Pathophysiology of Epilepsy Drugs (L1)

epilepsy is characterized by recurrent (____ or more) seizures that are ____________ and separated by >24 hours

2, unprovoked

epilepsy is characterized by recurrent (>2) seizures that are unprovoked and separated by >______

24 hours

aura is a subjective phenomenon that, in a given patient, may precede an observable seizure. if it happens alone, it constitutes a ______ ________ seizure

focal aware

_______ is a subjective phenomenon that, in a given patient, may precede an observable seizure. if it happens alone, it constitutes a focal aware seizure

aura

aura + tonic-clonic movements is the spread of ________ seizures into _________ __________ seizures

focal, bilateral tonic-clonic

__________ is defined as the seizure period or events due to the seizure

ICTAL (i.e. the seizure is happening rn)

seizures divided into ________-onset (where the patient is unconscious) and _________-onset (where the patient is either aware or has altered consciousness)

generalized, focal

seizures divided into generalized-onset (where the patient is _________) and focal-onset (where the patient is ___________)

unconscious, aware

partial/focal onset seizures: only part of the brain is affected. the symptoms and level of awareness depend on the ______________

area of brain involved (most are idiopathic/unknown cause)

ASM therapy is not indicated if the seizures are due to a __________ cause

reversible

ASM therapy is not indicated in certain epilepsies (ex: ________ seizures in kids)

febrile

which 4 ASMs are the best initial options for focal (aware or impaired) and focal-to-bilateral tonic-clonic seizures

CBZ, LMT, LEV, OXC (Carbamazepine, Lamotrigine, Levetiracetam, Oxcarbazepine)

which 3 ASMs are the best initial options for generalized onset seizures

LEV, LMT, TPM (Levetiracetam, Lamotrigine, Topiramate)

which ASM is the best initial option for absence or myoclonic generalized-onset seizures

VPA (valproic acid)

which 3 ASMs are the best initial options for atonic generalized-onset seizures

LMT, VPA, TPM (Lamotrigine, Valproic Acid, Topiramate)

which 3 ASMs are only used for focal-onset or focal-to-bilateral onset seizures types

OXC, CBZ, LCM (Oxcarbazepine, Carbamazepine, Lacosamide) (these 3 are not used for generalized-onset seizures)

which 3 ASMs can be used for basically every seizure type (focal and generalized) as either an initial choice or an alternative

LEV, LTG, VPA (Levetiracetam, Lamotrigine, Valproic Acid)

which of the ASMs is a CYP3A4 inducer

CBZ (Carbamazepine)

what is the big interaction to look out for with Carbamazepine

CYP3A4 induction

which 2 ASMs also have indications for migraines, depression, and bipolar disorders

CBZ, VPA (Carbamazepine, Valproic Acid)

which ASM can be induced or inhibited by other ASMs

LTG (Lamotrigine)

which ASM is most often associated with mood-altering SEs (Ex: agitation, anxiety, irritability)

LEV (Levetiracetam)

which ASM is most associated with teratogenic affects (8-20%)

VPA (Valproic Acid)

T or F: Patient is a 24 y/o female in clinic after experiencing her first seizure described as GTC (generalized tonic-clonic) seizure that happened last week. Her treatment plan should include initiation of an ASM.

False (only give ASM if >2 unprovoked seizures that are >24 hours apart)

which ASM would not be recommended as an initial option for a 24 y/o female with focal seizures with impaired awareness (partial ocmplex)

VPA (Valproic Acid d/t teratogenic affects)

which ASM would you recommend for a 56 y/o male with migraines who is on simvastatin (a CYP3A4 substrate)

VPA (CBZ is also indicated for migraines, but it is a CYP3A4 inducer)

which ASM would you not recommend for a 31 y/o male with h/o anxiety and agitation due to the medications common SEs

LEV

the frequency of skin rashes with __________ and _________ ASMs increased with rapid dose initiation and titrations

CBZ, LTG (Carbamazepine and Lamotrigine)

to avoid skin rashes caused by CBZ and LTG, start at a dose below ______ to _______ of the target dose and increase to the target dose over _________

1/3 to 1/4, several weeks

the decision for dose adjustment is based solely on ________ _________

clinical response (plasma conc. and PK guide the magnitude of dose adjustments)

35 y/o male receiving VPA 1200 mg/day (linear kinetics)

seizures: uncontrolled

SEs: none

[plasma]: 30mcg/mL (normal 50-100)

should you increase the dose or leave it

increase

35 y/o male receiving VPA 1200 mg/day (linear kinetics)

seizures: uncontrolled

SEs: mild (tolerable) sedation

[plasma]: 30mcg/mL (normal 50-100)

should you increase the dose or leave it

increase

35 y/o male receiving VPA 1200 mg/day (linear kinetics)

seizures: controlled

SEs: mild (tolerable) sedation

[plasma]: 30mcg/mL (normal 50-100)

should you increase the dose or leave it

leave it (only clinical response determines whether or not to dose adjust, [plasma] determines the magnitude of a needed adjustment)

60 y/o female receiving PHT (Phenytoin) 250mg/day (non-linear kinetics)

seizures: uncontrolled

SEs: none

[plasma]: 9 mcg/mL (normal 10-20)

A. increase the dose (double the dose)

B. increase the dose (don’t double the dose)

C. don’t change the dose

B (doubling the dose will cause drastically different response. just increase the dose a little bit)

OXC is indicated for _______-onset seizures

focal (aware, impaired-awareness, and focal-to-bilateral TC)

OXC is metabolized in the __________ into the active metabolite 10-monohydroxy metabolite (10-MHD)

liver

OXC is metabolized in the liver into the active metabolite ________________

10-monohydroxy metabolite (10-MHD)

AEs of OXC include CNS effects, hypo_______, and ____________

natremia, osteoporosis

AEs of OXC include CNS effects, ______natremia, and ____________

hypo, osteoporosis

OXC is a CYP_____ enzyme inducer

450

OXC is a CYP450 enzyme __________

inducer

OXC is a CYP450 enzyme inducer, which decreases the efficacy of other drugs like ______________

hormonal contraception (OCPs)

OXC displays ______-kinetics

linear (meaning doubling the dose is ok)

_____ and _____ have broad spectrums of activity (efficacy for both focal and generalized onset seizures)

VPA, LEV (Valproic Acid, Levetiracetam)

VPA is metabolized ___________

hepatically

VPA is an inhibitor that results in clinically important DDIs

CYP2C9 increases ___________ (ASM) concentration

PHT (Phenytoin)

VPA is an inhibitor that results in clinically important DDIs

CYP____ increases Phenytoin concentration

2C9

VPA is an inhibitor that results in clinically important DDIs

______________ which increases Lamotrigine concentration

glucuronidation

VPA is an inhibitor that results in clinically important DDIs

glucuronidation which increases __________ (ASM) concentration

LMT (Lamotrigine)

VPA is an inhibitor that results in clinically important DDIs

increased _______ 10,11-epoxide concentration

CBZ (Carbamazepine)

VPA displays ________ kinetics

linear (meaning doubling the dose is ok)

PHT displays ________ kinetics

non-linear (meaning we cannot double the dose)

VPA: does it treat focal, generalized, or both

both

OXC: does it treat focal, generalized, or both

focal

LEV: does it treat focal, generalized, or both

both

LEV is eliminated mainly unchanged __________

renally

_________ (ASM) has no enzyme induction/inhibition (no DDIs)

LEV (Levetiracetam)

__________ (ASM) should be avoided in patients with mood disorders

LEV (Levetiracetam)

LEV displays ________ kinetics

linear (meaning doubling the dose is ok)

74 y/o male with h/o DM, HTN, and newly diagnosed focal bilateral TC seizures in clinic for an eval. Reports 2 seizures in the past month. Recent labs: SCr 1.8mg/dL, K 4.5, weight 162lbs

The plan is to start him on LEV to minimize the risk of interactions with his other drugs

A. should be started on the smallest tablet available

B. should find out pts renal function

C. should find out pts liver function

D. should find out pts albumin level

B (LEV is eliminated mainly unchanged renally)