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Nội dung text 11. TDM OF DRUGS USED FOR SEIZURE DISORDERS.pdf

PHARMD GURU Page 1 THERAPEUTIC DRUG MONITORING OF VALPROIC ACID: GENERAL INTRODUCTION:  Valproic acid is an anti-convulsant, which is used to treat seizures.  It affects chemicals in the body that may be involved in causing seizures.  Sometimes used in combination with other drugs. USES:  Valproic acid is used to treat various types of seizure disorders. Valproic acid is sometimes used together with other seizure medications.  Valproic acid is also used to treat manic episodes related to bipolar disorder (manic depression), and to prevent migraine headaches. MECHANISM OF ACTION:  Valproic acid causes increased availability of GABA, an inhibitory neurotransmitter, to brain neurons.  It may also enhance the action of GABA or mimic its action at postsynaptic receptor sites.  Valproic acid also blocks voltage dependent sodium channels, which results in the suppression of high-frequency repetitive neuronal firing. PHARMACOKINETIC PROFILE: ABSORPTION: Absorption and Bioavailability:  Rapidly and completely absorbed (f = 1).  Oral (fasting) Peak: 1-3 hours.  Meal (food) peak late 6-8 hours.  Enteric coated absorbed delayed 3-5 hrs (lag time 2-4 hrs). DISTRIBUTION: Distribution and Protein binding: Vd = 0.15 L/Kg (0.1 - 0.5 L/Kg) Protein (Albumin) binding get saturated at a concentration >50 μg/ml TDM OF DRUGS USED FOR SEIZURE DISORDERS


PHARMD GURU Page 4 ADDITIONAL INFORMATION TDM OF CARBAMAZEPINE: INTRODUCTION:  Carbamazepine is an iminostilbene derivative related to the tricyclic antidepressants.  It used in the treatment of tonic-clonic (grand mal), partial or secondarily generalized seizures.  Carbamazepine is also a useful agent to treat trigeminal neuralgia and bipolar affective disorders.  The drug is used primarily as a prophylactic agent in the chronic therapy of epilepsy. NEED OF TDM: The accepted therapeutic range for Carbamazepine is 4-12 μg/ml when the drug is used for the treatment of seizures. 1) Carbamazepine plasma protein binding is quite variable among individuals because it is bound to both albumin and α1-acid glycoprotein (AGP). In patients with normal concentrations of these proteins, plasma protein binding is 75-80% resulting in a free fraction of drug of 20-25%. AGP secreted in large amount in diseases like trauma, heart failure, myocardial infarction.

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