Lecture VI

Question 1

Non-Depolarizing Blocking Drugs (Mechanism of Action)

Answer 1

Competitive antagonists at nicotinic acetylcholine receptors. Prevents membrane depolarization and end-plate potentials.

Overcome by Ach through:
Tetanic stimulation and Cholinesterase inhibitors

At higher concentrations blockade of channel pore developes and less sensitive to excess Ach.

Question 2

Pancuronium, Vecuronium, Mivacurium, Rocuronium

Half lives from longest to shortest

Answer 2

Pancuronium (patients on ventilators for days)>Vecuronium=Rocuronium>Mivacurium

Question 3

Pancuronium, Vecuronium, Mivacurium, Rocuronium

Clearance

Answer 3

Pancuronium (renal)
Vecuronium (Renal)
Rocuronium (Hepatic)
Mivacurium (enzymatic/metabolic)

Question 4

Pancuronium, Vecuronium, Mivacurium, Rocuronium

Answer 4

Blocks nicotinic receptors at neuromuscular junction

Uses:

• Surgical procedures
• Intubation (rocuronium, mivacurium)
• Reduce resistance during ventilation

Side Effects:

• Non- analgesic
• Apnea

Interactions:
*Inhalation anesthetics (enhances effect)

Antidotes:

• Cholinesterase inhibitors- neostigmine (increases Ach to overcome competition)
• Muscarinic blockers- glycopyrrolate (minimizes muscarinic effects of cholinesterase inhibitor)

Question 5

Depolarizing Blocking Drugs Mechanism of Action

Answer 5

Two Phases

Phase I: Occupancy of the receptor by drug causes opening of the ion channel and causes depolarization of motor end plate. Drug enters channel which causes prolonged flickering of ion conductance.

Depolarization at the membrane is prolonged since the drug is metabolized by plasma cholinesterase and not acetylcholinesterase. The Na+ channels are inactivated and can’t regain access to resting state until repolarized.

No action potential is propagated.

Chonlinesterase inhibitors augment the blockade

Phase II: Drug exposure exceeds ~30 min, the membrane is repolarized. Receptor remains desensitized.

Question 6

Succinylcholine

Answer 6

Depolarizing agent

Uses:

• endotracheal intubation
• Control convulsions during ECT

Side Effects:

• Non-analgesic
• Apnea
• Muscle pain from fasiculations
• Stimulation of nicotinic receptors of autonomic ganglia and cardiac muscarinic receptors in sinus node
• HYPERKALEMIA due to increase K+ release from motor end plain
• Malignant hyperthermia

Question 7

Baclofen

Answer 7

GABAb Agonist- reduces calclium influx and reduces the release of excitatory transmitters

Uses:

• Spinal spasticity
• MS

Side Effects:
*Drowsiness

Question 8

Benzodiazepines

Answer 8

Facilitate GABA mediated pre-synaptic inhibition

Uses:

• Spinal spasticity
• MS

Side Effects:
*Sedation and drowsiness

Question 9

Tizanidine

Answer 9

Alpha 2-adrenergic agonist promotes pre-and post- synaptic inhibition in the spinal cord

Uses:

• spinal spasticity
• MS

Side Effects:

• Drowsiness
• Hypotension

Question 10

Dantrolene

Answer 10

Blocks calcium release from sarcoplasmic reticulum in muscle

Uses:

• spasticity
• Hyperthermia

Side Effects:

• Muscle weakness
• Sedation