Subject: Pharmacology I

Unit 3

Topic: Drugs acting on ANS

Subtopics:
Parasympathomimetics
Parasympatholytics
Sympathomimetics
Sympatholytics

Presented by: Mr Rishabh Singh

 PARASYMPATHOMIMETICS

1. Cholinergic drugs are of two types: Cholinomimetic, Parasympathomimetic

2. Cholinomimetic and Parasympathomimetic drugs produce actions similar to Ach.
3. Cholinergic drugs classification is based on:
a. Drug binding with cholinergic receptors as agonist.

Cholinergic agonists
Choline esters: Alkaloids:
Acetylcholine, Methacholine, Muscarine
Carbachol, Bethanechol Pilocarpine
Arecoline

b. Drug increasing the avaibility of Ach by (Anti-cholinesterase)

Anti-cholinesterase
Reversible irreversible
Carbamates: Carbamates: Propoxur (Baygon)
Physostigmine, Neostigmine, Organophosphates: Dyflos, Malathion
Edrophonium, Rivastigmine, (insecticide)
Donepezil, Galantamine
Nerve gases like: Tabun, Soman, Sarin
Acridine: Tacrine

c. Depending on action at receptors:

Muscarinic Site Response Agonist
receptors:
M1 CNS, 1. Increase in cognitive functions. Acetylcholine,
(Promote Gastric 2. Stimulate glandular secretions. Carbachol,
release of glands, 3. Decrease release of dopamine Oxotremorine.
endothelial Salivary and reduction in locomotor
NO) glands. activity.
4. CNS excitation.
M2 Heart, 1. Decrease heart rate. Acetylcholine,
(decrease in Smooth 2. It contract smooth muscles. Carbachol,
Ca++ ions) muscles Oxotremorine.
M3 GIT, 1. Increase appetite. Acetylcholine,
smooth 2. Constriction of pupil (miosis). Carbachol,
muscles, 3. Dilation of blood vessels. Oxotremorine.
eye, 4. Increase glandular secretions.
glands
M4 CNS, 1. Facilitate dopamine release. Acetylcholine,
Lungs 2. Cause analgesia. Carbachol,
Oxotremorine.
M5 Substant 1. Facilitate dopamine release. Acetylcholine,
ia 2. Dilate cerebral arteries Carbachol,
niagra, Oxotremorine.
salivary
glands,
iris
 Nicotinic Site Response Agonist Antagonist
receptor
NM NMJ Depolarization and contraction Nicotine, d-
of skeletal muscle fiber. Acetylcholine, tubocurarine
Carbachol,
Suxamethonium.

Muscarinic action:

Effect on Muscarinic action of Ach

Heart Decrease in heart rate (bradicardia), Supress SA node, Cardiac arrest may
occur, Decrease force of contraction, It depress AV. It may cause AV block.
Blood vessels It cause vasodilation by acting on M3 receptor on endothelial cell and release
NO.
Blood pressure Released NO (Endothelial dereived relaxing factor) decrease BP.
Eye Constriction of pupil occur (Miosis).
Reduction in intraocular pressure.
Smooth muscle Peristalsis increases in GIT.
Sphincter relaxed.
Cause abdominal cramps.
Promote bowel evacuation.
Contractions in gall bladder, urinary bladder, ureter, bronchioles.
Glands Increases bronchial, lacrimal, salivary, secreations.
It also increases sweating.
Respiratory tract Bronchoconstriction, Bronchospasm may occur, Asthma attack
CNS Do not cross BBB. However, direct injection to brain cause primary
activation followed by depression, restlessness and behavioral abnormalities.

Nicotinic action

Effect on Nicotinic action of Ach

Autonomic Stimulate both sympathetic and parasympathetic nervous system.
ganglia Atropine+Ach= tachycardia, increase BP.
Skeletal muscle Cause skeletal muscle contraction by binding with NM receptor at NMJ.
Large dose of Cholinergic drug may cause persistent depolarization of
skeletal muscle (paralysis).

Oral administration: Destroyed in Gut.

IV administration: Destroyed in plasma by pseudocholinesterase.

MOA of Ach on M1,M3,M5 receptors:
MOA of Ach on M2, M4 receptors:
 PARASYMPATHOLYTICS (ANTI CHOLINERGIC DRUGS)

1. Parasympatholytics are also called anticholinergic drugs/cholinergic blockers/anti-muscarinic

drugs.
2. Classification of anticholinergic drugs:
Parasympatholytics /anticholinergic drugs/cholinergic blockers/anti-muscarinic drugs.

Muscarinic blocker Nicotinic blocker

Atropine, Scopolamine (hyosine) a) Ganglionic blocker: 1. Competitive non
depolarizing (Hexamethonium,
Pentolinium) 2.Persistant depolarizing
(Nicotine)
b) NMJ blockers: 1. Non depolarizing (d-
tubocurarine) 2.Persistant depolarizing
(Succinylcholine)

3. Anticholinergic drugs block the action of cholinergic drugs.

4. Antimuscarinic drugs/ Muscarinic antagonists/ Anticholinergic drugs bind with Muscarinic
receptors and antagonize the action of Ach.

Prototype: Atropine

1. Atropine is a natural Tropane alkaloid.

2. It is obtained from Atropa belladonna.

MOA:

a) Reversibly antagonize action of Ach.

b) Anti-muscaranic action can be overcome by increasing concentration of Ach at
Muscarinic neurorffector site.

Pharmacology of Atropine
CNS Overall CNS stimulant. Decrease tremors in Parkinsons disease. Atropine may cross BBB.
Overdose may cause euphoria, restlessness, slurred speech, memory disturbance etc.
CVS Tachycardia, Increase BP. However high dose of Atropine decrease BP.
Eye Dilation of pupil (Mydriasis). Cause photophobia. Increase intraocular pressure.
Smooth Relaxation of Smooth muscles, Decrease in peristalsis. Decrease stomach tone. Chyme
muscle movement decreases, Constipation may occur.
Gland Bronchial, salivary, lacrimal, gastric secretions decrease. Sweating will decrease.
Dryness of mouth.
Body Body temp will increase at high dose.
temperature
Respiratory Bronchodilation
tract
 Adrenergic /Sympathomimetic

1. Sympathomimetic drugs are those drugs which mimic the action of Sympathetic nervous system.
2. Neurotransmitters associated with Symapathetic nervous system: Noradrenaline

Sympatho= Symapathetic nervous system

Mimetic= to copy

Receptor Type Location MOA Effect Agonist

α1 Gq Vascular Activate Phospholipase C, Contraction of smooth Phenylephrine,
endothelium, Increase intracellular IP3 muscles Methoxamine,
liver, smooth and Ca++ Glycogenolysis, Increase in Xylometazoline,
muscles intraocular pressure and Oxymetazoline
mydriasis.
Systemic vasoconstrictors
(Used in treatment of
Hypotension and nasal
congestion).
α2 G i , Go Pancreatic beta Decrease Adenylyl cyclase Decrease insulin release. Clonidine,
cells, smooth Systemic vasodilators (Used Methyldopa
muscles in treatment of Hypertension
and glucoma).
β1 Gs Heart, kidney Increase Adenylyl cyclase Increase heart contraction, Dobutamine,
rate, rennin release increase. Isoproterenol,
Epinephrine
(non-selective)
β2 Gs Bronchial Increase Adenylyl cyclase Bronchodilator, Vasodilation, Terbutaline,
smooth Glycogenolysis Salbutamol,
muscles, Liver, Isoprenaline,
GIT
β3 Gs Adipose tissue Increase Adenylyl cyclase Lipolysis

Classification of Sympathomimetic drugs:

Direct acting sympathomimetic drugs: Directly act as agonist on α and β receptors or both: E.g. Adrenaline,
Noradrenaline, Isoprenaline, Salbutamol.
Indirect sympathomimetc drugs: Act on adrenergic nerve to release Noradrenaline. E.g. Tyramine, Amphetamine.
Mixed acting sympathomimetc drugs: The act directly or indirectly to mimic Sympathetic nervous system. E.g.
Ephedrine.
 Pharmacology of Sympathomimetic drugs
Heart Adrenaline increase heart rate by increasing pace maker activity of SA node.
At high dose: Arrhythmia and increase in BP.
Force of heart contraction increases.
Blood β2 receptor agonist : Vasodilation (Treatment of Hypertension)
vessels α 1 agonist: Vasoconstriction
Blood Nor adrenaline: Systolic BP rises, Diastolic BP rises, Mean BP increase.
pressure Isoprenaline: Systolic BP falls, Diastolic BP (no change), No change in BP. (β 1: Cardiac stimulation, β 2:
Vasodilation)
Adrenaline (slow infusion/i.m.): Systolic BP rises, Diastolic BP falls: BP normal after some time.
Adrenaline (rapid): Systolic and Diastolic BP increase: BP normal after some time.
Respiration Adrenalines are Isoprenaline (not NA) are potent bronchodilator. Β 2 agonist. (Treatment of Asthama)
Eye Mydriasis (dilation of pupil) (α 1 agonists), α 2 agonists decrease intraocular pressure (Treatment of
Glucoma)
GIT Gut relaxation, Decrease peristalsis, may cause contraction.
Uterus Adrenaline on α receptor: Contraction
Adrenaline on β receptor: Relaxation
Pregnant Adrenaline cause relaxation
uterus
Urinary Relax
bladder
Spinchters Constricts
CNS Poor penetration, Restlessness, tremors.
 Anti- adrenergic/Sympatholytics drugs

Anti- adrenergic drugs prevent the binding of noradrenaline with adrenergic receptors.

α blocker/antagonist
Non selective Selective
Ergot alkaloids: Ergotamine α1 blocker: Prazocine, Terazocine, Doxazocine,
Imidazoline: Phentalomine Alfuzocine
Hydrogenated ergot alkaloid:
Dihydroergotamine They are mainly used to treat benign prostatic
Haloalkyl amine: Phenoxybenzamine hyperplasia (BPH), and hypertension.
α2 blocker: Yohimbin, Phentolamine.

Alpha-2 blockers increase noradrenalin release.

Yohimbine was used as an aphrodisiac.

Pharmacology α blocker/antagonist
Blood Vasodilation, Reduce peripheral resistance, Cardiac output decrease, fall in BP.
vessels
Heart Reflex tachycardia may occur due to fall in mean arterial pressure.
Eye Miosis
Nose Nasal stiffness. Block α receptors on nasal blood vesssels.
GIT Peristalsis increase, Loose motions may occur.
Kidney Renal blood flow will decrease, GFR will decrease, Na+ and H2O absorption increase, Urine
outflow decrease.
Smooth Muscle tone of smooth muscles of sphincter and prostrate will decrease. Improve urine outflow in
muscles patients with prostrate hypertrophy.
Cholesterol Prazocine is found to decrease LDL cholesterol levels and increase HDL cholesterol levels in
levels blood.
 β Adrenergic blocking agents

Non selective Selective (Cardioselective β1 blocker)

Without ISA: Propranolol, Sotalol, Timolol Metoprolol, Atenolol, Acebutolol, Bisoprolol, Esmolol,
With ISA: Pindolol Nebivolol.
With α blocking activity: Labetelol, Carvedilol

β Adrenergic blocking agents

First generation Second generation Third generation
(Older, non-selective) (Cardio-selective β1 blocker) (With α blocking /vasodilator activity)
Propranolol Metoprolol Labetalol
Sotalol Atenolol Carvidilol
Timolol Acebutolol Celiprolol
Pindolol Bisoprolol Nebivolol
Esmolol
ISA: Intrinsic Sympathomimetic activity.

Pharmacological action of β blockers/ Antagonists

Heart Heart rate decrease, decrease force of heart contraction, decrease cardiac output, decreases
cardiac workload, decrease O2 consumption. Coronary blood flow decrease.
Treatment of hypertension, angina
Blood pressure BP falls (prolonged use) in hypertensive patients.
Blood vessels May cause vasoconstriction is small blood vessels. However, vasodilatation occurs due to α
receptor blocking activity (Labetelol, Carvedilol)
Respiration Broncho-constriction (contra-indicated in Asthama)
CNS Forgetfulness, Nightmares, Reduce anxiety.
Eye Intra-occular tension decrease. Treatment of Glucoma.
Skeletal Reduce tremors due to sympathetic stimulation.
muscles Exercise capacity decrease due to β2 blocking activity.
β2 blocking activity will reduce Lipogeneis and Glycogenolysis.
Uterus Relaxation of Uterus inpregnancy.
Metabolism Decrease Glycogenolysis due to blocking of sympathetic activity, Plasma triglyceride levels
increases, Increase LDL levels in blood (may precipitate atherosclerosis), Carbohydrate
tolerance may occur due to decreased Insulin release. β2 blocking activity will reduce
Lipogeneis and Glycogenolysis.

Atherosclerosis is a disease in which plaque formation occurs inside arteries. Plaque is made
up of fat, cholesterol, calcium, and other substances found in the blood. Over time, plaque
hardens and narrows your arteries.