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91 Cards in this Set
- Front
- Back
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targets for anti-sz drugs
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Na, Ca, K channels
enhance GABA inhibit excitatory NTs (glutamate) |
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main ion of depolarization in CNS
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sodium
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what drugs work through GABA
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benzos, barbs
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Na blockers
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carbamazepine
phenytoin topiramate lamotrigine valproate zonisamide |
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phenytoin MOA
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block voltage gated Na channels
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Na blockers work well with
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generalized sz
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phenytoin absorption and metabolism
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highly variable absorption
half life 20-60 hours extensive hepatic metab (CYP2C9 and 2C19) |
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phenytoin elimination
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first order until 10 mcg/mL
higher doses - 0 order |
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phenytoin IV S/E
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cardiac arrhythmias (bc Na channels in heart)
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phenytoin oral chronic S/E
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GINGIVAL HYPERPLASIA
nystagmus behavioral changes anemia, bone marrow suppression hirsutism GI effects |
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carbamazepine MOA
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sodium channel blocker
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half life normally ____ for carbamazepine but ____ on pt recieving ______
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10-20 hours
9-10 hours phenobarbitol or phenytoin |
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what happens over time with carbamazepine
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AUTOINDUCTION of liver enzymes
initial half life = 36 hours but 8-12 hours with continuous therapy |
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major short term S/E of carbamazepine
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diplopia
ataxia |
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long term S/E of carbamazepine
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HEMATOLOGIC -ANEMIA, LEUKOPENIA
SIADH erythematous skin rash |
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prodrug to carbamazepine
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oxcarbazepine
less potent but less toxic less potent enzyme inducer |
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oxcarbazepine S/E
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better tolerated than carbamazepine
sleepiness, dizziness, nausea, rash |
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lamotrigine MOA
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inhibits Na channels, inhibits Ca channels
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lamotrigine primarily metabolized by
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glucuronidation
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lamotrigine S/E
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dizziness, blurred vision, GI effect
skin rash if titrated too fast |
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lacosamide MOA
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blockade of sodium channels
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lacosamide PK
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100% bioavailability
no active metabolites, low protein binding No CYP effects |
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lacosamide S/E
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dizziness, nausea
LOW SIDE EFFECTS |
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Ca channel blockers
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valproate
ethosuximide |
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ethosuximide MOA
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reduces Ca current in brain
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ethosuximide S/E
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GI: N/V, anorexia
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ethosuximide PK
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good PO absorption
half life 40-50 hours completely metabolized by liver hydroxylation (no CYP) |
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valproic acid MOA
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Ca channel blockade
Na channel blockade increases GABA |
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valproic acid PK
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rapid PO absorption
CYP2C9 and 2C10 metabolism |
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valproic acid S/E
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GI - anorexia, N/V
occasional rash & alopecia elevated liver enzymes! |
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divalproex sodium
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less GI complaints! slower absorption
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molecule of GABA + lipophilic ring
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gabapentin
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gabapentin
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stimulates GABA release
Ca channel inhibition |
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gabapentin S/E
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minor
drowsiness, dizziness, ataxia, fatigue, usually resolves in a few weeks |
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drugs that enhance GABA
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barbs
benzos |
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barbiturates MOA
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allosteric site at GABA-a
enhances inhibitory effect of GABA |
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barb example
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primidone (metabolized to desoxyphenobarbital)
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GABA receptors are on a ____ channel
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Chloride
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barbs CYP effects
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powerful INDUCERS of liver enzymes
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barb s/e
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irritability in kids, confusion in elderly
nystagmus & ataxia resp depression at high doses anemia, osteomalacia - chronic use |
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benzo MOA
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allosteric effect at GABA-a receptor
depresses effect of excitatory NTs |
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benzo antagonists
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flumazenil
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benzo examples
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diazepam, lorazepam, clonazepam
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major limits of long term benzos
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tolerance can develop in 1-6 mod
profound sedation at antisz doses paradoxical hyperactivity in children |
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other anti-sz agents
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levetiracetam
tiagabine topiramate zonisamide |
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transporter in terminal of neuron that brings GABA up
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GAT-1
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tiagabine MOA
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inhibit GAT-1
(inhibit GABA uptake) |
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topiramate MOA
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Na blocker
potentiates GABA |
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zonisamide MOA
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Na, Ca blocker
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levetiracetam MOA
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effects GABA release
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ezogabine MOA
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activates K channels (hyperpolarizes neurons)
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sedation vs. hypnosis
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sedation - calms and relaxes you
hypnosis - makes you sleep |
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benzos can be used for
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hypnotics
anxiolytics (short term) anticonvulsant skeletal muscle relaxation |
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benzo examples
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diazepam, flurazepam, oxazepam, lorazepam, triazolam
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how many subtypes of GABA receptors
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3
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which GABA receptor do benzos work at
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GABA-a
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what effect do benzos have at the GABA-a channel?
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allosteric agonists!
don't directly open Cl channels, just lower quantities of GABA that will open the channels now |
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benzo CNS actions
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sedation
hypnosis decreased anxiety anterograde amnesia anticonvulsant muscle relaxation |
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benzo PK
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complete absorption from GIT
extensive CYP metabolism many yield active metabolites that extend their duration |
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which benzos dont have active metabolites?
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oxazepam
lorazepam |
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drawbacks for using benzos for insomnia
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effect REM & slow wave sleep, daytime sedation, tolerance, anterograde amnesia, dependence - insomnia if stopped
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benzos s/e
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lightheaded
motor & mental impairment confusion (elderly) daytime sleepiness |
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benzo antagonist
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flumazenil
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non-benzodiazepine
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buspirone
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buspirone relieves anxiety w/o
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marked sedation
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buspirone MOA
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partial 5HT agonist in brain
central dopamine receptor effects |
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buspirone adverse effects
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tachycardia
nervousness GI distress |
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major drawback to buspirone for tx insomnia or acute anxiety
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takes time!
2 weeks to effect! |
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advantage of buspirone in elderly pts
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less psychomotor impairment
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non-benzo sleep aids
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zolpidem (AMBIEN)
zaleplon (SONATA) |
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eszopiclone (Lunesta) effects through
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GABA-a receptor
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Lunesta approved for tx of
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CHRONIC INSOMNIA
no tolerance after 6 months! |
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depression r/t what NTs
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depressed serotonin and NE!
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agents for treating depression
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TCAs
SSRIs MAOIs SNRIs atypical agents |
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TCAs - how many rings
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3
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TCA examples
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imipramine
amitriptyline nortriptyline desipramine clomipramine trimipramine |
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major drawbacks of TCA's for depression
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lack of specificity
block Na channels in heart |
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be careful about what drug class with suicidal pts
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TCAs
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alpha 1 blockade causes
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orthostatic hypotension
reflex tachycardia dizziness |
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antihistaminergic effects
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sedation
weight gain |
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anticholinergic effects
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nausea
anorexia dry mouth, blurred vision constipation, urinary retention |
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TCA PK
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well absorbed from GIT
first pass metabolism extensive CYP450 metabolism |
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major advantage of SSRIs over TCAs
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similar effectiveness, but higher selectivity = reduced side effects
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SSRI examples
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fluoxetine, paroxetine, sertraline, citalopram, escitalopram
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SSRI S/E
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specificity - less adrenergic, histamine, and cholinergic effects
SEXUAL S/E GI effects (diarrhea, constipation) |
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SSRI vs TCA in r/t OD
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SSRI - can't OD
TCAs = easy to OD |
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serotonin syndrome symptoms
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hyperthermia
muscle rigidity myoclonus rapid fluctuations in VS and mental status |
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serotonin syndrome most likely to occur in
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SSRI and MAOI
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____ metabolizes serotonin
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MAO (monoamine oxidase)
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SSRI PK
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lipophilic - once daily dosing
liver metabolized |
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which SSRIs are potent inhibitors of CYP2D6
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paroxetine and fluoxetine
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