Term
Focal (Partial) and Generalized
Tonic-Clonic Seizure Drugs |
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Definition
• Phenytoin (Dilanatin)
• Carbamazepine (Tegretol)
• Oxcarbazepine (Trileptal)
• Phenobarbital (Luminal)
• Primidone (Mysoline)
• Valproic Acid (Depakene) |
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Term
Generalized Absence,
Myoclonic, or Atonic Seizures Drugs |
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Definition
• Ethosuximide (Zarontin)
• Valproic acid (Depakene)
• Clonazepam (Klonopin)
• Lamotrigine (Lamictal) |
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Term
| Adjunct for Focal ( Partial) |
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Definition
• Gabapentin (Neurontin)
• Clorazepate (Tranxene)
• Lamotrigine (Lamictal)
• Felbamate (Felbatol)
• Tiagabine (Gabitril)
• Levetiracetam (Keppra)
• Zonisamide (Zonegran)
• Pregabalin (Lyrica)
• Vigabatrin (Sabril) |
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Term
| Drugs that inhibit Na+ Channel-Mediated Inhibition |
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Definition
• AEDs phenytoin, carbamazepine, lamotrigine, lacosamide, and Valproic acid act directly on NA+ channels to increase inactivation
• Drugs that act on Na+ channels show strong specificity for treatment of focal and secondary generalized seizures
• Na+ channel blockers act in a use dependent manner:
- overactive (open/close at high frequency) channels get hit first
- low-activity channels are spared
• Other Na+ channel blockers (i.e. phenytoin) have little effect on absence seizures |
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Term
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Definition
Diphenyl-substituted hydantoin
- Much lower sedative properties than compounds with alkyl substituents in position 5
Mechanism of action
- Block high-frequency firing of neurons through action on voltage-gated Na+ channels
- ↓ synaptic release of glutamate
Clinical Applications
Focal and secondary generalized (tonic-clonic) seizures, status epilepticus, non-epileptic seizures
Seizures related to eclampsia (in pregnant women), neuralgia (change in neurological structure)
Ventricular arrhythmias unresponsive to lidocaine
Arrhythmias induced by cardiac glycosides
Adverse Effects
Agranulocytosis, leukopenia, pancytopenia (↓ of red/white cells and platelets), thrombocytopenia, megaloblastic anemia, hepatitis, Steven Johnson syndrome (toxic epidermal necrolysis), ataxia, nystagmus, incoordination, confusion, hirsutism, facial coarsening, gingival hyperplasia
Contraindicated
Sinus bradycardia, SA node block, 2nd and 3rd degree AV block, Stokes-Adam syndrome, Hydantoin hypersensitivity
Drug interaction
Interacts with a number of drugs, induces P450 enzymes, 95% bound to plasma albumin. Metabolism shows properties of saturation kinetics. Interacts with: Phenobarbital, Carbamazepine, Isoniazid, Felbamate, Oxcarbazepine, Topiramate, Fluoxetine, Fluconazole, Digoxin, Quinidine, Cyclosporine, Steroids, Oral Contraceptives, Others
Pharmacokinetics
Absorption is formulation-dependent, highly bound to plasma proteins, no active metabolites, dose-dependent elimination, t1/2 12–36 h, Fosphenytoin is for IV, IM routes |
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Term
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Definition
More soluble prodrug
- Available for parenteral use
- This phosphate ester compound is rapidly converted to Phenytoin in the plasma
Mechanism of action
- Block high-frequency firing of neurons through action on voltage-gated Na+ channels
- ↓ synaptic release of glutamate
Clinical Applications
Focal and secondary generalized (tonic-clonic) seizures, status epilepticus, non-epileptic seizures
Seizures related to eclampsia (in pregnant women), neuralgia (change in neurological structure)
Ventricular arrhythmias unresponsive to lidocaine
Arrhythmias induced by cardiac glycosides
Adverse Effects
Agranulocytosis, leukopenia, pancytopenia (↓ of red/white cells and platelets), thrombocytopenia, megaloblastic anemia, hepatitis, Steven Johnson syndrome (toxic epidermal necrolysis), ataxia, nystagmus, incoordination, confusion, hirsutism, facial coarsening, gingival hyperplasia
Contraindicated
Sinus bradycardia, SA node block, 2nd and 3rd degree AV block, Stokes-Adam syndrome, Hydantoin hypersensitivity
Drug interaction
Interacts with a number of drugs, induces P450 enzymes, 95% bound to plasma albumin. Metabolism shows properties of saturation kinetics. Interacts with: Phenobarbital, Carbamazepine, Isoniazid, Felbamate, Oxcarbazepine, Topiramate, Fluoxetine, Fluconazole, Digoxin, Quinidine, Cyclosporine, Steroids, Oral Contraceptives, Others
Pharmacokinetics
Absorption is formulation-dependent, highly bound to plasma proteins, no active metabolites, dose-dependent elimination, t1/2 12–36 h, Fosphenytoin is for IV, IM routes |
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Term
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Definition
Oral (prompt release): 100 mg capsules; 50 mg chewable tablets; 125 mg/5 mL suspension
Oral extended action: 30, 100 mg capsules
Oral slow release (Phenytek): 200, 300 mg capsules
Parenteral: 50 mg/mL for IV injection |
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Term
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Definition
Fosphenytoin (Cerebyx)
Parenteral: 75 mg/mL for IV or IM injection |
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Term
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Definition
- Tricyclic compound
- Effective also in bipolar depression
- Initially marketed for trigeminal neuralgia
- Many similarities to Phenytoin (better observed in 3D structures):
The ureide moiety (–N–CO–NH2) in the heterocyclic ring of most antiseizure drugs is also present in carbamazepine
Mechanism of action
- Similar to Phenytoin
- Blocks directly Na+ channels and stabilizes their inactivated state, reducing number of available channels and excitability levels, by inhibiting high-frequency repetitive firing
- Shows activity against maximal electroshock seizures (MES)
- Potentiates voltage-gated K+ currents
Clinical Applications
Focal and Tonic-clonic seizures
Bipolar disorder
Trigeminal neuralgia (intense facial pain)
Adverse Effects
Aplastic anemia, agranulocytosis, leukopenia, thrombocytopenia, atrioventricular block, arrhythmias, Steven Johnson syndrome (toxic epidermal necrolysis), hyponatremia, hypocalcemia, hepatitis, nephrotoxicity, nystagmus, incoordination, confusion, rash, blurred vision, syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH), porphyria
Contraindicated
Concomitant use of MAO (monoamino oxidase) inhibitors, history of bone marrow depression, prescreen for HLA-B*1502 in patients of Asian decent to avoid risk of Steven Johnson syndrome
Pharmacokinetics
- Rate of absorption varies widely
- Peak levels at 6–8 h
- Administration after meals ↓ absorption and ↑ toleration of larger doses
- Slow distribution, with a volume of distribution ̴ 1 L/Kg
- 70% bound to plasma proteins
- No displacement of other drugs from protein binding sites
- Half-life of 36 h after an initial single dose, then 8–12 h in chronic administration
- Needs dosage adjustments within the 1st week
Interactions
- The increased metabolic capacity of hepatic enzymes ↓ in steady-state Carbamazepine concentrations ↑ metabolism rate of Primidone, Phenytoin, Ethosuximide, Valproic Acid, and Clonazepam
- Valproic Acid may inhibit Carbamazepine clearance and ↑ steady-state carbamazepine blood levels
- Phenytoin and Phenobarbital ↓ steady-state concentrations of Carbamazepine through enzyme induction |
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Term
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Definition
Carbamazepine (generic, Tegretol)
Oral: 200 mg tablets; 100 mg chewable tablets; 100 mg/5 mL suspension
Oral extended-release: 100, 200, 400 mg tablets; 200, 300 mg capsules |
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Term
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Definition
Closely related to Carbamazepine
Active against same seizure types
Improved toxicity profile fewer hypersensitivity reactions
Activity almost exclusively in 10-hydroxy metabolite (especially the S(+) enantiomer, Eslicarbazepine)
Less potent than Carbamazepine need to be 50% higher to obtain equivalent seizure control
Mechanism of action
Blocks directly Na+ channels and stabilizes their inactivated state, reducing number of available channels and excitability levels, by inhibiting high-frequency repetitive firing
Interactions
Induces hepatic enzymes to a lesser extent than Carbamazepine, minimizing drug interactions
Adverse effects
Hyponatremia
see Carbamazepine
Pharmacokinetics
S(+) enantiomer (Eslicarbazepine) is the active metabolite
Half-life of only 1-2 h
Mostly excreted as the glucuronide of the 10-hydroxy metabolite (Eslicarbazepine |
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Term
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Definition
Mechanism of Action
- Similar to Phenytoin
- Suppresses sustained rapid firing and produces a voltage- and use-dependent blockade of Na+ channels
- Inhibits voltage-gated Ca2+ channels, notably N- and P/Q-type channels (efficacy in primary generalized seizures in childhood, including absence attacks)
- ↓ synaptic release of glutamate
Clinical Applications
monotherapy for partial seizures
absence and myoclonic seizures in children
seizure control in Lennox-Gastaut syndrome
bipolar disorder
Adverse Effects
Dizziness, headache, diplopia, nausea, somnolence, skin rash, dermatitis
Contraindications
Hypersensitivity reaction (pediatric patients at greatest risk)
Pharmacokinetics
Almost completely absorbed, with a volume of distribution of ̴ 1.2 L/Kg
Protein binding is low, ̴ 55%
Linear kinetics
Metabolized primarily by glucuronidation to the 2-N-glucuronide, excreted in urines
Half-life of ̴ 24 h in normal patients, ̴ 13–15 h in patients taking enzyme-inducing drugs
Interactions
- Twofold increase in half-life if using Valproate (initial dosage of Lamotrigine must be reduced to 25 mg every other day) |
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Term
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Definition
generic, Lamictal)
Oral: 25, 100, 150, 200 mg tablets; 2, 5, 25 mg chewable tablets |
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Term
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Definition
Introduced in 1960 as the 3rd of 3 marketed succinimides in USA, after Phensuximide and Methsuximide
- Very little activity against maximal electroshock (MES)
- Effective against pentylenetetrazol seizures
- Methsuximide and Phensuximide have phenyl substituents
- Ethosuximide is 2-ethyl-2-methylsuccinimide
Mechanism of action
- Effect observed in thalamic neurons T-type Ca2+ currents provide pacemaker currents in thalamic neurons responsible for generating the rhythmic cortical discharge of an absence attack
- Ethosuximide inhibits low threshold T-type Ca2+ channels, reducing low-threshold currents
- Effect on inwardly rectifying K+ channels (recently described)
Clinical Applications
Absence seizures (narrow spectrum of clinical activity)
Adverse Effects
Steven-Johnson syndrome, bone marrow suppression, systemic lupus erythematosus, seizures, GI irritation, ataxia, somnolence
Pharmacokinetics
- Complete absorption
- Peak levels at 3–7 h
- Not protein-bound completely metabolized, mainly by hydroxylation, to inactive metabolites
Very low total body clearance (0.25 L/Kg/d) half-life ̴ 40 h |
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Term
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Definition
Ethosuximide (generic, Zarontin)
Oral: 250 mg capsules; 250 mg/5 mL syrup |
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Term
| Diazepam, Lorazepam & Clonazepam (Benzo's) |
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Definition
Fusion of benzene ring and diazepine ring
First benzodiazepine, Chlordiazepoxide (Librium) discovered accidentally in 1955
On market in 1960 by Hoffmann–La Roche
Diazepam (Valium) available by Hoffman-La Roche since 1963
Effect of neurotransmitter gamma-aminobutyric acid (GABA-A)
Anticonvulsant…
…but also sedative, hypnotic, anxiolytic, and muscle relaxant
Classified as short-, intermediate- or long-acting
Usually short- and intermediate-acting insomnia
Mechanism of action
Potentiate GABAA responses
Once bound to BZD receptor, ligand locks BZD receptor into conformation with high affinity for GABA neurotransmitter ↑ frequency of opening of associated chloride ion channel and hyperpolarizes the membrane of associated neurons.
Inhibitory effect of available GABA is potentiated sedative and anxiolytic effects
Affinities can vary according to benzodiazepines
Diazepam
i.v. or rectally (gel) is highly effective against seizures (especially generalized tonic-clonic status epilepticus)
Occasionally given orally (as long-term treatment) rapid development of tolerance
Lorazepam
More effective and longer acting than Diazepam for status epilepticus
Clonazepam
Long-acting and highly efficient against absence and myoclonic seizures
One of most potent antiseizure agents
Sedation is prominent, especially on initiation of therapy; starting doses should be small |
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Term
| Diazepam, Lorazepam & Clonazepam (Benzo's) Dose Form |
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Definition
Diazepam (generic, Valium, others)
Oral: 2, 5, 10 mg tablets; 5 mg/5 mL, 5 mg/mL solutions
Parenteral: 5 mg/mL for IV injection
Rectal: 2.5, 5, 10, 15, 20 mg viscous rectal solution
Lorazepam (generic, Ativan)
Oral: 0.5, 1, 2 mg tablets; 2 mg/mL solution
Parenteral: 2, 4 mg/mL for IV or IM injection
Clonazepam (generic, Klonopin)
Oral: 0.5, 1, 2 mg tablets |
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Term
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Definition
Mechanism of Action
Inhibits irreversibly GABA aminotransferase (GABA-T), enzyme responsible for degradation of GABA
Inhibits vesicular GABA transporter
Produces a sustained ↑ of extracellular concentration of GABA
desensitization of synaptic GABAA receptors
prolonged activation of nonsynaptic GABAA receptors tonic inhibition
↓ in brain glutamine synthetase activity
Effective in a wide range of seizure models
Marketed as a racemate
S(+) enantiomer is active
R(–) enantiomer is inactive
Clinical Uses
Partial seizures
Infantile spasms
Pharmacokinetics
Half-life is ̴ 6–8 h
Pharmacodynamic activity more prolonged and not correlated with plasma half-life
Typical toxicities:
Drowsiness
Dizziness
Weight gain
Less common toxicities:
Agitation
Confusion
Psychosis
Adverse effects
Intramyelinic edema in infants, peripheral visual field defects in 30–50% of patients (long-term) due to irreversible retina damages
Contraindications
Preexisting mental illness |
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Term
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Definition
Vigabatrin (Sabril)
Oral: 500 mg tablets; 500 mg powder for solution
Note: In infants, dosage is 50–150 mg/day
In adults, it starts at 500 mg twice daily; a total of 2–3 g daily may be required for full effectiveness |
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Term
| Valproic Acid & Sodium Valproate |
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Definition
- Marketed in France in 1969
- Licensed in USA in 1978
- Fatty carboxylic acids with antiseizure activity
- Fully ionized at body pH
- Antiseizure activity greatest for carbon chain lengths of 5 to 8 atoms
- Amides and esters of valproic acid are also active antiseizure agents
Mechanism of action
- Similar to Phenytoin and Carbamazepine
- Inhibits low threshold T-type calcium channels blocks sustained high-frequency repetitive firing
Clinical Applications
Absence seizures
Tonic-clonic seizures
Atypical absence seizures
Focal seizures
Adverse Effects
Hepatotoxicity, pancreatitis, thrombocytopenia, hyperammonemia, GI irritation, weight gain, ataxia, sedation, tremor
Contraindications
Liver disease, urea cycle disorders
Pharmacokinetics
- Well absorbed after oral dose (bioavailability > 80%)
- Peak blood levels in 2 h
- Food delays absorption and ↓ toxicity
- 90% bound to plasma proteins
- Highly ionized and highly protein-bound distribution confined to extracellular water, with a volume of distribution ̴ 0.15 L/Kg
- Clearance for valproate is low half-life = 9 to 18 h |
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Term
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Definition
Valproic acid (generic, Depakene)
Oral: 250 mg capsules; 250 mg/5 mL syrup (sodium valproate)
Oral sustained-release (Depakote): 125, 250, 500 mg tablets (as divalproex sodium)
Parenteral (Depacon): 100 mg/mL in 5 mL vial for IV injection |
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Term
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Definition
Amino acid
- Analog of GABA
- Effective against partial seizures
- Originally a spasmolytic, found more effective as AED
Mechanism of action
- inhibits high voltage T-type Ca2+ channels
- Gabapentin and Pregabalin do NOT act directly on GABA receptors
- They affect synaptic or nonsynaptic release of GABA (GABA concentration ↑ when administering Gabapentin).
- Gabapentin is transported into the brain by the L-amino acid transporter
- Gabapentin and Pregabalin bind to α2δ subunit of voltage-gated Ca2+ channels decreasing Ca2+ entry
- Antiepileptic effect due to ↓ in synaptic release of glutamate
Clinical Applications
Focal seizures
Diabetic neuropathy
Prophylaxis for migraine
Adverse Effects
Steven-Johnson syndrome, sedation, dizziness, fatigue, GI irritation, ataxia
Pharmacokinetics - Gabapentin
- NOT metabolized and does NOT induce hepatic enzymes
- Absorption is nonlinear and dose-dependent at high doses
- Elimination kinetics are linear
- NOT bound to plasma proteins
- Drug-drug interactions are negligible
- Elimination via renal mechanisms excreted unmodified
- Half-life is short: 5 to 8 h administration 2-3 times/day |
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Term
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Definition
GABA analog (related to gabapentin) - Antiseizure and analgesic
Mechanism of action
- inhibits high voltage T-type Ca2+ channels
- Gabapentin and Pregabalin do NOT act directly on GABA receptors
- They affect synaptic or nonsynaptic release of GABA (GABA concentration ↑ when administering Gabapentin).
- Gabapentin is transported into the brain by the L-amino acid transporter
- Gabapentin and Pregabalin bind to α2δ subunit of voltage-gated Ca2+ channels decreasing Ca2+ entry
- Antiepileptic effect due to ↓ in synaptic release of glutamate
Clinical Applications
Focal seizures
Diabetic neuropathy
Prophylaxis for migraine
Adverse Effects
Steven-Johnson syndrome, sedation, dizziness, fatigue, GI irritation, ataxia
Pharmacokinetics - Pregabalin
- NOT metabolized
- Excreted unchanged in urines
- NOT bound to plasma proteins
- Virtually no drug-drug interactions
- Half-life is short: 4.5 to 7 h more than one administration/day |
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Term
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Definition
Gabapentin (Neurontin)
Oral: 100, 300, 400 mg capsules; 600, 800 mg film tabs; 50 mg/mL solution |
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Term
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Definition
Pregabalin (Lyrica)
Oral: 25, 50, 75, 100, 150, 200, 300 mg capsules |
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Term
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Definition
Triazole derivative with little similarity to other AEDs
Mechanism of Action
Protective in maximal electroshock and pentylenetetrazol tests in rats and mice
↓ sustained high-frequency firing in vitro
↑ inactive state of Na+ channels
No significant interactions with GABA systems or metabotropic glutamate receptors
Clinical Uses
Approved in USA for adjunctive treatment of seizures associated with the Lennox-Gastaut syndrome in patients age > 4 ys
Effective against all seizure types for Lennox-Gastaut, specifically against tonic-atonic seizures
Recent data effective against partial seizures
Adverse effects
Somnolence
Vomiting
Pyrexia
Diarrhea
Pharmacokinetics
Well absorbed, but plasma concentrations peak range 4 - 6 h
Half-life is 6–10 h
Minimal plasma protein binding
Extensively metabolized to inactive products
Most is excreted in urines
Drug Interactions
In one study no significant interactions with Topiramate, Lamotrigine, or Valproic Acid (used for the Lennox-Gastaut syndrome)
Conflicting data robust interactions with other AEDs, especially in children |
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Term
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Definition
Rufinamide (Banzel)
Oral: 200, 400 mg tablets
Note: - Treatment in children starts at 10 mg/Kg/day in 2 equally divided doses - Gradually ↑ to 45 mg/Kg/day or 3200 mg/day (whichever is lower)
- Adults begin with 400–800 mg/day in 2 equally divided doses
- Maximum of 3200 mg/day (as tolerated)
- Administered The drug should be given with food |
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Term
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Definition
- Approved and marketed in USA and in some European countries
- Effective in some patients with partial seizures
- Severe side effects classified as 3rd line drug for refractory cases
- Effective against seizures in Lennox-Gastaut syndrome
Mechanism of action
inhibits glycine binding site of NMDA receptor-ionphore complex causing suppression of seizure activity
It produces a use-dependent block of the NMDA receptor, with selectivity for the NR1-2B subtype. It also produces a barbiturate-like potentiation of GABAA receptor responses.
Clinical Applications
Refractory epilepsy
Focal seizures
Tonic-clonic seizures
Adverse Effects
Aplastic anemia, bone marrow suppression, Steven Johnson syndrome photosensitivity, GI irritation, abnormal gait, dizziness
Contraindications
Blood dyscrasia, Liver disease
Pharmacokinetics
- Half-life ̴ 20 h
- Shorter half-life when administered with Phenytoin or Carbamazepine
- Metabolized by hydroxylation and conjugation
- A significant % of the drug is excreted unchanged in urines
- When co-administered with other AEDs, it ↑ plasma Phenytoin and Valproic Acid levels, but ↓ levels of Carbamazepine |
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Term
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Definition
Felbamate (Felbatol)
Oral: 400, 600 mg tablets; 600 mg/5 mL suspension |
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Term
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Definition
Oldest of available AEDs (aside from bromides)
Other medications with lesser sedative effects have replaced it
Chemistry
4 derivatives of barbituric acid clinically useful against seizures are:
Phenobarbital
Mephobarbital
Metharbital
Primidone
Phenobarbital, Mephobarbital and Metharbital are similar
3D conformations are similar to Phenytoin
Both possess a phenyl ring and are active against partial seizures
Mechanism of Action
Unknown
Inhibitory processes and ↓ of excitatory transmission contribute
May selectively suppress abnormal neurons, inhibiting the spread and suppressing firing from the foci
Like Phenytoin, it ↓ high-frequency repetitive firing, acting on Na+ conductance, (only at high concentrations)
At high concentrations, barbiturates block some Ca2+ currents (L-type and N-type)
Binds to allosteric regulatory sites on GABAA receptor enhances GABA receptor-mediated current by prolonging the openings of Cl– channels
↓ excitatory responses
Both enhancement of GABA-mediated inhibition and ↓ of glutamate-mediated excitation occur at relevant doses
Clinical Uses
Partial seizures
Generalized tonic-clonic seizures
Little evidence in generalized seizures (e.g. absence, atonic attacks, and infantile spasms)
Pharmacokinetics
Phenobarbital mostly excreted unchanged
Mephobarbital, Metharbital and Primidone: only insignificant quantities excreted unmodified
Major metabolic pathway: oxidation by hepatic enzymes to form alcohols, acids, and ketones
Half-life is 4–5 days
Multiple dosing cumulative effects |
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Term
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Definition
Phenobarbital (generic, Luminal Sodium, others)
Oral: 15, 16, 30, 60, 90, 100 mg tablets; 16 mg capsules; 15, 20 mg/5 mL elixirs
Parenteral: 30, 60, 65, 130 mg/mL for IV or IM injection |
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Term
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Definition
Conclusions
• Seizures generated by episodic, synchronous neuronal discharges mainly in the cerebral cortex
• Classified as focal (partial) or generalized (primary or secondary) seizures, according to EEG recordings and clinical signs
• AEDs can:
- block voltage sensitive Na+ channels
- block T-type calcium channels
- ↑ inhibitory GABA neurotransmission
- block excitatory glutamate neurotransmission
• Carbamazepine, Phenytoin, Valproate Focal and generalized tonic-clonic seizures
• Ethosuximide Generalized absence seizures (mostly in children)
• Valproate, Clonazepam absence, myoclonic, atonic seizures
• Consider pharmacointeractions:
- Carbamazepine and Phenytoin ↑ cytochrome P450 enzymes activity and ↓ serum levels
• AEDs can cause GI and CNS side effects, sometimes severe hematological or hepatic toxicity
- e.g. Valproate and Phenytoin are teratogenic |
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Term
| Examples of Medications that Cause Seizures |
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Definition
Amoxapine
Bupropion
Clozapine
Theophylline
Mellaril
Thorazine
Ludiomil |
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Term
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Definition
Kongenital
Infections
Toxins
Trauma
Environmental factors
Neurologic disorders
Drugs
Viruses
Metabolic factors |
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Term
| Syndromes with Comorbid Seizure Disorders |
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Definition
Down’s Syndrome
Prader-Willi Syndrome
Fragile X Syndrome
Sturge-Weber Disease
Cerebral Palsy
Rett’s Syndrome
Tuberous Sclerosis |
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Term
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Definition
Neurologic emergency!
Defined as continuous seizure activity lasting >30 minutes; however, any seizure lasting > 5 minutes should be treated as impending status epilepticus
Can occur as generalized convulsive status epilepticus or nonconvulsive status epilepticus |
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Term
| Treatment for Status Epilepticus |
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Definition
Pharmacologic
Phenytoin
Lorazepam
Diazepam
Fosphenytoin
Nonpharmacologic
Oxygen
Ventilation
Assess for metabolic acidosis |
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Term
| 1st Generation Anticonvulsants |
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Definition
Phenobarbital and derivatives-1912
Primidone (Mysoline)-1938
Acetazolamide (Diamox®)-1953
Phenytoin (Dilantin®)-1954
Ethosuximide (Zarontin®)-1960
Carbamazepine (Tegretol®)1974
Valproic Acid (Depekene®)-1978
Divalproex Sodium (Depakote®, Depacon®)
Benzodiazepines
Clonazepam (Klonopin®), Lorazepam (Ativan®), Diazepam (Valium®), Clobazam, Clorazepate (Tranxene®) |
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Term
| 2nd Generation Anticonvulsants |
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Definition
Felbamate (Felbatol®)-1993
Lamotrigine (Lamictal®)-1993
Gabapentin (Neurontin®)-1994
Topiramate (Topamax®)-1996
Tiagabine (Gabitril®)-1997
Levetiracetam (Keppra®)-2000
Zonegran (Zonisamide®)-2000
Pregabelin (Lyrica®)-2006
Locasamide (Vimpat®)-2008
Rufinamide (Banzel®)-2008
Vigabatrin (Sabril®)-2008 |
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Term
| First Generation “Enhancements |
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Definition
Fosphenytoin (Cerebyx®)
Carbamazepine (Tegretol XR®, Carbatrol®)
Depakote (Depacon®, Depakote ER®)
Oxcarbazepine (Trileptal®)
Rectal Diazepam (Diastat®) |
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Term
| Nonanticonvulsants Used for Managing Seizures |
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Definition
Benzodiazepines
Lorazepam (Ativan®)
Diazepam (Diastat ®)
Clonazepam (Klonopin ®)
Clobazam |
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Term
| AED Mechanisms of Action -Enhance Inhibition |
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Definition
GABAA Channel: VPX, Barbiturates, Benzodiazepines
T-Ca Channel: VPX, FLB, LMG, GPN
NMDA Channel: FLB, GPN, LMG, PHT,CBZ |
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Term
| AED Mechanisms of Action - Modulate Excitation |
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Definition
Na Channel
CBZ FLB
PHT GPN
VPX LMG
Barbiturates
Benzodiazepines |
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Term
| Considerations with Broad-Spectrum Anticonvulsants |
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Definition
Valproic Acid/Divalproex
Lamotrigine
Topiramate
Felbamate
Klonazepam |
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Term
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Definition
Prodrug of phenytoin
IM & IV administration
Faster administration rate
PE (phenytoin equivalents)
Storage limitations |
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Term
| Diazepam Rectal Gel (Diastat®) |
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Definition
Rectal formulation used for cluster seizures
Not appropriate for status epilepticus
Repeat dose once after 5 minutes
Pediatric and Adult formulations |
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Term
| Anticonvulsants Requiring Plasma Monitoring |
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Definition
Carbamazepine
Primidone
Phenytoin
Valproate
Ethosuximide
Phenobarbital |
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Term
|
Definition
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Term
|
Definition
|
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Term
|
Definition
|
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Term
|
Definition
Trileptal®
Depakote ER® Topamax®
Lamictal®
Tegretol XR® Carbatrol® |
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Term
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Definition
Depakote ER®
Topamax®
Zonegran®
Trileptal® |
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Term
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Definition
Neurontin®
Trileptal®
Topamax® |
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Term
|
Definition
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Term
|
Definition
Clonazepam
Neurontin®
Topamax®
Zonegran® |
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Term
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Definition
Phenobarb
Primidone
Clonazepam
Topamax® |
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Term
| Anticonvulsants and Serotonin |
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Definition
5HT = GABA= Pain
AED increases 5-HT in brain stem and spinal cord.
AED increases peripheral conversion of
5-HT.
AED increases 5-HT in the brain. |
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Term
| Limitations with 1st Generation Anticonvulsants |
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Definition
Enzyme Induction/Inhibition
Michaelis-Menton Pharmacokinetics
SIADH/hyponatremia
Cognitive impairment
Metabolic Products
CBZ-epoxide, hyperammonaemia
Hematological Disorders
bone marrow depression, thrombocytopenia
Cosmetic Side Effects |
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Term
| 2nd Generation Anticonvulsants |
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Definition
Little or no protein binding*
No required therapeutic monitoring
Fewer Drug Interactions
Adjunct therapy & monotherapy; Indicated for partial seizures with or without generalization
Orally administered*
Not used for Status Epilepticus
Used “Outside of the Box” |
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