Muzika
Muzika Uses, Dosage, Side Effects, Food Interaction and all others data.
Originally developed in the 1950s as a malaria treatment, hydralazine showed antihypertensive ability and was soon repurposed. Hydralazine is a hydrazine derivative vasodilator used alone or as adjunct therapy in the treatment of hypertension and only as adjunct therapy in the treatment of heart failure. Hydralazine is no longer a first line therapy for these indications since the development of newer antihypertensive medications.
Hydralazine hydrochloride was FDA approved on 15 January 1953.
Hydralazine interferes with calcium transport to relax arteriolar smooth muscle and lower blood pressure. Hydralazine has a short duration of action of 2-6h. This drug has a wide therapeutic window, as patients can tolerate doses of up to 300mg. Patients should be cautioned regarding the risk of developing systemic lupus erythematosus syndrome.
Isosorbide dinitrate relaxes vascular smooth muscles by stimulating cyclic-GMP. It decreases left ventricular pressure (preload) and arterial resistance (afterload).
Isosorbide Dinitrate is a moderate to long acting oral organic nitrate used for the relief and prophylactic management of angina pectoris. It relaxes the vascular smooth muscle and consequent dilatation of peripheral arteries and veins, especially the latter. Dilatation of the veins promotes peripheral pooling of blood and decreases venous return to the heart, thereby reducing left ventricular end- diastolic pressure and pulmonary capillary wedge pressure (preload). Arteriolar relaxation reduces systemic vascular resistance, systolic arterial pressure, and mean arterial pressure.
| Trade Name | Muzika |
| Generic | Hydralazine + Isosorbide Dinitrate |
| Weight | 37.5mg |
| Type | Tablet |
| Therapeutic Class | |
| Manufacturer | Alkem Laboratories Ltd |
| Available Country | India |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Hydralazine is an antihypertensive agent used for the management of essential hypertension or severe hypertension associated with conditions requiring immediate action, heart failure, and pre-eclampsia or eclampsia .
Hydralazine is indicated alone or adjunct to standard therapy to treat essential hypertension. A combination product with isosorbide dinitrate is indicated as an adjunct therapy in the treatment of heart failure.
Isosorbide dinitrate tablets are used for the prevention of angina pectoris due to coronary artery disease. The onset of action of immediate-release oral isosorbide dinitrate is not sufficiently rapid for this product to be useful in aborting an acute anginal episode.
Muzika is also used to associated treatment for these conditions: Heart Failure, Hypertension,Essential, Hypertensive crisis, Severe HypertensionAngina Pectoris, Coronary Artery Disease (CAD), Heart Failure, High Blood Pressure (Hypertension)
How Muzika works
Hydralazine may interfere with calcium transport in vascular smooth muscle by an unknown mechanism to relax arteriolar smooth muscle and lower blood pressure. The interference with calcium transport may be by preventing influx of calcium into cells, preventing calcium release from intracellular compartments, directly acting on actin and myosin, or a combination of these actions. This decrease in vascular resistance leads to increased heart rate, stroke volume, and cardiac output.
Hydralazine also competes with protocollagen prolyl hydroxylase (CPH) for free iron. This competition inhibits CPH mediated hydroxylation of HIF-1α, preventing the degradation of HIF-1α. Induction of HIF-1α and VEGF promote proliferation of endothelial cells and angiogenesis.
Isosorbide dinitrate is converted to the active nitric oxide to activate guanylate cyclase. This activation increases levels of cyclic guanosine 3',5'-monophosphate (cGMP). cGMP activates protein kinases and causes a series of phosphorylation reactions which leads to dephosphorylation of myosin light chains of smooth muscle fibres. Finally there is a release of calcium ions which causes smooth muscle relaxation and vasodilation.
Dosage
Muzika dosage
The usual starting dose of Isosorbide Dinitrate is 5 mg to 20 mg, two or three times daily. Formaintenance therapy, 10 mg to 40 mg, two or three times daily is recommended. Some patients may require higher doses. A daily dose-free interval of at least 14 hours is advisable to minimize tolerance. The optimal interval will vary with the individual patient, dose and regimen.
Should be taken on an empty stomach. Take ½ hr before meals
Side Effects
Rebound hypertension (uncommon), syncope, unstable angina flushing, hypotension/orthostatic hypotension, lightheadedness, palpitations, tachyarrhythmia, Dizziness, headache, restlessness, weakness, Nausea, Methemoglobinemia (infrequent)
Toxicity
The oral LD50 in rats is 173-187mg/kg and the highest known dose an adult human has survived is 10g orally.
Patients experiencing an overdose may present with hypotension, tachycardia, headache, flushing, myocardial ischemia, myocardial infarction, cardiac arrhythmia, and shock. Overdose can be treated through emptying the gastric contents and administering activated charcoal, though these treatments may cause further arrhythmias and shock. Supportive and symptomatic treatment should be administered.
Symptoms of overdose include reduced cardiac output and hypotension.
Precaution
Raised intracranial pressure, hypotension, hypovolaemia. Mitral valve prolapse, arterial hypoxaemia, glaucoma, elderly, hypothyroidism, malnutrition, pregnancy, lactation
Interaction
Increased hypotensive effects with alcohol or vasodilators. Marked orthostatic hypotension may occur when used with calcium channel blockers. Vasodilatory effect may be reduced with dihydroergotamine. Ergotamine effects may be enhanced. Reduced effectiveness of sublingual form with disopyramide.
Volume of Distribution
The volume of distribution is 1.34±0.79L/kg in congestive heart failure patients and 1.98±0.22L/kg in hypertensive patients.
- 2 to 4 L/kg
Elimination Route
Taking oral hydralazine with food improves the bioavailability of the drug. An intravenous dose of 0.3mg/kg leads to an AUC of 17.5-29.4µM*min and a 1mg/kg oral dose leads to an AUC of 4.0-30.4µM*min. The Cmax of oral hydralazine is 0.12-1.31µM depending on the acetylator status of patients.
Absorption of isosorbide dinitrate after oral dosing is nearly complete, but bioavailability is highly variable (10% to 90%), with extensive first-pass metabolism in the liver. The average bioavailability of isosorbide dinitrate is about 25%.
Half Life
Hydralazine has a half life of 2.2-7.8h in rapid acetylators and 2.0-5.8h in slow acetylators. The half life in heart failure patients is 57-241 minutes with an average of 105 minutes and in hypertensive patients is 200 minutes for rapid acetylators and 297 minutes for slow acetylators.
1 hour
Clearance
The majority of hydralazine clearance is extrahepatic- 55% for rapid acetylators and 70% for slow acetylators. The average clearance in congestive heart failure patients is 1.77±0.48L/kg/h, while hypertensive patients have an average clearance of 42.7±8.9mL/min/kg.
Elimination Route
9
Pregnancy & Breastfeeding use
Pregnancy Category-C. Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks
Lactation: Unknown whether drug is distributed into breast milk
Contraindication
Severe hypotension or anaemia, hypovolaemia, heart failure due to obstruction, or raised intracranial pressure due to head trauma or cerebral haemorrhage.
Acute Overdose
Symptoms: Increased intracranial pressure, throbbing headache, confusion, moderate fever; vertigo; palpitations; visual disturbances; nausea and vomiting; syncope; air hunger and dyspnoea; diaphoresis; heart block and bradycardia; paralysis; coma; seizures; and death. Methaemoglobinaemia.
Storage Condition
Store at room temperature (25° C).
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