Drugs And The Neuromuscular Junction and adverse drug reactions

Question 1

ACh

Answer 1

Synthesised in neurones from acetyl-CoA and choline

Question 2

Choline-acetyltranferase

Answer 2

Synthesise ACh from acetylcholine-CoA and choline

Question 3

ACh is stored in

Answer 3

Vesicles and then released into the synaptic cleft following electrical stimulation

Question 4

ACh in the synaptic cleft is metabolised

Answer 4

Rapidly by the enzyme acetylcholinesterase into acetate and choline

Question 5

Nicotinic cholinergic receptor

Answer 5

Opens in presence of ACh but only for microseconds -> will then close, causes depolarisation of the membrane

Question 6

Botulinum toxin

Answer 6

Toxin produced by the anaerobic soil bacterium - C. Botulinum

Muscle paralyser

Protease enzyme that selectively attacks and breaks down proteins required for docking of synaptic vesicles with presynaptic membrane -> this inhibits the release of neurotransmitter release, lowering conc of transmitter in the synaptic cleft

Question 7

Non depolarising neuromuscular blockers

Answer 7

Competitive antagonists of the nicotinic cholinergic receptor

Atracurium, rocuronium, vecuronium, pancuronium

Question 8

Depolarising blockers

Answer 8

Initial agonists which are followed by continued binding and shutting of the ion channel

Suxamethonium -> two linked ACh molecules which are less favourable for breakdown by acetylcholinesterase

Question 9

Anticholinestersases

Answer 9

Reduce the rate of breakdown of ACh and therefore potentials cholinergic transmission

Question 10

Reversible anticholinesterases

Answer 10

Are used in the treatment of conditions like myasthenia gravis and Alzheimer’s

Can also be ides as a anaesthetic

Reversible as rapidly hydrolysed

Question 11

Irreversible anticholinesterases

Answer 11

Contain a phosphate ester bond so can resist hydrolysis

Dangerous -> can cause muscle paralysis and respiratory failure and a cholinergic crisis in the autonomic nervous system

Agents are extremely poisonous -> nerve agent ‘sarin’ and organophosphates

Question 12

Skeletal muscle relaxants

Answer 12

Differ fundamentally in cartoon from the neuromuscular junction blocking agents used in anaesthesia

Can relieve chronic muscle spasm

Question 13

Drugs acting centrally in the CNS to reduce descending stimulators signals to the muscles

Answer 13

Baclofen, diazepam

Question 14

Drugs that act peripherally - directly on the muscles

Answer 14

Dantrolene

Question 15

Drugs acting at both CNS and directly on muscles

Answer 15

Cannabis extract

Question 16

Dantrolene sodium

Answer 16

Inhibits calcium release from sarcoplasmic reticulum which is a prerequisite for the interaction of the contractile proteins actin and myosin

Question 17

Diseases that result in spasm of voluntary muscles

Answer 17

Stroke, MS, cerebral palsy

Question 18

The actions of ACh are terminated by

Answer 18

Enzymatic breakdown by the enzyme acetylcholinesterase in the synaptic cleft

Question 19

Many adverse drug reactions are

Answer 19

Avoidable

Question 20

Type A adverse drug reactions

Answer 20

Predictable from the known pharmacology of the drug and dose-related

Question 21

Type B adverse drug reactions

Answer 21

Unrelated to the known pharmacology of the drug and idiosyncratic

Question 22

Teratogenesis

Answer 22

Drugs which effect embryo development

-Affect cell division or protein/DNA synthesis

Question 23

Pharmacovigilance

Answer 23

The scientific study concerned with the detection and evaluation of adverse effects of drugs

Question 24

Detecting adverse drug reactions

Answer 24

Animal (pre-clinical) studies

Phase I-III clinical studies

Voluntary reporting systems e.g. yellow cards

Prescription event monitoring

Population statistics/record linkage

Medical literature

Question 25

What the yellow card scheme can detect

Answer 25

Unrecognised ADRs (signal generation
Identification of predisposing factors
Comparing ADR profiles of drugs
Continual safety monitoring

Question 26

What changes might follow the yellow card scheme

Answer 26

Restriction in use

Reduction in dose

Special warnings and precautions

Product withdrawn

Question 27

Weakness of spontaneous reporting

Answer 27

Low reporting rates

Relies on ADR being recognised

Reporting rate is high early after launch but then falls rapidly

Reporting rate influenced by publicity and reports tend to arise after reaction established

Cannot provide an estimate of risk

Question 28

Black triangle

Answer 28

Signifies that a drug I’d new and that all adverse reactions should be reported

Question 29

Many adverse drug reactions are not known until

Answer 29

After licensing and distribution has begun -> implies a careful review of accumulating data in the post licensing period