Drug Therapy of Seizure Disorders Flashcards
Injectable drugs
Phenytoin, phosphrnytoin, valproic acid, levetiracetam
1st vs. 2nd and 3rd gen
1st are mainstays but oftne have more SEs
Na blocker rationale
Act at presynaptic to suppress pre-synaptic generation of APs
Na blocker selectivity
Frequency dependent block
Bind in the open or inactivated state…if more often open or inactivated then more binding…drug accumulates and has greater effect
Pheny and fosphy MOA and uses
Ph - GTC, Status, focal
Fos - only Status
Phenytoin better for LT, fos better for status
Fos vs. pheny toin and how it is metabolized and drug interactions
Phenytoin is not as water soluble…fos is a prodrug
Hepatic metabolism
Induces CYP2C9 and enhances metabolism of other drugs
Phenytoin dosing
As a certain point, non-linear pharmacokinetics
SE of phenytoin
Hypotension/cardiac inhibition (limit rate of IV)
Decreased bone mineral density
Gingival overgrowht
Some CNS
SE of phnytoin more serious
SJS
DRESS - hepatic necrosis is danger
If it leaks out, could cause Purple Glove syndrome
Carbamzaepine MOA and uses
GTC, focal
Na channel blocker
Used for long term
Can aggrevate absence seizures
Carbamazepine metab and pharmacokinetics vs. phenytoin
Induces multiple CYP450 isozymes
First order elimination makes dosing safer…still tons of interactions
Carbamazepine dosing
It autoinduces the enzymes that metabolize it so need to start low and titrate high
Carbamazepine and serious side effects
SJS - Esp east asian (HLA-B*1502 genotype)
Carb other SEs
Ataxia and other CNS
Decreased bone mineral density
Other hypersensitivty
Lamotrigine MOA and what it works on
GTC and focal
Works on absence but not prefferred
Na blocker and weak Ca blocker
Lamotrigine elimintion and drug interactions
Hepatic glucuronidation
It has miniamal effects on other drugs
Carbamazepine decrease blood levels by inducing elimination
Valproic acid increases blood levels by inhibitng elimiantion
Lamotrigine SEs
CNS
Hypersensitivity (SJS)…avoid in pediatrics…dose titrate
Vaproic acid MOA and uses
Mostly absence and focal
Also GTC and status
Na channel blocker and Ca blocker
Best for complicated syndromes with multiple seizrue types
Mech of valproic acid
Mostly on Na channels
Low-threshold Ca blocker
Enhancment of GABA
Valproi acid elimination and drug interactions
Glucuronidation (also fatty acid)
Phenytoin and carbamazepine induce enzymes that metabolize so will decrease concentration
Valrpoic acid SEs
Teratogenic
Hepatotoxicity/pancreatitis (younger)
CNS
Topiramate MOA and uses
GTC and focal
Na nlocker
Glutmate antaginist
GABA nergic enhancer
Topiramate SEs
Sedation, cog
Metabolic acidosis
Weight loss
Topiramate elimination and drug interactions
Primarily renal elimination
Few drug interactions except with carbonic anhydrase inhibitors
Ethosuximide MOA and use
Generalized absence
Blcoker of neuronal low-threshold Ca channels
Mech of low threshold Ca channels
Ca channels open and depoalizre thalamic relay neurons
The PDS brings relay neuron closer to threshold for Na
Burst of APs
APs conducted to cortical neurons
Ethosuximide disrupts these Ca channels
Ethosuximde drug interactions and SE
Mostly CYP3A4 but some renal
GI distress and bone marrow depression
Preferred for absence seizures because greater efficacy than lamotrigine and less effect on cog than valprpoci
Levetiracetam MOA and use
GTC, status, Focal
Useful for combo
Synaptic transmission modulator
Binds to SV2A, secretory vesicle glycoprotein
Levetiracetam eliminatioin and SEs
Renal excretion
Fatigue, asthenia, behavioral
Mechs of
Pheny Carba Lamo Topir Valpro Etho Levetir
Na channel Na channel Na, Ca channel Na, gabanergic, glutamate antag Na, Ca, enahnce Gaba Ca Decrease vesicle release by binding to SV2A
Protoypes that alter hepatic metabolism
Phenytoin - induces glucordination of lamotrigine and valproic acid
Carb - induces glucuronidation of lamotrigine and valproic acid
Valproic acid - inhibits glucuronidation of lamotrigine
