Anticonvulsants and Antiepileptic Drugs Flashcards
what is anticonvulsant therapeutics?
reduce seizure activity either by decreasing excessive excitatory glutamatergic neurotransmission and/or increasing inhibitory neurotransmission= restore balance
what are the drugs used for Tonic-clonic and/or Partial seizures?
phenytoin
carbamazepine
Valproate
Topiramate
Lamotrigine
Levetiracetam
what are the drugs used for absence seizures?
Ethosuximide
Valproate (multiple MOA)
what are the drugs used for Status Epilepticus and Acute Seizures?
BZDs (1st line) Lorazepam (Ativan) Clonazepam (Klonopin)
Barb’s (2nd line) Phenobarbital (Luminal)
what are the drugs used for neuropathic pain?
Gabapentin
Pregabalin
Carbamazepine
List the drugs whose MOA is Voltage-Gated Na⁺ Channel (VGNa⁺) Blockers
Phenytoin (Dilantin)
Carbamazepine (Tegretol)
Lamotrigine (Lamictal)
Valproate (Depakote)
List the drugs whose MOA is T type Voltage-Gated Ca²⁺ Channel (VGCC) Blocker
Valproate (Depakote)
Ethosuximide (Zarontin)
List the drug whose MOA is GABA Metabolism Inhibitor
Valproate (Depakote)
List the drugs whose MOA is N Type voltage- gated calcium channel (VGCC) blockers
Gabapentin (Neurontin)
Pregabalin
what is a benefit to using Barbiturates as an anti-epileptic drug?
reduce intracranial pressure if brain injury
what are the main differences between Benzodiazepines and Barbiturates ?
- BZDs: safer, wide therapeutic index, has reversal agents
- BARBs: drug interactions, narrow therapeutic index, death, respiratory depression, and lacks reversal agents
what are first line BZDs used for and can they be used long term?
acute drug induced seizures, acute relief of Status Epilepticus, or drug withdrawal seizures
- no they cannot be used long term (tolerance)
what is the BZD antidote if dose is too high?
flumazenil, but use with care: can precipitate more seizures if use too much
Why are lorazepam (Ativan) and clonazepam (Klonopin) the top choices for acute siezures?
L: due to no active metabolites;
C: long-acting if drug withdrawal causing seizures
how does Phenobarbital (Luminal) cause lots of dangerous drug interactions?
it is a CYP enzyme inducer
what is the MOA for the Voltage-gated Na+ Channel (VGNaC) Blockers (Phenytoin, Carbamazepine, Lamotrigine, Valproate)
- Do NOT bind to resting sodium channels
- Bind to the inactivated state of VGNaC
- “Use-Dependent” Block (bind to Overactive Neurons)
what are the pharmacokinetics for Phenytoin?
- Zero order kinetics
- narrow therapeutic index (TI)
- can use IV fosphenytoin for rapid onset (metabolized to phenytoin in body)
- Cyp450 enzyme inducer can cause drug interactions
what are the pharmacokinetics for Carbamazepine?
- first order kinetics
- induces CYP3A4, it speeds up metabolism of many drugs, reducing their effectiveness
- induces its own metabolism
- need to monitor blood levels
what are other clinical uses for Carbamazepine?
mood stabilizer and for neuropathic pain
- 1st line treatment for trigeminal neuralgia
what are the major adverse effects for Phenytoin?
- gingival hyperplasia
- dermatological: Steven-Johnson and TENS
- hepatotoxicity
- arrythmia (can be fatal)
what are the major adverse effects for Carbamazepine?
- dermatological: Steven-Johnson and TENS
- hepatotoxicity
- hematological
- suicidal ideation risk
what are other uses for Lamotrigine (Lamictal)?
Mood stabilizer ~ helps bipolar depression
- some efficacy in absence seizures but some black box issues
what are the benefits of Lamotrigine (Lamictal)?
- Less drug interactions than others
- Doesn’t inhibit/induce enzymes
- Doesn’t promote weight gain
what are the adverse effects for Lamotrigine (Lamictal)?
- Generally better tolerated then others
- Diplopia common
- Mild rash common (10%): less than 0.1% develop serious rash
what is the black boxed for Lamotrigine (Lamictal)?
Higher incidence of SJS & TENS then other VGNaC blockers
AED “Jack of All Trades”
Valproate (Depakote) due to multiple MOA
* Inhibits GSK-3 & decreases protein kinase C
what is a common use for Valproate (Depakote)?
mood stabilizer in bipolar depression
what are the issues of Valproate (Depakote)?
- no rapid onset
- Undergoes complicated hepatic metabolism & can produce hepatotoxic metabolites
Major Adverse: Common - hair loss, weight gain (increases risk metabolic syndrome), dermatological possible
what are the 2 Black Boxes for Valproate (Depakote)?
- Hepatotoxicity…monitor liver function…especially dangerous to infants
- Pancreatitis…uncommon but can progress rapidly… monitor for severe abdominal pain
what are the benefits of Levetiracetam (Keppra)?
- Rapid onset and generally well tolerated
- Versatile ~ don’t know all mechanisms
- can be used in pregnant patients
what are the adverse effects of Levetiracetam (Keppra)?
- Dizziness, ataxia
- Anxiety ~ Recent FDA warnings of Increase in moodiness/aggressive behavior; Very
rare but serious psychosis
drugs inhibiting the T-type Voltage-Gated Ca²⁺ Channel (VGCC) reduce the
abnormal T-current in absence seizures
what type of drug can worsen absence seizures?
pure Na+ blockers
what are the indications for Ethosuximide (Zarontin)?
1st line for absence seizures – not effective for generalized seizures
what are the adverse effects pf Ethosuximide (Zarontin)?
- Common effect –dizziness
- Vomiting initially but generally well tolerated
what drug is often used in mixed tonic-clonic/absence seizures?
Valproate (Depakote)
what are the common uses for Topiramate (Topamax)?
- used for partial seizures
- infantile seizures
- adjuvant with other AEDs
- migraine prevention
- weight loss
what are the adverse effects of Topiramate (Topamax)?
dizziness
paresthesias
confusion
some get mental health issues (including psychotic reactions)
***FDA warning: visual problems and glaucoma
what is the MOA of Gabapentin (Neurontin)?
- Voltage-Gated Ca²⁺ Channel (VGCC) Blockers α2delta subunit
- increases GABA synthesis and release
what can Gabapentin (Neurontin) be used to treat and why?
Neuropathic and chronic pain
- reduces aberrant sensitized C-fiber firing
- use in diabetes with neuropathic pain
Partial seizures
- adjuvant “good mixer” drug
- Lack hepatic metabolism
- Generally well-tolerated
what are common issues with Gabapentin (Neurontin) ?
dizziness & ataxia
what are the special considerations for DISCONTINUATION?
- abrupt withdraw can cause rebound seizures
- avoid drug interactions causing break-through seizures
what are the special considerations for PREGNANCY
several anticonvulsants are teratogenic
- Polytherapy associated with birth defects
- Monotherapy reduces birth defect risk
which drugs alter estrogen metabolism?
Carbamazepine, oxcarbazepine, phenobarbital, topiramate
*decreases birth control effect
what drug can cause hepatotoxicity in infants & young children due breastfeeding or if taken during pregnancy?
Valproate
Valproate relative contraindication in pregnancy
- 1st trimester teratogenic: neural tube defects & Spina bifida
- Low IQ in babies exposed later in pregnancy
PTH, CZB relative contraindication in pregnancy
- Fetal Hydantoin Syndrome (FHS)
- Epoxide metabolites build up in baby & cause damage
Topiramate relative contraindication in pregnancy
- Increased risk cleft lip ~ common use as migraine preventative
