IC4 Flashcards
phenytoin MOA
block voltage-dependent Na+ channels to reduce the membrane excitability
not suitable for absence seizures
CBZ MOA
block voltage-dependent Na+ channels
not suitable for absence seizures
VAL MOA
block voltage dependent Na+ and Ca2+ channels
suitable for all types of seizures
what are the general dose-related side effects of ASMs
drowsiness
confusion
nystagmus (eyes move rapidly, uncontrollably)
ataxia (no coordination)
slurred speech
nausea
unusual behavior/mental changes
coma
what are non-dose related side effects of ASMs
hirsutism
acne
gingival hyperplasia
folate deficiency
osteomalaica
hypersx SJS/TEN
benzodiazepines MOA
potentiates influx of cl- ions entering the GABA receptors cl- channels leading to hyperpolarisation = decreased excitability
(enhance effect of inhibitory GABA neurotransmitters)
GABA-A receptors.
GABA is the inhibitory neurotransmitter.
DOA of benzodiazepines
varying DOA
midazolam is the shortest acting with appx 3h t1/2. rarely used for epilepsy but general anaesthetic procedures
clonazepam, lorazepam
intermediate acting appx 12-30h t1/2
diazepam
long acting appx 43h t1/2
more suitable for status epilepticus
ADR benzodiazepines
acute toxicity/overdose
- severe respiratory depression (esp with alcohol use) = slow shallow breathing rate
- treat with flumazenil (benzo antagonist)
during use
- drowsy, confusion, amnesia
- impaired muscle coordination (impair manual skills)
how to treat respiratory depression from benzodiazepines
flumazenil
binds to benzodiazepines but does not activate it = gets displaced
management AND PROBLEM of benzodiazepine ADRs.
tolerance develops with increased frequency of use.
HOWEVER, may also cause dependence with overuse. = withdrawal effects like disturbed sleep, rebound anxiety, tremor, convulsions.
IF WITHDRAW = DO IT GRADUALLY
RISK OF ABUSE.
phenobarbital MOA?
also potentiates GABA-A mediated CL- currents
BUT at a different site
what is the other indication of phenobarbital and benzodiazepines
sedative hypnotic
although benzodiazepines replaced them due to increased tendency of barbiturates to cause tolerance and dependence
common indication of phenobarbital?
ASM
for pediatric or neonatal patients
(IV loading > IV/oral maintenance)
DOA of phenobarbital
long acting (1-2days) = anticonvulsant = phenobarbital
short (3-8h) = sedative hypnotic = pentobarbital, amobarbital
ultrashort (20min) = IV induction of anaesthesia = thiopental
pk of phenobarbital vs benzodiazepines
dose dependent depression
increasing dose of benzodiazepines will eventually reach a peak in how much it can cause CNS effects (max medullary depression)
however, phenobarbitals has no peak effect and may induce coma at high doses.
PK of levetiracetam
highly soluble and permeable
similar linear profile like phenytoin
low intra and inter subject variability
ORAL AND IV
common and rare ADR levetiracetam
common: headache, vertigo, cough, depression, insomnia
rare: agranulocytosis, suicide, delirium, dyskinesia (abnormal invol movement)
MOA of lamotrigine
blocks voltage gated Na+ channels
inhibit release of glutamate
impedes sustained repetitive neuronal depolarisation
what special ASM indication for lamotrigine?
use as initial or adjunct to lennox gastaut syndrome
PK of lamotrigine (t1/2)
oral (chewable)
t1/2 short for children
t1/2 reduced with co-admin of CBZ, PH
t1/2 increased with co-admin of VAL
common and rare ADR lamotrigine
common: headache, irritable/aggression, tiredness
rare: agranulocytosis, hallucination, movement disorder (worsen PD), SJSTEN, hepatic failure
topiramate MOA
UNCLEAR
increase gaba activation of gaba-a receptor to enhance induction of cl-?
but does not increase channel opening time
may act on benzodiazepine insensitive subtype of GABA-A receptors
what special ASM indication for topiramate?
lennox-gastaut
ADJUNCT therapy
other indications for topiramate
prophylaxis of migraine in ADULTS
PK of topiramate
oral long plasma half life
renal clearance
not a potent inducer of drug-metabolising enzymes
common and rare ADR of topiramate
common: depression, drowsy, fatigue, nausea, weight change
rare: neutropenia, mania, tremor, transient blindness, SJS/TEN, hepatic failure
implication of serotonin in migraine
Serotonin may be an important mediator of migraine headache:
Agonists of vascular and neuronal 5-
HT1 receptor subtypes = 1) vasoconstriction of meningeal blood vessels and
2) inhibition of vasoactive neuropeptide release and pain signal transmission.
PK of cafergot
tmax
BA
metabolism
oral and rectal
rapidly absorbed with max plasma conc reached in 1.5-2hours
high plasma protein binding, low absolute BA (2-5%)
inhibits cyp3a4 = risk of elevated toxicity and vasospasm/tissue ischemia
ADR common and rare of cafergot
common: N/V
rare: hypersx, myocardial infarction, vascular ischemia (ergotism)
PK of sumatriptan
oral. nasal. iv
rapidly absorbed
low plasma protein binding
eliminated by MAO
C/I sumatriptan
hypersx to triptans
concurrent admin with MAOi
myocardial infarction
common and rare ADR of sumatriptan
common: dysgeusia (unpleasant taste), transient BP increase, flushing, sensation of cold, pressure, tightness
rare: minor disturbances in LFT
PK of erenumab and how long for effect
SQ injection monthly
benefit in 3 months
linear kinetics = saturable binding of cgrp receptor
ADR erenumab
hypersx
injection site reactions
constipation
pruritis
