Apresoline

Apresoline 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. Apresoline 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. Apresoline is no longer a first line therapy for these indications since the development of newer antihypertensive medications.

Apresoline hydrochloride was FDA approved on 15 January 1953.

Apresoline interferes with calcium transport to relax arteriolar smooth muscle and lower blood pressure. Apresoline 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.

Apresoline
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Apresoline
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
Weight	10mg, 100mg, 25mg, 50mg,
Type	Injection, Oral Tablet
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	Australia, United States,
Last Updated:	September 19, 2023 at 7:00 am

Uses

Apresoline 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 .

Apresoline 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.

Apresoline is also used to associated treatment for these conditions: Heart Failure, Hypertension,Essential, Hypertensive crisis, Severe Hypertension

How Apresoline works

Apresoline 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.

Apresoline 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.

Apresoline 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

Apresoline 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 C_max of oral hydralazine is 0.12-1.31µM depending on the acetylator status of patients.

Half Life

Apresoline 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.