Monogram of Respiridone
General description of Respiridone:
Respiridone is an antipsychotic drug with dopaminergic and serotonergic effect. Respiridone is used to treat schizophrenia, the mixed and manic states associated with bipolar disorder, and irritability in children with autism. The drug was developed by Janseen-Cilag.
RISPERDAL ® ( risperidone) s a psychotropic agent belonging to the chemical class of benzisoxazole derivatives. The chemical designation is 3-[ 2-[ 4-( 6-fluoro-1,2-benzisoxazol-3-yl) -1-piperidinyl ] ethyl ] -6,7,8,9-tetrahydro-2-methyl-4H-pyrido [ 1,2-a ] pyrimidin-4-one. Its molecular formula is C23H27FN4O2 and its molecular weight is 410.49.
Risperidone is a white to slightly beige powder. It is practically insoluble in water, freely soluble in methylene chloride, and soluble in methanol and 0.1 N HCl. (http://www.healthcentral.com/druglibrary/408/risperdal-drug_description.html)
Therapeutic group:
Respiridone is the categorized in the therapeutic group of drug for the antipsychotic drug.
Mode of action:
Risperidone is extensively metabolized in the liver. The main metabolic pathway is through hydroxylation of risperidone to 9-hydroxyrisperidone by the enzyme, CYP 2D6. A minor metabolic pathway is through N-dealkylation. The main metabolite,
9-hydroxyrisperidone has similar pharmacological activity as risperidone. Consequently, the clinical effect of the drug (e.g., the active moiety) results from the combined concentrations of risperidone plus 9-hydroxyrisperidone.
CYP2D6, also called debrisoquin hydrozylase, is the enzyme responsible for metabolism of many neuroleptics, antidepressants, antiarrhythimics, and other drugs, CYP 2D6 is subject to genetic polymorphism (about 6% -8% of Caucasians, and a very low percentage of Asians, have little or no activity and are “poor metabolizers”) and to inhibition by a variety of substrates and some non-substrates, notably quinidine. Extensive CYP 2D6 metabolizers convert risperidone rapidly into 9-hydroxyrisperidone, whereas poor CYP 2D6 metabolizers convert it much more slowly. Although extensive metabolizers have lower risperidone and higher 9-hydroxyrisperidone concentrations than poor metabolizers, the pharmacokinetics of the active moiety, after single and multiple doses, are similar in extensive and poor metabolizers.
Respiridone contraindication:
Respiridone is contraindicated in patients with a known hypersensitivity to the product and who have a history of high blood sugar and diabetes, and older patient treated for mental illness from dementia. Patient with history of seizures, cardiovascular disease, cerebrovascular disease, dehydration, diabetes, hyperglycemia, pancreas problem, hypovolemia, Alzheimer’s disease, hypothyroidism, pregnancy and hepatic impairment have to consult with doctor before using Respiridone. (http://www.resource4defectivedrugs.com/topics/risperdal.html)
Indications:
Respiridone is indicated for acute and chronic schizophrenic psychoses and other psychotic conditions with positive and negative symptoms and even indicated for affective symptoms associated with schizophrenia (ABPI, 1998). This drug has some effect on the bipolar affective disorder. Respiridone has been used to SSRIs in obsessive compulsive disorder. (http://priory.com/focus9.htm#Clinical%20Indications)
Interactions of Respiridone
Risperidone could be subject to two kinds of drug-drug interactions First, inhibitors of CYP 2D6 interfere with conversion of risperidone to 9-hydroxyrisperidone. This occurs with quinidine, giving essentially all recipients a risperidone pharmacokinetic profile typical of poor metabolizers. The therapeutic benefits and adverse effects of risperidone in patients receiving quinidine have not been evaluated, but observations in a modest number (n@70) of poor metabolizers given risperidone do not suggest important differences between poor and extensive metabolizers. Second, co-administration of known enzyme inducers (e.g. phenytoin, rifampin, and phenobarbitital) with risperidone may cause a decrease in the combined plasma concentrations of risperidone and 9-hydroxyrisperidone. It would also be possible for risperidone to interfere with metabolism of other drugs metabolized by CYP 2D6. Relatively weak binding of risperidone to the enzyme suggest this is unlikely
Side effects of Respiridone:
agitation, anxiety; blurred vision; confusion; constipation; cough; decreased sexual interest or ability; dysfunction of erection; ejaculation and orgasmdiarrhea; difficulty breathing or swallowing; difficulty falling asleep or staying asleep; difficulty urinating; dizziness; dreaming more than usual; drowsiness; dry mouth; dry or discolored skin; fainting; faintness; fast or irregular pulse; fast, pounding, or irregular heartbeat; fever; heartburn; hives; increased appetite; itching; muscle or joint pain; muscle stiffness; painful erection of the penis that lasts for hours; rash; restlessness; runny nose; seizures; slow movements or shuffling walk; sore throat; stomach pain; sweating; unusual movements of your face or body that you cannot control; upset stomach; weight gain.
Precautions while using Respiridone
RISPERDAL (risperidone) may induce orthostatic hypotension associated with dizziness, tychycardia, and in some patients, syncope, especially during the initial dose-titration period, probably reflection its alpha-adrenergic antagonistic properties. A dose reduction should be considered if hypotension occurs. RISPERDAL should be used with particular caution in patients with known cardiovascular disease (history of myocardial infraction or ischemia, heart failure, or condition abnormalities), cerebrovascular disease, and conditions, which would predispose patients to hypotension, e.g., dehydration and hypovolemia. Clinically significant hypotension has been observed with concomitant use of RISPERDAL and antihypertensive medication.
Special warnings
A 2003 study for the Risperdal reported that 49% more cases of diabetes among the users of Risperdal than amoung older anti-pscyhotic drug. So, Risperdal has been linked to type 2 diabetes, juvenile diabetes, hyperglycemia, other blood sugar disorders, diabetic coma, and pancreatitis- a dangerous inflammation of the pancreas. Respirdone is even linked with excessive weight gain, Neuroleptic malignant Syndrome (NMS) and Tardive Dyskinesia. Elderly patient treated with Rispierdal for demential had a higher chances of death by stroke and cardiac arrest than patient who did not take the drug.( http://www.resource4defectivedrugs.com/topics/risperdal.html)
