1. DRUGS ACTING ON
AUTONOMIC NERVOUS SYSTEM
Abhijeet Lokras
M. Pharm (Pharmacology) – University of Mumbai, India
MSc (Drug Development) – University of Copenhagen, Denmark
DRUGS ACTING ON AUTONOMIC NERVOUS SYSTEM
From the book – Essentials of Medical Pharmacology by KD
Tripathi
All copyrights to original authors and publishers

3. RECEPTOR DISTRIBUTION

4. CLASSIFICATION OF CHOLINERGIC AGONISTS
Cholinergic Agonists OR Parasympathomimetics OR Cholinomimetics
1. Choline esters
Acetylcholine
Methacholine
Carbachol
Bethanechol
2. Alkaloids
Muscarine
Pilocarpine
Arecoline

5. ACTIONS

6. INTERACTIONS AND USES
• INTERACTIONS:
Anti-cholinesterases potentiate Ach
Atropine and congeners competitively antagonize muscarinic
actions
Adrenaline is a physiological antagonist
• USES
Not used anymore because of evasive and non-selective action
Pilocarpine (0.5-4% drops). Third-line drug against open angle
glaucoma and to prevent or break adhesion of iris with lens

7. CLASSIFICATION OF ANTI-CHOLINESTERASES
1. Reversible Anti-cholinesterases
a) Carbamates – Physostigmine, Neostigmine, Pyridostigmine
b) Acridine – Tacrine
2. Reversible Anti-cholinesterases
a) Organophosphates – Dyflos, Echothiophate, Parathion, Malathion
b) Carbamates – Carbaryl and Propoxur

8. ACTIONS
Qualitatively similar to cholinergic agonists
Lipid soluble agents (physostigmine and OP) – Marked muscarinic and CNS effects,
stimulating ganglia but not skeletal muscles
Lipid insoluble agents (neostigmine) – Marked effect on skeletal muscles, stimulate
ganglia but no CNS and muscarinic effects
Ganglia – AChEs stimulate ganglia through M receptors. High doses cause
persistent depolarization of ganglionic nicotinic receptors and blockade of
transmission
CVS – Muscarinic action causes bradycardia, ganglionic stimulation increases HR
and BP. Medullary centres (stimulation followed by depression)

9. USES
1. Miotic
Pilocarpine is preferred. DOA 4-6 hours. Causes diminution of vision because of pupil constriction
2. Myasthenia Gravis
3. Urinary retention (0.5-1 mg neostigmine sc)
4. Post operative decurarization – reversal of muscle paralysis
5. Cobra bite - Neostigmine + Atropine to prevent respiratory paralysis

10. ANTICHOLINESTERASE POISONING
Local manifestations followed by complex systemic effects
1. Irritation of eye, salivation, blurring of vision, breathlessness
2. Fall in BP, bradycardia, arrhythmias
3. Muscular fasciculations, weakness and respiratory paralysis
4. Excitement, tremor, ataxia, convulsions
5. Death due to respiratory failure
TREATMENT:
1. Termination of further exposure to agent
2. Maintain airway
3. Maintain BP
4. Atropine – Higher doses required to counteract systemic effects
5. Cholinesterase reactivators – Oximes.
Oximes provide reactive OH to displace organophosphates. Pralidoxime attaches
to anionic site of enzyme (unoccupied in presence of organophosphorous inhibitors). IV
Injection 1-2 grams, start within 24 hours (prevent aging of enzyme)

11. CLASSIFICATION OF ANTICHOLINERGIC DRUGS
Muscarinic receptor antagonists, Atropinic, Parasympatholytic
1. Natural alkaloid – Atropine, Hyoscine
2. Semi-synthetic derivatives – Homatropine, Ipratopium, Tiotropium
3. Synthetic derivatives
a) Mydriatics – Cyclopentolate, Tropicamide
b) Antisecretory-antispasmodics
i) Quaternary ammonium compounds – Propantheline, Pipenzolate, Isopropamide
ii) Tertiary amines – Dicyclomine, Valethamate, Pirenzipine
c) Vasicoselective – Oxybutynin, Tolterodine
d) Antiparkinsonian – Benzhexol, Procyclidine, Biperiden

12. ACTIONS

13. 1. CNS
• overall CNS stimulant action
• Hyoscine produces central effects (depressant) even at low doses
• Suppresses tremor and rigidity of Parkinsonism
2. CVS
Heart: Tachycardia due to blockade of M2 receptors on SA node
BP: No consistent effect. Atropine blocks vasodepressor action of cholinergic agonists
3. Eye
Atropine causes mydriasis, abolition of light reflex and cycloplegia (7-10 days)

15. 4. Smooth muscles
• Visceral smooth muscles innervated by parasympathetic division are
relaxed by Atropine (M3 blockade)
• Tone of muscles is reduced
• Constipation may occur
• Peristalsis is partially inhibited
• Broncho dilatation and reduced airway resistance

16. 5. Glands
• Atropine markedly decreases salivary, tracheobronchial and lacrimal
secretions (M3 blockade). Skin and eyes become dry
• Atropine decreases secretion of acid, pepsin and mucus in the
stomach
• Higher doses are required and thus less effective than H2 Blockers
6. Body Temperature
• Rise in temp at higher doses (inhibition of sweating and stimulation of
temperature regulating centres)

17. PHARMACOKINETICS
• Rapidly absorbed from GIT
• Freely penetrate cornea on application
• BBB restricted
• 50 % atropine metabolized in liver, rest excreted unchanged in urine
• Half life of 3-4 hours
• Hyoscine has better BBB permeability

18. USES
1. As antisecretory
a) Pre-anesthetic medication
b) Peptic ulcer: Decrease gastric acid secretion, symptomatic relief in peptic ulcer
2. As antispasmodic
a) Intestinal and renal colic, abdominal cramps: Symptomatic relief if no mechanical obstruction
b) Nervous and drug induced diarrhea
c) Spastic constipation, IBS
d) Pylorospasm
3. Bronchial asthma, COPD
a) Bronchodilators – oral administration. Less effective than adrenergic drugs
b) Dry up the secretions of respiratory tract leading to plugging of bronchioles and then alveolar collapse
4. As mydriatic and cycloplegic
a) Diagnostic: Testing error of refraction, both mydriatics and miotics are required
b) Therapeutic: Reduces spasm of intraocular muscles. Treatment of keratitis, iridocyclitis. Breaking and preventing
adhesions between iris and lens or iris and cornea

19. 5. As cardiac vagolytic
Countering bradycardia and partial heart block where vagal tone is responsible
6. For central action
a) Parkinsonism: Mild cases and only as adjuvant to levodopa
b) Motion sickness: Hyoscine most effective. Prophylactic 0.2 mg, action lasts 4-6 hours

20. CLASSIFICATION OF GANGLIONIC
STIMULANTS

21. CLASSIFICATION OF GANGLIONIC BLOCKERS

22. ACTIONS

23. ADRENERGIC SYSTEM AND DRUGS
• Restricted to sympathetic division of ANS
• Three closely related catecholamines:
a) Noradrenaline (NA) – Transmitter at post-ganglionic sites and certain areas of
brain
b) Adrenaline (Adr) – Transmitter role in brain
c) Dopamine (DA) – Major NT in basal ganglia, limbic system, CTZ etc

24. SYNTHESIS OF CATECHOLAMINES
1. Synthesis of CAs
• From AA phenylalanine
• Tyrosine hydroxylase is rate determining enzyme, blockage by alpha-methyl-p-
tyrosine results in depletion of Cas
• Synthesis of NA occurs in ALL Adrenergic neurons, Adr Only in Medulla
2. Storage of CAs
• Synaptic vesicles within the nerve terminal
• Vesicular membrane active takes up DA from cytoplasm
• Final step of NA synthesis occurs in vesicle containing beta-hydroxylase
• NA stored as a complex with ATP (4:1) adsorbed on chromogranin
• Cytoplasmic pool kept low by MAO

25. 3. Release of CAs
• Nerve impulses causes exocytosis which releases CA
• Vesicular contents poured out
• The release is modulated by alpha-2 presynaptic receptors
4. Uptake
• Efficient
• Axonal uptake – Active Amine Pump (NET), transfers NA by Na+ coupled
mechanism
• VMAT – Transport CA from cytoplasm to storage vesicle
• Extraneuronal uptake