(From Baby Katzung and lecture, by Brian Buschman)
Seizures can be focal (partial) of generalized. A focal seizure can be simple where it is confined to a single area of the brain or a focal complex seizure that includes sensory hallucinations and/or loss of consciousness.
General seizures affect both hemispheres and have a rapid loss of consciousness. They may be tonic-clonic (t/c, gran mal), absence (petit mal), myoclonic and febrile (in children).
These drugs in general work on all of these areas, they are all teratogenic and all induce liver cyt P-450 systems.
Phenytoin works to block t/c, status epilepticus and partial seizures by blocking inactivated Na+ channels just like it does when given as a class 1b antiarrhythmic.
Phenytoin is metabolized by microsomal systems so when mechanisms are saturated it’s plasma concentration increases rapidly WRT dose. It is also albumin bound. It’s P-450 induction effects are demonstrated in increased metabolism of levadopa, antiepileptics, anti-coagulants and so on. Drugs like warfarin and cimetidine that use the same breakdown pathway cause increased phenytoin levels.
Adverse affects of phenytoin include:
1) Gum hyperplasia
2) GI problems
3) Vit B12 deficiency megaloblastic anemia
4) It blocks insulin secretion (hyperglycemia)
In pregnancy it causes “fetal hydantoin syndrome” with cleft lip/palate, congenital heart disease. Epileptics pregnant women leads to anoxic periods for the fetus.
Carbamazepine, like phenytoin, bocks Na+ channels and is the DOC for partial seizures and t/c seizures. It is also used for trigeminal (CN V) neuroalgia and in bipolar disorder.
But carbamazepine is metabolized by cyt P-450 systems. With chronic administration you must increase the dose as it induces it’s own metabolic pathway.
Adverse effects include respiratory depression and water retention from ADH secretion. This is one way to differentiate it from phenytoin.
Phenobarbital increases the inhibitatory effects of many GABA neurons. It is a first choice for seizures in children, especially febrile seizures. It also can be used for partial, t/c and status epilepticus but NOT for partial complex.
Phenobarbital also induces P-450 and is degraded by microsomal systems. Barbiturates can cause rebound seizures (and rebound insomnia).
Primidone is a prodrug that is converted to two metabolites, one being phenobarbital. It is used for partial simple, febrile and t/c because of the phenobarbital but can also be used for partial complex because of the other metabolite.
Valproic acid is DOC for myoclonic seizures and is also used for absense and t/c (the two mals).
It does not induce P-450 systems but causes :
1) Hepatotoxicity
2) Decreased barb toxicity
3) Increased bleeding time from thrombocytopenia and decreased platelet production
Ethosuximide reduces abnormal propagation in the brain. It is the DOC for absence seizures. It does not increase the cyt P-450.
It cannot be used with T/C, renal impairment or pregnancy.
Diazepam is the DOC for status epilpiticus
Clonazepam is the DOC for myoclonic seizures and is used for absense seizures
Gabapentin and lamotrigine are new antiseizure drugs that cau be used for both types of partial seizures.
In infants the DOC for seizures are ACTH and corticosteroids