Hydralazine interaction

Hofstra, A. and Uetrecht, J.P., Metabolism of hydralazine to a reactive intermediate by the oxidizing system of activated leukocytes, Chemico-Biol. Interact., 89,183, 1993. 

Drugs that may interact with hydralazine include beta blockers (eg, metoprolol, propranolol) and indomethacin. 

Drug/Food interactions Taking with food results in higher plasma hydralazine levels. 

Drugs that may interact with zalcitabine include antacids, chloramphenicol, cisplatin, dapsone, didanosine, disulfiram, ethionamide, glutethimide, gold, hydralazine, iodoquinol, isoniazid, metronidazole, nitrofurantoin, phenytoin, ribavirin, vincristine, cimetidine, metoclopramide, amphotericin, aminoglycosides, foscarnet, antiretroviral nucleoside analogs, pentamidine, and probenecid. 

Hydralazine (Apresoline/ Others) [Antihypertensive/ Vasodilator] Uses Mod-severe HTN CHF (w/ Isordil) Action Peripheral vasodilator Dose Adults. Initial 10 mg PO qid, T to 25 mg qid 300 mg/d max Peds. 0.75-3 mg/kg/24 h POq6—12h -i in renal impair V CBC ANA before Caution [C, +] -1- Hqjatic Fxn CAD T tox w/ MAOI, indomethacin, BBs Contra Dissecting aortic aneurysm, mitral valveAheumatic heart Dz Disp Tabs, inj SE SLE-like synd w/ chronic high doses SVT following IM route, p ipheral neuropathy Interactions T Effects W/ antih5 pertensives, diazoxide, diuretics, MAOIs, nitrates. 

Isosorbide Dinitrate Hydralazine (BiDil) [Antianginal, Antihypertensive/Vasodilator, Nitrate] Uses HF in African Amer-icans improve survival functional status, prolong time between hospitalizations Action Relaxes vascular smooth muscle peripheral vasodilator Dose Initially 1 tab tid PO (if not tol ated reduce to 1/2 tab tid), titrate >3-5 d as tolerated Max 2 tabs tid Caution [C, /-] recent MI, syncope, hypovolemia, hypotension, hep impair Contra For children, concomitant use w/ PDE5 inhibitors (sildenafil) Disp Tabs SE HA, dizziness, orthostatic hypotension, sinusitis, GI distress, tach, paresthesia, amblyopia Interactions t Risk of severe hypotension W/ antihypertensives, ASA, CCBs, MAOIs, phenothiazides, sildenafil, tadalafil, vardenafil, EtOH X pressor response Wf i -1- effects W7 NSAIDs EMS Use ASA, antihypertensives and CCBs w/ caution, may t hypotension concurrent Viagra-type drug use can lead to profound hypotension concurrent EtOH use can t effects OD May cause N/V, profound hypotension, skin flushing, HA from ICP, bradycardia, confusion, and circulatory collapse activated charcoal may be effective, epi use is contraindicated... 

Approximately 85% of the hydralazine in plasma is bound to plasma proteins. Although this does not appear to be a major therapeutic concern, the potential for interactions with other drugs that also bind to plasma proteins does exist. The plasma half-hfe of hydralazine in patients with normal renal function is 1.5 to 3 hours. 

Beta-blockers interact with a large number of other medications. The combination of beta-blockers with calcium antagonists should be avoided, given the risk for hypotension and cardiac arrhythmias. Cimetidine, hydralazine, and alcohol all increase blood levels of beta-blockers, whereas rifampicin decreases their concentrations. Beta-blockers may increase blood levels of phenothiazines and other neuroleptics, clonidine, phen-ytoin, anesthetics, lidocaine, epinephrine, monoamine oxidase inhibitors and other antidepressants, benzodiazepines, and thyroxine. Beta-blockers decrease the effects of insulin and oral hypoglycemic agents. Smoking, oral contraceptives, carbamazepine, and nonsteroidal anti-inflammatory analgesics decrease the effects of beta-blockers (Coffey, 1990). 

LE cells are neutrophil polymorphs, which have phagocytosed the basophilic nuclear material of leucocytes, which has been altered by interaction with antinuclear antibodies. The development of ANA requires a lower intake of hydralazine and occurs more quickly in slow acetylators than in rapid acetylators, and rapid acetylators have significantly lower titers of ANA than slow acetylators. There is also a significant correlation between the cumulative dose of hydralazine and the development of ANA, but as indicated above, patients who develop LE do not have a significantly different cumulative intake of hydralazine from those patients who do not develop the syndrome. 

McLean AJ, Skews H, Bobik A, Dudley FJ. Interaction between oral propranolol and hydralazine. Clin Pharmacol Ther 1980 27(6) 726-32. 

Lessen T. ao D-C. Interactions between drug substances and excipients. 1. fluorescence and HPLC studies of triazolr thalazine derivatives from hydralazine hydrochloride and starch. J Pharm Sci 1996 85 326-9. 

Clinically important, potentially hazardous interactions with alcohol, amiodarone, anticholinergics, antihistamines, barbituates, cisapride, dofetilide, doxazosin, erythromycin, guanethidine, hydralazine, levodopa, lithium, methyldopa, metoclopramide, moxifloxacin, piperazine, quinidine, sibutramine, sotalol, thiazide diuretics, thioridazine... 

Thus interaction of hydralazine or a metabolite with macromolecules may underlie the immune response. An alternative or additional hypothesis involves inhibition of the complement system. The complement system helps remove immune complexes by solubilization, but if it is inhibited deposition and accumulation of such complexes would be increased. Hydralazine and some of its metabolites interfere with part of the complement system, inhibiting the covalent binding of complement C4 by reaction with the thioester of activated C4. However, the conentrations required are high relative to the normal therapeutic concentration. More recently it has been shown that hydralazine inhibits DNA methylation in the T-cell. The inhibition of DNA methyl transferase may initiate immune reactions via activation of genes as a result of this interference with DNA methylation. However, although the mechanism of hydralazine-induced LE is not yet understood, it is an important example of drug-induced toxicity for two reasons ... 

Hydralazine. Vasodilator drug which causes systemic lupus erythematosus in a significant proportion of patients. Several predisposing factors have been identified dose (>25 mg) duration of therapy (mean 18 months) acetylator phenotype (slow) HLA type (DR4) gender (females males, 4 1). Antinuclear antibodies and antihydralazine antibodies detected in serum. Causes a Type III immune reaction. Mechanism is unclear but may involve reaction of parent drug or metabolite with protein. Interference with the complement system and interaction with nucleic acids also occur. Metabolism also may be mediated by myeloperoxidase in activated neutrophils. 

Pinacidil is three- and tenfold more potent than hydralazine and minoxidil, respectively. It does not interact with alpha, beta, cholinergic, or histaminergic receptors, and also does not produce vasodilation via an indirect effect that is mediated by adenosine, prostaglandin, or endothelial-derived relaxant factor. Its vasodilating activity does not resemble that brought about by the conventional calcium-channel antagonists. Thus, pinacidil-induced vascular relaxation is a direct effect mediated by a novel mechanism. 

Hydralazine (Apresoline) Directly relaxes arterioles (not veins) independent of sympathetic interactions. Causes decrease in blood pressure leading to reflex tachycardia and increased cardiac output. Directly increases renal blood flow. Moderate hypertension. May be used in pregnant women who are hypertensive. Reflex tachycardia, palpitations, fluid retention, systemic lupus erythematosis-liKe syndrome. Chronic therapy may lead to peripheral neuritis (due to interference with vitamin B6 metabolism in neural tissue). 

V. Drug or iaboratory interactions. Intravenous infusions may be incompatible with 10% dextrose solutions, amphotericin, or hydralazine. 

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