This document discusses the autonomic nervous system and drugs that affect it. It begins by describing the organization of the nervous system and autonomic nervous system. It then discusses exceptions in the sympathetic nervous system related to sweat glands, kidneys, and adrenal glands. The document goes on to classify drugs that can mimic or block neurotransmitters in the autonomic nervous system like acetylcholine and adrenaline. It also discusses indirect-acting drugs and different receptor types like muscarinic, nicotinic, alpha, and beta receptors. The locations and functions of these receptors are explained. Finally, examples of drugs are provided that can act as agonists or antagonists at these different receptor types.

1. AUTONOMIC PHARMACOLOGY
Pharm.(Mrs.)M.O.Ologe

2. Organization of the Nervous System
Nervous system
CNS PNS
ANS SNS

3. Organization of the ANS

4. Exceptions in the Sympathetic NS
• Sweat glands
Postganglionic nerves involved with
thermoregulation release ACETYLCHOLINE,
muscarinic receptors.
• Kidneys
Postganglionic neurones to the smooth
muscle of the renal vascular bed release
DOPAMINE, D1 receptors.

5. Sympathetic NS exceptions contd
• Adrenal gland
Preganglionic neurons do not synapse in the
paravertebral sympathetic ganglion.
They synapse directly in the adrenal gland,
release ACh and activate nicotinic receptors
on the adrenal gland.
Adrenal glands release adrenaline and
noradrenaline (in lesser amounts) into
systemic circulation.

6. How do drugs influence the ANS
• Mimic or block the effects of the two primary
neurotransmitters – ACH and ADR
• Drugs that mimic neurotransmitters are called
Receptor agonists – they activate receptors.
• Drugs that block neurotransmitters are
referred to as Receptor antagonists – they
block the endogenous neurotransmitters from
activating receptors.

7. Classification of drugs affecting the ANS
• Parasympathetic Nervous System
Mimic ACh = cholinergic = muscarinic agonist
= parasympathomimetic
Block ACh = anticholinergic = muscarinic
antagonists = parasympatholytic
• Sympathetic Nervous System
Mimic NA = adrenergic =adrenergic agonists
=sympathomimetic
Block NA = antiadrenergic = adrenergic
antagonist= sympatholytic

8. Indirect acting drugs
• Do not affect neurotransmission by acting on
receptors.
• Promote release of neurotransmitters
E.g Sym NS - Amphetamine
Parasym NS - No known drug
• Inhibit neurotransmitter reuptake in sym
nervous sys e.g. Cocaine
• Inhibit neurotransmitter degradation in para
sym nervous sys e.g. Anticholinesterases
• Note: Botulinum toxin is a potent inhibitor of
ACh release

9. Acetylcholine receptors

10. Locations of Acetylcholine
receptors

11. Muscarinic receptors

12. Location and functions of
muscarinic receptors
• M1,M4, M5 , in CNS
memory, arousal, attention & analgesia
• M1 – gastric parietal cells, autonomic ganglia
↑sed salivary & intestinal secretions
• M2 - ↓se conduction velocity at SA & AV →
↓sed heart rate, ↓sed CO

13. Location and functions of muscarinic
receptors contd
• M3 – smooth muscle of bladder, bronchial
tissue, exocrine gland, eyes etc.
bladder - ↑sed tone of dextrusor muscle
eye – i. pupil constriction : miosis (constrict
pupillae sphincter muscle)
ii. stimulate ciliary muscle contraction
for near vision
bronchioles – bronchoconstriction
stimulates secretion

14. Muscarinic agonists
• Acetylcholine
• No therapeutic importance because of :
1. multiple actions
2. rapid inactivation by acetylcholinesterase.
• Choline esters– synthetic, resistant to
acetylcholinesterase
Bethanechol, Carbachol, Methacholine
• Pilocarpine – tertiary amine, high lipid sol.
emergency lowering of intraocular pressure in
closed-angle & open-angle glaucoma

15. Muscarinic antagonists
• Wide clinical uses unlike cholinomimetics
• Atropine (Hyoscamine)
opthalmic uses – mydriasis & cycloplegia,
refractive errors are measured without
interference with accomodation.
antispasmodic agent – git , bladder
antisecretory- upper & lower resp tract before
surgery
cholinergic poisoning as antidote
anaesthesia – block vagal slowing of the heart

16. Muscarinic antagonists contd
• Hyoscine (scopolamine)
prevention of motion sickness
short-term memory blockade in anaesthesia
• Ipratropium – asthma
• Benzhexol – parkinson’s disease

17. Indirect- acting cholinomimetics
• Anticholinesterases
Reversible - Edrophonium
Neostigmine
Physostigmine
Pyridostigmine
Irreversible – Echothiophate
(Organophosphates) Isofluorophate
Parathion
Malathion

18. Cholinesterase reactivator
• Pralidoxime – Cholinesterase reactivator,
reactivates the action of acetylcholinesterase.

19. Nicotinic receptors

20. Sympathetic NS- Alpha receptors

21. α1–receptors contd

22. Effects of α1–receptor activation
• Vascular smooth muscle
• vasoconstriction → ↑sed peripheral resistance,
↑sed blood pressure
• Mydriasis
contract iris radial muscle → pupil dilatation
• Genitourinary tract smooth muscle
a. ↑sed closure of internal sphincter of
bladder
b. constriction of smooth muscle of bladder
neck and prostate
• ↑sed constriction of git sphincter muscle

23. Effects of α2–receptor activation

24. Drugs affecting alpha receptors

25. Drugs affecting alpha receptors
• alpha 1 agonists
Nasal decongestant drugs - naphazoline,
phenylephrine and propylhexedrine.
• alpha 1 antagonists
Prazosin, Doxazosin, Terazosin – hypertension,
benign prostatic hypertrophy
common adverse effects: orthostatic
hypotension, nasal congestion,headache, etc
Tamsulosin - alpha 1A receptor selective

26. Drugs affecting alpha receptors contd
• Alpha 2 agonists – centrally-acting
Clonidine – hypertension, symptoms
associated with opioid withdrawal
Alpha-methyldopa – hypertension in
pregnancy
• Non – selective alpha antagonists:
Phentolamine
Phenoxybenzamine

27. Beta receptors
• three sub-groups :
beta 1, 2, and 3

28. Beta 1 receptors

29. Beta 2 receptors

30. Beta 2 receptors

31. Drugs acting on β-receptors
• β1- agonists- stimulate force of heart
contraction
• Dopamine – low dose Dopamine has an
advantage over Noradrenaline in shock
management and cardiac decompensation
associated with hypotension. What is this
advantage?
• Dobutamine
• Isoproterenol (Isoprenaline)

32. Drugs acting on β-receptors contd
• β2- agonists
• Salbutamol (Albuterol)
• Salmeterol
• Ritodrine
• Terbutaline etc.

33. • Non-selective β-blockers, prototype is
Propanolol.
Clinical uses of Propanolol and other non-
selective beta-blockers,
Adverse effects
Contraindications
•β1- selective blockers- cardioslective, main
relevance in hypertension and other
cardiovascular conditons
E.g Atenolol, Metoprolol, Neviprolol, Esmolol
Drugs acting on β-receptors contd

34. Drugs acting on β-receptors
• Some β-blockers have intrinsic
sympathomimetic activity, i.e. they are partial
agonists. E.g Acebutolol
• Clinical indications and adverse effects of
these drugs

35. FURTHER READING
• Clinical uses of autonomic drugs
• Adverse effects of these drugs, especially those
that are peculiar to a particular group, and the
physiologica/pharmacological basis for those
adverse effects
Example: postural (orthostatic) hypotension is
common with α1- blockers (antagonist).
Why? Venous pooling of blood to the periphery,
needed for maintenance of blood pressure in
upright position, is controlled by α-receptors so
when they are blocked by α1-blockers; postural
hypotension occurs

36. REFERENCES
• Harvey, Richard; Champe, Pamela (series editors).
“Lippincott illustrated reviews: Pharmacology”,
4th edition. LWW: 2009
• Rang, H.P.;Dale, M.M.;Ritters, J.M.;Moore,P.K.;
”Pharmacology” 6th edition. Churchill Livingstone
2007
• Katzung, B. “Basic & Clinical Pharmacology”, 10th
Edition. Mc Graw Hill Medical: 2007
• Golan, David E (editor). “Principles of
Pharmacology: The Pathophysiologic Basis of
Drug Therapy”, 2nd edition. LWW: 2008.

37. Thank you for listening