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hydralazine (Apresoline)

Tradename: Apresoline. Indications: 1) hypertension, especially in combination with a diuretic 2) useful in treatment of regurgitant valvular lesions 3) in combination with nitrates, hydralazine enhances survival in patients with heart failure 4) obstetrics: a) agent of choice in eclampsia b) long history of use in obstetrics c) it appears to be harmless to the fetus Contraindications: 1) recent cerebral hemorrhage 2) dissecting aortic aneurysm 3) not first line treatment of hypertension in pregnant women due to reflex tachycardia & fluid retention (edema) [7] Caution: - hydralazine increases myocardial oxygen consumption, making this drug unfavorable for most hypertensive emergencies Dosage: 1) IV infusion 0.2-0.5 mg/min 2) IV bolus 10 mg every 3-4 hours 3) 20-40 mg IV/IM every 4-6 hours 4) oral a) start 10 mg QID b) BID dosing may be as effective as QID dosing [5] c) max dose: 300 mg/day; 200 mg/day [6] Tabs: 10, 25 50, 100 mg. Injection: 20 mg/mL (1 mL). Pharmacokinetics: 1) onset of action a) oral is 1 hour b) IV is 10-20 minutes c) IM is 10-30 minutes 2) oral bioavailability is variable a) 35% for slow acetylators b) 16% for rapid acetylators 3) 87% is bound to plasma proteins 5) metabolized by the liver to multiple metabolites 6) 1-15% of drug is excreted unchanged into the urine Adverse effects: 1) common (> 10%) - headache - palpitations from reflex tachycardia - diarrhea - anorexia - nausea/vomiting - angina pectoris 2) less common (1-10%) - constipation, hypotension, redness or flushing of the face, dyspnea, lacrimation, nasal congestion 3) uncommon (< 1%) - dizziness, edema, malaise, peripheral neuritis, fever, rash, arthralgias, weakness, positive ANA & positive LE cells (lupus-like syndrome) 4) other - fluid retention (edema) [7] Tolerance: may occur, but may be reduced by concomitant diuretic use Drug interactions: 1) metoprolol & propranolol increase levels of hydralazine & visa versa (via decrease in 1st pass metabolism) 2) NSAIDs may decrease antihypertensive effects of hydralazine Mechanism of action: 1) direct arterial vasodilating agent 2) produces direct relaxation of arteriolar smooth muscle 3) effect is greater on arterioles than on veins 4) reduces afterload 5) may cause reflex tachycardia

Interactions

drug interactions drug adverse effects of antihypertensive agents

General

pyridazine; orthodiazine; oizine; 1,2-diazine vasodilator agent

Properties

MISC-INFO: elimination route LIVER KIDNEY onset-of-action 10-30 MIN {IV} 1/2life 2-5 HOURS pregnancy-category C safety in lactation +

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 118.
  3. AHFS Drug Information, American Society of Health-System Pharmacists, Bethesda, 1998
  4. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  5. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  6. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 476
  7. Medical Knowledge Self Assessment Program (MKSAP) 19. American College of Physicians, Philadelphia 2021

Component-of

hydralazine/hydrochlorothiazide/reserpine; hydralazine/HCTZ/reserpine (Ser Ap Es) hydralazine/hydrochlorothiazide; hydralazine/HCTZ (Apresazide) hydralazine/isosorbide dinitrate (BiDiL)