Hydralazine Propranolol

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). 

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

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. 

Guanethidine sulfate Hydralazine hydrochloride Melhyidopa Propranolol Reserpine... 

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,... 

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

Peters, C. E. and Chaplin, D. J. (1992) Blood flow modification in the SCCVII tumor effects of 5-hydroxytryptamine, hydralazine and propranolol. Inti. J. 

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... 

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... 

Also analyzed acebutolol, acepromazine, acetaminophen, acetazolamide, acetophenazine, albuterol, amitriptyline, amobarbital, amoxapine, antipsrrine, atenolol, atropine, azata-dine, baclofen, benzocaine, bromocriptine, brompheniramine, brotizolam, bupivacaine, buspirone, butabarbital, butalbital, caffeine, carbamazepine, cetirizine, chlorqyclizine, chlordiazepoxide, chlormezanone, chloroquine, chlorpheniramine, chlorpromazine, chlorpropamide, chlorprothixene, chlorthalidone, chlorzoxazone, cimetidine, cisapride, clomipramine, clonazepam, clonidine, clozapine, cocaine, codeine, colchicine, qyclizine, (yclo-benzaprine, dantrolene, desipramine, diazepam, diclofenac, diflunisal, diltiazem, diphenhydramine, diphenidol, dipheno late, dipyridamole, disopyramide, dobutamine, doxapram, doxepin, droperidol, encainide, ethidium bromide, ethopropazine, fenoprofen, fentanyl, flavoxate, fluoxetine, fluphenazine, flurazepam, flurbiprofen, fluvoxamine, fii-rosemide, glutethimide, glyburide, guaifenesin, haloperidol, homatropine, hydralazine, hydrochlorothiazide, hydrocodone, hydromorphone, hydro g chloroquine, hydroxyzine, ibuprofen, imipramine, indomethacin, ketoconazole, ketoprofen, ketorolac, labetalol, le-vorphanol, lidocaine, loratadine, lorazepam, lovastatin, loxapine, mazindol, mefenamic acid, meperidine, mephenytoin, mepivacaine, mesoridazine, metaproterenol, methadone, methdilazine, methocarbamol, methotrexate, methotrimeprazine, methoxamine, methyl-dopa, methylphenidate, metoclopramide, metolazone, metoprolol, metronidazole, midazolam, moclobemide, morphine, nadolol, nalbuphine, naloxone, naphazoline, naproxen, nifedipine, nizatidine, norepinephrine, nortriptyline, oxazepam, oxycodone, oxymetazo-line, paroxetine, pemoline, pentazocine, pentobarbital, pentoxifylline, perphenazine, pheniramine, phenobarbital, phenol, phenolphthalein, phentolamine, phenylbutazone, phenyltoloxamine, phenytoin, pimozide, pindolol, piroxicam, pramoxine, prazepam, prazosin, probenecid, procainamide, procaine, prochlorperazine, procyclidine, promazine, promethazine, propafenone, propantheline, propiomazine, propofol, propranolol, protriptyline, quazepam, quinidine, quinine, racemethorphan, ranitidine, remoxipride, risperidone, salicylic acid, scopolamine, secobarbital, sertraline, sotalol, spironolactone, sulfinpyrazone, sulindac, temazepam, terbutaline, terfenadine, tetracaine, theophylline, thiethyl-perazine, thiopental, thioridazine, thiothixene, timolol, tocainide, tolbutamide, tolmetin, trazodone, triamterene, triazolam, trifluoperazine, triflupromazine, trimeprazine, trimethoprim, trimipramine, verapamil, warfarin, xylometazoline, yohimbine, zopiclone... 

Harrison, P.M. Tonkin, A.M. McLean, A.J. Simple and rapid analysis of atenolol and metoprolol in plasma using solid-phase extraction and high-performance liquid chromatography. J.Chromatogr, 1985, 339, 429-433 [plasma SPE fluorescence detection LOD 10 ng/mL non-interfering chlorothiazide, disopyramide, furosemide, hydralazine, lidocaine, methydopa, prazosin, verapamil simultaneous alprenolol, oxprenolol, pindolol, practolol, propranolol, timolol]... 

Noninterfering albuterol, allopurinol, alprenolol, aspirin, atenolol, captopril, carbimazole, clonidine, coloxyl, danthron, diazepam, digoxin, doxepin, glibenclamide, hydralazine, in-domethacin, labetalol, metformin, methyldopa, metoprolol, mianserin, minoxidil, nifedipine, nitrazepam, oxazepam, oxprenolol, pindolol, prazosin, propranolol, senokot, theophylline, trifluoperazine... 

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