pharmacology drugs acting on autonomic nervous system

1. Dr. Haji Bahadar, PharmD, PhD.
Assistant Professor, KMU-IPMS
Drugs Acting on autonomic
nervous system

4. OVERVIEW
Drugs affecting the autonomic nervous system (ANS) are
divided into two groups according to the type of neuron
involved in their mechanism of action. The cholinergic
drugs, act on receptors that are activated by acetylcholine
(ACh), whereas the adrenergic drugs act on receptors
stimulated by norepinephrine or epinephrine.

5. Cholinergic system
 The cholinergic system is composed of nerve
cells that use the neurotransmitter acetylcholine.
 It is an enzyme that catalyzes the breakdown of
acetylcholine

7. DIRECT
ACTING
Indirect acting
(irreversible
inhibitors of
acetylcholinesterase
Indirect acting
(reversible inhibitors of
acetylcholinesterase)
Acetylcholine Echothiophate Neostigmine
Pilocarpine Physostigmine
Carbachol Pyridostigmine
Bethanechol Galantamine
cholinergic drugs( parasympathomimetics)
A parasympathomimetic drug or cholinomimetic drug, is
a substance that stimulates the parasympathetic nervous
system.

8. Muscarinic receptors
 M1 receptors: found on gastric parietal cells,
 M2 receptors on cardiac cells and smooth
muscle,
 M3 receptors on the bladder, exocrine glands,
and smooth muscle.

9. Acetylcholine
 Action on cardiovascular system:
A. acetylcholine causes decrease in heart rate and cardiac
output (negative chronotropy) and negative ionotrophy)
B. Blood pressure: acetylcholine causes vasodilation and
lowering of blood pressure. acetylcholine activates M3
receptors found on endothelial cells lining the smooth
muscles of blood vessels causing vasodialation
 Gastrointestinal (GI) tract: acetylcholine increases salivary
secretion and stimulates intestinal secretions and motility
 Respiratory system: acetylcholine enhances bronchiolar
secretions and cause bronchoconstriction(M3)
 Urinary system: acetylcholine increases the tone of the
detrusor muscle, causing urination(M3)
 Effect on eye: In the eye, acetylcholine(not topical) is
causing miosis (constriction of pupils)
 Exocrine Glands????

10. Clinical uses
1. Bethanechol: post operative urinary retention
and paralytic ileus: Bethanechol has more
pronounced effects on smooth muscles
2. Pilocarpine is used to treat
increased pressure inside the eye and dry
mouth
3. Neostigmine: it is used to improve muscle
strength in patients with a certain muscle
disease (myasthenia gravis).

13. Cholinergic Antagonists
Those drugs which antagonize the effect of
acetylcholine.
 Atropine
 Scopolamine(hyoscine)
 Ipratropium bromide
 Tropicamide
 Glycopyrolate
 Propantheline
 Pirenzepine (M1 selective antagonist)
 Clidinium (M1 selective antagonist)(Librax)
 Dicyclomine
 Oxybutynin (Ditropan)
atropa belladona

14. MECHANISM OF ACTION
 Anticholinergic drugs combine reversibly with
muscarinic cholinergic receptors thus preventing
access of neurotransmitter acetylcholine.

15. Atropine
 Eye: Atropine blocks muscarinic activity in the eye,
resulting in mydriasis (dilation of the pupil)
 Gastrointestinal (GI): Atropine reduce activity of
the GI tract. can be used as an antispasmodic.
 Secretions: Atropine blocks muscarinic receptors
in the salivary glands, producing dryness of the
mouth (xerostomia). The salivary glands are
exquisitely sensitive to atropine. Sweat and lacrimal
glands are similarly affected.
 Cardiovascular: Atropine produces diverse effects
on the cardiovascular system, depending on the dose
At low doses, atropine causes decrease in heart
rate. Higher doses of atropine cause a progressive
increase in heart rate by blocking the M2 receptors on
the sinoatrial node.

16.  CNS: Atropine has CNS stimulant action at high
dose. High doses cause cortical excitation,
restlessness, disorientation, hallucination & delirium
followed by respiratory depression & coma. It
suppresses tremor & rigidity of parkinsonism.
 Smooth muscles: All visceral smooth muscles that
receive parasympathetic motor innervation are
relaxed by atropine due to M3 blockade
 Glands: Atropine decreases sweat, salivary,
bronchial & lacrimal secretions by M3 blockade
 Body temperature : - Rise in body temperature
occur at high doses due to both inhibition of
sweating as well as stimulation of temperature
regulating centre in the hypothalamus

17. Therapeutic uses of
anticholinergics
 Pre-anesthetic medication : reduces excessive
salivation(Sialorrhea ) & respiratory secretions.
(glycopyrrolate and scopolamine)
 Peptic ulcer : decreases gastric secretions (clidinium)&
provide symptomatic relief in peptic ulcer now been
superseded by H2 blockers.
 As anti-spasmodic:intestinal & renal colic, abdominal cramps
 To relive urinary frequency & urgency or involuntary
urination (enuresis)(Oxybutynin, Propantheline)
 Bronchial Asthma (ipratropium)
 As mydiatric & cycloplegic.
 As cardiac vagolytic
 Organophosphates Poisoning and mushroom poisoning.
 Antidote for cholinergic agonists: Atropine is used for
the treatment of organophosphate (insecticides, nerve gases)
 Treatment of excessive sweating (hyperhidrosis)

18. Side effects
 Belladona poisoning • Dry mouth, difficulty in
swallowing and talking. • Dry,flushed and hot skin.
Dilated pupil • Fever difficulty in micturition,
Excitement, ataxia, delirium, hallucination. •
Convulsion and coma may occur in severe
poisoning. •
 Treatment of 3Ds : Physostigmine 15- 60 micro
gram / kg IV every 1- 2 hourly.
cycloplegia : paralysis of the ciliary muscle of the eye.

19. Organophosphates poisoning
 The organophosphate (OP) pesticides inhibit
acetylcholinesterase. Hence, acetylcholine
accumulates at nerve synapses and
neuromuscular junctions, stimulating muscarinic
and nicotinic receptors and the central nervous
system.
 Reactivation of acetylcholinesterase
 Pralidoxime can reactivate inhibited AChE.
However, it is unable to penetrate into the CNS
and therefore is not useful in treating the CNS
effects of organophosphates.