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Clozapine used, side effects, dose & more....

 Clozapine 

Brand name:- Lozapin , Sizopin, Skizoril 25, 100mg tabs.

Clozapine is an atypical antipsychotics. It works by modulating the action of certain chemical messengers in the brain that affects thoughts.

pharmacodynamic:-

Clozapine is classified as an atypical antipsychotic drug because it binds to serotonin as well as dopamine receptors.It acts as an antagonist at both receptors.

Clozapine is an antagonist at the 5-HT2A subtype of the serotonin receptor, putatively improving depression, anxiety, and the negative cognitive symptoms associated with schizophrenia.

A direct interaction of clozapine with the GABAB receptor has also been shown. GABAB receptor-deficient mice exhibit increased extracellular dopamine levels and altered locomotor behaviour equivalent to that in schizophrenia animal models. GABAB receptor agonists and positive allosteric modulators reduce the locomotor changes in these models.

Clozapine induces the release of glutamate and D-serine, an agonist at the glycine site of the NMDA receptor, from astrocytes,and reduces the expression of astrocytic glutamate transporters. These are direct effects that are also present in astrocyte cell cultures not containing neurons. Clozapine prevents impaired NMDA receptor expression caused by NMDA receptor antagonists.

 Pharmacokinetics:-

The half-life of clozapine is approximately 12 hours, with a blood clearance rate of 250 mL/min. Upon ingestion, 97% of clozapine is bound to serum proteins and is metabolized by way of three hepatic P450 isoenzymes before being excreted through urine (50%) and feces (30%)

Mechanism of action:- 

The mechanism by which clozapine exerts its effects involves the blocking of 5-HT²À/5-HT2C serotonin receptors and the D1-4 dopamine receptors, with the highest affinity for the D4 dopamine receptor.As a serotonin and D4 dopamine antagonist, clozapine is able to elicit its antipsychotic effects without inducing many of the extrapyramidal motor effects associated with D2 dopamine receptor antagonists.

Used:-

Used treat severely ill patients with schizophrenia who have used other medicines that did not work well. It is also used to lower risk of suicidal behavior in patients with schizophrenia or schizoaffective disorder.

 Side effects:-

Dizziness, Fainting, Constipation, Fever, Weight gain, Decreased white blood cell count, Extrapyramidal symptoms, Increased liver enzymes, Drowsiness, Seizure, Increased white blood cell count (eosinophils), Anticholinergic effects, Tachycardia, Excessive salivation.

 Dose:- 100-300mg/day , as directed by your doctor.

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