Muscle agents

Question 1

Types of somatic autonomic drugs:

Answer 1

Depolarizing and nondepolarizing

Question 2

Five ways to produce muscle paralysis

Answer 2

1. Nicotinic ACh receptor antagonist (tubocurarine)
2. NMJ nicotinic ACh receptor agonist (succinylcholine)
3. High ganglionic ACh receptor agonist (nicotine)
4. Increase ACh in synapse (malathion [AChEI])
5. Presynaptic: botulinum toxin (prevents release of ACh)

Question 3

General properties of Nm blockers

Answer 3

• All are charged (ie no CNS activity), administered IV and the onset of action is within several minutes.
• Causes paralysis of skeletal muscles.
• Works in a descending order of muscle blockade (twitch/fast muscles–>limb–>respiratory).
• Causes hypotension (including histamine release with some, venous pooling, and slight ganglionic blockade) and tachycardia (reflex from hypotension)

Question 4

Indications of Nm blockade

Answer 4

• Muscle blockade during surgery
• Muscle blockade during electroconvulsive shock therapy
• Block pt control of respiration during respiratory support/mechanical ventilation

Question 5

Toxicity associated with Nm blockade

Answer 5

• Complete respiratory paralysis, which is not too unlikely to happen. When using these agents, physicians need to be prepared to intubate and mechanically ventilate the pt.
• Treatment should include positive pressure ventilation and the use of agents to counteract the blockade (neostigmine [AChEI, atropine or glycopyrrolate [counteract muscarinic stimulation] and antihistamines [counteract release of histamine])

Question 6

Pts that are at a higher risk for Nm blockade toxicity:

Answer 6

• Pts with myasthenia gravis (due to decreased number of functional Nm receptors)
• Pts on another agent that stabilizes membrane potential and/or inhibits ACh release from motor nerve terminals (general anesthetics, local anesthetics, pts with hypokalemia)

Question 7

Succinylcholine

Answer 7

Depolarizing Nm blocker. Only clinically usefull depolarizing blocker remaining. Rapid onset of action, with short duration of action (about 5 mins). Not metabolized by AChE, but is metabolized by BChE in the blood. Admin by infusion, which allows rapid adjustment of the degree of muscle blockade.

Question 8

Tubocurarine

Answer 8

Nondepolarizing Nm blockers. Duration of action 90-120 minutes. Causes release of histamine from mast cells and hypotension

Question 9

Atracurium

Answer 9

Nondepolarizing Nm block. Short duration of 20-30 minutes. Useful for pts with renal and hepatic failure as it is metabolized by Hoffman degradation. Fewer side effects than Tubocurarine, causes little histamine release.

Question 10

Succinylcholine
+tubocurarine:
+succinylcholine:
+AChE inhibitor:

Answer 10

Succinylcholine
+tubocurarine: reversal
+succinylcholine: augmentation
+AChE inhibitor: augmentation

Question 11

Tubocurarine
+tubocurarine:
+succinylcholine:
+AChE inhibitor:

Answer 11

Tubocurarine
+tubocurarine: augmentation
+succinylcholine: reversal
+AChE inhibitor: reversal

Question 12

Pancuronium

Answer 12

Nondepolarizing Nm blocker. Long duration of action at 120-180 minutes. 3x more potent than tubocurarine with fewer side effects

Question 13

Adverse drug reactions of muscle blocking agents:

Answer 13

Malignant hyperthermia: depolarizing Nm blockers with halothane anesthesia. Characterized by contraction of all muscles, hypercapnia, metabolic acidosis, tachycardia, and hyperthermia. Treat with dantrolene (interferes with Ca++ release).
Hyperkalemia: Depolarizing Nm blockers. Widespread cellular depolarization leads to movement of potassium into the bloodstream.
Histamine release: nondepolarizing Nm blockers. May cause hypersensitivity reactions.
Ganglionic blockade: At high doses, Nm blocking drugs can effect Nn receptors at the ganglions.

Question 14

Uses of Nm blocking agents

Answer 14

Adjuncts to surgical anesthesia: blockade of the diaphragm and intercostals facilitates artificial ventilation, so the pt does not fight the ventilator
Realignment of bone fx: blockade of muscles around fractures facilitates realignment
Tracheal intubation: blockade of skeletal muscles surrounding upper respiratory tract facilitates intubation
Laryngoscopy and esophagoscopy: removes reflex resistance to these procedures.

Question 15

Diazepam

Answer 15

Benzodiazepin. Facilitates the action of GABA in the CNS. Reduces spasticity.

Question 16

Baclofen

Answer 16

Partial GABA agonist. Activation of GABA receptors results in hyperpolarization with three distinct actions:
1. closure of presynaptic Ca++ channels
2. increased postsynaptic K conductance
3. inhibition of dendritic Ca++ influx channels
Baclofen works via reduced release of excitatory transmitters in the brain and spinal cord, suppressing activity of sensory afferent, spinal interneurons, and motor neurons.
Reduces pain from spasticity by inhibiting the release of substance P in the spinal cord.
Overall muscle strength is not reduced as much as by dantrolene.

Question 17

Cyclobenzaprine, methocarbamol

Answer 17

Muscle relaxer related to tricyclic antidepressants. Has anti-muscarinic side effects, which can cause significant sedation. Tricyclic antidepressants block the reuptake of neurotransmitters–mechanism of action is thought to inhibit the muscle stretch reflex in the spinal cord. Ineffective in treating muscle spasm due to CP or spinal cord injury, but is effective in acute injury related to muscle spasm.

Question 18

Dantrolene

Answer 18

Muscle relaxer. Inhibits Ca++ release from the SR of skeletal muscle. Does not effect neuromuscular transmission. Not useful for treatment of acute muscle spasm of local origin.
Especially efficacious in managing acute malignant hyperthermia and neuroleptic malignant syndrome.