pharmacology of the neuromuscular junction

Question 1

How do non-depolarising blockers act?

Answer 1

they are ANTAGONISTS of the NMJ - they Reversibly bind to the nicotinic acetyl choline receptor at the NMJ and prevent Ach from binding, decreasing the motor end plate potential.

Question 2

How do non-depolarising blockers work?

Answer 2

they are AGONISTS of the NMJ - they work by causing prolonged depolarisation of the muscle membrane, which prevents the voltage-gated sodium channels from closing to regenerate an action potential (i.e. the sodium channels remain refractory)

Question 3

what is the first phase of a depolarising block?

Answer 3

• muscle fasciculations, then muscle paralysis
• repolarisation inhibited and potassium leaks from the cell causing hyperkalemia
• voltage gated sodium channels kept inactivated

Question 4

what is the second phase of a depolarising block?

Answer 4

• prolonged/increasedexposure to drug

- desensitisation blockade

Question 5

what is the ‘desensitisation blockade’?

Answer 5

this is when the nicotinic acetyl choline receptors close because of the effect of the depolarising blocker and will not open even in the present elf acetyl choline.

Question 6

what is the suffix of the AMINOSTEROIDAL class of non-depolarising blockers?

Answer 6

-curonium

Question 7

what is the suffix for the BENZYLISOQUIOLINIUM class of non-depolarising blockers?

Answer 7

-curium

Question 8

what are the 5 side effects of SUXAMETHONIUM?

Answer 8

• bradychardia (slow HR)
• cardiac dysrhythmias
• raised intraocular pressure
• postoperative myalgia (muscle fasciculations
• malignant hyperthermia

Question 9

which NMJ blocking drugs are metabolised by PLASMA cholinesterase’s?

Answer 9

mivacurium and suxamethonium

these drugs are therefore short acting because the plasma cholinesterase breaks them down in the blood

Question 10

which NMJ blocking drugs are broken down in the liver and kidney?

Answer 10

pancuronium and vecuronium

Question 11

what is the effect of anti cholinesterase drugs?

Answer 11

they inhibit the cholinesterase enzymes and therefore prevent them from breaking down ACh. There is therefore more ACh to compete with the non-depolarising blockers on the active site of the nicotinic ACh receptors.

Question 12

what are the two CLINICALLY used acetyl cholinesterase?

Answer 12

neostigmine and pyridostigmine

Question 13

how do the two clinically used acetyl cholinesterase work?

Answer 13

by formation of a carbamylated enzyme complex

Question 14

what are two acetyl cholinesterase that are used NON-CLINICALLY?

Answer 14

dyflos and parathion

Question 15

how do dyflos and parathion work?

Answer 15

gy phosphorylating the active site of the cholinesterase enzymes (irreversible process)

Question 16

What are the effects of anticholinesterases on the Autonomic nervous system?

Answer 16

SLUDGE
(Salivation, Lacrimation, Urination, Defecation, Gastrointestinal upset, Emesis)
Bradycardia, hypotension, bronchoconstriction, pupillary constriction (miosis)

Question 17

what are 4 clinical uses of anticholinesterases?

Answer 17

• in anaesthesia (to reverse non-depolarising uncle blockade)
• in Myasthenia Gravis (increases neuromuscular transmission)
• Glaucoma (decreases intraocular pressure)
• Alzheimer’s disease (enhance the cholinergic transmission in the CNS)

Question 18

what is Sugammadex?

Answer 18

a selective relaxant binding agent that reverses the effects of ROCURONIUM and VECURONIUM