FoM

Question 0

Give examples of muscarinic antagonists

Answer 0

Atropine - reduces secretions

Ipatropium - bronchodialator

Hyoscine - motion sickness, facilitates endoscopy

Tropicamide - eye drops to induce mydriasis

Question 1

Describe the action of muscarinic antagonists

Answer 1

Compete with acetylcholine at muscarinic receptors and so inhibit the parasympathetic nervous system and sweat glands* as muscarinic receptors are found primarily in the PNS.

*Muscarinic receptors are also found on sweat glands even though sweat glands are sympathetically innervated

Question 2

Describe the action of ACE inhibitors

Answer 2

Inhibit the action of acetylcholinesterases leading to a build up of ACh in the synaptic cleft.

This thereby overstimulates the parasympathetic nervous system and also the action of sweat glands (even though sweat glands are under sympathetic control)

This also has effects at NMJs, causing spastic paralysis

Question 3

Give examples of ACE inhibitors

Answer 3

Physostigmine
Pyridostigmine

Short-acting: endrophonium (used in the diagnosis of myasthenia gravis)

Medium duration: neostigmine (used in the treatment of myasthenia gravis)

Irreversible: pesticides such as organophosphates; poison gases such as sarin and dyflos

ACE inhibitors are also used in the treatment of early alzheimer’s as alzheimer’s causes a loss of cholinergic neurons

Question 4

Describe the action of beta-2 adrenoceptor agonists

Answer 4

Stimulate beta-2 adrenoceptors which are found on bronchial smooth muscle. Thus, they stimulate bronchodilation and are used in the treatment of asthma.

Beta-2 adrenoceptors are also found on uterine smooth muscle, where they cause relaxation; and on skeletal muscle blood vessels where they cause vasodilation

Beta-2 adrenoceptors are GPCRs which use cAMP as a second messanger

Question 5

Give examples of beta-2 adrenoceptor agonists

Answer 5

Salbutamol

Question 6

Describe the action of NMJ blockers

Answer 6

These are competitive antagonists of nicotinic type-2 receptors. They therefore prevent skeletal muscle from contracting (i.e. They are muscle relaxants)

They are used to paralyse skeletal muscle during major operations.

Question 7

Give examples of NMJ blockers

Answer 7

Vecuronium

Question 8

Give an example of a drug which causes ACh release and describe its mechanism of action.

Answer 8

Latrotoxin - black widow spider venom

It causes a massive release of ACh in the NMJ and ANS

In the NMJ, it causes pain, spastic paralysis and possibly death

In the ANS it causes excessive stimulation of the parasympathetic nervous system

Question 9

Describe the action of muscarinic agonists

Answer 9

Mimic the action of ACh at muscarinic receptors which are found in the PNS as well as on sweat glands (even though swear glands are sympathetically innervated).

These drugs thereby stimulate the PNS as well as causing sweating.

Question 10

Give examples of muscarinic agonists

Answer 10

Pilocarpine - used as eyedrops in the treatment of glaucoma

Bethanecol - stimulates the contraction of urinary and GI smooth muscle. Used in the treatment of urinary retention and to stimulate the return of normal GI function after anaesthesia.

Question 11

Give an example of a drug which prevents ACh release and describe its mechanism of action.

Answer 11

Botulinum toxin (botox) - poison isolated from clostridium botulinum and is responsible for food poisoning

It inhibits the release of ACh

It is used in the treatment of dystonia caused by stroke or cerebral palsy. It is injected directly into the affected muscle so as not to cause systemic flaccid paralysis and to prevent effects in the ANS

Botox is also used for cosmetic purposes

Question 12

Give examples of drugs which modify the synthesis and re-uptake of noradrenaline

Answer 12

Reserpine - blocks the packaging of noradrenaline into granules

Amphetamine - displaces noradrenaline from the granules

Cocaine and SNRIs - block the the re-uptake of Noradrenaline

Question 13

Give examples of drugs which inhibit the metabolism of noradrenaline

Answer 13

MAOI - antidepressants (side-effects resemble atropine effects as this drug promotes sympathetic function)

COMT inhibitors - used in parkinson’s to prevent the breakdown of dopamine

Question 14

Give examples of beta agonists and detail their effects and side effects

Answer 14

Isoprenaline - general beta adrenoceptor agonist

Dobutamine - beta 1 agonist. Stimulates a failing heart. Side effects include dysrhythmia and reduced cardiac efficiency.

Salbutamol - beta 2 agonist. Bronchodilator used in asthma and also used to prevent premature labour

Adrenaline - general adrenoceptor agonist. Used in cardiac arrests

Question 15

Give examples of alpha-1 adrenoceptor antagonists and detail their various uses

Answer 15

• Prazosin & Doxazosin - alpha 1-blockers; used to treat resistant hypertention and benign prostate hypertrophy (BPH is treated via the relaxation of smooth muscle, thereby bringing about easier urinary flow)
• Have long plasma half lives so can be taken once a day. Side effects include postural hypotension and erectile dysfunction
• Alpha-1 blockers have been found to reduce the trophic effect normally observed in hypertension

Question 16

Give examples of beta adrenoceptor antagonists and detail their various uses, side effects and mechanisms of action

Answer 16

Propanolol - beta-blocker; used to treat anxiety, angina and hypertension*

Beta blockers have very little effects under resting conditions but will reduce cardiac output and inhibit sympathetic function during exercise. Exercise tolerance will be diminished due to lack of vasodilation in skeletal muscle.

*beta blockers treat hypertension by reducing cardiac output and sympathetic functions.

Side effects of beta blockers include:
Bradycardia
Hypoglycaemia
Fatigue
Cold extremities
Bronchoconstriction (in asthmatics)

Question 17

Give examples of alpha-1 adrenoceptor agonists and detail their various uses

Answer 17

Adrenaline - although it is equally selective for both alpha and beta adrenoceptors, it has special usage as an alpha 1 adrenoceptor agonist as detailed below: Lidocaine is a local anaesthetics which is usually administered alongside adrenaline. Adrenaline, being an alpha 1 agonist, causes vasoconstriction. In so doing, the rate with which lidocaine is being removed from the site of administration is reduced and hence, lidocaine can have a longer-lasting effect.

Pseudoephedrine & oxymetazoline - cause vasoconstriction of nasal blood vessels, thereby reduces nasal secretions. In other words, they act as nasal decongestants

Question 18

Give examples of alpha-2 adrenoceptor agonists and detail their main use

Answer 18

Clonidine & Methyldopa (which is converted by the body into Methylnoradrenaline)

These drugs work by stimulating alpha-2 adrenoceptors, thereby inhibiting the release of noradrenaline. Hence, this results in the promotion of parasympathetic functions.

These drugs are therefore used in the treatment of resistant hypertension

Question 19

Briefly describe the downstream signalling mechanisms of each adrenoceptor family.

Answer 19

All adrenoceptors are GPCRs.

Alpha 1 adrenoceptors activate phospholipase C which inceases the IP3, DAG and Ca++ concentrations

Alpha 2 adrenoceptors inhibit adenylate cyclase which decreases the cAMP concentration

All beta adrenoceptors activates adenylate cyclase which increases the cAMP concentration

Question 20

Name the CYP450 inducers

Answer 20

Carbamazepine (anti-epileptic)
Rifampicin (anti-TB)
Alcohol (chronic use)
Phenytoin (anti-epileptic)

Griseofulvin (anti-fungal)
Phenobarbitone (anti-epileptic)
Sulphonylureas (oral hypoglycaemics)

induce…

Question 21

Name the CYP450 inhibitors

Answer 21

Sodium valproate (anti-epileptic)
Isoniazid (anti-TB)
Cimetidine (anti-histamine)
Ketoconazole (anti-fungal)
Fluconazole (anti-fungal)
Alcohol (binge)
Chloramphenicol (anti-microbial)
Erythromycin (anti-microbial)
Sulphonamide (anti-microbial)
.
Ciprofloxacin (anti-microbial)
Omeprazole (proton pump inhibitor)
Metronidazole (anti-microbial)

Grapefruit juice (breakfast)
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inhibit…