.
• Blurring of vision, increased iris pigmentation, thickening and darkening of
eyelashes have occurred in some cases.
• Macular edema can develop during treatment with any PGF2α analogue.

Travoprost
• Another selective FP-prostanoid receptor agonist, it lowers i.o.t mainly by
increasing uveoscleral outflow and a minor effect on trabecular outflow.
• The effects start within two hours, peaks at 12 hours and last for 24 hours or
more.
• Side effects are comparable to Latanoprost.

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Bimatoprost
• A synthetic prostamide derivative
• It is found to be equally or more effective than Latanoprost in lowering i.o.t.
• Ocular side effects are similar, but some patients may tolerate it better.

*The current approach of treatment of open angle glaucoma can be summarized as*

❖ Initial monotherapy with Latanoprost or another prostaglandin analogue or a

topical beta blocker.
❖ Brimonidine or dorzolamide are used only when there are contraindications to
PG analogues and/ or beta blockers.
❖ Topical miotics and oral acetazolamide are added only as the last resort.

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3. ALPHA ADRENERGIC BLOCKERS

USES:

A. Pheochromocytoma
• Tumor in adrenal medullary cells, resulting in secretion of excess
catecholamine
• Alpha blockers normalize blood volume and fluid distribution
• Phenoxybenzamine and prazosin are used as definitive therapy in
inoperable malignant cases. Administration of Phenoxybenzamine
maintains BP
• Phentolamine test:
Phentolamine 5mg i.v. over 1 minute is administered to
d patient. A fall greater than 35 mm hg systole and 25 mm hg
diastole is indicative of Pheochromocytoma.

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B. Hypertension
• Phenoxybenzamine/ Phentolamine are used in controlling episodes
of rise in BP during clonidine withdrawal and during cheese reactions
in patients on MAO inhibitors

C. Benign prostatic hypertrophy

• Two classes of drugs are available
▪ Alpha 1 adrenergic blockers – prazosin like – they
decrease tone of prostate or bladder neck muscles.
▪ 5 – α reductase inhibitors – finasteride/ dutasteride –
they arrest the growth or reduce the size of prostate.
D. Peripheral vascular diseases
• Prazosin / Phenoxybenzamine afford symptomatic relief when
vasoconstriction is the most prominent feature

E. Impotence
• PIPE – papaverine/Phentolamine induced penile erection therapy
• In PIPE, injecting papaverine (3 – 20 mg) with/ without Phentolamine
(0.5 -1 mg) in corpus cavernosum produces penile tumescence.

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4. ALPHA AND BETA ADRENERGIC BLOCKERS

• Labetalol
• Carvedilol

1. LABETALOL
INTRODUCTION:
➢ first adrenergic antagonist capable- of blocking both alpha and beta
receptors
➢ It has four diastereomers.
PHARMACOLOGICAL ACTION:
➢ Displays β1, β2, α1, blocking and β2 agonistic activity.
➢ It is 3 – 4 times more potent in blocking beta than alpha receptors.
➢ Fall in BP [α1 and β1 blockade of β2 agonistic].
➢ Higher dose results in reduced cardiac output and total peripheral
resistance.
➢ Limb blood flow increased.
➢ Inhibit Noradrenaline uptake.
PHARMACOKINETICS:
➢ Route of administration is oral.
➢ Has higher first pass metabolism.
USES:
It is a potent antihypertensive, very useful in
➢ Pheochromocytoma.
➢ Clonidine withdrawal.
➢ Preeclampsia – pregnancy induced hypertension.
➢ Hypertensive emergencies.
➢ Essential hypertension.
ADR:
➢ Postural hypotension.
➢ Failure of ejaculation.

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2. CARVEDILOL
INTRODUCTION:
➢ It is alpha +beta adrenergic blockers.
➢ It Blocks β1+β2+α1 adrenoreceptors.
PHARMACOKINETICS:
➢ Orally active.
➢ Bioavailability – 30%.
➢ Metabolized CYP2D6.
➢ T1/2 – 6-8 hours.
PHARMACOLOGICAL ACTION:
➢ Vasodilatation - α1 blockade, calcium channel blockers.
➢ It has exhibited antioxidant property but its clinical relevance is uncertain.
USES:
➢ As antihypertensive.
➢ In treating congestive heart failure (β blockers have cardio protective
property).

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5. Angle Closure Glaucoma:

• It occurs in individuals having a narrow irido-corneal angle and shallow
anterior chamber.
• The i.o.t remains normal until an attack is precipitated, usually by mydriasis.
• The i.o.t rises rapidly to very high values (40-60mmHg).
• It is an emergent condition with marked congestion of eyes and severe
headache.
• Failure to lower i.o.t quickly may result in loss of vision.

Treatment to reduce i.o.t:

MNEMONIC: HAMTA
• Hypertonic mannitol (20%) 1.5 – 2 g/kg or glycerol (10%)
→ PK: I.V Infusion
→ MOA: Decongest the eye by osmotic action. A retention enema of
50% glycerine is also sometimes used.
• Acetazolamide 0.5 g
→ PK: I.V Infusion, oral twice daily
→ MOA: Carbonic anhydrase inhibitor reduces aqueous humour
secretion leading to reduced intraocular tension.
• Miotic: Pilocarpine 1-4% every 10 minutes initially and then at longer
intervals.
→ MOA: Contraction of sphincter pupillae changes the direction of
forces in the iris to lessen its contact with the lens and spreads the
iris mass centrally -->pupillary block is removed and irido-corneal
angle is freed. Not to use when i.o.t is very high.
• Topical Beta blocker: Timolol 0.5% instilled 12 hourly in addition.
• Apraclonidine (1%) /Latanoprost 0.005% instillation maybe added.

*NOTE: Drugs are used to terminate the attack. Definitive treatment is

surgical or laser iridotomy.*

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6. Four cardioselective beta blockers :

● Metoprolol
● Atenolol
● Acebutolol
● Esmolol

7. Four first generation beta blockers:

• Propranolol
• Timolol
• Sotalol
• Pindolol

8. Drugs for benign prostatic hypertrophy:

• Alpha adrenergic blockers: prazosin etc

• 5- alpha reductase inhibitor: finasteride / dutasteride

9. Advantages of topical beta blockers over miotics:

• No change in pupil size – no diminution of vision in dim light and in

patients with cataract.
• No induced myopia which is essentially troublesome in younger patients.
• No headache or brow pain due to persistent spasm of iris and ciliary
muscles.
• No fluctuation in i.o.t. as it happens with Pilocarpine drops.
• Convenient twice or once daily application is sufficient.

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