Anti-Epileptics Flashcards
Definitions
seizure
epilepsy
status epilepticus
Seizure
- abnormal neruonal firing in the cortex: physical or sensory manifestation
- an acute neurological event
- diferent types, severity, apperance based on location of firing
- a seizure does NOT = epiliepsy dx.
Epilepsy
- the occurance of 2+ seizures separated by at LEASE 24 hours
- a chronic, recurring disorder with an underlying process
Status Epilepticus
- any seziure last > 5 minutes : this is when neuronal damange can occur
- or any 2 seizures happening without complete recovery or consciousness/recovery of first seizure between
How do you select the proper drug for seizure management
- identify the underlying cause of the seizure: if its due to hypoglycemia: give dextrose!
- type of seizure (tonic-clonic, absence, etc.) guides
- MOA of drug: if on multiple: want different MOAs
- ADE: of the meds can guide therapy
what are some medications that can worsen seizure
the common ones
& ones to be aware of
Common meds to cause/worsen seizures
- meperidine (opioid)
- flumazemil (benzo reversal agent)
- contrast dyes!!
- vaccines
- phenothiazines (anti-psychotics)
Imipenem = can reduce seizure threshold
buproprion = can lower seizure threshold
withdrawl from benzos, alcohol and opioids can worsen seizures
MOA: Sodium channel antagonism
MOA
- these AED’s will antagonize the sodium channels: prolonging the inactivity and ability for the Na+ channels to open
- this then reduces the ability of a neuron to fire = decreasing excitabilty and propagation of APs
MOA: Calcium Channel Modulators
MOA
- these drugs antagonize the calcium channel (N-type)
- they prevent the channels from releasing Ca+
- if Ca+ cannot be releasd: then there is no ability for the vesicel full of glutamate to fuse to the cleft and release into the synapse
- without the release of glutamate: there can be no excitatory potentiation down the cleft: no depolarizaiton
MOA: drugs that act on GABA
GABA: an inhibitory NT
some drugs = enhance GABA: thus inhibiting the ability for an AP to occur, decrease excitability
some drugs = inhibit GABA-transaminase: thus inhibiting the breakdown of GABA: leading to more
what AED (anti-epileptic drugs) can be used for an Absence seizure
EL VZ!!
E: ethosuximide (can ONLY be used for absence seizures)
L: Lamotrigine
V: Valproate
Z: Zonisamide
what AED’s must be AVOIDED in myoclonic and absence seizures
AVOID the following for absence and myoclonic seizures
- carbamazepine
- oxcarbmazepine
- gabapentin
- tiagabine
- pregabalin
these will all exacerbate the seizure
role of benzodiazepines in seizure control
what is used for status epi. vs. what is used for add-on
Reserved for Status Epi.
- Lorazepam
- midazolam
- diazepam
Used for Add-on to gain control with AED
- clonazepam
- clobazam
Benzodiazepines
MOA
Indications (seizure and other)
Benzodiazepines: MOA
- bind to post-synaptic GABA A receptors: increase the inhibition that GABA gives
Indications
- Benzos are first line in status epilepticus (lorazepam, midazalam, diazepam)
- can be used for focal or general seizures (clonazepam, clobazam)
- can be used to control Lennox-Gastuat (a seizure syndrome)
Additional Indications
- anxiety, insomnia, ICU sedation, alcohol withdrawl, etc.
Benzodiazepines
side effects
monitoring
Drug interactions
Side Effects/ADR
- respiratory depression : in status epi. youll intubate because you’re giving in such high doses
- drowsiness
- ataxia
- hypotension: dose-related, propylene glycol can be given with lorazepam and diazepam to help decrease this effect
- watch for withdrawal symptoms upon abrupt discontinuation: taper off
Monitoring
- watch RR: work of breathing, O2 status
- mental stauts & neuro exam
- BP! wathc for hypotension
Drug Interactions
- no monitoring needed
- watch interactions with otehr CNS depressants (opioids, alcohol,etc.)
Carbamazepine
MOA
Uses
Adverse Effects /ADR
Carbamazepine: AED (Tegretol)
- fast sodium channel inactivator with active metabolite also inactiving the Na+ channel
Uses
- focal and general seizures (no absence)
- bipolar disorder
- trigeminal neuralgia
- neuropathic pain
ADR
- these are all concentration dependent
- diplopia, drowsiness and sedation
- slgnificant N/V
- leukopenia
- Aplastic anemia
- hyponatermia
- rash: SJS risk
- decreased BMD
- teratogenic
Carbamazepine
Contraindications to Use
Monitoring Parameters
what about metabolism
Contraindiciations
- bone mineral density suppression: depression
- use of MAO within 14 days
- using nefaxdone
- using NNRTI (HIV med)
- presence of the HLA-B 1502 gene: if you CANNOT TEST FOR THIS; you CANNOT USE this med
Monitoring
- drug level 4-12mcg/mL
- must screen for HLA-B1502 gene
- monitor CBC: WBC > 2,500 & ANC > 1,000
- Na: keep 135-145
Metabolism
Carbamazepine is an AUTOinducer:meaning it will metabolize itself quicky at 3A4 then over time level out
- increase dose every week until adequte concentration
- starts 3- 5days; ends 21-28 : check levels weekly for first 3-5 weeks
PT. MUST BE ON FOLIC ACID 1-4 MG DOSING IF THEY ARE ON CARBAMAZEPINE
Oxcarbazepine
MOA
Indications
MOA
- a prodrug: converted and then its metabolite inactivates fast sodium channels
Indications
- generalized and focal seizures
- can be usd in those not responding to carbamaizepine
Side Effects
- well tolerated
- diplopid, dizzty, somnelence
- rash: watch if they had it to carbamaz. they’ll probs have it here too
- hyponatremia: more likely
Oxcarbazepine
monitoring
metabolism
Monitoring
- no therapeudic monitoring needed
- watch neuro exam
- watch sodium levels
Metabolism
- no autoinduction
- this drug can decrease the bioavalibility of estrogen in OCP medications
Ethosuximide
MOA
Indications (specific)
Side Effects
Monitoring
Ethosuximide:MOA
- a calcium channel modulator
Indications
only used for absence seizures!!!!! : the first-line medication
Side Effects
- well tolerated
- N/V
- ataxia and sedation
- neutropenic: monitor CBC
- rash
- hepatoxicity
Monitoring
drug levels should be 40-100mcg/mL
Felbamate
MOA
Indications (specific)
Side Effects
Drug Interactions
Contraindication!!
Felbamate: MOA
- glutamate activity inhibitor
Indications
- LAST LINE CHOICE: use for pt. who are not responding to other agents
Side Effects (many = hence last line)
- anxiety/insomnia
- nausea
- weight loss
- HA severe
- Aplastic anemia: need to monitor CBC
- Acute liver failure: monitor LFTs
Drug Interactions
- increased CNS depressant with others
- no monitoring of levels needed
Contraindication
- hisotry of blood disorder (dyscrasias)
- history of hepatic dysfunction
Gabapentin (neurontin)
MOA
Indications
Side Effects
Gabapentin: MOA
- enhances GABA inhibition activity
- modulates calcium channels
Indications
- used for focal and general seizures (usually adjuct)
- used on elderly
- post-herpetic neuralgia
- neuropathic pain
- diabetic neuropathy
Side Effects
- well tolerated
- sedation/drowsy
- peripheral edema & weight gain
- on withdrawal: anxiety, insomnia, nausea, sweating etc. (syndrome)
Pearls
- no monitoring, contraindications, enzyme issues
- watch in renal: need to renally adjust
Lacosamide
MOA
Indications
Side Effects
Lacosamide: MOA
- slow sodium channel inactivation
Indications
- can be indicated for those who failed other sodium channel blocking meds (phenytoin)
- focal seziures
- last line salvage in status. epi.
Side Effects
- dizzy, diplopia, N/V, HA
- increased LFTs : monitor
- PR interval prolongation: EKG
due to prolonged PR: caution use in those with 2nd or 3rd degree heart block
Lamotrigine
MOA
Indications
Side Effects
Lamotragine: MOA
- fast sodium channel inactivation
Indications
- absence seizures
- focal, tonic-clonic and general
- bipolar disorder too
Side Effects
- drowsy, HA, diplopia, insomnia, etc.
- Rash: within 3-4 weeks and can progress to SJS
- rash seen more commonly with concurrent use of valproic acid + lamotragine
Drug Intercations
- lamotragine decreases the levogresterol component in OCPS
- ethinyl estradiol impacts lamotragine
- if used with carbamaziepine: CNS effects
Levetiracetam (Keppra)
MOA
Indications
Side Effects
Elimination
Levetiracetam: MOA
- modulates synaptic vescile protien
Indications
- focal & general: very good with seizures treatment and preventing
Side Effects
- sedation, dizzy, depression
- hallucinations: agitation and psychosis if underlying psych. disease
Metabolism
- renally eliminated: adjust as needed
Phenobarbital
MOA
Indications
Side Effects
Phenobarbital: MOA
- fast sodum channel inactivator
Indications
- general or focal seizures
SIde Effects
- ataxia, droswy, sedation (significant!)
- hyperactivity in some pt.
- osteoporosis
- rash
- blood disorders: agranulocytosis, thrombocyotpenia, megaloblastic anemia
Phenobarbital
Contraindications
Monitoring levels
Drug Interactions
Contraindications
- hepatic dysfunction
- airway issues/dyspena
- history of sedative/hyponotic abiuse
- nephritic pt.
Monitoring
goal 15-40 mcg/mL
- CBC
- neuro exam
Drug Interactions
- strong CYP - 3A4 inducer: speeds up metabolism of lots of meds
- ethanol will increase metabolism of pehnobarb.
- cimetidine will decrease metabolism
Phenytoin (Dilantin)
MOA
Indications
SE (by level) and general
Phenytoin: MOA
- fast sodum channel inhibitor
Indications
- status epi: use
- focal or general seizures
Side Effects: depend on concentration
- all: dizzy, diplopia, drowsy sedation
- normal levels 10-20
- > 20 = nystagmus
- > 30 = ateral nystagmus and ataxia
- > 40 = decreased mentation
- > 100 = death
other SE
- anemia
- gingival hyperplasia
- hirsutism
- lymphadenopathy
- osteporosis
- rash
- hepatotoxic
- teratogenic
Phenytoin
Concentration and plasma
monitoring
difference between free and bound
Concentration Considerations
- phenytoin will be 95% bound to the plamsa albumin protein
- but there is a nonlinear relationship between dose and concentration
- as the dose increases, the body can no longer metabolize it as fast, so you get increased serum concentrations once fully saturated in its bound to plasam form
- small chages in dose of phenytoin can lead to large changes in serum concentration
Monitoring
- monitor tough levels (before next dose)
- TOTAL phenyotoin (bound and unbound) = 10-20
- FREE phenyotoin (unbound) = 1-2
TOTAl levels: can be falsely low in those with low albumin: seems ok but when you do the free levle you see there SO much unbound (thus active) that you get bad SE
Equation for Free and Total Phenyotinin levels
check a free level in
- hypoalbuminemia
- reanl failure
- pregnant
- critically ill
- babies
- those with lots of protein bound drugs
For Hypoalbuminemia
adjusted = TOTAL concentration/ (0.2 x albumin) + 0.1
For CrCl < 10
adjusted = TOTAL concentration/ (0.1 x albumin) + 0.1
if calculating both: dose ajust base on whichever one is worse
Phenytoin
drug interactions
contraindications to IV phenytoin
Phenytoin Drug INteractions
major substart at 2C9 and 19
induces 3A4
highly preotien bound drug: so drug interactions can occur with other drugs that are highly bound as well
Contraindication to IV Phenyotoin
- sinus brday
- SA block
- 2nd and 3rd degree heart block
Pregabalin
MOA
Indications
Pregabalin: MOA
- calcium channel modulator
Indications
- focal seizure adjuct
- fibromyaliga
- postherpetic nerualgia
- neuropathic pain
- controlled substance
Side effets
- dizzy, sedation, dry mouth, blurry vision
- peripheal edema & weight gain
- wihtdrawl syndrome possible
Pearls
- renally eliminated: dose
- no drug interactions or monitoring
Tiabaine
MOA
Indications
Side Effects
Drug Interactions
MOA
- enhances GABA
Indication
- add on for focal seizures
SIde Effects
- dizzy
- sonolence
- slow thinking
- CNs depressant
Drug Interactions
- major CYP 3A4 substarte: watch with inducers/inhibitors
Toperimate
MOA
Indications
Side Effects
Drug Indications
Toperimate: MOA
- fast sodium channel inactivtion
- enhances GABA activity
- inhibits glutamate activity
Indications
- focal and general seziures
- migraine prophylaxis
Side Effects
- ataxia, dizzy, drowsy
- acute angle glaucoma
- ** renal calculi**
Contraindications
- with extended release: no alcohol within 6 hours; risk of metabolic acidosis if taking metformin
Drug Interactions
- increases etrogen clearance
- carbamazepine, phenytoin and valporate can decrease toperimate concentrations
Valproic Acid
Types
MOA
Indications
Valproic Acid: Types
- immediate release med: Depakene
- delayed release: stavzor
- IV: valproate sodium
- enteric coated
- bioavaiblity between formulations varies
MOA
- fast sodium channel inactivation
Indications
- for all seizures
- migraine prophylaxis
- mania
- diabetic neuropathy
Valproic Acid
Side Effects
Monitoring
Contraindications
Teratogenic
Side Effects
- nausea, drowsy
- tremor
- acute hepatotoxicity
- acute pancreatitis
- osteperosis
- weight gain
Monitoring
trough: 50-100
Contraindications
- hepatic dz. pt.
- urea cycle disorders
- mitochondrail disorders
- pregnant pt.
Valproic Acid
Drug Interactions
Drug Interactions
- highly protein bound drug: watch interaction with phenytoin!
- oral contraceptives increase clearance of valproic acid
- valproic acid levels can be decreases by carbapenems
- additive effects of CNS depressants
Vigabatrin
MOA
Indications
Side Effects
Vigabatrin: MOA
- GABA transaminase
Indications
- only for REFRACTORY foacl onset seizures
- you NEED to D/C this med in anyone with subclinical benefits
Side Effects
- convulsions
- dizzy
- HA
- weight gain
- permanent vision loss and blindness DOES HAPPEN
Vigabatrin
Monitoring Parameters
Monitoring
- vision assessment: at baseline, before 4 weeks of administeration, then every 3 months AND 3-6 months after d/c med
no monitoring of levels
no contraindications
Zonisamide
MOA
Indications
Side Effects
Contraindications
Zonisamide: MOA
- sodum and calcium channels
Indications
- foacl onset seizures
Side Effects
- dizzy, somnolence
- metabolic acidosis
- oligohydrosis
- paresthesias
- renal calculi
Contraindications
SULFONAMIDE ALLERGY!!
Cost Issues with AEDs
- rx. can be made for BRAND NAME only if necessary : since sometimes the bioavalibility varies and pt. can be sensitive
Drug Levels to Know
waht two drugs clearance from the body are increased with OCP use
Carbamazpine ; 4-12
Ethosuximide: 40-100
phenobarbital: 15-40
phenyotoin: 10-20 (total) 1-2 bound
valproic acid: 50-100
OCP use: increases clearance of valproic acid and lamotrigine
Teratogencity
which meds are
how much folic acid
Valproic Acid
Carbamazpine
these have risk of neural tube defects and hypospadias
Barbituates (phenobarb) & phenytoin
- heart defects, cleft lipe and others
women of childbearing age = MUST take 1-4 mg of folic acid daily if on these (or any AED) med
Osteoporosis and malacia with AEDs
chronic AED use = increased risk
phenyotoin, phenobarbital, carbamazepine, valproic acid
add cacium and Vit D after 6montsh of therapy to decrease risk
D/C medications of AED
how is it done
AED withdrawal can be considered for those meeting ALL THE FOLLOWING CRITERIA!!!
- extended period of seizure free (2 years if absence, 5 years if others)
- normal neuro exam
- normal IQ
- normal EEG
- single type of seizure dx.
how to D/c
- slow taper over 1-3 months
- 60% chance they will remain seizure free
