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Glu, stroke,epilepsy

Physical neuropharmacology

TermDefinition
What is the MoDA, clinical use and side effects of perampanel? Non-competitive antagonist of AMPAR (Glu) -> prevent depolarisation -> treat epilepsy -> can cause severe mood disturbances
What is the MoDA of memantine? NMDA channel blocker (Glu) -> treat Alzheimer's
What is the MoDA of ketamine? NMDA channel blocker (Glu) -> dissociative anaesthetic
What is the MoDA of 7-chlorokynurenic acid? Inhibits Gly binding to NMDA channel (Glu co-agonist)
What is the MoDA of ifenprodil? Blocks spermine modulatory site on NMDA channel -> spermine cannot shift GluN subunit to acidic pH -> spermine cannot inhibit GluN2B (selectivity)
What is the MoDA of spermine? Activatory modulatory of NMDAR (Glu) -> shifts IC50 to acidic pH
What is the MoDA and clinical use of alteplase? Recombinant tissue plasminogen activator -> fibrinolytic drug -> converts plasminogen to plasmin -> cleave fibrin thrombi -> treat stroke for <4.5 hrs -> longer prioritises side effects of haemorrhage from tissue damage
What is the MoDA and clinical use of statins? Reduce blood cholesterol -> prevent atherosclerosis/plaque formation -> prevention for stroke
What is the MoDA and clinical use of aspirin? Inhibit platelet TX synthase -> lower TXA production -> repress vasoconstriction/platelet aggregation -> prevention for stroke
What is the MoDA of bicuculline? GABA-A antagonist -> causes epileptic seizures
What is the MoDA of picrotoxin? GABA-A channel blocker -> convulsant
What is the MoDA of benzodiazepines? +ve allosteric modulator of GABA-A -> bind to alpha-gamma interface -> allosterically increase GABA affinity -> increase GABA channel open probability -> enhance GABA function
What is the pharmacokinetics, clinical use and side effects of diazepam? Benzodiazepine (GABA-A enhancer) -> 1/2 life of >20 hrs -> long duration of action -> treat anxiety/epilepsy -> drowsiness/amnesia/impaired motor coordination/nausea -> increased tolerance w/ use -> require increased receptor occupancy w/ time
What is the pharmacokinetics and clinical use of lorazepam? Benzodiazepine (GABA-A enhancer) -> 1/2 life of 8-12 hrs -> short duration of action -> sleep inducer -> less induced tolerance than longer active drug
What is the MoDA, clinical use and side effects of flumazenil? GABA-A benzodiazepine antagonist -> treat benzodiazepine overdose -> somewhat anxiogenic/proconvulsant
What is the MoDA of ethyl-beta-carboline-3-carboxylate (beta-CCE)? GABA-A benzodiazepine inverse agonist -> A binds GABA (Cl- influx -> enhance GABA sensitivity), B cannot bind GABA (decrease GABA sensitivity) -> cause increased anxiety/proconvulsant
What is the MoDA, clinical use and pharmacokinetics of zolpidem? Non-benzodiazepine binding to their GABA-A binding site -> selective for alpha-1 GABA-A subunit -> sedative rather than anxiolytic (alpha2) -> short 1/2 life of 2 hrs -> less addictive
What is the MoDA, clinical use and side effects of neurosteroids/barbiturates? +ve allosteric modulator of GABA-A -> increase single-channel open time of GABA-A -> used in anaesthesia induction phase -> narrow therapeutic window can lead to respiratory depression -> coma/death
What is the clinical use of thiopental? Neurosteroid/barbiturate (GABA-A enhancer) -> fastest acting anaesthesia -> unconscious w/in 10 seconds
What is the clinical use and pharmacokinetics of phenobarbital? Neurosteroid/barbiturate (GABA-A enhancer) -> longest acting anaesthesia -> used as anticonvulsant (anti-epileptic) -> 1/2 life of 2-7 days
What is the MoDA. clinical use and side effects of baclofen? GABA-B agonist -> inhibit spinal cord -> treat spasticity from MS, stroke, spinal injury -> may activate GABA-B in brain -> drowsiness/motor incoordination
What is the MoDA and clinical use of saclofen? GABA-B antagonist -> closes GABA-B GIRK -> depolarisation -> inactivates T-type Ca2+ channels -> less neurotransmitter release -> abnormal 3 Hz spike/wave discharges interrupted -> prevents thalamo-cortical circuit overfiring -> treat absence seizures
What is the MoDA. clinical use and pharmacokinetics of vigabatrin? Irreversibly inhibits GABA transaminase -> inhibit brain GABA degradation -> increased GABA release -> inhibit CNS -> treat epilepsy refractory cases -> short 1/2 life of 5-8 hrs -> irreversible action -> only taken once daily
What is the MoDA, clinical use and pharmacokinetics of tiagabine? Inhibits GAT1 (GABA reuptake) -> increased [GABA]e -> inhibits CNS -> add-on therapy for partial seziures -> short 1/2 life of 7 hrs
What is the MoDA, clinical use and side effects of carbamazepine? Nav blockers -> reduce depolarisation -> reduce PDS effect as bind to inactivated Navs from sudden depolarisation -> widely used antiepilpetic xcp avsence seizures -> drowsiness, ataxia
What is the MoDA, clinical use and side effects of phenytoin? Nav blockers -> reduce depolarisation -> reduce PDS effect as bind to inactivated Navs from sudden depolarisation -> widely used antiepileptic xcp absence seizures -> rashes, ataxia, headache, high plasma [ ] -> confusion, gum hyperplasia, hirsutism
What is the pharmacokinetics of phenytoin? Antiepileptic (Nav blocker) -> 80-90% bound to plasma albumin (greater plasma []/hepatic clearance) -> inactivation rate doesn't increase w/ plasma [ ] above therapeutic range -> plasma 1/2 life increases w/ dose, ss plasma [ ] doesn't follow dose
What is the MoDA, clinical use and pharmacokinetics of lamotrigine? Nav blockers -> reduce depolrisation -> reduce PDS effect as bind to inactivated Navs from sudden depolarisation -> widely used antiepileptic -> wider therapeutic profile than carbamezapine/phenytoin
What is the MoDA and clinical use of lacosamide? Enhances slow inactivation of Nav -> less Navs available for activation after PDS -> treat partial seizures
What is the MoDA and clinical use of ethosuximide? Blocks T-type Ca2+ channel -> decreased neurotransmitter release -> treat absence seizures
What is the MoDA, clinical use and side effects of valproate? Blocks T-type Ca2+ channel -> decreased neurotransmitter release, weakly inhibits GABA transaminase (GABA degradation) -> enhance postsynaptic GABA function -> inhibit Nav -> treat other forms of epilepsy -> hair thinning/curling, hepatotoxicity
What is the MoDA and clinical use of gabapentin? Binds to Cav accessory subunit alpha2delta1 -> reduce Cav PM expression -> reduce Ca2+ influx -> treat partial seizures/neuropathic pain (Cav upregulated)
What is the MoDA and clinical use of topiramate? Blocks Nav, Cav, AMPAR, facilitates GABA-A -> treat partial/generalised seizures
What is the MoDA and clinical use of zonisamide? Blocks Nav, Cav, enhance GABA-A -> adjunt therapy to treat partial/generalised seizures
What is the MoDA and clinical use of levetiracetam? Binds SV2A (synaptic vesicle protein 2A) -> prevent synaptic vesicle docking -> reduce nerotransmitter release -> treat partial/generalised seizures
Created by: vykleung
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