Hydralazine Diazoxide

VASODILATOR ANTIHYPERTENSIVES BETA-BLOCKERS t hypotensive effect Additive hypotensive effect with diazoxide, hydralazine, minoxidil and sodium nitroprusside. In addition, hydralazine may T the bioavailability of beta-blockers with a high first-pass metabolism (e.g. propanolol and metoprolol), possibly due to alterations in hepatic blood flow or inhibited hepatic metabolism Monitor BP closely... 

ANG II is also known to induce release of catecholamines from the adrenal medulla and to suppress the reflex inhibition of the heart rate, with the latter probably the inhibiting vagal (cholinergic) neurons to the heart. This has a specific clinical effect that is useful in the use of ACE inhibitors as antihypertensives (see later) namely, the absence of reflex tachycardia seen with other types of blood pressure-lowering drugs such as a-blockers, diazoxide, hydralazine, and ganglionic blockers. 

Vasodilators (e.g. hydralazine) Beta blockers + Hydralazine Diazoxide + Hydralazine Guanethidine + Minoxidil Nicorandil + Vasodilators... 

The answer is d. (Hardman, pp 794-795.) Hydralazine, minoxidil, diazoxide, and sodium nitroprusside are all directly acting vasodilators used to treat hypertension. Because hydralazine, minoxidil, nifedipine, and diazoxide relax arteriolar smooth muscle more than smooth muscle in venules, the effect on venous capacitance is negligible. Sodium nitroprusside, which affects both arterioles and venules, does not increase cardiac output, a feature that enhances the utility of sodium nitroprusside in the management of hypertensive crisis associated with MI. 

Presently on the U.S. market there are three compounds commonly considered as peripheral dilating hypotensive agents. These are hydralazine (I), placed on the market in 1953 by CIBA, diazoxide (II) from Schering in 1973 and sodium nitroprusside (III) made available by Roche in 1974. 

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. 

Cardiovascular Acetyldigosin, ajmaline, amiodarone, aprindine, bepridil, bezaflbrate, captopril, dinepazide, clopidogrel, coumarins, diazoxide, digoxin, dipyridamole, disopyramide, doxazosin, enalapril, flurbiprofen, fur-oxemide, hydralazine, lisinopril methyldopa, metolazone, nifedipine, phenindione, procainamide, propanolol, propafenone, quinidine, ramapril, spironolactone, thiazide diuretics, ticlopidine, vesnarinone... 

This chapter describes four vasodilators in detail. Two of these agents, hydralazine and minoxidil, are effective orally and are used for the chronic treatment of primary hypertension. The other two drugs, diazoxide and sodium nitroprusside, are effective only when administered intravenously. They are generally used in the treatment of hypertensive emergencies or during surgery. 

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. 

In contrast to hydralazine, minoxidil, and diazoxide, sodium nitroprusside relaxes venules as well as arterioles. Thus, it decreases both peripheral vascular resistance and venous return to the heart. This action limits the increase in cardiac output that normally follows vasodilator therapy. Sodium nitroprusside does not inhibit sympathetic reflexes, so heart rate may increase following its administration even though cardiac output is not... 

Diuretics are frequently used in combination with other antihypertensive agents. The appropriateness of this combination becomes even more apparent when it is realized that nondiuretic antihypertensives (e.g., hydralazine or diazoxide) produce some increase in plasma volume that if not corrected, would lead to an eventual decrease in their activity (see Chapter 20). 

This class of drugs includes the oral vasodilators, hydralazine and minoxidil, which are used for long-term outpatient therapy of hypertension the parenteral vasodilators, nitroprusside, diazoxide, and fenoldopam, which are used to treat hypertensive emergencies the calcium channel blockers, which are used in both circumstances and the nitrates, which are used mainly in angina (Table 11-3). 

The peripheral receptors activated by noradrenaline fall into at least two classes, a-receptors and /3-receptors, which differ in their function and in their response to drugs. The a-receptors cause constriction of blood vessels and compounds used to block them include indoramin (216), prazosin (217) and phentolamine (218). Another imidazoline, tolazoline (2-benzyl-2-imidazoline), is a useful vasodilator but is unsuitable for the treatment of hypertension since it stimulates the heart. Other drugs described as peripheral vasodilators are diazoxide (219), which is related to the thiazide diuretics, hydralazine (220) which also depresses the CNS, hydracarbazine (221) and minoxidil (222). The /3-receptors control the action of adrenaline on the heart (among other effects) and the agents that block them are mostly nonheterocyclic aromatic compounds with aminoethanol or 3-amino-2-hydroxypropoxy side-chains. They have proved effective in the treatment of hypertension. One heterocyclic compound of this class, timolol (223), is in use. 

Diazoxide (Hyperstat) Hydralazine (Apresoline) Minoxidil (Loniten) Nitroprusside (Nipride, Nitropress)... 

Diazoxide [dye az OX ide] is a direct-acting arteriolar vasodilator. It has vascular effects like those of hydralazine. For patients with coronary insufficiency, diazoxide is administered intravenously with a p-blocker, which diminishes reflex activation of the heart. Diazoxide is useful in the treatment of hypertensive emergencies, hypertensive encephalopathy, and eclampsia. Excessive hypotension is the most serious toxicity. 

VASODILATOR ANTI HYPERTENSIVES VASODILATOR ANTI HYPERTENSIVES Profound, refractory J- BP may occur when diazoxide is co-administered with hydralazine Additive effect uncertain why the effect is so refractory to treatment Avoid co-administration of diazoxide with hydralazine... 

Minoxidil is a vasodilator selective for arterioles rather than for veins, similar to diazoxide and hydralazine. Like the former, it acts through its sulphate metabolite as an ATP-dependent potassium channel opener. It is highly effective in severe hypertension, but causes increased cardiac output, tachycardia, fluid retention and hypertrichosis. The hair growth is generalised and although a cosmetic problem in women, it has been exploited as a topical solution for the treatment of baldness in men. 

Direct-acting vasodilators lower the peripheral vascular resistance mainly by causing arteriolar dilation. Drugs discussed are nitroprusside, hydralazine, minoxidil, and diazoxide. 

IV verapamil, diltiazem Vasodilators hydralazine, nitroprusside, diazoxide, minoxidil ... 

Direct vascular smooth-muscle relaxants evaluated in primary pulmonary hypertension include hydralazine, isosorbide dinitrate, and diazoxide. In general, the hemodynamic effects of these drugs include modest reduction in mean pulmonary artery pressure, which parallels a significant reduction in systemic arterial pressure, decreased pulmonary vascular resistance, and increased cardiac output. 

Salt and water retention result from increased proximal tubular reabsorption due to reduced renal perfusion pressure and reflex stimulation of renal tubular a adrenergic receptors. Similar antinatriuretic effects are observed with other arteriolar dilators (e.g., diazoxide and hydralazine). 

Vasodilators Hydralazine, nifedipine, nitroprusside Minoxidil, verapamil, diazoxide ... 

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