Neuromuscular pharm

Question 1

how do neuromuscular blocking drugs work

Answer 1

Block transmission between motor neurons & skeletal muscle by acting either as antagonists (“non-depolarizing block”) or agonists (“depolarizing block”) at the muscle-type nAChR

Question 2

how do non-depolarizing blockers differ and what are some examples

Answer 2

Today several non-depolarizing NM blockers are available (e.g., rocuronium, mivacurium, atracurium, etc.) which differ mainly in duration of action, time to onset of effect, and route of elimination

Question 3

what is the most commonly used non-depolarizing neuromuscular
blocker in vet med

Answer 3

atracurium

Question 4

what is the most common clinical use of non-depolarizing neuromuscular
blockers

Answer 4

-To prevent eye movement during ocular surgery

-Can achieve complete muscle relaxation
without the need for higher anesthetic doses
= Safer, with faster recovery than simply
using higher anesthetic dose

Question 5

what is the mechanism of atracurium? what depends on dosage?

Answer 5

-Atracurium is chemically similar to ACh
-It competitively blocks AChRs at NMJ  causes intense relaxation/paralysis
of voluntary muscle

-Intensity and duration depend on dosage

Question 6

pharmacokinetic details of atracurium; route of administration, duration, metabolism and interval of dosage

Answer 6

-Must be injected IV because positively charged, highly polar = doesn’t cross membranes
-Maximum block occurs in ~3 min., duration varies with dosage (typically 20-30 min., ~1 h with higher dosages)
-Metabolized in blood by plasma esterases
-Can be injected periodically to maintain
relaxation without extending recovery time
(usual recovery time follows last dose)

Question 7

advantages of using atracurium
what reverses it?

Answer 7

Rapid reversal can be achieved with drugs that inhibit ACh esterase (e.g., neostigmine, edrophonium)
 elevates ACh concentration

Question 8

cautions when using atracurium

Answer 8

-N-M blockers do not produce sedative or analgesic effects, they just immobilize patients
-Dose-dependent respiratory paralysis occurs (use ventilator if necessary)

Question 9

what is the first muscle paralyzed

Answer 9

extraocular

Question 10

what is an example of a depolarizing blocking agent agonist

Answer 10

Succinylcholine

Question 11

features of Succinylcholine

Answer 11

-Composed of 2 ACh molecules linked together
-Similar but longer effects compared to ACh, but effect
lasts only ~90 s
-Technically a nicotinic agonist (not antagonist) = muscle
tremors, then flaccid paralysis

Question 12

mechanism of Depolarizing blocking agents (agonists)

Answer 12

• Initial depolarization causes muscle contraction, but
  repolarization cannot occur so Na+ channels remain inactivated and no further impulse generation occurs ->
  flaccid paralysis

Question 13

pharmacokinetics of depolarizing blocking agents (agonists)

Answer 13

• Rapid onset, very short duration
• Metabolism by plasma pseudocholinesterase

Question 14

toxicity of Depolarizing blocking agents (agonists)

Answer 14

• Painful contractions may follow sole use; hypertension; tachycardia
• Malignant hyperthermia risk, as for volatile hydrocarbon inhalants

Question 15

what are muscle relaxants generally used for and types

Answer 15

• Decrease muscle tone & spasticity without completely inhibiting voluntary contractions
• Used to alleviate painful muscle spasms associated with intervertebral disk disease, urethral obstructions, etc.
• Centrally-acting & peripherally-acting forms

Question 16

what are three centrally acting muscle relaxants

Answer 16

benzodiazepines, methocarbamol and guaifenesin

Question 17

what is a peripherally acting muscle relaxant

Answer 17

dantrolene

Question 18

what does dantrolene do

Answer 18

inhibits calcium rom SR

Question 19

what is dantrolene used for and what are some adverse effects we might see

Answer 19

• Used for urethral obstruction, equine rhabdomyolysis,
  malignant hyperthermia
• May see hepatotoxicity, sedation, muscle weakness

Question 20

what is the oral bioavailability of dantrolene

Answer 20

poor oral bioavailability, highly bound to albumin

Question 21

what does guaifenesin do

Answer 21

inhibits interneurons in motor reflexes

Question 22

what is guaifenesin used for

Answer 22

Used IV with injectable anesthetics for induction

Question 23

side effects we might see with guaifenesin

Answer 23

hypotension, decreased respiration in horses

Question 24

what do benzodiazapines do

Answer 24

facilitates GABA activity in CNS

Question 25

what are benzos used for and what might happen as a result

Answer 25

-Excellent muscle relaxation
-decrease spasms with disk disease, tetanus, urethral obstruction
-May cause CNS depression
-Other drugs may alter metabolism

Question 26

when is methocarbamol contraindicated

Answer 26

in various renal diseases

Question 27

side effects of methocarbamol

Answer 27

May cause sedation, salivation, emesis, lethargy, ataxia