Propranolol with hydralazine

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

In the treatment of hypertension, a major use of beta-blockers is in combination with hydralazine. The direct vasodilators bring about reflex cardiac stimulation, and beta-blockers prevent these adverse effects (see also Figure 67). Beta-blockers also reduce blood pressure by exerting a central effect or a peripheral action, or both, which decreases renin activity. Metoprolol and atenolol are beta selective, and they are safer agents in patients with asthma, diabetes mellitus, or low-renin hypertension. Some beta-blocking agents such as pindolol have intrinsic sympathomimetic activity and may be used in the treatment of pronounced bradycardia (sick sinus syndrome). Unlike propranolol, metoprolol is not a very lipid-soluble... 

Byrne AJ, McNeil JJ, Harrison PM, Louis W, Tonkin AM, McLean AJ. Stable oral availability of sustained release propranolol when co-administered with hydralazine or food evidence implicating substrate delivery rate as a determinant of presystematic drug interactions. BrJ CUn Pharmacol ( 9S4) 17, 45S-50S. 

Orton TC, Lowery C (1977) Irreversible protein binding of (C " ) practolol metabolite(s) to hampster liver microsomes. Br J Pharmacol 60 319-320 Osborne DR (1977) Propranolol and Peyronie s disease (letter). Lancet 2 1111 Paz MA, Seifter S (1972) Immunological studies of collagens modified by reaction with hydralazine. Am J Med Sci 263 281-290... 

Developments in clinically useful anti hypertensives - There has been a great deal of discussionis on work carried out to evaluate the therapeutic potential of combining a vasodilator with a 6-adrenoreceptor blocker in order to counteract the tachycardia associated with the former. The combination of hydralazine with propranolol (p.o.) is effective in hypertensive patients at doses which separately do not give a satisfactory hypotensive effect a similar situation holds for dihydralazine. Alprenolol (i.v.) also reduced the cardiac stimulation observed in normotensive and hypertensive patients after dihydralazine (i.v.). Minoxidil (PDP), in combination with propranolol and hydrochlorothiazide, appears to be more effective in refractory hypertensive patients than hydralazine. Practolol effectively blocks the tachycardia in normotensive dogs treated with hydralazine (i.v.) without potentiating the hypotensive effects, which suggests that tachycardia does not diminish the hypotensive effect of hydralazine. 

In a study with 3427 male and female patients having DBP of 95—109 mm Hg (12—15 Pa), and no clinical evidence of cardiovascular diseases, half of the patients were placebo-treated and half were SC antihypertensive dmg-treated, ie, step 1, chlorothiazide step 2, methyldopa, propranolol [525-66-6], or pindolol [13523-86-9], and step 3, hydralazine, or clonidine [4205-90-7] (86). Overall, when the DBP was reduced below 100 mm Hg (13 Pa), there were more deaths in the dmg-treated group than in the placebo group. The data suggest reduction of blood pressure by antihypertensive dmg treatment that includes a diuretic is accompanied by increased cardiovascular risks. 

Because of their reflex cardiac effect, vasodilators, if used alone in the treatment of hypertension, have not been a successful therapeutic tool. However, the reflex tachycardia and increase in cardiac output can be effectively blocked by the therapeutic association with a sympathetic blocker guanethidine, reserpine, methyldopa, or clonidine. More specifically, blockade of the cardiac beta-adrenergic receptors will also prevent the cardiac response to hydralazine. Thus, the therapeutic combination of hydralazine and propranolol can be successfully employed for effective blood pressure reduction(11). 

Hydralazine is generally reserved for moderately hypertensive ambulatory patients whose blood pressure is not well controlled either by diuretics or by drugs that interfere with the sympathetic nervous system. It is almost always administered in combination with a diuretic (to prevent Na+ retention) and a p-blocker, such as propranolol (to attenuate the effects of reflex cardiac stimulation and hyperreninemia). The triple combination of a diuretic, -blocker, and hydralazine constitutes a unique hemodynamic approach to the treatment of hypertension, since three of the chief determinants of blood pressure are affected cardiac output (p-blocker). 

The hemodynamic effects of diazoxide are similar to those of hydralazine and minoxidil. It produces direct relaxation of arteriolar smooth muscle with little effect on capacitance beds. Since it does not impair cardiovascular reflexes, orthostasis is not a problem. Its administration is, however, associated with a reflex increase in cardiac output that partially counters its antihypertensive effects. Propranolol and other -blockers potentiate the vasodilating properties of the drug. Diazoxide has no direct action on the heart. Although renal blood flow and glomerular filtration may fall transiently, they generally return to predrug levels within an hour. 

Among drugs considered to be absorbed more quickly with food are carbamazepine, phenytoin, diazepam, dicoumarol, erythromycin (contentious), griseofulvin, hydralazine, hydrochlorothiazide, lithium citrate, labetalol, propranolol, metoprolol, nitrofurantoin, propoxyphene and spironolactone,... 

Hydralazine (Apresoline) is a phthalazine derivative that has been in use for more than three decades, primarily in combination with other types of antihypertensives. One innovation was to combine it with (3-blocking propranolol, which effectively prevents reflex cardiac stimulation and allows lower dosages. Adding a diuretic to the regimen prevents the usual sodium and water retention. Its molecular mechanism of action is not fully understood. Its toxic effects at higher doses can resemble a syndrome of symptoms simulating... 

However, the probable best usage of propranolol shall be its combination with an antihypertensive vasodilators e.g. hydralazine, minoxidil etc., to preferentially check and prevent the reflex tachycardia. ... 

Three hours after receiving intravenous cisplatin 70 mg/m a patient experienced severe nausea and vomiting and his blood pressure rose from 150/90 to 248/140 mmHg. This was managed with furosemide 40 mg intravenously, hydralazine 10 mg intramuscularly, diazoxide 300 mg intravenously and propranolol 20 mg orally twice daily for 2 days. Nine days later the patient showed evidence of renal impairment (creatinine raised from about 88 micromol/L to 283 micromol/L), which resolved within 3 weeks. The patient was subsequently similarly treated on two occasions with cisplatin and again developed hypertension, but no treatment was given and there was no evidence of renal impairment. The reasons for the renal impairment are not known, but a study in rats indicate that kidney damage may possibly be related to the concentrations of cisplatin, and that furosemide can increase cisplatin levels in the kidney. However, another study in patients found that there was no difference in the toxicity or pharmacokinetics of cisplatin when furosemide was used to induce diuresis, compared with mannitol. Two other studies have also found that furosemide does not alter cisplatin pharmacokinetics. Another study showed that sodium chloride solution with or without furosemide was associated with less cisplatin nephrotoxicity than sodium chloride solution with mannitol. ... 

Cubey RB, Taylor SH (1975) Ocular reaction to propranolol and resolution on continued treatment with a different beta-blocking drug. Br Med J 4 327-328 Dammin GJ, Nova JR, Rearden JB (1955) Hydralazine reaction case with L.E. cells ante mortem and post mortem and pulmonary renal splenic and muscular lesions of dissem-minated lupus erythematosus. J Lab Clin Med 46 806-809 Davies DM, Beedie MA, Rawlings MD (1975) Antinuclear antibodies during procainamide treatment. Br Med J 3 682-683... 

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