Drugs that affect the autonomic nervous system

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.