Drugs for Epilepsy Lecture PDF Flashcards
2 ways antiseizure drugs work
1) act on neurons within a focus to reduce excessive rate of discharge
2) drugs can prevent propagation of seizure activity from a focus to other brain regions
5 primary mechs thru which anti seizure medications work
1) suppression of Na+ influx
2) suppression of Ca2+ influx at T type calcium channels
3) Enhancing activity of GABA
4) Antagonism of glutamate (which is excitatory neurotransmitter)
5) Promotion of K+ efflux
Therapeutic goal of antiseizure meds
Reduce seizures to extent that enable patient to live normal or near normal life, may not be possible without intolerable side effects so may have to balance
Treatment with antiseizure meds requires matching the proper medication with…
….specific seizure disorder
Antiepileptic drug treatment timeline protocol
Begin initial therapy, should it fail try 2nd and 3rd options alone then try combo, once one is selected, need trial period to determine effectiveness (pt should not drive or do other activities that are hazardous during this time)
Epilepsy therapy needs this common practice
Monitoring plasma drug levels
Withdrawal of antiseizure medications
Because some forms of epilepsy undergo spontaneous remission at some point discontinuation must be considered, no firm guidelines are indicated but most important rule is that withdrawal must be done slowly tapering the dosage down to prevent status epilepticus. If on multi drug regimen, taper off each drug sequentially
Cause of 50% of treatment failures in patients that are withdrawing from antiepileptic drugs
Nonadherance to medication therapy (patient compliance)
Suicide risk with antiepileptics (3)
- only some antiepileptic drugs raise risk
- risk linked more to illness than the medication
- suicide attempts are quite rare but should require monitoring
Antiepileptic drug ADR’s (2)
- suicidality
- reduced bone density
Antiepileptic drug interactions (1)
-contraceptive failure when on PO contraceptives
Antiepileptic drugs are indicated in pregnancy at low dose because….
…considered less risk of harm (although some evidence exists of lowered IQ’s) to the fetus than if the mother has a seizure
Phenytoin (dilantin) function, mech of action, pharmacokinetics, ADR’s (5), therapeutic range
- Broad spectrum antiseizure agent, active against partial seizures as well as tonic clonic seizures, no longer drug of choice because of ADR’s and interactions
- Stabilizes membranes by decreasing Na+ conductance during high frequency repetitive firing exerting effect only when neuronal activity is abnormally high allowing normal conductance of AP in CNS but halting seizure activity
- Has sharp rise beyond therapeutic range making pharmacokinetics difficult to balance
- CNS sedation (dizziness, visual disturbances, cognitive impairment) at high supratherapeutic levels, gingival hyperplasia, skin rash, cardiac arrhythmia when given IV too fast, teratogen
- between 10-20 ug/mL in plasma
Fetal hydantoin syndrome
Growth deficiency in pregnancy causing cranofacial distortion, positional deformities of limbs, and impaired neurodevelopment seen in pregnant women who take phenytoin
Penobarbital function, mech of action, therapeutic uses (all except one), ADR’s (3), interactions (2)
- Can reduce seizures without causing sedation
- Binds to GABA receptors enhancing GABA activity at the receptor resulting in potentiation of inhibitory effects of GABA
- Effective against all types of epilepsy except absence seizures
- Drowsiness, depression, toxicity
- CNS depressants, induction of drug metabolizing enzymes decreasing effects of other drugs such as oral contraceptives
Primidone (Mysoline) function
Active against all major seizure disorders with exception of absence seizures, very similar to phenobarbital
Carbamazepine (tegretol) function, mech of action, therapeutic uses (3), ADR’s (5), drug interactions (4)
- effective against all forms of epilepsy except absence seizures
- Appears to act by delaying recovery of inactivated Na+ channels
- Epilepsy, trigeminal/glossopharyngeal neuralgia, bipolar disorder
- CNS minimal effects (unlike phenytoin), leukopenia, aplastic anemia, dermatologic rxns, birth defects
- induction of drug metabolizing enzymes, phenytoin, phenobarbital, grapefruit juice
Ethosuximide (zarontin) mech of action, indication (1), ADR’s (1)
- suppresses neurons in hypothalamus responsible for generating absence seizures thru inhibition of ca2+ influx thru T channels
- Only used for absence seizures
- devoid of significant ADR’s
Valproic acid (depakene) and divalproex sodium (depakote) mech of action, therapeutic uses (3), ADR’s (4), drug interactions (2)
- suppress high frequency neuronal firing thru blockade of na+ channels
- used to widely treat all seizures, treat bipolar disorder, treat migraine
- GI upset, hepatotoxicity, teratogenic category D (may cause fetal abnormalities but may be used if only thing that controls seizure in mother), pancreatitis
- phenobarbital and phenytoin
Clonazepam (Klonopin) mech of action, function
- Benzodiazepine that does not suppress abnormal excitability wihtin seizure focus thought to be due to enhancement of GABA
- used to treat different kinds of seizures
Oxcarbazepine (trileptal) therapeutic uses (3), ADR’s (1)
- monotherapy or adjunctive in treatment of partial seizures, bipolar, and neuropathic pain
- Less severe than carbamezapine
Lamotrigine (lamictal) mech of action, function, ADR’s (2)
- regulates release of glutamate and aspartate which are excitatory neurotransmitters
- used in adjunctive therapy for seizures
- rash, suicidal thoughts
Gabapentin neurontin) function, mech of action, dosing
- adjunctive therapy for partial seizures with and without secondary generalization in patients >3 years old
- analog of GABA that enhances release rather than binding directly to GABA receptors
- must be titrated upward
Pregabalin (lyrica) function and ADR’s (3)
- Analog of GABA similar to gabapentin used in neuropathic pain as alternative to gabapentin
- weight gain, dizziness, reproductive adverse effects in men AND women
Levetiracetam (keppra) mech of action, therapeutic uses (1)
- unknown
- adjunctive therapy for partial or direct treatment for other types of seizures
Topirimate (topamax) therapeutic uses, mech of action, ADR’s (3)
- tonic clonic seizures
- 4 major mechanisms
- difficulty concentrating, drowsiness, dizziness
Antiseizure med that affects K+ efflux
Ezogabine (potiga)
Diazepam function, ADR (1)
- First line choice in seizure convulsion abortion in 90% of patients, effects are short lived and must be administered in repeated doses
- IV venous thrombosis
Lorazepam (aivan)/valium function
-Preferred to diazepam for seizure convulsion abortion because has longer duration up to 72 hours meaning follow up with long acting drug may be unecessary unlike diazepam
