Drugs- Anticonvulsants (Kinder) Flashcards
what is the definition of epilepsy
a) Definition: occurrence of at least two unprovoked seizures separated by 24 hours.
b) Results from disturbed electrical activity in the brain.
i) Neuronal hyperexcitability and hypersynchrony.
partial focal seizures
x3
simple partial
complex partial
secondarily generalized seizure
simple partial seizures
(1) Minimal spread of abnormal discharge; normal consciousness; preserved awareness.
complex partial seizure
the 4 a’s
(1) Localized onset but discharge becomes widespread; almost always involves limbic system.
(2) Patient may have automatisms (lip smacking, swallowing, fumbling, scratching), memory loss, or aberrant behavior.
A's aura alteration of consciousness automatisms amnesia
mostly in temporal lobe
what are secondary generalized seizures
(1) Partial seizure immediately precedes a generalized tonic-clonic seizure.
what are the 5 main types of generalized seizures
generalized tonic clonic (grand mal) seizure
absence
myoclonic -(1) Brief, shock-like muscle contractions; occur in wide variety of seizures.
atonic -(1) Sudden loss of postural tone: head drop, fall to floor, slumping.
(2) Many patients wear helmets to prevent head injury.
status epilepticus
ii) Generalized tonic-clonic (grand mal) seizure
(1) Sudden, sharp tonic contraction followed by rigidity and clonic movements.
(2) Patient may cry/moan, lose sphincter control, bite tongue, or develop cyanosis.
(3) After seizure, patient may have altered consciousness, drowsiness, or confusion (postictal).
absence seizure
(1) Sudden onset and abrupt cessation; altered consciousness; a blank stare.
(2) Occurs in young children through adolescence.
what are the goals of therapy in epilepsy
control seizures, avoid medication side effects, and help restore quality of life. AED treatments suppress seizures but do not cure or prevent epilepsy.
monotherapy preferred
The patient should be warned not to stop taking an AED abruptly and not to allow a prescription to run out or to expire.
what epilepsy drugs are considered the older, 1st generation AED’s
phenobarbital
phenytoin
carbamazepine
valproate
which antiepileptics are highly protein bound
phenytoin
tiagabine
valproic acid
competes with other drugs for protein binding sites; must consider patients albumin level when interpreting therapeutic levels.
other highly protein bound drugs (e.g., sulfonamides) may displace phenytoin from binding sites increasing free drug.
phenytoin
MOA
a) MOA: blocks sustained high frequency firing of action potentials due to preferential binding to and prolongation of the inactivated state of the Na+ channel (effect also seen with carbamazepine, lamotrigine, valproate). Also decreases synaptic release of glutamate and enhances release of GABA.
what are important considerations when giving phenytoin
don’t give IM - precipitates
highly protein bound
metabolism via CYP2C9-
i) Narrow therapeutic index – difference between effective and toxic doses is small.
ADR’s of phenytoin
gingival hyperplasia
hirsutism
diplopia, nystagmus
ataxia
long term use–> worsening facial features, peripheral neuropathy , osteomalacia
cardiac–> hypotension, bradycardia, arrythmia
how does phenytoin interact with other drugs
competes for metabolism through CYP2C9 & 2C19 (e.g., warfarin primarily metabolized via 2C9, interaction may lead to increased INR/increased risk of bleeding).
Phenytoin is also a potent CYP inducer (e.g., CYP3A4 increasing metabolism of oral contraceptives, increasing risk of unplanned pregnancy).
Carbamazepine and oxcarbazepine
MOA
a) MOA: actions on Na+ channels result in inhibition of high frequency repetitive firing. Also acts presynaptically to decrease synaptic release of glutamate.
DDI’s of carbamazepine
CYP inducer
increased metabolism of other drugs: primidone, phenytoin, ethosuximide, oral contraceptives, valproic acid
also induces its own metabolism
iii)t1/2 36 hours observed in subjects after an initial single dose, decreases to as little as 8-12 hours in subjects receiving continuous therapy. It is possible for patients to achieve therapeutic concentrations but have levels fall even with continued dosing and good compliance. Considerable dose adjustments expected during first weeks of therapy.
ii) Valproic acid may also inhibit carbamazepine clearance resulting in increased levels.
ADR’s of carbamazepine
diplopia, ataxia
GI upset
drowsy
hyponatremia
Blood dyscrasia- anemia, agranulocytosis, leukopenia
which group of individuals are at higher risk of developing carbamazepine-induced Stevens Johnson syndrome
iii) Carbamazepine can cause rash and rare, but serious, reactions such as Stevens-Johnson syndrome. The FDA reported Asian patients that carry the human leukocyte antigen (HLA)-B*1502 allele have a 10X higher incidence of carbamazepine-induced Stevens Johnson syndrome compared to other ethnic groups.
phenobarbital MOA
barbituate
a) MOA: binds allosteric site on GABA receptor, enhances GABA mediated current by prolonging openings of the Cl- channels. Can also decrease excitatory responses through effect on glutamate release.
long half life 53-140 hrs
CYP inducer
