Anticonvulsants and BZDs Flashcards by Jordan Cyr

Differentiate seizures and epilepsy.

seizure:
-sudden, uncontrolled burst of electrical activity in the brain
-changes in behavior, movements, feelings, consciousness
-most last 30s-2min (>5min=emergency)
epilepsy:
-two or more seizures at least 24 h apart that dont have a known cause

How well did you know this?

Not at all

Perfectly

Differentiate generalized and focal seizures.

generalized:
-happen in both sides (hemispheres) of the brain
-more severe effects and symptoms
focal:
-only happen in one hemisphere
-symptoms only happen on one side or specific part of the body
-can spread and become generalized seizures

How well did you know this?

Not at all

Perfectly

What are the types of generalized seizures?

absence seizures
myoclonic seizures
tonic seizures
tonic-clonic seizures
atonic seizures

How well did you know this?

Not at all

Perfectly

Which class of medications is used to treat epilepsy and other seizure disorders?

anticonvulsants

How well did you know this?

Not at all

Perfectly

Provide a recap of seizure mechanism.

imbalance of inhibitory and excitatory activity
-more excitatory activity
-glutamate > GABA

How well did you know this?

Not at all

Perfectly

What is the MOA of carbamazepine and phenytoin?

block voltage gated Na+ channel
-stop glutamate release/binding

How well did you know this?

Not at all

Perfectly

What is the MOA of barbiturates and BZDs?

behave like GABA
-enhancement of inhibitory transmission

How well did you know this?

Not at all

Perfectly

Describe the absorption of CBZ.

slow, unpredictable
tmax: 4-8 hours
delay owing to anticholinergic effects
some evidence of enterohepatic recirculation

How well did you know this?

Not at all

Perfectly

Describe the distribution of CBZ.

Vd = 0.8-2 L/kg
plasma protein binding: 76%
-not suitable for dialysis

How well did you know this?

Not at all

Perfectly

Describe the metabolism of CBZ.

CBZ –> CBZ 10,11 epoxide (via 3A4)
-CBZ 10,11 epoxide is active and toxic
CBZ 10,11 epoxide –> trans-CBZ-diol (via epoxide hydrolase)

How well did you know this?

Not at all

Perfectly

Describe the elimination of CBZ.

autoinduction
-t1/2 initial: 25-65h
-t1/2 after multiple doses: 12-17h
-t1/2 CBZ 10,11 epoxide: 5-10h
*drug as well as toxic metabolite induce CYPs

How well did you know this?

Not at all

Perfectly

What is the therapeutic range of CBZ?

20-50 umol/L (narrow therapeutic window)
-toxicity develops within TR

How well did you know this?

Not at all

Perfectly

What are the systems affected by CBZ toxicity?

neurologic (nystagmus, ataxia)
respiratory
cardiovascular

How well did you know this?

Not at all

Perfectly

What are symptoms of toxicity from chronic use of CBZ?

headache
diplopia
ataxia
ECG abnormalities
hyponatremia due to SIADH

How well did you know this?

Not at all

Perfectly

What kind of impacts can VPA and lamotrigine have on CBZ?

enzyme inhibitors of epoxide hydrolase
-therefore accumulation of the 10,11 epoxide active metabolite

How well did you know this?

Not at all

Perfectly

What is the antidote to CBZ?

no antidote

How well did you know this?

Not at all

Perfectly

How is CBZ toxicity managed?

supportive/symptomatic care
-hydration, airway, electrolytes, ABCs
-BZDs for refractory seizures due to CBZ

How well did you know this?

Not at all

Perfectly

What is the decontamination method for CBZ?

SDAC
-binds
-1 to 2 hr window

How well did you know this?

Not at all

Perfectly

What are the elimination methods for CBZ?

MDAC
-if severe
hemodialysis
-if theres lots of drug in the body, free proportion increases

How well did you know this?

Not at all

Perfectly

Is death common due to phenytoin toxicity?

rare if good supportive care

How well did you know this?

Not at all

Perfectly

What is the problem if IV phenytoin is released too quickly?

local tissue damage
cardiotoxicity

How well did you know this?

Not at all

Perfectly

Describe absorption of phenytoin.

erratic absorption following PO administration
tmax: 3-12h after a single oral dose
-bezoar would increase time to tmax

How well did you know this?

Not at all

Perfectly

Describe distribution of phenytoin.

rapidly distributed to all tissues
extensive PPB (88-93%)
-serum levels may not represent total drug
-TR but patient may exhibit signs of toxicity

Describe metabolism of phenytoin.

95% hepatically metabolized to inactive metabolite
polymorphism
-2C9, 2C19 poor metabolizers may experience toxicity at therapeutic levels

What happens to elimination of phenytoin as the concentration increases?

1st to zero order kinetics

What are therapeutic levels of phenytoin?

40-80 umol/L

What level do toxic effects of phenytoin start showing up?

after 80 umol/L

What is nystagmus?

rapid eye movement

Which systems are impacted by phenytoin toxicity?

neurologic CV GI/hepatic

What is the antidote for phenytoin?

no antidote

What is the management of phenytoin toxicity?

ABCs supportive/symptomatic care mainstay: -if hypotension from IV = reduce infusion rate, IV fluids, vasopressors -airway protection

What is a decontamination method for phenytoin?

SDAC -binds; consider but no evidence of any change in clinical course

What are the elimination methods for phenytoin?

MDAC -generally not necessary hemodialyis -current toxicology resources do not recommend hemodialysis for phenytoin toxicity

What are examples of barbiturates?

phenobarbitone butobarbitone pentobarbitone thiopentone methohexitone

What do most BZDs end in?

pam -except chloradiazepoxide

Why did BZDs replace barbiturates?

safer profile in terms of respiratory depression -however they can still cause some respiratory depression

What is the MOA of BZDs?

stimulating GABA-a receptor -thereby opening Cl channel lower the potential difference between the interior and exterior of the cell, blocking ability of cell to conduct nerve impulses

What is the antidote to BZDs?

flumazenil

Describe absorption of BZDs.

rapid and complete orally tmax: 1-3h relative lipophilic -more lipophilic means faster onset and longer duration half-life ranges from 2-50h

Describe distribution of BZDs.

Vd 0.75-1.5 L/kg highly protein bound

How are BZDs eliminated?

hepatically metabolized metabolites excreted renally

Describe BZD toxicity.

mortality from pure BZD overdose is rare toxicity depends on: -coingestants especially CNS depressants -shorter acting BZD = more toxicity -IV more likely to cause significant toxicity -tolerance skews the course

What is a very important piece of information to gather when someone presents with BZD toxicity?

co-ingestants

What happens with chronic use of BZDs?

tolerance

What do urine levels test for in regards to BZDs?

substances metabolized to oxazepam and nordiazepam false-negative if not metabolized to oxazepam/nordiazepam

What are decontamination methods for BZD toxicity?

SDAC (maybe) -if within 1h of ingestion gastric lavage (no)

What are elimination methods for BZD toxicity?

MDAC (no) hemodialysis (ineffective)

What is the MOA of flumazenil?

selective competitive antagonist of GABA receptor out competes BZD at recognition site on receptor complex thereby reversing BZD effect on CNS

What is the onset of flumazenil?

1-2 min *effect is short lived*

What are safety concerns with flumazenil?

seizures dysrhythmias possible when mixed overdose re-sedation

What are the pros and cons of flumazenil?

pros: -adverse effects minimal cons: -seizure risk -withdrawal risk

Is flumazenil effective at reversing respiratory depression?

effective at reversing CNS depression but not respiratory depression

Which patients is it ideal to use flumazenil in?

BZD-naive and single BZD-ingested patients

When is flumazenil a poor option?

unknown overdoses because of life threatening seizures and dysrhythmias can also precipitate seizure and withdrawal in BZD-dependent patients *safer to prioritize ABC in unknown overdose*

What are the indications for flumazenil?

pure BZD OD non-tolerant AND CNS depression, normal vital signs, normal ECG, normal neurological exam

Differentiate the MOA of barbiturates and BZDs.

barbiturates: -enhance binding of GABA to GABA-a receptor -prolong duration of channel opening -narrow therapeutic index BZD: -enhance binding of GABA to GABA-a receptor -increase frequency of channel opening -wider therapeutic index than barbiturates