Antiseizure Drugs Flashcards
1
Q
Myoclonic seizure
A
Single / multiple muscle spasms lasting only 1 sec
2
Q
What is best tx for status epilepticus?
A
IV lorazepam is best. IV diazepam also works. Both are benzos.
3
Q
General strategies to inhibit neuronal activity
A
- Inhibit Na, Ca, NMDA, AMPA / KA receptors
- Potentiate GABA receptors: positive modulation of GABA-A receptor. GABA uptake inhibitors, GABA transaminase inhibitor.
4
Q
Time course of seizure meds
A
Once initiated, antiseizure tx is usually continued for at least 2 years, w/ tapering / discontinuing if seizure-free after 2 years. 80% of recurrences occur w/in 4 months of discontinuing therapy
5
Q
What do all anti seizure meds have in common?
A
ALL antiseizure meds have black box warning for increased risk of suicidal ideation.
6
Q
Barbiturates Mechanism 2 main drugs Adverse rxns 3 main differences from benzos
A
- Mechanism – increase the duration of GABA-induced Cl channel openings and directly activate GABA-A receptor at high concentrations. Also depress actions of glutamate by binding to AMPA receptor
- 2 main drugs:
- Phenobarbital – 1st ever antiseizure drug. Still used.
- Thiopental – IV drug used for anesthesia, not seizures. Very short half-life.
- Adverse Rxns
- Only CV effect is slight drop in BP
- Additive CNS depression w/ alcohol and other sedatives / hypnotics. Depress respiratory drive / rhythm.
- Depress REM sleep (not restorative).
- Avoid sudden DC → insomnia, anxiety, seizures
- Residual effects – Mood distortions, impaired motor skills, poor judgment
- Paradoxical excitement in kids and elderly
- May worsen pain perception
- Allergic skin rxn, especially in pxs w/ asthma, urticaria, and angioedema
- CYP inducers → tolerance / drug interactions
- Pregnancy risk D
- Blood dyscrasias such as megaloblastic anemia / thrombocytopenia. Do regular blood tests.
- 3 main differences from benzos: benzos do NOT produce anesthesia, depress respiratory drive, or induce CYPs
7
Q
Phenobarbital Notable characteristic Use Mechanism Adverse rxns
A
- Oldest and longest-acting barbiturate
- Use – effective in all seizures except absence seizures.
- Mechanism – Increases duration of GABA-induced Cl channel opening at GABA-A receptors. Inhibits spread of seizure activity and increases threshold for stimulation of motor cortex.
- Adverse rxns
- CNS – drowsiness, lethargy, depression
- PULM: respiratory depression, bronchospasm
- DERM: rash, serious hypersensitivity rxns
8
Q
Phenytoin Type of drug Use Mechanism Pharmacokinetics Adverse rxns
A
- Oldest nonsedative antiseizure drug
- Use – prophylaxis of partial seizures and generalized tonic-clonic seizures.
- Mechanism – Preferential binding to inactivated state of V-gated Na channels (use-dependent block) inhibits sustained repetitive neuronal firing. Also decreases glutamate release and increases GABA release via actions at T-type Ca and K channels. No effect on seizure threshold.
- Metabolic capacity can be saturated; becomes zero order
- Adverse rxns
- CNS – lethargy, dizziness, nystagmus, ataxia
- GINGIVAL HYPERPLASIA / HIRSUTISM
- Dermatose
9
Q
Carbamazepine
Use
Mechanism
Adverse rxns
A
- Use – Partial seizures and tonic-clonic seizures. Preferred over Phenobarbital in kids. Tx trigeminal neuralgia and post-herpetic pain. Tx manic phase of bipolar and prevents manic relapse.
- Mechanism – use-dependent block of V-gated Na channels. GABA-A allosteric modulator (increases amount of Cl flux)
- Adverse rxns
- CNS: dizziness, drowsiness, ataxia
- CV: AV block, arrhythmias, HF, edema, syncope
- HEME: bone marrow depression, blood dyscrasias
- GI: hepatitis, ↑ LFTs
- DERM: rash, urticaria, exfoliative dermatitis, Stevens-Johnson syndrome; linked to a variant HLA-B gene found in ASIAN populations (screen for this gene in Asian pxs before starting tx)
10
Q
Valproic Acid
Use
Mechanism
Adverse rxns
A
- Use – effective for ALL seizures. Tx acute mania, bipolar, and migraine prophylaxis.
- Mechanism – 1) prolongs Na channel inactivation, 2) inhibits T-type Ca channels in thalamic relay neurons, 3) increases GABA by stimulating glutamate decarboxylase, 4) inhibits GABA-T and SSA-DH, which break down GABA
- Adverse rxns
- CNS: drowsiness, tremor, dizziness, nervousness
- GI: NVD, GI pain; taking the drug with food may minimize GI effects; ↑ LFTs; pancreatitis (rare but potentially fatal)
- HEME: thrombocytopenia or abnormal coagulation parameters, hyperammonemia
- DERM: alopecia, rash, pruritus
11
Q
Ethosuximide
Use
Mechanism
Adverse rxns
A
- Use – DOC for absence seizures. Does not work for complex partial / tonic-clonic seizures. Oral.
- Mechanism – Blocks T-type Ca channels in thalamic relay neurons to suppress paroxysmal 3 Hz bursts in absence seizures. Bursts regulated by GABAergic neurons.
- Adverse rxns
- CNS: drowsiness, headache, dizziness, euphoria, irritability, restlessness, anorexia
- GI: NVD, GI pain, epigastric distress (e.g., dyspepsia, hiccups); ↑ LFTs
- HEME: blood dyscrasias e.g. leukopenia, eosinophilia, agranulocytosis, aplastic anemia
- DERM: rash, pruritus, urticaria
12
Q
Gabapentin Brand Name Use Mechanism Adverse rxns
A
- Neurontin
- Use – Adjunctive therapy for partial seizures. Tx painful neuropathies (postherpetic neuralgia).
- Mechanism – GABA analog inhibits presynaptic N-type Ca channel → decreased release of glutamate. Does NOT bind to GABA receptors, but increase brain GABA concentration.
- Adverse rxns – usually mild and resolve w/in 2 weeks of onset
13
Q
Pregabalin
Use
Mechanism
Adverse rxns
A
- Use – Adjuntive therapy for partial seizures. Neurogenic pain such as diabetic peripheral neuropathy, postherpetic pain, or fibromyalgia
- Mechanism – GABA analong inhibits N-type Ca channel → decreases glutamate release. Does NOT bind to GABA receptors or increase brain GABA concentration.
- Adverse rxns – usually mild and resolve w/in 2 weeks of onset
14
Q
Lamotrigine Use Not used for? Mechanism Adverse rxns
A
- Use – Monotherapy or adjunctive therapy for partial seizures w/ or w/o generalized tonic-clonic seizures. Lennox –Gastaut syndrome in kids. Depressive / maintenance phase for bipolar.
- Lamotrigine is not effective long-term for absence seizures. Ethosuximide and valproic acid are better.
- Mechanism – Delays recovery from inactivation of Na channels, inhibits Ca channels, and decreases release of glutamate.
- Adverse rxns
- CNS: dizziness, diplopia, ataxia, headache
- GI: NVD
- DERM: rash, Stevens-Johnson
15
Q
Topiramate
Use
Mechanism
Adverse rxns
A
- Use – Mono / adjunctive therapy for partial or generalized tonic-clonic seizures, Lenox-Gastaut syndrome, and migraine prophylaxis
- Mechanism – Reduces V-gated Na currents, activates hyperpolarizing K current, enhances post-synaptic GABA-A receptor current, limits activation of AMPA glutamate receptors, and inhibits carbonic anhydrase.
- Adverse rxns – well tolerated
