Pharm Term 1

Question 1

What effect do muscarinic receptor antagonists have on the CNS? (atropine and hyoscine)

Answer 1

The parasympathetic nervous system is important in the CNS in terms of attention, memory and certain sleep pathways.
Atropine:
normal dose- little effect
toxic dose- CNS stimulant, restlessness and even agitation

Hyoscine
Normal dose – Sedation, amnesia (memory loss)
Toxic dose – CNS depression (slow down brain activity) or paradoxical CNS excitation (associated with pain)

A paradoxical reaction or paradoxical effect is an effect of medical treatment, usually a drug, opposite to the effect which would normally be expected. An example of a paradoxical reaction is pain caused by a pain relief medication.

Question 2

Location of muscarinic receptors

Answer 2

M1 = mone = stomach
M2 = heart
M3 = all the smooth muscles of gut (constriction), bronchial (constriction) and vasculature (vasoDILATION via stimulating NO release). If you had to guess, choose M3 in exam
M4/5 CNS

Question 3

Describe the type of G protein receptor for each muscarinic

Answer 3

M1,3,5 = Gq
M2,4 = Gi

Question 4

How does Para NS cause Vasodilation

Answer 4

stimulating NO production after muscarinic stimulation

Question 5

2 types of directly acting cholinomimetics ? ( aka muscarinic agonist)

Answer 5

Choline Esters – Bethanechol

Alkaloids - Pilocarpine

Question 6

2 types of nicotinic receptors and their subunits

Answer 6

Muscular- 2 alpha + beta+ delta+ epsilon (m=more subunit types)
Ganglion= 2b3a

Question 7

bethanechol selectivity

Pilocarpine selectivity

Answer 7

B: m3 selective agonist
P: Non selective muscarinic agonist (Muscarinic>nicotinic)

Question 8

What type of compounds are irreversible anticholinesterase drugs?

Answer 8

Organophosphates

Question 9

Example of reversible and irrerversible anticholinesterases

Answer 9

reversible : physostigmine, neostigmine (stigmines)

Irreversible: sarin gas, ecothiopate

Question 10

2 types of NMJ blockers

Answer 10

depolarising (suxamethonium)

Non-depolarising (tubocurarine and atracurium)

Question 11

side effects of suxamethonium

Answer 11

1. Post-operative muscle pains
   Due to initial fasciculations
2. Hyperkalaemia
   If there is soft tissue injury leading to denervation hypersensitivity suxamethnoium will cause bigger influx of sodium and bigger efflux of potassium (hyperkalaemia)

3.Bradycardia 
direct muscarinic (PNS) action on the heart but prevented by giving atropine 

4.Raised intraocular pressure
contraction of extraocular muscles (S,I,L,M rectus, SO and IO and LPS)

Question 12

what would you use to reverse NM blockers

Answer 12

anticholinesterase inhibitor

Question 13

side effects of tubocurarine

Answer 13

MAIN EFFECTS: This drug causes ganglion block (autonomic ganglia have nicotinic AChR AND histamine release from mast cells.

This leads to the following side effects:
 HYPOTENSION – histamine can act on H1 receptors and cause vasodilation, ganglion block so reduced sympathetic tone (reduced TPR)
 TACHYCARDIA – reflex tachycardia in response to hypotension. Blockade of ganglia (esp. vagal ganglia) will reduce resting vagal tone on heart.
 BRONCHOSPASM – caused by histamine release
 EXCESSIVE SECRETIONS (bronchial and salivary) – caused by histamine