Neuromuscular Junction Drugs

Question 1

Succinylcholine: MOA

Answer 1

Chemical structure resembles Ach. Stimulates nicotinic Ach receptor at NMJ and parasympathetic n.s., sympathetic n.s. ganglia, and muscarinic receptors in SA node.

Question 2

Succinylcholine: Indications

Answer 2

Paralytic agents induce skeletal muscle paralysis. Muscle relaxation facilitates tracheal intubation, improves surgical condition, and prevents movement during surgery.

Question 3

Succinylcholine: Side Effects

Answer 3

Cardiovascular effects: Arrythmias, brady- or tachycardia, hypotension. Not metabolized by acetylcholinesterase=>produces prolonged muscle contraction prior to paralysis. This skeletal muscle depolarization can cause hyperkalemia and myalgia. Also is a trigger for malignant hyperthermia.

Question 4

Conditions that alter effects of neuromuscular junction blockade (both depolarizing and non-depolarizing agents)?

Answer 4

Conditions that affect NMJ, cause denervation injuries, or disrupt Ach receptor. Examples: Burn injury, muscular dystrophy, myasthenia gravies, central or peripheral nerve injury, severe or chronic disease/infection.

Question 5

What are the non-depolarizing neuromuscular blockers?

Answer 5

Cisatracurium, pancuronium, rocuronium, vecuronium

Question 6

MOA for non-depolarizing neuromuscular blockers?

Answer 6

Bind Ach receptors but are incapable of opening ion channel. Competitive antagonists. No action potential generated.

Question 7

Non-depolarizing neuromuscular blockers: Indications

Answer 7

Tracheal intubation, improved surgical condition, no movement during surgery.

Question 8

Which non-depolarizing neuromuscular blocker is associated with histamine release?

Answer 8

Cisatracurium

Question 9

Which non-depolarizing neuromuscular blocker is best to use with critically ill children?

Answer 9

Vecuronium (minimal CV side effects and histamine release)

Question 10

Side effects of non-depolarizing neuromuscular blockers?

Answer 10

Histamine release (cisatracurium); tachycarida; hypo/hypertension.

Question 11

What prevents depolarizing and non-depolarizing NMJ blockers from working as well as they should?

Answer 11

Drugs that upregulate hepatic enzymes and alter amount of Ach available at nerve terminal: Antibiotics, anticonvulsants, antiarrhythmics, cholinesterase inhibitors, magnesium, lithium, inhalation anesthetics.

Question 12

What are peripherally acting cholinesterase inhibitors?

Answer 12

Pyridostigmine and neostigmine

Question 13

MOA of pyridostigmine and neostigmine?

Answer 13

Peripherally acting cholinesterase inhibitors. Stop breakdown of Ach=> Indirectly increasing muscarinic and nicotinic receptor activity.

Question 14

Indication for pyridostigmine

Answer 14

Increase muscle strength in patients with myasthenia gravis. Given in low doses for orthostatic hypotension.

Question 15

Indication for neostigmine

Answer 15

Reverse effects of non-depolarizing muscle relaxants at end of surgery.

Question 16

Peripheral acting cholinesterase inhibitors side effects?

Answer 16

Muscarinic: GI–Diarrhea, N/V, abdominal cramps
Increased bronchial/oral secretions
Miosis
Diaphoresis
Nicotinic: Muscle cramps, fasciculations, muscle weakness (if dose is too high)

Question 17

Drug interactions for peripheral acting cholinesterase inhibitors?

Answer 17

Potentiate all drugs with cholinergic properties. Diminish effects of drugs with anticholinergic properties. Profound interactions with neuromuscular blocking agents used in anesthesia.

Question 18

Which drugs should be avoided when patient is on peripheral acting cholinesterase inhibitors?

Answer 18

Avoid these combinations: Centrally acting acetylcholinesterase inhibitors (drugs for dementia), eye drops for glaucoma (act via parasympathetic stimulation), and neuromuscular blocking agents.