Parasympathetic Pharmacology

Question 1

State the roles of parasympathetic activation

Answer 1

Rest & Digest - pupil constriction 
- near point accommodation
-bronchiole constriction
bradycardia, hypotension
-incr in GI mobility and secretions 
-contraction of urinary bladder
-exocrine secretions (salivation, lacrimation)

Question 2

Describe the characterisation of muscarinic receptors

Answer 2

Activated by MUSCARINE. All act via METABOTROPIC events. M1 brain, M2 heart, M3 smooth muscle/exocrine (including bronchi). Has two different messengers - intracellular CA2+ release and protein phosphorylation

Question 3

How does mAChR Signalling Mechanisms compare with adrenoceptors?

Answer 3

M3 glandular = incr in Ca2+ gives exocrine secretion, smooth muscle contraction
M2 cardiac = decr in cAMP - decr PKA = inactivates CA2+ channels.
Activates K+channels = decr Ca2+ channel activity
They both reduce chance of contraction = bradycardia

Question 4

Describe the parasympathetic control of bladder function

Answer 4

Automatic reflex arc. Loss of higher control: incontinence (multiple sclerosis, diabetic neuropathy). Antagonist to inhibit reflex arc at target organ (M3)

Question 5

Muscarinic receptor antagonist - OXYBUTYNIN - how does it work?

Answer 5

Non-selective anti-muscarinic. prevents unwanted bladder contractions.

Question 6

What do you think the side effects of a muscarinic receptor antagonist (nonselective)?

Answer 6

Blurred vision, tachycardia, dry mouth

Question 7

Muscarinic agonist PILOCARPINE is used for glaucoma - why would you use this drug?

Answer 7

M3 agonist - able to promote miosis

• constriction of circular muscle
• opens up drainage channel
• incr aqueous humour drainage
• decr of intraocular pressure

Question 8

Muscarinic antagonist - TROPICAMIDE used for ocular examination, why?

Answer 8

M3 antagonist. Used to cause mydriasis

• relaxation of circular muscle of iris
• relaxation of ciliary muscle

Question 9

Muscarinic receptor antagonist - HYOSCINE, how is it different to atropine?

Answer 9

Non-selective. Lipophilicity greater- easily crosses BBB- greater CNS effects and duration of action. It is a CNS depressant - for travel sickness and inhibits smooth muscle mobility in bowel

Question 10

What are anti-cholinesterases?

Answer 10

Effect all cholinergic neurotransmission. Block AChE and prolong it at receptors- indirectly prolongs life of neurotransmitter.

Question 11

Give two examples of reversible anticholinesterases

Answer 11

Physostigmine - for glaucoma - stimulates bladder in urinary retention
Neostigmine - more effective at NMJ, to treat myasthemia gravis (AChR antibodies

Question 12

Give an example of irreversible anticholinesterases

Answer 12

Insecticides - covalently modify AChE

Question 13

List short term symptoms of antocholinesterase poisoning

Answer 13

MUSCARINIC - miosis, salivation, sweating, bradycardia
NICOTINIC - fasciculation, paralysis
CNS - anxiety, restlessness, dizziness

Question 14

What is the treatment of anticholinesterase poisoning?

Answer 14

Use ANTI-MUSCARINIC drugs - decr the availability of mAChR to alleviate symptoms.
Or use atropine - blocks mAChR.
Or use oximes to dephosphorylate acetylcholinesterase