Week 4 Flashcards
Depolarizing Block
ex. ACh+anticholinesterase or succinyl choline
Phase 1 block: Muscle is depolarized near E(ACh), ACh receptors are occupied, voltage-dependent sodium channels are inactivated at end plate
Phase 2 block: Voltage-dependent sodium channels at end plate are no longer inactivated. ACh receptor is still occupied by Sux and it is desensitized so no current is produced
Uses of neuromuscular blockade in anesthetized patients
Safe facilitation, orthopaedic manipulations, endotracheal intubations, diagnostic scopy’s
Tubocurarine
Obsolete, releases histamine, ganglionic block, hypotension, renal clearance
Pancuronium
steroid, duration of action is 1 hour, does not release histamine, ganglionic blocakde minmal, tachycardia due to vagus nerve block, renal clearance
Vecuronium
intermediate duration of action, no tachycarida, no histamine release, no cardiovascular effects, biliary excretion
Atracurium
benzylisoquinolinium, intermediate duration of action, Hoffman elimation or via plasma esterases, neither hepatic nor renal clearance, no vagal or ganglionic block, some histamine release, seizures
Cisatracurium
better version of Atracurium
Sux
Uses- intubation
Side effects- bradycardia, tachy cardia, malignant hyperthermia
Contraindications- Burn patients, cardiac arrhythmias, ChE deficiency, myalgia
End-plate potentials lead to muscle contraction
depolarization at the end point will reach t-tubule that is responsible for bringing action potential into the muscle fiber stimulating calcium release from the sarcoplasmic reticulum
Cholinesterase inhibitors
Neostigmine- used to treat myasthenia gravis by increasing the amount of ACh available
Edrophonium- an anticholinesterase that is rapidly hydrolyzed used to diagnose MG
Principle of synergy
When two blockers act at different sites along this chain then their effects are multiplicative and may be profound
Loci of muscarinic and nicotinic receptors in the ANS
Muscarinic- autonomic neuroeffectors
Ionotropic- autonomic ganglia, skeletal neuromuscular junction
Treatment of anticholinesterase toxicity
decontaminate, atropine (heroic amounts), artificial respiration, reactivation of enzyme via 2-PAM, pyridostigmine pretreatmnet, anticonvulsants
Indications of muscarinic blockade toxicity and treatment
Indications: decreased secretions, urinary retention, vasodilation, decreased sweating, mydriasis, CNS deficit
Treatment- emesis, gastric lavage, activated charcoal, physostigmine
Identify the differences between adrenergic and cholinergic transmission
Ne action is terminated by upake not by destruction like Ach
Presynaptic receptors for Ne (alpha 2)
Catecholamine synthesis
Tyrosine–> Dopa–>Dopamine–> NE–> Epi
hydroyxlation, decarboxylation, hydroxylation, methylation
Adrenergic uptake
Uptake 1- on nerve terminal membrane, major route for NE inactiviation due to closeness of neuro and effector, high affinity, low capacity
Uptake 2- OCT or ENT transporter, found on effector membrane, relied upon when neuro and effector far, low affinity, high capacity
Metabolism
MAO (phase 1 non-cyp), COMT (Phase 2)
Peripheral (due to aldehyde dehyrogenase) VMA
CNS (due to aldehyde reductase)- MHPG
Rocuronium
popular for intubation, rapid onset, 100% biliary excretion
Dantrolene
used to treat malignant hyperthermia, prevents huge amounts of calcium release caused by SUX
Contraindications
burn patients, cardiac arryhthmia, genetic ChE deficiency, myalgia
Brain barostatic reflex
Increase in blood pressure- Nerves 9 and 10 go NTS to vagal nerve (bradycardia)
Decrease in blood pressure- Decrease in baroreceptor firing increases NE release to increase vasomotor tone and increase heart rate
