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Chapter: Clinical Pharmacology: Neurologic and neuromuscular drugs

Carboxamides

Oxcarbazepine, a carboxamide, is chemically similar to carba-mazepine but causes less induction of hepatic enzymes.

Carboxamides

 

Oxcarbazepine, a carboxamide, is chemically similar to carba-mazepine but causes less induction of hepatic enzymes. Oxcar-bazepine is a prodrug. It’s useful as adjunctive therapy or monotherapy for adults with partial seizures and as adjunctive therapy for children with partial seizures.

Pharmacokinetics

Oxcarbazepine is completely absorbed and extensively metabo-lized by hepatic enzymes to the 10-monohydroxy metabolite (MHD) that’s responsible for its pharmacologic activity. MHD is excreted primarily by the kidneys.

9 hours in half

 

The half-life of MHD is about 9 hours. Unlike carbamazepine, ox-carbazepine doesn’t induce its own metabolism.

Pharmacodynamics

 

The precise mechanism of action of oxcarbazepine and its metabolite MHD is unknown, but antiseizure activity is thought to occur through blockade of sodium-sensitive channels, which pre-vents seizure spread in the brain.

Pharmacotherapeutics

 

Oxcarbazepine is FDA-approved as adjunctive therapy for partial seizures in adults and children older than age 4 and as monothera-py for adults.

 

As with carbamazepine, it’s also effective for generalized seizures but may worsen myoclonic and absence seizures.

Drug interactions

 

Carbamazepine, phenytoin, phenobarbital, valproic acid, and ve-rapamil may decrease the levels of oxcarbazepine’s active metabolite MHD.

 

Pill worries

 

·                 Oxcarbazepine may decrease the effectiveness of hormonal contraceptives and felodipine.

 

·                 Dosage reductions are necessary for patients with renal impairment (creatinine clearance less than 30 ml/minute) and those at risk for renal impairment, such as elderly patients. (See Adverse reactions to oxcar-bazepine.)

 

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Clinical Pharmacology: Neurologic and neuromuscular drugs : Carboxamides |


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