Week 8 - Chapter 16 (Nicotinic Cholinergic Blockers)

Question 1

Curare

Answer 1

• Is an arrow poison used for hunting by South American Indians. When shot into a small animal, curare-tipped arrows cause relaxation (paralysis) of skeletal muscles. Death results from paralyzing the muscles of respiration.
• The clinical utility of the neuromuscular blockers is based on the same action that is useful in hunting: production of skeletal muscle relaxation. Relaxation of skeletal muscles is helpful in patients undergoing surgery, endotracheal intubation, mechanical ventilation, and other procedures.

Question 2

Depolarization

Answer 2

When the membrane depolarizes, positive charges move from outside to inside. So many positive charges move inward that the inside of the membrane becomes more positive than the outside.
Under physiologic conditions, depolarization of the muscle membrane is followed almost instantaneously by repolarization.

Question 3

Depolarizing Neuromuscular Blockade

Answer 3

Succinylcholine produces a state known as depolarizing neuromuscular blockade. Like acetylcholine, succinylcholine binds to nicotinicM receptors on the motor end-plate and thereby causes depolarizing. This this depolarization produces transient muscle contractions (fasciculations). Then, instead of dissociating rapidly from the receptor, succinylcholine remains bound, and thereby prevents the end-plate from repolarizing. That is, succinylcholine maintains the end-plate in a state of constant depolarization. Because the end-plate must repeatedly depolarize and repolarize to maintain muscle contraction, succinylcholine’s ability to keep the end-plate depolarized causes paralysis (following the brief initial period of contraction). Paralysis persists until plasma levels of succinylcholine decline, thereby allowing the drug to dissociate from its receptors.

Question 4

Excitation-Contraction Coupling

Answer 4

-the process by which an action potential in a motor neuron leads to contraction of a muscle.

Question 5

Malignant Hyperthermia

Answer 5

-Rare and potentially fatal condition that can be triggered by succinylcholine
-Muscle rigidity associated with a profound elevation of body temperature, sometimes to as high as 43º C
-Cardiac dysrhythmias, unstable blood pressure, electrolyte derangements, and metabolic acidosis
-Left untreated, the condition can rapidly prove fatal
Genetically determined reaction
Treatment:
(1) immediate discontinuation of succinylcholine,
(2) cooling the patient with external ice packs and IV infusion of cold saline, and
(3) administering IV dantrolene, a drug that stops heat generation by acting directly on skeletal muscle to reduce its metabolic activity.

Question 6

Neuromuscular Blocking Agents

Answer 6

-Prevent acetylcholine from activating nicotinicM receptors
-Cause muscle relaxation (paralysis)
-Used for muscle relaxation during surgery, endotracheal intubation, mechanical ventilation, and other procedures
-No oral forms
-Cannot cross:
>Blood-brain barrier: No impact on central nervous system (paralysis, not sedation)
>Placenta: Minimal effects on fetus

Question 7

Competitive (Nondepolarizing) Neuromuscular Blockers

Answer 7

-Are drugs that compete with acetylcholine for binding to nicotinicM receptors. These drugs are also known as nondepolarizing neuromuscular blockers, because, unlike depolarizing neuromuscular blockers, they do not depolarize the motor end-plate.
Example: Pancuronium

Question 8

Polarization

Answer 8

Positive charges cover the outer surface of the membrane and negative charges cover the inner surface. Because of this uneven charge distribution, the resting membrane is said to be polarizing.

Question 9

Pseudocholinesterase

Answer 9

Is an enzyme present in plasma. (Got it’s name to distinguish it from “true” cholinesterase, the enzyme found at synapses where acetylcholine is the transmitter.) Because of its presence in plasma, pseudocholinesterase is also known as plasma cholinesterase. In most individuals, pseudocholinesterase is highly active and can eliminate succinylcholine in minutes.

Question 10

Quaternary Ammonium Compounds

Answer 10

All of the neuromuscular blockers are quaternary ammonium compounds (+ charge), and therefore must be administered parenterally (almost always IV) because it cannot cross membranes.

Question 11

Repolarization

Answer 11

Repolarization is accomplished by pumping positively charged ions out of the cell. Repolarization restores the original resting membrane state, with positive charges on the outer surface and negative charges on the inner surface.

Question 12

Pancuronium

Answer 12

Mechanism of competitive neuromuscular blockade. Pancuronium , a competitive blocker, competes with acetylcholine (ACh) for binding to nicotinicM receptors on the motor end-plate. Binding of Pancuronium does not depolarize the end-plate, and therefore does not cause contraction. At the same time, the presence of Pancuronium prevents ACh from binding to the receptor, so contraction is prevented.

Question 13

Succinylcholine

Answer 13

Therapeutic use: muscle relaxation during intubation
▪ Succinylcholine, the only depolarizing neuromuscular blocker in use, binds to nicotinicM receptors, causing the end-plate to depolarize; the drug then remains bound, which keeps the end-plate from repolarizing. Cholinesterase inhibitors can reverse the effects of competitive neuromuscular blockers but will intensify the effects of succinylcholine.
▪ Can trigger malignant hyperthermia, a life-threatening condition.
▪ Is eliminated by plasma cholinesterase. Accordingly, effects are greatly prolonged in patients with low plasma cholinesterase activity.