Antiepileptic Drugs Flashcards
Drugs for Partial and Generalized Tonic-Clonic Seizures
Carbamazepine Oxacarbazepine Eslicarbazepine Phenytoin Fosphenytoin Phenobarbital Primidone Valproate
Carbamazepine, Oxacarbazepine and Eslicarbazepine - MoA
Block voltage sensitive Na+ channels in neuronal cell membrane and inhibits the spread of abnormal electrical discharges from the seizure focus to other neurons by preventing the release of excitatory neurotransmitter from nerve terminals
Also blocks adenosine receptors in a way that leads to up-regulation of these receptors, and it blocks norepinephrine reuptake in the same way that tricyclic antidepressants block is.
Carbamazepine - Clinical use
Partial seizures
Generalized tonic-clonic seizure
Trigeminal neuralgia
Bipolar disease (alternative to lithium)
Carbamazepine - Adverse effects
Drowziness Ataxia GI reactions (Nausea) Aplastic Anemia (Rare) Litium toxicity Hyponatremia Cognitive impairment
Carbamazepine - Interactions
Induce cytochrome P450 enzymes and accelerates metabolism of lamotrigine, phenytoin, topiramate and valproate.
Increase lithium toxicity
Oxacarbazepine - Clinical use
Trigeminal neuralgia
Eslicarbazepine - Clinical use
Partial-onset seizures as a sole agent (monotherapy) or as an adjunct to other AEDs
Phenytoin - MoA
Block voltage sensitive Na+ channels, by prolonging the inactivation state of the channel. Enables it to inhibit the repetitive firing of neurons in seizures.
Phenytoin - Clinical use
Partial seizure
Generalized tonic-clonic seizures
Phenytoin - Adverse effects
Interferes with folate metabolism and can lead to Megaloblastic anemia and fetal hydantoin syndrome (Cardiac defects, malformation of ears, lips, palate, mouth, and nasal bridge, mental retardation and microcephaly)
By impairing cerebellar function, phenytoin can cause ataxia, diplopia, nystagmus, and slurred speech.
By interfering with vitamin D metabolism and decreasing calcium absorption from the gut, phenytoin sometimes causes osteomalacia
Gingival hyperplasia (effects collagen metabolism)
Hirsutism
Steven-Johnsons symdrome
Toxic epidermal necrosis
Hypoprothrombinema and bleeding (give vitamin K supplements when using this drug)
Phenytoin - Interactions
Induce cytochrome P450 enzymes and accelerates the metabolism of other antiepileptic agents including felbamate, lamotrigine, topiramate, and valproate
It can also reduce levels of digoxin, steroids, vitamin K
Phenytoin - Contraindications
Bradycardia Hypersensitivity Severe AV block Sinoatrial dysfunction Children because of adverse effects
Category D pregnancy; may reduce folate levels, two to three times increased risk of birth defects, fetal hydatoin syndrome
Phenobarbital - MoA
Enhances GABA-mediated chloride flux that causes membrane hyperpolarization.
Phenobarbital - Clinical use
Partial seizures
Generalized tonic-clonic seizures
Phenobarbital - Adverse effects
Ataxia Dizziness Drowsiness Cognitive impairment Respiratory depression Hypersensitivity (most frequently manifests as rash)
Phenobarbital - Contraindications
Hypersensitivity
Porphyria
Respiratory depression
Severe liver disease
Category D pregnancy; bleeding at birth, minor congenital defects
Primidone - MoA
Block sodium channels and preventing membrane depolarization. It can also potentiate GABA via formation of phenobarbital
Primidone - Clinical use
Partial seizures
Generalized tonic-clonic seizures
Essential tremor with propranolol
Primidone - Adverse effects
Ataxia Dizziness Drowsiness Cognitive impairment Respiratory depression Hypersensitivity (most frequently manifests as rash)
Primidone - Contraindications
Hypersensitivity
Category D Pregnancy
Valproate - MoA
Inhibit voltage sensitive sodium channels and T-type calcium channels; increase GABA synthesis and decreases GABA degradation; and it may decrease glutamate synthesis. By these actions, valproate inhibits the repetitive firing of neurons and the spread of epileptic seizures.
Valproate - Clinical use
Broadest spectrum Partial seizures All forms of generalized seizures Manic phase of bipolar (alternative to lithium) Migraine prophylaxis
Valproate - Adverse effects
Mild hepatotoxicity Fetal hepatotoxicity (Rare) Spina bifida Weight gain Impaired cognitive development Nausea GI complaints
Valproate - Interactions
Inhibits cytochrome P450 enzymes, increases levels of lamotrigine, phenobarbital, and primidone
Adjunct Drugs for Partial Seizures
Clorazepate Felbamate Gabapentin Lamotrigine Topiramate Perampanel Tiagabine Levetiracetam Brivaracetam Zonisamide Pregabalin Vigabatrin Lacosamide Ezogabine Rufinamide Clobazam
Clorazepate - MoA
Prodrug, converted to diazepam
Clorazepate - Clinical use
Anxiety disorders
Partial seizures
Clorazepate - Adverse effects
Drowsiness
Lethargy
Clorazepate - Contraindications
Hypersensitivity
Category D pregnancy; increased risk of birth defects
Felbamate - MoA
Block glycine coactivation of NMDA receptors and thereby inhibit processes responsible for the initiation of seizures
Felbamate - Clinical use
Partial seizures that are refractory to other drugs
Felbamate - Adverse effects
Fatal aplastic anemia
Acute hepatic failure
Felbamate - Contraindications
Bone marrow depression
Hepatic disease
Hypersensitivity
Category C pregnancy
Gabapentin and Pregabalin - MoA
Increase the release of GABA from central neurons
Also inhibits the L-type Calcium channel like pregabalin.
bind to the α2δ subunit of voltage-gated Ca2+ channels.
Gabapentin - Clinical use
All forms of partial seizures
Postherpetic neuralgia
Restless leg syndrome
Gabapentin - Adverse effects
Ataxia Dizziness Drowsiness Nystagmus Tremor
Lamotrigine - MoA
Block voltage-sensitive sodium channels and interfere with neuronal membrane conduction, and release of excitatory neurotransmitters such as glutamate.
Lamotrigine - Clinical use
Partial seizure in adult and children
Generalized tonic-clonic, atonic and absence seizures
Lennox-Gastaut syndrome
Manic phase of bipolar disorder
Lamotrigine - Adverse effects
Aseptic meningitis
Rash –> Stevens-Johnson syndrome
Cerebellar dysfunction
Drowsiness
Lamotrigine - Interactions
Serum levels are decreased by carbamazepine and phenytoin and increased by valproate
Lamotrigine - Contraindications
Hypersensitivity
Use cautiously in patient taking valproate or have hepatic or liver disease
Category C pregnancy; may reduce folate levels
Topiramate - MoA
Block voltage-sensitive sodium channels, augumentation of GABA activation of GABAa receptors, and blockade of two types of excitatory glutamate receptors, kainate receptors and AMPA receptors (3-hydroxy-5-methyl-4-isoxazole proprionate acid)
Topiramate - Clinical use
Partial seizures
Topiramate - Adverse effects
Cleft palate
Ataxia
Dizziness
Drowsiness
Topiramate - Contraindications
Hypersensitivity
Use cautiously during pregnancy, lactation, or hepatic and renal disease
Category D pregnancy; recent date showed increased incidence of cleft palate
Perampanel - MoA
Noncompetitive antagonist of the ionotropic AMPA glutamate receptor on postsynaptic neurons.
Perampanel - Clinical use
Partial seizure
Primary generalized tonic-clonic seizures in patients 12 years of age or older
Tiagabine - MoA
Blocks GABA reuptake by binding to GABA reuptake transport protein
Levetiracetam - MoA
Binds to a synaptic vesicle protein (SV2A), reducing vesicular packaging of GABA and impending neurotransmission across synapses
Levetiracetam - Clinical use
Partial seizure in children
Levetiracetam - Adverse effects
Somnolence
Asthenia (weakness)
Infection
Dizziness
Brivaracetam - MoA
High and selective affinity for SV2A
Brivaracetam - Clinical use
Partial seizures
Zonisamide - MoA
Act at sodium channels and voltage-dependent transient inward currents of calcium channels. Blocks sodium channels in the inactivated state and reduces the ion flow in calcium channel proteins
Zonisamide - Clinical use
Partial seizures
Zonisamide - Adverse effects
Metabolic acidosis
Pregabalin - Clinical use
Seizures
Neuropathic pain associated with diabetes
Posthepatic neuralgia
Fibromyalgia
Neuropathic pain after spinal cord injury
Vigabatrin - MoA
Irreversible inhibition of GABA transaminase, the enzyme responsible for the breakdown of GABA in the brain. The inhibition of GABA-T enzyme leads to increase levels of the inhibitory neurotransmitter GABA
Vigabatrin - Clinical use
Partial seizures
Vigabatrin - Adverse effects
Amnesia Blurred vision Blue-yellow color blindness Decreased vision Eye pains Increase in seizures (rare)
Lacosamide - MoA
Enhances inactivation of voltage-gates sodium channels, resulting in stabilization of hyperexcitable neuronal membranes and inhibition of repetitive neuronal firing.
Ezogabine - MoA
Increase potassium ion flow, hyperpolarizes neurons and decrease their firing potential, enhance GABA mediated chloride ion currents
Rufinamide - MoA
Modulate activity of sodium channels, prolong the inactive state of the channel
Rufinamide - Clinical use
Seizures in children and adults with LGS
Clobazam - MoA
Increases the inhibition by GABA at GABAa receptors
Clobazam - Clinical use
Seizures in children and adults with LGS
Drugs for Generalized Absence, Myoclonic, or Atonic Seizures
Ethosuximide
Clonazepam
Ethosuximide - MoA
Inhibit T-type calcium channels in thalamic neurons
Ethosuximide - Clinical use
Generalized absence seizures in children
Ethosuximide - Adverse effects
Dizziness
Drowsiness
GI distress
Nausea
Ethosuximide - Interactions
Valproate inhibits metabolism and increases levels
Clonazepam - Clinical use
Absence, myoclonic and atonic seizures.
Drugs for Status Epilepticus
Diazepam
Lorazepam
Phenytoin
Phenobarbital
Drugs of choice for status epilepticus
Diazepam and Lorazepam
Drug to use after diazepam or lorazepam has been administered for status epilepticus
Phenytoin
Drug that may be effective if a benzodiazepine or phenytoin fails to control the seizures in status epilepticus
Phenobarbital
