1.Cabamazepine
Trade names: |
Tegretol, Degranol and Sandoz-Carbamazepine |
Oral dosage form tablet: |
sustained release tablet and suspension |
Primary drug for partial and generalized tonic clonic seizures |
Not effective in absence seizure |
Mechanism of action
▪ In seizure dysfunctional sodium channels allow for too much influx of Sodium
ion which prolongs neuronal excitability (depolarization)
▪ Carbamazepine limits repetitive firing of action potential
(limits too much influx of sodium ion)
▪ This is due to prolonging the Sodium channel inactivation |
Side effects and Toxicity
Cardiac arrhythmias with or without hypertension |
Behaviroal change |
Gastroinstinal symptoms |
Hirudism |
Megaloblastic anemia |
Pharmacokinetics
• Phenytoin distributes into the body tissues, including the brain,
within 30 to 60 minutes after reaching the systemic circulation
• Effective for up to 24 hours
• Metabolized by hepatic cytochrome P450 |
Drug interactions:
Reduces the effect of oral contraceptives |
Reduces the effect of warfarin |
Could result in unplanned pregnancy |
Could result in deep vain thrombosis |
5.Valproate
Trade Names: |
Epilium liquid, Epilium CR, Epilium IV, Epilium crushable, Convulox, Navalpro, Eprolep |
Oral and parantral dosage form: |
Tablet, capsule, suspension, IV |
Effective against absence, myoclonic partial and tonic clonic seizures, suitable for HIV positive children with epilepsy |
Mechanism of action
▪ Mechanism of action is not fully understood
▪ It is believed that valproic acid leads to increased production of GABA
▪ In addition to this, valproate is also thought to enhance the effect of GABA that already exists in the area on the receptors.
▪ Valproate mimics the action of GABA |
Pharmacokinetics
• Absorbed rapidly and completely after oral administration with 81-89% bioavailability. Active for around 9-16 hours
• Metabolized by hepatic cytochrome P450 |
Side Effects and Toxicity
Anorexia |
Vomiting |
Nausea |
Sedation atexia |
Tremor |
Rash |
Alopecia |
Increased appetite |
Drug interactions
All benzodiazepines cause excessive sedation when combined with other medications that slow the brain's processes. (i.e, alcohol, barbiturates narcotics, and tranquilizers) |
|
|
2. BENZODIAZEPINES
Drug type: |
Trade names: |
Indication: |
Clonazepam |
Rivotril, Clonam |
Drops, tablet, IV |
Diazepam |
Pax, Valium, A-Lenon, Transjet, Betapam, Doval |
Tablet, IV |
Lorazepam |
Ativan, Tranqipam |
Tablet, IV |
Midazolam |
Accord, Sabax, Midaium, Dormicum, Midazoject |
IV, tablet, INF |
Indication of Benzodiazepines
▪ Prolonged seizure activity, less than 5 minutes between seizures
▪ Can last up to 20 minutes or more
▪ EML recommends which drug to stop status epilepticus |
Mechanism of action
▪ Benzodiazepines cause activation of the GABAa receptor and opening of the
Chlorine channels associated with the receptor
▪ The neuronal membrane is hyperpolarized and is less likely to fire
▪ Also inhibit excitatory glutamate receptors |
Benzodiazepines
Clonazepam |
Diazepam |
Lorazepam |
Midazolam |
Used for broad spectrum of seizures |
First line treatment in Status Epilepticus |
First line treatment in Status Epilepticus |
First line treatment in Status Epilepticus |
Effective in Status Epilepticus |
Rarely used for long term |
Rarely used for long term |
Rarely used for long term |
Absence seizure |
Good oral absorption |
Better than Diazepam |
Effective in Status Epilepticus that has not improved following other treatments or when intravenous access can not be obtained |
Given in combination |
Completely metabolized in liver and excreted in urine |
Good oral absorption |
Good oral absorption |
Good oral absorption |
|
Completely metabolized in liver and excreted in urine |
. |
Not for long term use - develops tolerance |
. |
Completely metabolized in liver and excreted in urine |
. |
Side Effects and Toxicity
Drowsiness and confusion |
Blurred vision |
Slurred speech |
Lack of coordination and weakness |
Difficulty breathing |
Coma |
|
|
3.Phenobarbital
Trade names |
Phenobarb Vital, Propain Forte, Donatal Elexir, Lethyl Sedabarb |
Only oral dosage form |
Tablet, syrup |
Low toxicity, inexpensive, widely used for young children |
Non-selective to the type of seizure. Mainly used for generalized tonic clonic and partial seizures and status epilepticus 20mg/kg, crushed and given by nasogastric tube (if one dose of midazolam or two doses of diazepam fail to show response) |
Mechanism of action
❑Through its action on GABA receptors, phenobarbital increases flux of chlorine
ions into the neuron which decreases excitability.
❑ Direct blockade of excitatory glutamate signaling is also believed to contribute
to the hypnotic/anticonvulsant effect |
Pharmacokinetics
• Oral absorption is complete but slow
• Peak concentration in plasma is seen after several hours (8-12 hours) after oral administration
• Remains in the body for a long time (2-7 days)
• Metabolized by liver (cytochrome p450) |
Side effects and Toxicity
Sedation (tolerance develops after continues use) |
Driving and use of heavy machinery must be avoided |
Irritability and hyperactivity in children |
Agitation and confusion in the elderly |
Some skin allergies in rare cases |
Drug interactions:
Reduces the effect of oral contraceptives |
Reduces the effect of warfarin |
Could result in unplanned pregnancy |
Could result in deep vain thrombosis |
4. Phenytoin
Trade Names: |
Epanutin Forte suspension, Epanutin Infatabs, Epanutin Ready Mixed Parantral |
Oral and parantral dosage form: |
Tablet, capsule, suspension, IV |
Active against all types of partial and tonic clonic seizures but not absence seizures |
Causes antiseizure activity without causing general CNS depression |
Mechanism of action
▪ In seizure dysfunctional sodium channels allow for too much influx of Sodium ion which prolongs neuronal excitability (depolarization)
▪ Phenytoin Limits repetitive firing of action potential (too much influx of sodium ion)
▪ This is due to slowing the rate of recovery of Sodium channels from inactivation. |
Pharmacokinetics
• Phenytoin distributes into the body tissues, including the brain,
within 30 to 60 minutes after reaching the systemic circulation
• Effective for up to 24 hours
• Metabolized by hepatic cytochrome P450 |
Side effects and Toxicity
Cardiac arrhythmias with or without hypertension |
Behaviroal change |
Gastroinstinal symptoms |
Hirudism |
Megaloblastic anemia |
|
