Neuromuscular pharm Flashcards
how do neuromuscular blocking drugs work
Block transmission between motor neurons & skeletal muscle by acting either as antagonists (“non-depolarizing block”) or agonists (“depolarizing block”) at the muscle-type nAChR
how do non-depolarizing blockers differ and what are some examples
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
what is the most commonly used non-depolarizing neuromuscular
blocker in vet med
atracurium
what is the most common clinical use of non-depolarizing neuromuscular
blockers
-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
what is the mechanism of atracurium? what depends on dosage?
-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
pharmacokinetic details of atracurium; route of administration, duration, metabolism and interval of dosage
-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)
advantages of using atracurium
what reverses it?
Rapid reversal can be achieved with drugs that inhibit ACh esterase (e.g., neostigmine, edrophonium)
elevates ACh concentration
cautions when using atracurium
-N-M blockers do not produce sedative or analgesic effects, they just immobilize patients
-Dose-dependent respiratory paralysis occurs (use ventilator if necessary)
what is the first muscle paralyzed
extraocular
what is an example of a depolarizing blocking agent agonist
Succinylcholine
features of Succinylcholine
-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
mechanism of Depolarizing blocking agents (agonists)
- Initial depolarization causes muscle contraction, but
repolarization cannot occur so Na+ channels remain inactivated and no further impulse generation occurs ->
flaccid paralysis
pharmacokinetics of depolarizing blocking agents (agonists)
- Rapid onset, very short duration
- Metabolism by plasma pseudocholinesterase
toxicity of Depolarizing blocking agents (agonists)
- Painful contractions may follow sole use; hypertension; tachycardia
- Malignant hyperthermia risk, as for volatile hydrocarbon inhalants
what are muscle relaxants generally used for and types
- 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
what are three centrally acting muscle relaxants
benzodiazepines, methocarbamol and guaifenesin
what is a peripherally acting muscle relaxant
dantrolene
what does dantrolene do
inhibits calcium rom SR
what is dantrolene used for and what are some adverse effects we might see
- Used for urethral obstruction, equine rhabdomyolysis,
malignant hyperthermia - May see hepatotoxicity, sedation, muscle weakness
what is the oral bioavailability of dantrolene
poor oral bioavailability, highly bound to albumin
what does guaifenesin do
inhibits interneurons in motor reflexes
what is guaifenesin used for
Used IV with injectable anesthetics for induction
side effects we might see with guaifenesin
hypotension, decreased respiration in horses
what do benzodiazapines do
facilitates GABA activity in CNS
what are benzos used for and what might happen as a result
-Excellent muscle relaxation
-decrease spasms with disk disease, tetanus, urethral obstruction
-May cause CNS depression
-Other drugs may alter metabolism
when is methocarbamol contraindicated
in various renal diseases
side effects of methocarbamol
May cause sedation, salivation, emesis, lethargy, ataxia
