Term
| what is the depolarizing neuromuscular blocking agent (NMBA)? what is its MOA? |
|
Definition
| succinylcholine. limited use: initially causes a reaction resulting in skeletal muscle activation. MOA: initial activation by depolarization of receptor (causes stimulation of muscles) followed by persistent occupation that markedly delays repolarization and blocks recovery. |
|
|
Term
| what are the nondepolarizing neuromuscular blocking agents (NMBA)? what is their MOA? |
|
Definition
| *isoquinolone derivatives: atracurium, cisatracurium, doxacurium, metocurine, and tubocurarine. *steroid derivatives: pancuronium, pipecuronium, rocuronium, and vecuronium. these are the major drugs used in the OR. MOA: competitively antagonizes ACh at receptor site - prevents depolarization of postsynaptic membrane = flaccid paralysis. |
|
|
Term
| what is the action of the neuromuscular blocking drugs generally? |
|
Definition
| interference with transmission of cholinergic impulse between somatic motor neurons and skeletal muscle fibers (neuromuscular junction) = paralysis. specificity for the neuromuscular junction only occurs w/therapeutic doses - in higher amounts the cholinergic antagonism extends to additional sites (i.e., autonomic ganglia and postganglionic parasympathetic sites) and causes ADRs, e.g., cardioaccel-eration, arrhythmias, hypotension). the BBB is also not penetrated at therapeutic concentrations - minimal CNS effects. |
|
|
Term
| what is the result of the intracellular histamine release caused by some of the older neuromuscular blocking drugs? |
|
Definition
| bronchospasm, increased salivary + mucosal secretions, hypotension, tachycardia, and urticaria. |
|
|
Term
| which skeletal muscles are affected at low, medium and high doses of NMBAs? |
|
Definition
| low: rapidly contracting small muscles (eyes/eyelids, speech/swallowing, fingers). medium: limbs, neck, trunk. high: respiration (intercostal muscles, diaphragm). (recovery occurs in reverse order) |
|
|
Term
| what characterizes the therapeutic index of NMBAs? |
|
Definition
| the difference in sensitivity among muscles is small; margin between effective dose and toxic dose is also small. (slight overdose can cause serious impairment of respiration and severe hypotension). |
|
|
Term
| what are the clinical uses for NMBAs? |
|
Definition
| adjuncts to GA, facilitation of intubation, improvement of respiration in pts on mechanical ventilation, and reduction of injury in shock therapy. |
|
|
Term
| which drugs produce additive effects along w/NMBAs? |
|
Definition
| aminoglycosides, lincosamides, polymixins, inhalation GA (enflurane > isoflurane > halothane), ketamine, local anesthetics, lithium, and quinidine. |
|
|
Term
| which drugs reduce the effect of NMBAs? |
|
Definition
| cholinergic drugs, corticosteroids, ranitidine, and theophyline |
|
|
Term
| what do NMBAs not provide? |
|
Definition
| analgesia or reduction of consciousness (need additional meds for pain control) |
|
|
Term
| what is the biphasic action of depolarizing NMBAs? |
|
Definition
| 1) initial depolarization of the muscle end plate = immediate by transient activation (depolarization) and brief muscle contractions (fasciculations) occur. 2) secondary persistent occupation of receptor site which desensitizes receptor site to ACh (may persist past actual presence of the drug), prevents repolarization, and paralysis (this second phase block persists for 10-30 min). |
|
|
Term
| what characterizes succinylcholine? |
|
Definition
| this prodrug is rapidly hydrolyzed by plasma cholinesterases -> biotransformed to succinylmonocholine, the active metabolite. succinylmonocholine is weaker than the parent drug, is slowly hydrolyzed, accumulates w/prolonged or large doses and may result in lengthy paralysis. onset is 1 min after IV and muscle paralysis lasts 5-10 min. mainly used for intubation. |
|
|
Term
| what ADRs are associated with succinylcholine? |
|
Definition
| muscle twitching, muscle pain, tachycardia, HTN, arrhythmias, respiratory depression, apnea, excessive salivation, increased intraocular pressure (IOP), and malignant hyperthermia (hypermetabolic disease of skeletal muscle). early signs of malignant hyperthermia: muscle rigidity, tachycardia, hyperthermia, metabolic acidosis. to prevent: monitor body temperature during administration. there is an increased chance of malignant hyperthermia in the presence of GA. |
|
|
Term
| what are contraindications for succinylcholine? |
|
Definition
| hx of malignant HTN, narrow-angle glaucoma, a genetically determined deficiency of plasma pseudocholinesterase (plasma cholinesterase levels should be measured before use), pts on digitalis/quinidine (may cause arrhythmias by sudden K+ release), and pts on cholinesterase inhibitors (reduce action of plasma pseudocholinesterase). |
|
|
Term
|
Definition
| a reversible inhibitor of plasma cholinesterases - does not affect intracellular cholinesterase as do other cholinesterase inhibitors. it is used exclusively w/succinylcholine to delay enzymatic hydrolysis to reduce initial muscle fasciculations and prolong muscle paralysis. onset: 2-3 min, duration: approximately 30 min. |
|
|
Term
| what characterizes the nondepolarizing NMBAs? |
|
Definition
| aka antidepolarizing, stabilizing, or curariform agents, these derive from the first anti-depolarizing muscle relaxant: alkaloid d-tubocurarine, the active principle of a group of south american arrow poisons collectively called curare. the nondepolarizing NMBAs act as reversible competitive antagonists of ACh at postsynaptic neuromuscular cholinergic (nicotinic-II) receptor sites = skeletal muscle contraction being blocked. |
|
|
Term
| what are the isoquinolone derivative nondepolarizing NMBAs? |
|
Definition
| tubocurarine, atracurium, doxacurium, metocurine, and mivacurium |
|
|
Term
| what characterizes tubocurarine? |
|
Definition
| it can be used to dx myasthenia gravis (positive response is an increase in muscle weakness - small doses can elicit an exaggerated response). it also causes a histamine release and use of tubocurarine and diazepam may increase possibility of malignant hyperthermia. |
|
|
Term
| what characterizes atracurium? |
|
Definition
| this is less likely to release histamine than metocurine or d-tubocurarine and a hypotensive effect is minimal at recommended doses. if administered under isoflurane or enflurane anesthesia, reduce dose by 1/3. onset in 2-5 min and recovery begins in 20-30 min (nearly complete w/in 1 hour). ADRs: flushing, mild hypotension. repeated doses have no cumulative effect on duration of neuromuscular blockade if recommended dosage intervals are followed. |
|
|
Term
| what characterizes doxacurium? |
|
Definition
| little or no release of histamine. immediate onset, max effect in 2-3 min and duration: 20-30 min. the drug may accumulate in the body w/repeated injections and is excreted largely unchanged in the urine. doxacurium's effects may be increased in the presence of hypokalemia and decreased renal clearance. |
|
|
Term
| what characterizes metocurine? |
|
Definition
| releases histamine upon IV injection but less than d-tubocurarine. |
|
|
Term
| what characterizes mivacurium? |
|
Definition
| possible significant release of histmaine. |
|
|
Term
| what are the steroid derivative nondepolarizing NMBAs? |
|
Definition
| pancuronium (~5x as potent as tubocurarine), pipecuronium (little/no release of histamine), and vecuronium (little/no release of histamine). |
|
|
Term
| how is a nondepolarizing agent OD treated? |
|
Definition
| artificial respiration, vasopressors, and cholinesterase inhibitors (edrophonium, neostigmine - NOT for depolarizing NMBAs like succinylcholine [further intensifies paralysis]) |
|
|
Term
| what is the direct-acting skeletal muscle relaxant? |
|
Definition
| dantrolene, which has no interference w/transmission of impulses between motor nerves and skeletal muscle - just a direct effect on the skeletal muscle fibers themselves: *reduced release of Ca++ from binding sites in the sarcoplasmic reticulum and reduced contractability of skeletal muscles (affects fast reflex > slow voluntary muscles). it is used to treat muscle spasticity resulting from chronic neurologic disorders (e.g., cerebral palsy, multiple sclerosis, spinal cord injury, stroke). t1/2: 9 hours and therapeutic effects may not occur until 1-2 wks. |
|
|
Term
| how can dantrolene be used for emergency tx of malignant hyperthermia? |
|
Definition
| dantrolene IV can reduce Ca++ from the sarcoplasmic reticulum, impair catabolism in muscle cells, and reduce potentially lethal body temp elevations. |
|
|
Term
| what ADRs are are associated w/dantrolene? |
|
Definition
| hepatoxicity - esp w/high doses, long term tx, or in females > 35 y/o. use only with appropriate and frequent monitoring of hepatic function and discontinue if no observable benefit w/in 45 days. limited CNS effects: dissiness, drowsiness, weakness. others: GI disturbances, difficulty swallowing, and photosensitization. |
|
|
