Term
|
Definition
| partial seizure and generalized tonic-clonic seizure (indicated in table on last slide) |
|
|
Term
| phenytoin (side effects?) |
|
Definition
-Ataxia and nystagmus.
-Cognitive impairment.
-Hirsutism
-Gingival hyperplasia.
-Coarsening of facial features.
-Dose-dependent zero order kinetics.
-Exacerbates absence seizures.
-teratogen |
|
|
Term
| phenytoin (mechanism of action?) |
|
Definition
| Primarily targets Na+ channels but also may influence Ca2+ and K+ conductances |
|
|
Term
|
Definition
-Oldest “nonsedative” antiepileptic drug.
-VA studies in 1985 documented that overall treatment success with phenytoin was similar to carbamazepine
-Fosphenytoin, a more soluble prodrug is used for parenteral use.
-“Fetal hydantoin syndrome”
I-nhibits high frequency repetitive firing.
-One of the few drugs for which the rate of elimination varies as a function of its concentration (i.e., the rate is nonlinear) until it reaches a saturation (dose-dependent zero order kinetics) |
|
|
Term
| carbemazepine (indication?) |
|
Definition
| most effective against partial complex seizures and had fewer adverse effects than valproate |
|
|
Term
| carbemazepine (side effects?) |
|
Definition
-Autoinduction of metabolism.
-Nausea and visual disturbances.
-Aplastic anemia.
-Exacerbates absence seizures. |
|
|
Term
| carbemazepine (mechanism of action?) |
|
Definition
|
|
Term
| carbemazepine (other info) |
|
Definition
-Tricyclic antidepressant analog
-3-D conformation similar to phenytoin.
-Mechanism of action similar to phenytoin.
-Inhibits high frequency repetitive firing.
-Metabolite is active. |
|
|
Term
| OXCARBAZEPINE (indication?) |
|
Definition
| partial seizure and generalized tonic-clonic seizure (indicated in table on last slide) |
|
|
Term
| OXCARBAZEPINE (side effects?) |
|
Definition
-Hyponatremia
-Less hypersensitivity and induction of hepatic enzymes than with CBZ |
|
|
Term
| OXCARBAZEPINE (mechanism of action?) |
|
Definition
|
|
Term
| OXCARBAZEPINE (other info) |
|
Definition
-Analog of carbamazepine.
-Improved toxicity profile due to lack of formation of toxic metabolite.
-Less potent than carbamazepine.
-Active metabolite.
-Mechanism of action, similar to carbamazepine; alters Na+ conductance and inhibits high frequency repetitive firing. |
|
|
Term
| PHENOBARBITAL (indication?) |
|
Definition
| Useful for partial, generalized tonic-clonic seizures, and febrile seizures |
|
|
Term
| PHENOBARBITAL (side effects?) |
|
Definition
-Sedation.
-Cognitive impairment.
-Induction of liver enzymes (drug-drug interactions).
-May worsen absence and atonic seizures |
|
|
Term
| PHENOBARBITAL (mechanism of action?) |
|
Definition
| Prolongs opening of GABA-gated Cl- channels |
|
|
Term
| PHENOBARBITAL (other info) |
|
Definition
-Except for the bromides, it is the oldest antiepileptic drug.
-Although considered one of the safest drugs, it has sedative effects.
-Many consider it the drug of choice only for seizures in infants |
|
|
Term
|
Definition
| Effective against partial and generalized tonic-clonic seizures |
|
|
Term
| PRIMIDONE (side effects?) |
|
Definition
-Same as phenobarbital
-Sedation occurs early
-Gastrointestinal complaints |
|
|
Term
| PRIMIDONE (mechanism of action?) |
|
Definition
| Primarily targets Na+ channels but also may influence Ca2+ and K+ conductances (Its mechanism of action may be closer to phenytoin than the barbiturates) |
|
|
Term
|
Definition
-Metabolized to phenobarbital and phenylethylmalonamide (PEMA), both active metabolites.
-Absorbed completely, low binding to plasma proteins.
-Should be started slowly to avoid sedation and GI problems. |
|
|
Term
|
Definition
-As effective as CBZ in controlling generalized tonic clonic seizures.
-Also used for absence and myoclonic seizures |
|
|
Term
| VALPROATE (side effects?) |
|
Definition
-Elevated liver enzymes, autoinduction of metaboloism
-Nausea and vomiting.
-Abdominal pain and heartburn.
-Tremor
-Hair loss
-Weight gain.
-Idiosyncratic hepatotoxicity.
-Adverse interactions with other antiepileptics.
-Teratogen: spina bifida |
|
|
Term
| VALPROATE (mechanism of action?) |
|
Definition
-Inhibits succinate semialdehyde dehydrogenase and GABA transaminase
-May increase levels of GABA in brain.
-May increase potassium conductance |
|
|
Term
| ETHOSUXIMIDE (indication?) |
|
Definition
| Drug of choice for absence seizures |
|
|
Term
| ETHOSUXIMIDE (side effects?) |
|
Definition
-Gastric distress, including, pain, nausea and vomiting
-Lethargy and fatigue, sedation
-Headache
-Hiccups
-Skin rashes |
|
|
Term
| ETHOSUXIMIDE(mechanism of action?) |
|
Definition
| Mechanism of action involves reducing low-threshold Ca2+ channel current (T-type channel) in thalamus |
|
|
Term
| ETHOSUXIMIDE (other info) |
|
Definition
-High efficacy and safety.
-Little plasma protein binding |
|
|
Term
|
Definition
-Long acting drug with efficacy for absence seizures.
-Also effective in some cases of myoclonic seizures |
|
|
Term
| CLONAZEPAM (side effects?) |
|
Definition
-Sedation.
-Ataxia
-Rapid development of tolerance |
|
|
Term
| CLONAZEPAM (mechanism of action?) |
|
Definition
| Increases the frequency of GABA-gated Cl- channel opening |
|
|
Term
|
Definition
|
|
Term
|
Definition
| Used for partial seizures |
|
|
Term
| VIGABATRIN (side effects?) |
|
Definition
-Drowsiness
-Dizziness
-Weight gain
-Agitation
-Confusion
-Psychosis |
|
|
Term
| VIGABATRIN (mechanism of action?) |
|
Definition
| GABA-transaminase (enzyme responsible for metabolism of GABA) => Increases inhibitory effects of GABA |
|
|
Term
|
Definition
| Contraindicated if preexisting mental illness is present |
|
|
Term
| LAMOTRIGINE (indication?) |
|
Definition
-Broad spectrum drug used as both monotherapy and as an adjunctive for partial seizures +/-
-Also used in primary generalized epilepsy (absence, myoclonic) +/- secondary generalization |
|
|
Term
| LAMOTRIGINE (side effects?) |
|
Definition
-Dizziness
-Headache
-Diplopia
-Nausea
-Somnolence
-Rash |
|
|
Term
| LAMOTRIGINE (mechanism of action?) |
|
Definition
| Suppresses sustained rapid firing of neurons and produces a voltage and use-dependent inactivation of sodium channels |
|
|
Term
|
Definition
-Favorable cognitive and behavioral profile
-Often used with valproate to reduce the dose of valproate (valproate slows metabolism of lamotrigine)
-Can benefit patients with depression (especially bipolar disorder)
-Must be titrated slowly to minimize the incidence of rash |
|
|
Term
|
Definition
| Broad spectrum agent as both monotherapy and adjunctive against partial and generalized seizures but has severe side effects. Not first line medication |
|
|
Term
| FELBAMATE (side effects?) |
|
Definition
-Aplastic anemia
-Severe hepatitis
-Headache/dizziness
-Lethargy
-Anorexia
-Nausea/vomiting
-Insomnia |
|
|
Term
| FELBAMATE (mechanism of action?) |
|
Definition
| Na+ channel and NMDA receptor (glycine site) antagonist properties |
|
|
Term
|
Definition
-Used only for refractory cases.
-Remains on market but with a black box warning for aplastic anemia and hepatic failure |
|
|
Term
|
Definition
| Broad spectrum drug used as adjunctive treatment for partial seizures and generalized tonic clonic seizures |
|
|
Term
| TOPIRAMATE (side effects?) |
|
Definition
-Somnolence
-Fatigue
-Dizziness
-Cognitive slowing
-Altered verbal fluency
-Decreased appetite |
|
|
Term
| TOPIRAMATE (mechanism of action?) |
|
Definition
-May block voltage-gated sodium channels
-Some glutamate receptor antagonist properties. |
|
|
Term
|
Definition
-No significant effects on other AEDs
-May help patients with migraine
-Teratogenic in animal models. |
|
|
Term
|
Definition
| Modest but significant adjunctive efficacy against partial and generalized tonic-clonic seizures (often brought in secondarily) |
|
|
Term
| TIAGABINE (side effects?) |
|
Definition
-Dizziness
-Tremor
-Difficulty concentrating
-Depression
-Asthenia
-Emotional lability
-Skin rash |
|
|
Term
| TIAGABINE(mechanism of action?) |
|
Definition
| GABA uptake inhibitor (GAT-1). |
|
|
Term
|
Definition
| Negligible effects on other AEDs |
|
|
Term
|
Definition
-Broad spectrun activity with efficacy against generalized as well as partial seizures.
-Effective as adjunctive against partial and myoclonic seizures |
|
|
Term
| ZONISAMIDE (side effects?) |
|
Definition
-Drowsiness
-Cognitive impairment
-Rash
-Weight loss
-Renal stones |
|
|
Term
| ZONISAMIDE (mechanism of action?) |
|
Definition
-Mechanism of action may involve voltage-gated sodium channels.
-May also involve T-type Ca2+ channels. |
|
|
Term
|
Definition
-Sulfonamide derivative.
-Minimal interactions with other AEDs |
|
|
Term
|
Definition
| Used as adjunctive therapy for partial seizures +/- secondary generalization |
|
|
Term
| GABAPENTIN (side effects?) |
|
Definition
-Somnolence.
-Dizziness.
-Ataxia.
-Weight gain
-Behavioral changes |
|
|
Term
| GABAPENTIN (mechanism of action?) |
|
Definition
| Binds with high affinity to α2δ subunits of calcium channel (HAS GABA IN THE NAME OF DRUG -> DEVELOPED AS PRO-DRUG BUT DOES THIS INSTEAD) |
|
|
Term
|
Definition
-Does not induce liver enzymes.
-No influence on plasma concentrations of other AEDS.
-Wide margin of safety but with modest efficacy.
-More than 80% of prescriptions are for off-label uses (eg. neuropathic pain, migraine, spasticity, bipolar disorder)
-An analog of GABA that does not act on GABA receptors. |
|
|
Term
| Levetiracetam (indication?) |
|
Definition
| Adjunctive treatment of adults with partial seizures |
|
|
Term
| Levetiracetam (side effects?) |
|
Definition
-Somnolence
-Asthenia
-Behavioral disturbances
-Headache |
|
|
Term
| Levetiracetam (mechanism of action?) |
|
Definition
| May target synaptic vesicle protein 2A (may prevent glutamate release); has high safety margin |
|
|
Term
| Levetiracetam(other info) |
|
Definition
-No interaction with other AEDs
-High safety margin compared with other AEDs |
|
|
Term
|
Definition
|
|
Term
| Pregabalin (mechanism of action?) |
|
Definition
| Specific ligand of the α2δ type 1 and 2 subunits of voltage-gated calcium ion channels, like GBP (HAS GABA IN THE NAME OF DRUG -> DEVELOPED AS PRO-DRUG BUT DOES THIS INSTEAD) |
|
|
Term
|
Definition
-Effective at treating chronic pain in disorders such as fibromyalgia and spinal cord injury
-Favorable adverse effects
-Good patient compliance -> good adjunctive therapy |
|
|
Term
|
Definition
| Approved as an adjunctive treatment of partial-onset seizures in patients > 18 years old |
|
|
Term
| Ezogabine (mechanism of action?) |
|
Definition
-Allosteric modulator of KCNQ2-5 K+ channels
(Increases open probability of KCNQ2-5 channels and shifts the voltage-dependent activation to more hyperpolarized potentials. This translates to an increased hyperpolarizing current). |
|
|
Term
|
Definition
| Known as retigabine in Europe |
|
|
Term
| DIAZEPAM AND LORAZEPAM (indication?) |
|
Definition
| 1° for treating status epilepticus |
|
|
Term
| DIAZEPAM AND LORAZEPAM (side effects?) |
|
Definition
-Sedation
-Children may manifest a paradoxical hyperactivity.
-Tolerance (for epilepsy use) |
|
|
Term
| DIAZEPAM AND LORAZEPAM (mechanism of action?) |
|
Definition
Allosteric modulators of GABA receptors.
(Potentiates GABA function, by increasing the frequency of channel opening) |
|
|
Term
| DIAZEPAM AND LORAZEPAM (other info) |
|
Definition
-Benzodiazepines.
-Given I.V.
-Lorazepam may be longer acting.
-Have muscle relaxant activity |
|
|
Term
| Treatment of Status Epilepticus in adults |
|
Definition
Initial
Diazepam, i.v. 5-10 mg (1-2 mg/min)
repeat dose (5-10 mg) every 20-30 min.
Lorazepam, i.v. 2-6 mg (1 mg/min)
repeat dose (2-6 mg) every 20-30 min.
Follow-up
Phenytoin, i.v. 15-20 mg/Kg (30-50 mg/min).
repeat dose (100-150 mg) every 30 min.
Phenobarbital, i.v. 10-20 mg/Kg (25-30mg/min).
repeat dose (120-240 mg) every 20 min. |
|
|
Term
| Broad Spectrum anti-epileptic drugs (AEDs) (reasonable initial choices in most adult patients regardless of type of seizure or syndrome) |
|
Definition
-valproate
-lamotrigine
-topiramate
-levetiracetam
-zonisamide |
|
|
Term
| Narrow Spectrum anti-epileptic drugs (AEDs) (restricted to patients who have focal epilepsy with partial and secondarily generalized seizures) |
|
Definition
-carbamazepine
-phenytoin
-gabapentin
-tiagabine
-oxcarbazepine
-pregabalin |
|
|
