P1

Question 1

Atropine

Answer 1

An antimuscarinic agent

MoA: Atropine binds to and inhibits the muscarinic acetylcholine receptor.

Use: It prevents/abolishes bradycardia or asystole produced by injection of choline esters, anticholinesterase agents or other parasympathomimetic drugs, and cardiac arrest produced by stimulation of the vagus. Atropine may also lessen the degree of partial heart block when vagal activity is an etiologic factor.

Question 2

Betamethasone

Answer 2

Betamethasone is a glucocorticoid receptor agonist

MoA: Binding of betamethasone to the glucocorticoid receptor, forms a complex, which moves to the nucleus, binds DNA causing alteration in gene transcription. This alter gene transcription causes the production of lipocortins, which inhibits phospholipase A2, and therefore reduces the biosynthesis of prostaglandins and leukotrienes.

Use: Anti-inflammatory, immunosuppressive and anti-mitogenic effects of steroids.

Question 3

Digoxin

Answer 3

A cardiac glycoside

MoA: Inhibition of the Na-K-ATPase membrane pump, resulting in an increase in intracellular sodium. This causes in turn the sodium calcium exchanger (NCX) to extrude the sodium and pump in more calcium. High calcium is thought to promote activation of contractile proteins (e.g. actin, myosin).

Digoxin also acts on the electrical activity of the heart, increasing the slope of phase 4 depolarization, shortening the action potential duration, and decreasing the maximal diastolic potential.

Use: Treatment of congestive heart failure, and supraventricular arrhythmias. Still used in AF, but now very much third line treatment option. Rarely used in heart failure as much better drugs available

Question 4

Edrophonium

Answer 4

Rapid-onset, short-acting cholinesterase inhibitor

MoA: Prolongs the action acetylcholine, via inhibiting acetylcholinesterase at sites of cholinergic transmission.

Edrophonium increases the amount of acetylcholine at the nerve endings, therefore allowing the remaining receptors to function more efficiently.

Use: Cardiac arrhythmias + diagnosis of myasthenia gravis (MG) – Tensilon test; otherwise pyridostigmine used for MG

Question 5

Ketoconazole

Answer 5

Broad spectrum anti-fungal agent.

MoA: Inhibition of 14-α demethylase, a cytochrome P-450 enzyme which converts lanosterol to ergosterol.

This inhibition of ergosterol causes increased fungal cellular permeability.

Contraindicated with:

• Alprazolam, midazolam, triazolam
• HMG-CoA reductase inhibitors: lovastatin, simvastatin
• Ergot alkaloids: ergotamine, dihydroergotamine
• Others: cisapride, nisoldipine, dofetilide, pimozide

Question 6

Morphine

Answer 6

Opiate

MoA: Binds to mu-opioid receptors. GABA inhibitory interneurons – morphine inhibits the activity of these and therefore limits the descending pain inhibition pathway. Therefore, without the inhibitory signals, pain modulation can proceed downstream

Question 7

Naloxone

Answer 7

Opiate antagonist

MoA: Antagonise all 3 opioid receptors (Mu, Kappa, and Gamma), although it has the strongest binding to the Mu receptor.

Use: prevents or reverses the effects of opioids (resp depression, sedation, hypotension)

Question 8

Tamoxifen

Answer 8

Selective oestrogen receptor modulator (SERM)

MoA: Binding of to the oestrogen receptor (ER), leading to a conformational change in the receptor and therefore altering the expression of oestrogen dependent genes.

Question 9

Suxamethonium

Answer 9

A depolarising skeletal muscle relaxant.

Class: ACh analogue

MoA: Mimic acetylcholine at the neuromuscular junction. Suxamethonium is hydrolysed much slower than ACh, causing prolonged depolarisation and therefore desensitisation, and muscle relaxation. Unlike the non-depolarising neuromuscular blocking drugs.

Note: Suxamethonium cannot be reversed and recovery is spontaneous. Suxamethonium is given after a general anaesthetic as muscle relaxation can be preceded by painful muscle fasciculations.

Question 10

Neostigmine

Answer 10

Anticholinesterase

Use: Used together with atropine to end the effects of neuromuscular blocking medication of the non-depolarising type.

Question 11

Tubocurarine

Answer 11

Neuromuscular blocker

MoA: Tubocurarine binds stereo-selectively to nicotinic-cholinergic receptors at the autonomic ganglia, the adrenal medulla, neuromuscular junctions, and in the brain.

Use: Has 2 main effects, stimulation and reward. The stimulatory effect occurs mainly in the cortex via the locus ceruleus whilst the reward effect is exerted in the limbic system. At low doses the stimulant effects predominate while at high doses the reward effects predominate.

Note: Tubocurarine has been superceded by Suxamethonium as the clinically used depolarising neuromuscular blocker

Question 12

Pyridostigmine

Answer 12

A cholinesterase inhibitor

MoA: Reversible inhibition of acetylcholinesterase in the synaptic cleft by competing with acetylcholine for attachment to acetylcholinesterase. This inhibition leads to a reduction in the hydrolysis of acetylcholine, prolonging its effects.

Note: Pyridostigmine is a quaternary amine therefore it is poorly absorbed in the gut and doesn’t cross the blood-brain barrier.

Question 13

List (1) non-depolarising and (2) depolarising

peripherally acting
(primarily antinicotinic,
NMJ block) skeletal muscle relaxants.

Answer 13

Non-depolarising:

• Tubocurarine
• Alcuronium
• Pancuronium
• Rocuronium

Depolarising:

• Suxamethonium
• Hexamethonium