Hypophthalin
Hypophthalin 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. Hypophthalin 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. Hypophthalin is no longer a first line therapy for these indications since the development of newer antihypertensive medications.
Hypophthalin hydrochloride was FDA approved on 15 January 1953.
Hypophthalin interferes with calcium transport to relax arteriolar smooth muscle and lower blood pressure. Hypophthalin 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.
| Trade Name | Hypophthalin |
| Availability | Prescription only |
| Generic | Hydralazine |
| Hydralazine Other Names | 1-Hydrazinophthalazine, 1-Phthalazinylhydrazine, 6-Hydralazine, Hidralazina, Hydralazin, Hydralazine, Hydralazinum, Hydrallazine, Hydrazinophthalazine, Hypophthalin, Idralazina |
| Related Drugs | amlodipine, lisinopril, metoprolol, losartan, furosemide, carvedilol, hydrochlorothiazide, spironolactone, nifedipine, captopril |
| Type | |
| Formula | C8H8N4 |
| Weight | Average: 160.1759 Monoisotopic: 160.074896276 |
| Protein binding | Hydralazine is 87% protein bound in serum likely to human serum albumin. |
| Groups | Approved |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Hypophthalin 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 .
Hypophthalin 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.
Hypophthalin is also used to associated treatment for these conditions: Heart Failure, Hypertension,Essential, Hypertensive crisis, Severe Hypertension
How Hypophthalin works
Hypophthalin 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.
Hypophthalin 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.
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.
Food Interaction
- Take with or without food. Food increases exposure to hydralazine, though this may not be clinically significant.
Hypophthalin Drug Interaction
Moderate: aspirin, aspirinMinor: furosemide, furosemide, metoprolol, metoprolol, metoprolol, metoprololUnknown: apixaban, apixaban, omega-3 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, insulin glargine, insulin glargine, clopidogrel, clopidogrel, cyanocobalamin, cyanocobalamin, cholecalciferol, cholecalciferol
Hypophthalin Disease Interaction
Major: bone marrow suppression, coronary artery disease, lupus erythematosus, valvular heart diseaseModerate: cerebral vasculopathy, renal dysfunction
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.
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.
Half Life
Hypophthalin 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.
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
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