LG 1.16 - Pharm of Muscle Relaxants

Question 1

(1) what’s happening at #1?

Answer 1

1. an agonist (ACh) is activating a ligand-gated ion channel at a motor end-plate. the agonist will bind to receptor to open ion gate, and…
2. ions (Na+ in this case) will flow into motor endplate and cause action potential - i.e. muscle contraction.
3. A (very) short time later, agonist will leave binding site so the end plate can REpolarize to prepare for next interaction with a Ach.

Question 2

(1) what’s happening at #2? what’ the antidote for this?

Answer 2

1. a NONdepolarizing neuromuscular blocker (e.g., rocuronium) is blocking the site that usually accepts ACh.
2. The result is Na+ cannot flow into motor end plate–>end plate cannot depolarize–>muscle paralysis.
3. Since this is competitive antagonism, neostigmine can be used as antidote

Question 3

(1) what’s happening at #3? what’s the antidote for this?

Answer 3

1. Phase I block, aka depolarizing neuromuscular blockade - succinylcholine interacts with receptor,
2. opening Na+ channel
3. Action potential (depolarization) occurs and muscle contracts
4. succinylcholine also blocks Na channel from closing, so end plate cannot repolarize, and the end plate must repolarize before it can depolarize again –>result is muscle paralysis
5. since this is non-competitive antagonism, this is irreversible (i.e. there is no antidote)

Question 4

(2) Why is Phase 2 called desensitization? Does this occur with nondepolarizing agents or depolarizing agents?

Answer 4

1. happens with depolarizing agents - AFTER Phase 1
2. after succinylcholine wears off, the receptors are not responsive to activation/binding from ACh (and therefore muscle is still paralyzed). This time period is short and can be overcome with additional ACh

Question 5

how does neostigmine work?

Answer 5

1. inhibits acetylcholinestrase = acetylcholine concentration increases
2. Antagonizes the effect of nondeplorizing neuromuscular blockade drugs (since nondepolarizing drugs are competitive antagonists), used to restore muscle function

Question 6

What’s GABA?

Answer 6

1.Major inhibitory neurotransmitter in the mammalian CNS

2. GABAA – chlorine (ionotropic)
3. GABAB – potassium (metabotropic)

Question 7

What’s Glutamate?

Answer 7

major excitatory neurotransmitter in CNS

Question 8

What is the difference between muscarinic and nicotinic receptors?

Answer 8

• Muscarinic is GCPR.

- Nicotinic is a ligand-gated channel.

Question 9

What is spasticity? What diseases is it associated with?

Answer 9

• Characterized by increased muscle stiffness and weakness.

- stroke, cerebral palsy