neuromuscular blockers

Question 1

what types of cholinergic receptor antagonists are there?

Answer 1

-anti-muscarinic

-anti-nicotinic
>ganglion blockers (not clinically useful)
>neuromuscular blockers

Question 2

properties of anti-muscarinics

Answer 2

Anti-Muscarinic
* Non-selective blockers of all M receptors (M1 – M5)
* Many clinically useful drug

Question 3

properties of neuromuscular blockers. which are clinically useful?

Answer 3

• NM receptor blockade
• The only clinically useful nicotinic antagonists are those that block skeletal muscle type nAChRs (Nm)

Question 4

on what part of the nervous system do neuromuscular blcokers act? what do they inhibit?

Answer 4

-work in the somatic nervous system
-inhibit skeletal muscle type nACHRs (Nm)

Question 5

neuromuscular blocking drugs are structural analogues of what? How are they administered

Answer 5

Structural analogues of acetylcholine, given IV

Question 6

what do Neuromuscular Blocking Drugs block, specifically?

Answer 6

• 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 7

are animals conscious using Neuromuscular Blocking Drugs?

Answer 7

Animals are fully conscious unless an anesthetic is used concurrently

Question 8

what type of Neuromuscular Blocking Drugs are used almost exclusively now

Answer 8

Non-depolarizing blockers

Question 9

one of the most commonly used non-depolarizing neuromuscular blockers in veterinary medicine. What is its clinical use?

Answer 9

atracurium

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 10

what is the mechanism of action of atracurium?

Answer 10

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 11

pharmacokinetics of atracurium? what does duration vary with?

Answer 11

• 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 12

main advantage of atracurium

Answer 12

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

Question 13

cautions of using atracurium or other NM blockers

Answer 13

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

Question 14

order of paralysis of muscles from NM block

Answer 14

1. Extraocular (main use)
2. Neck, head, face, hands and feet
3. Abdomen, arms and legs
4. Eye blink
5. Respiratory & diaphragm
   Recovery occurs in reverse order

Question 15

what is an important Depolarizing blocking agents (agonist)

Answer 15

Succinylcholine

Question 16

what is Succinylcholine? what are its effects and uses? toxocity?

Answer 16

Depolarizing blocking agents (agonist)
* Similar but longer effects compared to ACh, but effect lasts only ~90 s

• Technically a nicotinic agonist (not antagonist)  muscle tremors, then flaccid paralysis

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

Pharmacokinetics:
* Rapid onset, very short duration
* Metabolism by plasma pseudocholinesterase

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

Avoid in recovery situations
**May be useful in getting horse to go down smoothly prior to euthanasia

Question 17

atracurium potency, onset time, action time

Answer 17

potency: 2-3 (higher in horses)
onset: ~3 min
duration: long (~45 min, depends on dose)

Question 18

general use of muscle relaxants. what forms are there?

Answer 18

• 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 19

important centrally acting muscle relaxants

Answer 19

Benzodiazepines
Methocarbamol
Guaifenesin

Question 20

what are Benzodiazepines? what do they do and how?

Answer 20

centrally acting muscle relaxants

Benzodiazepines (e.g., Valium®)
Facilitates GABA activity in CNS (GABA is the major inhibitory NT in brain)
* Excellent muscle relaxation
* reduce spasms with disk disease, tetanus, urethral obstruction
* May cause CNS depression
* Other drugs may alter metabolism

Question 21

what is Methocarbamol? what does it do and how?

Answer 21

centrally acting muscle relaxant

Methocarbamol (Robaxin®, Robaxacet®, etc.)
Mechanism unknown
* Efficacy uncertain
* May cause sedation, salivation, emesis, lethargy,
weakness, ataxia
* Contraindicated in various renal diseases

Question 22

what is Guaifenesin? what is it used for?

Answer 22

centrally acting muscle relaxant
Inhibits interneurons in motor reflexes
* Used IV with injectable anesthetics for induction

Question 23

what is Dantrolene? what is it used for?

Answer 23

peripherally-acting muscle relaxant
InhibitsCa2+ release from sarcoplasmic reticulum
* Used for urethral obstruction, equine rhabdomyolysis, *malignant hyperthermia