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ANTI MANIC DRUGS

LITHIUM CARBONATE

Often referred to as an anti-manic drugs.


Virtually complete within 6-8 hours; peak plasma levels in 30 minutes to 2 hours. In total body water; slow entry into intracellular compartment. Initial volume of distribution 0.5 L/kg, rising to 0.7-0.9 L/kg. No protein binding. None. Virtually entirely in urine. Lithium clearance about 20% of creatinine. Plasma half-life about 20 hours.

Absorption Distribution

Metabolism Excretion

Pharmacodynamics

MOA : remains unclear Major possibilities are : Its effects on electrolytes and ion transport. Its effects on neurotransmitters and their release by the dopamine receptor supersensitivity and the cholinergicmuscarinic activity. Effects on second-messenger and intracellular enzymes that mediate transmitters action.

Clinical Pharmacology

When mania is mild, lithium alone may be effective treatment. In more severe cases, needs to add clonazepam or lorazepam and often to give one of the antipsychotic drugs as well. After mania is controlled, the antipsychotic drug may be stopped, then the benzodiazepine and lithium continued as maintenance therapy

Dosage

Daily doses of lithium may range between 250500 mg/d, given 1-2 times/d and raise 250 mg/week. Effective dose = 1000-1500 mg/d. Medication is best taken with or shortly after meals.

Monitoring & Maintenance Treatment


Relied on measurement of serum concentration for assessing both the dosage required for satisfactory treatment of acute mania and adequacy of maintenance treatment. These measurement are customarily taken 1012 hours after the last dose.

Drug Interaction

Lithium + Thiazide 50% [serum lithium] Lithium + ACE Inhibitor [serum lithium] Lithium + Haloperidol (>20mg/d) neurotoxic effects (dyskinesia, ataxia) Lithium + ACE Inhibitor [serum lithium] Lithium + NSAIDs (Indomethacin, Ibuprofen) [serum lithium]

Adverse Effects & Complication

Neurologic Adverse Effects Psychiatric Adverse Effects Effect on Thyroid Function Renal Adverse Effects Edema Cardiac Adverse Effects Use During Pregnancy: -Lithium toxicity in newborn Miscellaneous Adverse Effects : -Transient acneform eruption, leukocytosis

Overdoses

Any value over 1.5 meq/L must be considered as indicating likely toxicity. Early symptoms of overdoses: Vomiting, diarrhea, tremor, concentration.

HALOPERIDOL

Is a potent dopamine antagonist that act on delusion and hallucination and has the inhibitory effect through its activity on basal ganglia. It presents an effective psychomotor sedative effect, so can treat mania and other agitation syndromes.

Pharmacokinetic

Peak plasma concentration: 2-6hr Bioavailability: 60-70% Half life:24 hr Plasma protein binding : 92 % Metabolize at hepar ; 60% of its metabolites excreted through faeces and the rest via urine.

Dosage

Recommended dosage : 4.5-15mg/d

Contraindication
Comatose condition and severe CNS depression, Parkinson dz, hypersensitivity to Haloperidol

CARBAMAZEPINE

It is a tricyclic compound effective in treatment of bipolar depression. MOA: Blocks sodium channels at therapeutic concentration and inhibits high-frequency repetitive firing in neurons. Acts presynaptically to decrease synaptic transmission. Inhibits uptake and release of norepinephrine from brain but does not influence GABA uptake in brain.

Clinical Usage

Partial seizures Mania

Pharmacokinetics
Rate of absorption varies Peak levels usually achieved 6-8 hours after administration. Distribution is slow, volume distribution is roughly 1L/kg Only 70% bound to plasma proteins Completely metabolized in human.

Therapeutic Levels & Dosage


Drugs of choice in partial seizures. Available only in oral forms Childrens : 15-25mg/kg/d Adults : 400-600 mg/d,2-3 x/d.

Drug Interactions
Propoxyphene, troleandomycin, and valproic acid may inhibit carbamazepine clearence and increase steady-state of carbamazepine blood levels

Toxicity

Diplopia and ataxia is the commonest Other dose-related complaints include: Mild gastrointestinal upsets Unsteadiness Higher dose >> drowsiness

VALPROIC ACID & SODIUM VALPROATE

Sodium valproate, also used as the free acid, valproic acid, was found to have antiseizure properties. MOA:
Blocks sustained high frequency repetitive firing of neurons in culture at therapeutically relevant concentrations. May exert an action through a direct effect on the potassium channel of the membranes

Clinical Use

Seizures Bipolar disorder Migraine prophylaxis.

Pharmacokinetics
Well absorbed following an oral dose, with bioavailability greater than 80%. Peak blood levels are observed within 2 hours 90% bound to plasma proteins Clearance is very slow. Half life varies from 9 hours to 18 hours.

Therapuetic Levels & Dosage


3 x 250 mg/d Therapeutic levels range from 50ug/mL to 100ug/mL

Drug Interaction
Displace phenytoin from plasma protein. Inhibit metabolism of several drugs: Phenobarbital: May cause increase level of barbiturate to rise precipitously Phenytoin Carbamazepine Causing a higher steady-state concentration of these agents.

Toxicity

Common dose related adverse effect are : Nausea Vomiting Other gastrointestinal complaints; abdominal pain, heartburn. Fine tremor. Idiosyncratic toxicity largely limited to hepatotoxicity; thrombocytopenia. Increase incidence of spina bifida in the offspring of women who took the drug during pregnancy.