The document discusses drugs that affect the autonomic nervous system. It describes how the autonomic nervous system regulates involuntary body functions and is divided into the sympathetic and parasympathetic divisions. It then summarizes different types of drugs that act on these divisions, including cholinergic drugs that stimulate the parasympathetic nervous system, anticholinergic drugs that block the parasympathetic nervous system, adrenergic drugs that activate the sympathetic nervous system, and adrenergic blockers that inhibit the sympathetic nervous system. Clinical uses are provided for several of these drug classes.

1. Drugs that affect the
autonomic nervous system

2. Topics
Introduction
Autonomic nervous system
Cholinergics
Anti-Cholinergics
Adrenergics
Anti-Adrenergics

4. AUTONOMIC NERVOUS SYSTEM
The autonomic nervous system (ANS) is a
division of the peripheral nervous system that
influences the function of internal organs.
It is a control system that acts largely unconsciously
and regulates bodily functions such as the heart
rate, digestion, respiratory rate, pupillary
response, urination, and sexual arousal.
This system is the primary mechanism in control of
the fight-or-flight response and the freeze-and-
dissociate response.

5. Fig : Schematic diagram comparing some anatomic and
neurotransmitter features of autonomic and somatic motor nerves.
Anatomy of autonomic nervous system

6. Anatomy of autonomic nervous system
 The autonomic nervous system is devided into two major portions:
the sympathetic (thoracolumbar) division and the parasympathetic
(craniosacral) division
 The sympathetic preganglionic fibers leave the
central nervous system through the thoracic and lumbar spinal nerves.
 The parasympathetic preganglionic fibers
leave the central nervous system through the cranial nerves
(especially the third, seventh, ninth, and tenth) and
the third and fourth sacral spinal roots

8. CHOLINERGICS
 Parasympathomimetics or cholinomimetics
 Stimulate parasympathetic nervous system in same
manner as does acetylcholine
 May stimulate cholinergic receptors directly or slow
acetylcholine metabolism at synapses (affect the
enzyme acetylcholinesterase)

9. MOA of cholinomimetic drugs

10. CHOLINERGIC AGONISTS
 Direct cholinergic agonists
 Methacholine
 Carbachol (both muscarinic and nicotinic agonist)
 Bethanechol
 Pilocarpine
 Indirect cholinergic agonists
 Physostigmine
 Neostigmine
 Rivastigmine
 Pyridostigmine
 Edrophonium
 Ecothiophate

11. ORGAN SYSTEM EFFECTS
 Eye
 Miosis
 Enhance drainage of aqueous humor from the
anterior chamber
 Cardiovascular system
 Bradycardia(This is due to receptor activation)
 Decreased inotropic and chronotropic effects
 Vasodilation(This is due to M3 receptor
activation)

12. CONT…
Respiratory tract
 Bronchoconstriction
 Stimulation of bronchial secretions.
 GIT
 Increase in muscle tone
 Increase in peristaltic contractions
 Stimulation of gastric secretions
 Genitourinary tract
 Relax the trigone and sphincter muscle of the bladder,
thus promote voiding.

13. CLINICAL USE OF CHOLINERGIC AGONISTS
1. Treatment of glaucoma :
Carbachol and Pilocarpine are the direct agents chosen.
Physostigmine is an anticholinesterase used.
2. Treatment of atony of GIT:
Bethanechol is the most widely used direct agent and
Neostigmine is the most widely used anticholinesterase
for this purpose.
3. Treatment of xerostomia:
Bethanechol and pilocarpine are used to increase
salivary secretion to treat xerostomia (dry mouth).

14. CLINICAL USE OF CHOLINERGIC AGONISTS
CONT…
1. Myasthenia gravis:
Neostigmine, pyridostigmine and ambenonium are
most widely used. Edrophonium is used as the
diagnostic agent.
2. Alzheimer’s disease:
Anticholinesterase such as tacrine (no longer used
widely), galantamine, rivastigmine, donezepil are
used in alzheimer’s disease.

15. ANTICHOLINERGICS
 Anticholinergics are the class of drugs that block
the actions of acetylcholine in the PSNS.
 Anticholinergics are competitive antagonists that
compete with acetylcholine for binding at the
muscarinic receptors of the PSNS, inhibiting nerve
transmission.
 This effect occurs at the neuroeffector junctions of
smooth muscle, cardiac muscle, and exocrine
glands.

16. Muscarinic Receptor Subtypes
M1 M2 M3 M4 M5
Location • CNS
• Stomach
• Heart
• CNS
• Airway
Smooth
Muscle
• CNS
• Salivary
glands
• Airway
smooth
muscle
• Vascular
endothelial
cells
• CNS
• Heart
• CNS
Clinical
Effects
• Hydrogen
Ion Secretion
• Bradycardi
a
• Salivation
• Bronchodilat
ion
• Vasodilation
? ?
Clinically
selective
drugs
available
Yes No No No No

17. CHOLINERGIC ANTAGONISTS
Natural alkaloids
 Atropine
 Scopolamine
Semi-synthetic and synthetic drugs
 Propantheline
 Glycopyrrolate
 Pirenzepine
 Dicyclomine
 Tropicamide
 Cyclopentolate
 Procyclidine
 Oxybutynin

18. ORGAN SYSTEM EFFECTS
 Eye
 Cyclopegia
 Mydriasis
 Photophobia (due to mydriasis)
 CVS
 Bradycardia at lower dose
 Tachycardia at higher dose(Blocking of M2 receptor of heart)
 Respiratory tract
 Broncodilation
 Inhibition of bronchial, nasal secretion.
 GIT
 Decrease muscle tone in the GIT
 Decrease peristaltic contraction.
 Decrease gastric secretions.
 Decrease salivary secretions (dry mouth).

19. CONT…
 CNS
 Restlessness
 Irritability
 Hallucination
 CNS depression (when dose of atropine is above 2mg)
 Paralysis of respiratory muscle, cardiac reflex etc.
 Genitourinary tract
 Relaxes smooth muscle of the ureters and bladder wall and
slows voiding.
 Sweat gland
 Suppresses thermoregulatory sweating.

20. CLINICAL USE
 CNS disorders:
Parkinson’s disease: Benztropine, benzhexol etc. are used.
Motion sickness: Scopolamine has been used.
 Ophthalmic disorders: Usually atropine, tropicamide and
cyclopentolate are used.
 Respiratory disorders: Anti-muscarinic agents such as
ipratropium bromide and tiotropium therefore are very effective
bronchodilators.
 Gastrointestinal disorders:
 Anti-muscarinic agents can be used in the treatment of peptic
ulcer (e.g. pirenzepine, dicyclomine).
 They can also be used for diarrhea.
 They are used to shut down GIT before surgery.

21. CONT…
 Urinary disorders:
 Oxybutynin is used to relieve post-operative urinary bladder spasm.
 Oxybutynin and some new drugs (Darifenacin, solifenacin) are used
to treat urinary incontinence in geriatric patients.
 Cholinergic poisoning: Atropine is used as antidote in the poisoning by
cholinergic agonists .Pralidoxime is also used.

22. ADRENOCEPTOR ACTIVATING DRUGS
Drugs that mimic the action of epinephrine or
norepinephrine are called adrenoceptor activating or
sympathomimetic drugs.
 Available Drugs
𝜶 𝟏
Selective
𝜶 𝟐
Selective
β 𝟏
Selective
β 𝟐
selective
Non-selective
Tetrahydrozoline Clonidine Dobutamine Terbutaline Isoprenaline
Naphazoline α-methyldopa Albuterol Epinephrine

23. Synthesis of adrenergic neurotransmitter
Fig : Synthesis of epinephrine

24. WHERE ARE THE ADRENERGIC RECEPTORS?
Receptor: α1 α2 β1 β2 β3
localization blood
vessels
pancreas heart lungs adipose
tissue
vas
deferens
g.i. tract kidney g.i. tract
uterus
(pregnant)
CNS uterus
(non-
pregnant)
adipose
tissue
ureter stomach salivary
glands

25. MOA of β-agonist
Fig: Schemetic diagram of mechanism of β-agonist.

26. Clinical Use & Side Effect
adrenoceptor activating drugs
 Anaphylactic shock:
 In cardiac arrest and bradycardia
 During surgery.
 In bronchial asthma.
Side Effect:
 Arrhythmia
 Hypertension
 Tremor
 Headache
 Urinary retension

27. ADRENERGIC BLOCKER
Bind to adrenergic receptors, but inhibit or block
stimulation of the sympathetic nervous system (SNS)
Have the opposite effect of adrenergic agents
Also known as
-adrenergic antagonists or sympatholytics

29. Clinical pharmacology the alpha receptor
blocking drugs
 Pheochromocytoma: The major clinical use of
phenoxybenzamine is in the management of
pheochromocytoma. Pheochromocytoma is a tumor of the
adrenal medulla or sympathetic ganglion cells.
 Chronic Hypertension;Members of the prazosin family of
α1-selective antagonists are efficacious drugs in the
treatment of mild to moderate systemic hypertension.
 Urinary Obstruction:Prazosin, doxazosin, and terazosin
are all efficacious in patients with Benign prostatic
hyperplasia.

30. Clinical pharmacology the beta-
receptor blocking drugs
 Hypertension:The β-adrenoceptor–blocking drugs have proved to be
effective and well tolerated in hypertension.
 Ischemic Heart Disease:Beta-adrenoceptor blockers reduce the
frequency of anginal episodes and improve exercise tolerance in many
patients with angina.Timolol,propranolol, or metoprolol are used in
patients who have myocardial infarction.
 Cardiac Arrhythmias:Beta antagonists are often effective in the treatment
of both supraventricular and ventricular arrhythmias.
 Glaucoma:Systemic administration of β-blocking drugs for other
indications was found serendipitously to reduce intraocular pressure in
patients with glaucoma.