CNS 5 Flashcards
(32 cards)
Second generation antiepileptic drugs
- gabapentin,
- lamotrigine,
- topiramate,
- levetiracetam,
- oxcarbazepine,
- zonisamide
Are most often used as an adjunctive therapy for myoclonic as well as for partial and generalized tonic-clonic seizures
Diazepam, and lorazepam
Has a shorter pharmacokinetic half-life but stays in the brain longer than diazepam.
Lorazepam
Is available for rectal administration to avoid or interrupt prolonged generalized tonic-clonic seizures or clusters.
Diazepam
Reduces the propagation of abnormal impulses in the brain by blocking sodium channels, thereby inhibiting the generation of repetitive action potentials in the epileptic focus and preventing their spread. Effective for treatment of partial seizures and secondarily generalized tonic-clonic seizures.
Carbamazepine
- 10,11-epoxide metabolite of the drug → implicated in causing blood
dyscrasias - A characteristic rash may develop early in therapy but may not require
a change in treatment. - Hyponatremia may be noted in some patients, especially the elderly →
could indicate a need for change of therapy. - SHOULD NOT BE PRESCRIBED FOR PATIENTS WITH ABSENCE SEIZURES BECAUSE IT MAY CAUSE AN INCREASE IN SEIZURES.
Carbamazepine
Is a combination of sodium valproate and valproic acid and is reduced to valproate when it reaches the gastrointestinal tract. It was developed to improve gastrointestinal tolerance of valproic acid.
Divalproex sodium
It is effective for the treatment of partial and primary generalized epilepsies
Divalproex
Is bound to albumin (greater than 90 percent), which can cause significant interactions with other highly protein bound drugs
Valproate
Teratogenicity is of great concern of this drug
Divalproex
- reduces propagation of abnormal electrical activity in the brain, most likely by inhibiting T-type calcium channels.
- It is effective in treating only primary generalized ABSENCE seizures.
- Use of this is limited because of this very narrow spectrum.
Ethosuximide
• has a broad spectrum of anticonvulsant action.
• The drug has multiple proposed mechanisms including:
1) blocking voltage-dependent sodium channels
2) competing with the glycine-coagonist binding site on the N-methyl-D-aspartate
(NMDA) glutamate receptor
3) blocking calcium channels
4) potentiation of GABA actions
• It is reserved for use in refractory epilepsies (particularly Lennox-Gastaut syndrome)
because of the RISK OF APLASTIC ANEMIA (about 1:4000) and HEPATIC FAILURE.
Felbamate
• An analog of GABA
• However, it does not act at GABA receptors nor enhance GABA
actions, nor is it converted to GABA.
• It is approved as adjunct therapy for partial seizures and for treatment of postherpetic neuralgia.
Gabapentin
Has been shown to be well tolerated by the elderly population with partial seizures due to the relatively mild adverse effects and a good choice due to limited or no reported
pharmacokinetic drug interactions.
Gabapentin
- Blocks sodium channels as well as high voltage dependent calcium channels.
- is effective in a wide variety of seizure disorders, including partial seizures, generalized seizures, typical absence seizures, and the Lennox-Gastaut syndrome.
- It is approved for use in bipolar disorder as well.
- The half-life of lamotrigine (24 to 35 hours) is decreased by enzyme-inducing drugs (for example, carbamazepine and phenytoin) and increased by greater than 50% with addition of valproate.
Lamotrigine
- dosages should be reduced when adding valproate to therapy unless the valproate is being added in a small dose to provide a boost to the lamotrigine serum concentration.
- Rapid titration to high serum concentrations of it have been reported to cause a rash, which in some patients may progress to a serious, life-threatening reaction.
- has also been shown to be well tolerated by the elderly population with partial seizures
Lamotrigine
- is approved for adjunct therapy of partial onset seizures, myoclonic seizures, and primary generalized tonic-clonic seizures in adults and children.
- It demonstrates high affinity for a synaptic vesicle protein (SV2A). In Levetiracetammice, this was associated with potent antiseizure action.
Levetiracetam
- is a prodrug that is rapidly reduced to the 10-monohydroxy (MHD) metabolite which is responsible for its anticonvulsant activity.
- MHD blocks sodium channels preventing the spread of the abnormal discharge.
Oxcarbazepine
- It is approved for use in adults and children with partial onset seizures.
- is a less potent inducer of CYP3A4 and UGT than carbamazepine.
Oxcarbazepine
- The primary mechanism of action is the enhancement of inhibitory effects of GABA-mediated neurons.
- The primary use for phenobarbital in epilepsy is in treatment of status epilepticus.
- adverse effects of sedation, cognitive impairment, and potential for osteoporosis, this drug should only be considered for chronic therapy once a patient is found to be refractory to many other drugs, and the benefits of therapy outweigh the multiple risks.
Phenobarbital
- It blocks voltage-gated sodium channels by selectively binding to the channel in the inactive state and slowing its rate of recovery.
- At very high concentrations, it can block voltage-dependent calcium channels and interfere with the release of monoaminergic neurotransmitters.
- It is effective for treatment of partial seizures and generalized tonic-clonic seizures and in the treatment of status epilepticus.
- The drug is 90% bound to plasma albumin. It is an inducer of drugs metabolized by the CYP2C, and CYP3A families and the UGT enzyme system.
Phenytoin
- exhibits saturable enzyme metabolism at a low serum concentration → small increases in a daily dose can produce large increases in the plasma concentration → drug-induced toxicity
- Depression of the CNS occurs particularly in the cerebellum and vestibular system, causing nystagmus and ataxia. The elderly are highly susceptible to this effect.
- Gingival hyperplasia may cause the gums to grow over the teeth.
- Long-term use may lead to development of peripheral neuropathies and osteoporosis.
Phenytoin
- It is a prodrug and is rapidly converted to phenytoin in the blood, providing high levels of phenytoin within minutes.
- It may also be administered intramuscularly (IM).
- ___ sodium should never be given IM because it can cause tissue damage and necrosis.
- It is the drug of choice and standard of care for IV and IM administration.
Fosphenytoin
- It binds to the a2-d site, an auxiliary subunit of voltage-gated calcium channels in the CNS, inhibiting excitatory neurotransmitter release.
- the drug has proven effects on partial onset seizures, neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, and fibromyalgia.
- Pregabalin is greater than 90% eliminated renally, with no indication of CYP involvement.
- Drowsiness, blurred vision, weight gain, and peripheral edema have been reported.
Pregabalin
