Anti-Epileptics (Ethosuximide, Carbamazepine, Valproic Acid) Flashcards
Metabolism of Ethosuximide? Half life? Excretion.
3A4, but it is not an inducer or inhibitor. Long half life, 50-60 hrs in adults 30 hrs in kids. Renal excretion.
Where is it thought the Absence seizures originate from?
Thought to arise from thalamic neurons
MOA of Ethosuximide (and also Valproate has this MOA)?
Reduces the low threshold Ca currents (T type currents) in the thalamic neurons to tx absence seizures. This stops the spike and wave pattern of absence sz’s. It also increases the seizure threshold.
AE’s of Ethosuximide?
GI stuff (n/v/d and constipation), sedation, dizziness, fatigue, headaches, hiccups. Irritability, depression, aggression, euphoria, psychosis, NIGHT TERRORS. EPS REPORTED. BLOOD DYSCRASIAS. DRUG INDUCED SLE. Allergic rxns.
DDI’s of ethosuximide and preggo use?
Crosses the placenta but no harm reported, anything that messes with 3A4 will mess with Ethosuximide, and drugs that also block the T type Ca channels will have increased AE’s int he patient.
How does Carbamazepine compare with Oxcarbazepine in terms of CYP metabolism and half life?
Carbamazepine is metabolized by 3A4 but it is a strong inducer of other CYPs and PGP’s. Further, it can do autoinduction. Oxcarbazepine meanwhile is hepatically converted to the active MHD compound, it is only a strong inducer of 3A4 but cannot do autoinduction. Carbamazepines have a much longer half life than Oxcarazepine. Despite the autoinduction of carbamazepine they eventually stabilize after several weeks.
What is the MOA of Carbamazepine and Oxcarbazepine?
Block the voltage gated Na channels (i.e. binds to the inactive form of the voltage gated Na channels thus prolonging hyperpolarization, similar to other Na channel blocker of the anti epileptic drugs).
Tx uses of Carbamazepine and Oxcarbazepines?
Carbamazepine and Oxcarbazepine for partial seizures, but only carbamazepine for tonic-clonic seizures. Oxcarbazepine however tends to have more tolerable side effects.
Non seizure use of carbamazepine?
Trigeminal neuralgia, acute mania associated with bipolar disorder.
How does carbamazepine relate to phenytoin?
The side effects of Carbamazepine is more tolerable then Phenytoin (i.e. the cosmetic side effects, etc). However, phenytoin produces LESS sedation and LESS effect on cognitive function.
AE’sof Carbamazepine and Oxcarbazepine?
Acute, dose related: dizziness, somnolence, ataxia, nystagmus, nausea, and diplopia. Potentially fatal blood dyscrasias. Skin rash and hepatotox HS rxns esp in asians with HLA-B*1502. SIADH, leading to hyponatremia and water intoxication (hyponatremia more common in oxcarbazepine).
Preggo and DDI’s of carbamazepine and oxcarbazepine?
Congenital problems reported in preggo, and since they are both strong inducers of 3A4 (and carbamazepines are strong inducers of other CYPs) there are tons of DDIs.
What’s notable about the PK of valproic acid?
It is protein binding saturable, and is conc dependent.
How is valproic acid metabolized and any CYP interactions?
Since it is a fatty acid it has mitochondrial beta oxidation, as well as glucronide conjugation and CYP mediated metabolism. It inhibits 2C9 and induces 2A6.
What is the MOA of Valproic acid?
It has voltage gated Na channel blocking like in Phenytoin and carbamazepine/oxcarbazepine, but in addition it blocks the T type Ca channels as well, like Ethosuximide. Has a 3rd MOA involving GABA.
