NMBA

Question 1

What is the mechanism of action of NMBAs at the presynaptic level?

Answer 1

They promote the presynaptic release of acetylcholine, which is associated with an influx of calcium.

Question 2

How does inhibition of calcium influx affect muscle relaxants?

Answer 2

It can potentiate the effects of muscle relaxants.

Question 3

What substances inhibit calcium influx and enhance NMBA effects?

Answer 3

Magnesium (competitive inhibitor), calcium channel blockers, and aminoglycosides.

Question 4

What role do presynaptic acetylcholine receptors play?

Answer 4

They facilitate the release of acetylcholine; NMBAs block both presynaptic and postsynaptic receptors.

Question 5

How are postsynaptic acetylcholine receptors classified?

Answer 5

Into mature receptors (lifespan ~2 weeks) and immature receptors (24-hour lifespan, more easily depolarized).

Question 6

Where are nicotinic acetylcholine receptors located?

Answer 6

At the neuromuscular junction, CNS, and autonomic ganglia.

Question 7

What is a competitive block in the context of NMBAs?

Answer 7

A competitive block involves acetylcholine or non-depolarizing NMBAs competing for postsynaptic nicotinic receptors.

Question 8

What characterizes a non-competitive (Phase I) block?

Answer 8

Caused by depolarizing NMBAs (e.g., succinylcholine); not metabolized by acetylcholinesterase, causes fasciculations followed by paralysis, and prevents activation of perijunctional sodium channels.

Question 9

What is a Phase II (non-depolarizing) block?

Answer 9

Seen with high or repeated doses of depolarizing agents or decreased plasma cholinesterase activity; resembles non-depolarizing block with tetany or TOF fade; reversible with acetylcholinesterase inhibitors.

Question 10

What is a desensitization block?

Answer 10

Acetylcholine binds but does not activate the receptor due to high agonist levels from acetylcholinesterase inhibition or exposure to certain drugs like nicotine, barbiturates, or local anesthetics.

Question 11

What is a channel block in the context of NMBA action?

Answer 11

Non-competitive inhibition of acetylcholine receptor channel gating; can occur in open, closed, or flickering states; not reversed by acetylcholinesterase inhibitors; may be caused by drugs like pancuronium, quinidine, or cocaine.

Question 12

What is the role of acetylcholinesterase at the neuromuscular junction?

Answer 12

It hydrolyzes acetylcholine into acetic acid and choline, terminating neurotransmission.

Question 13

What are the parasympathetic effects of acetylcholinesterase activation and how can they be countered?

Answer 13

Increased salivation and decreased heart rate; countered by atropine or glycopyrrolate.

Question 14

What is the difference between reversible and irreversible acetylcholinesterase inhibitors?

Answer 14

Reversible inhibitors are used perioperatively; irreversible inhibitors include certain pesticides and nerve gases (e.g., sarin, VX) and can cause cholinergic crisis.

Question 15

What is the structural requirement common to all NMBAs?

Answer 15

At least one quaternary amine group.

Question 16

What is the typical amine composition of most NMBAs?

Answer 16

Most NMBAs contain two amine groups; some have two quaternary amines. For example, d-tubocurarine, vecuronium, and rocuronium have a quaternary and a tertiary amine.

Question 17

What is the significance of bisquaternary structure in steroidal NMBAs?

Answer 17

It favors blockade of post-ganglionic muscarinic receptors, making them vagolytic.

Question 18

Which NMBA class has higher potential for histamine release?

Answer 18

Benzylisoquinolines (e.g., d-tubocurarine, mivacurium, atracurium).

Question 19

How does receptor affinity affect NMBA onset of action of NMBAs?

Answer 19

Lower receptor affinity shortens onset (e.g., rocuronium has faster onset than vecuronium).

Question 20

What are the mechanisms of histamine release in response to NMBAs?

Answer 20

IgE (true anaphylactic reaction), IgG/IgM (complement activation), and direct mast cell activation (especially by tertiary amines).

Question 21

What tissues are most affected by histamine release from NMBAs?

Answer 21

Mucosal tissues (bronchial and GI) and serosal tissues (vasculature, skin, and connective tissue).

Question 22

What are common signs and symptoms of NMBA-induced histamine release?

Answer 22

Erythema, blistering, tachycardia, and hypotension.

Question 23

Which NMBA class is more likely to cause histamine release?

Answer 23

Benzylisoquinolines&raquo_space;> Steroids (except rapacuronium).

Question 24

How can histamine release from NMBAs be prevented?

Answer 24

By slower, graded, or repetitive administration (tachyphylaxis) and premedication with H1 or H2 blockers.

Question 25

How common are true anaphylactic reactions to NMBAs, and who is at higher risk?

Answer 25

They are rare; female patients may be at higher risk due to exposure to cosmetics and cleaning chemicals.

Question 26

What does NMBA potency refer to, and how is it measured?

Answer 26

Potency is measured by ED₉₅ and ED₅₀—doses required to suppress twitch response in 95% and 50% of patients, respectively.

Question 27

What does onset mean in the context of NMBA pharmacology?

Answer 27

It is the interval between injection and the achievement of maximal neuromuscular block.

Question 28

What does DUR₅ and DUR₂₅ represent in NMBA pharmacology?

Answer 28

Clinical duration of action; the time between injection and 25% or 95% recovery of twitch response.

Question 29

What is the Recovery Index in NMBA use?

Answer 29

It measures the speed of offset of action (how quickly muscle function returns).

Question 30

What is the total duration of action for NMBAs?

Answer 30

The time from injection to recovery of TOF (Train-of-Four) ratio to ≥ 0.7.

Question 31

How are NMBAs typically administered and absorbed?

Answer 31

Administered IV—results in rapid onset, fast distribution, and predictable elimination; IM/SQ less predictable with non-depolarizing agents but succinylcholine is rapidly and effectively absorbed; not absorbed orally.

Question 32

Factors influencing pharmacokinetics of NMBAs?

Answer 32

– Positive charge quaternanary ammonium group leads to minimal binding to lipids – Bound to albumin and globulins – Higher the affinity for the receptor, the slower the onset. – Fast injection produces decreased onset time, but may increase risk of histamine release – Perfusion affects onset time – Obesity – Age * Higher doses needed for children; also have more sensitive neuromuscular junction * Elderly—delayed metabolism and excretion – Pregnancy: Increase potency and duration when magnesium is used. Minimal placental transfer – Temperature: Increased duration with hypothermia

Question 33

How does the quaternary ammonium structure of NMBAs affect pharmacokinetics?

Answer 33

Their positive charge leads to minimal lipid binding.

Question 34

What plasma proteins do NMBAs bind to?

Answer 34

Albumin and globulins.

Question 35

How does receptor affinity impact NMBA onset time?

Answer 35

Higher receptor affinity slows the onset of action.

Question 36

What is the effect of injection speed on NMBA onset and safety?

Answer 36

Faster injection shortens onset time but may increase the risk of histamine release.

Question 37

What physiologic factors influence NMBA onset time?

Answer 37

Tissue perfusion, obesity, and age.

Question 38

How does age affect NMBA dosing and metabolism?

Answer 38

Children may need higher doses and are more sensitive; elderly patients have delayed metabolism and excretion.

Question 39

How does pregnancy affect NMBA pharmacokinetics?

Answer 39

Pregnancy increases potency and duration (especially with magnesium use) but has minimal placental transfer.

Question 40

How does temperature affect NMBA pharmacokinetics?

Answer 40

Hypothermia increases the duration of neuromuscular blockade.

Question 41

How are quaternary amine NMBAs eliminated?

Answer 41

Through renal elimination due to their ionized, water-soluble nature.

Question 42

Ways that NMBA's can be metabolized?

Answer 42

* Ester hydrolysis * Non-enzymatic decay (Hoffman Elimination) * Hepatic

Question 43

How are succinylcholine and mivacurium metabolized?

Answer 43

By plasma cholinesterase via ester hydrolysis.

Question 44

What is the significance of atypical plasma cholinesterase in NMBA metabolism by ester hydrolysis?

Answer 44

It results in prolonged blockade; heterozygous patients (1:480) have minimal effects, while homozygous patients (1:3200) may experience prolonged paralysis for hours.

Question 45

What does the dibucaine test do and dibucaine number indicate?

Answer 45

It inhibits normal plasma cholinesterase activity —Normal: >70%, Heterozygous: 35–65%, Homozygous: <30%.

Question 46

What are causes of acquired cholinesterase deficiency?

Answer 46

Caused by: Cholinesterase inhibitors (neostigmine, pyridostigmine), pancuronium, metoclopramide, liver failure, burn injury, renal insufficiency, and pregnancy.

Question 47

What is non-enzymatic decay (Hoffman Elimination) in NMBA metabolism?

Answer 47

It is spontaneous degradation of drugs like atracurium and cisatracurium into inactive metabolites (laudanosine and monoacrylate).

Question 48

How is atracurium metabolized?

Answer 48

Besides Hoffman Elimination, Atracurium also undergoes ester hydrolysis.

Question 49

Which NMBAs undergo hepatic metabolism?

Answer 49

Steroidal relaxants such as rocuronium, pancuronium, and vecuronium.

Question 50

What is the hepatic process involved in the metabolism of steroidal NMBAs?

Answer 50

Deacetylation in the liver to active metabolites.

Question 51

When can recovery from steroidal NMBAs be delayed?

Answer 51

With prolonged use or in the presence of hepatic and/or renal dysfunction.