neuromuscular blocking drugs Flashcards
tubcurarine: define the nature of the antagonism of tubocurarine on the effects of acetylcholine (ACh) at the motor end-plate and explain how the log dose curve showing the response of skeletal muscle to increasing concentrations of Ach would be altered in the presence of tubocurarine
what type of drug is tubocurarine
non-depolarising NM blocker (all have similar effects and mechanism of action but different duration of action)
tubocurarine: mechanism of action
competitive nAChR antagonist, with 70-80% block necessary to achieve maximum flaccid paralysis
tubocurarine: effect
flaccid paralysis of skeletal muscle due to relaxation
tubocurarine: order of flaccid paralysis effect (and therefore reverse order of recovery)
extrinsic eye muscles (double vision) -> small muscles of face, limbs and pharynx (trouble swallowing) -> respiratory muscles (respiratory arrest)
tubocurarine: effect on NM transmission
end-plate potential not sufficient to generate action potential, so no contraction of skeletal muscle fibre (flaccid paralysis)
tubocurarine: 2 clinical uses
relaxation of skeletal muscle during surgical operations (e.g. GIT), so can use less anaesthetic (safer procedure with faster recovery from anaesthesia); permit artificial ventilation to relax respiratory muscles
what can reverse actions of non-depolarising NM blockers and how
anticholinesterases (raise endogenous level of ACh, overcoming competitive block, so can terminate operation more quickly), e.g. neostigmine, with atropine given as well to damp down stimulation of muscarinic receptors (only want to overcome nAChR)
tubocurarine: pharmacokinetics (administration, impact on foetus, duration, metabolisation, excretion)
administered IV (highly charged), doesn’t cross BBB or placenta (so can be used in caesarean), long duration of paralysis (1-2 hours), not metabolised -> excreted unchanged in urine (70%) and bile (30%) - must take care if renal or hepatic function impaired (much larger effect as not excreted as quickly, so use atracurium as same mechanism of action but chemically unstable so short duration of 15 mins)
tubocurarine: 2 unwanted effects due to ganglion blockade and histamine release together, and how
hypotension (SNS ganglion blockade decreases TPR; histamine release causing vasodilation and decreased TPR); apnoea (so always assist respiration)
tubocurarine: 2 unwanted effects due to release of histamine from mast cells
bronchospasm, excessive secretions (bronchial and salivary)
tubocurarine: unwanted effect due to ganglion blockade
tachycardia (may be reflex due to hypotension, or due to blockade of vagal ganglia so dampens PSNS effect on heart, causing possible arrhythmias)
