Diuretics diazoxide

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. 

Replacement of the sulfonamide group at the 7 position by chlorine markedly diminishes the diuretic effect in this series. One such compound, diazoxide (169), exhibits instead potent anti-... 

Changing the substitution pattern on the carbo-cyclic ring of the benzothiadiazine diuretics is well known to have a marked effect on the qualitative biological activity. Thus, the direct analogue of the diuretic chlorothiazide (199) in which chlorine replaces one sulfonamide group, diazoxide (200), shows negligible diuretic activity instead the compound is a potent antihypertensive vasodilator. 

Diazoxide (II) has been known since the early 1960 s (9.) and must be considered as a well known lead. It bears a structural resemblance to the diuretic agent, chlorothiazide (XIX) but, unlike chlorothiazide, it is non-diuretic. Analogs have been prepared by scientists at Schering (10) and by a group in Italy (11). The Italian group reported that compound XX lowers blood pressure and heart rate intravenously in rats but causes... 

The thiazide diuretics possess antihypertensive properties, in part consequent upon electrolyte and plasma-volume changes but mainly resulting from a direct cardiovascular depressant effect. This is clearly illustrated by the non-diuretic thiazide, diazoxide, which is an effective hypotensive [326b, c]. It is not therefore, surprising that both these properties should be found (in varying proportions) in other, structurally related, compounds. One particular line of research, aimed at modification of the thiazide heterocycle (the o-chlorobenzenesulphonamide moiety was untouched as it was believed essential to activity-the subsequent advent of ethacrynic acid questions this belieO examined first the corresponding... 

There are a number of extremely important thiazide diuretics not listed above. These widely used drugs include hydroflumethiazid, trichlormethiazide, methylcyclothiazide, cyclothiazide, benzothiazide, diazoxide, and others, whose methods of synthesis and pharmacological action are practically identical to those listed above. 

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... 

Diazoxide (Hyperstat) is chemically similar to the thiazide diuretics. It is devoid of diuretic activity and causes Na and water retention. Diazoxide is a very potent vasodilator and is available only for intravenous... 

Since diazoxide is not often used for long-term treatment, toxicities associated with chronic use are rare. The chief concern is the side effects associated with the increased workload on the heart, which may precipitate myocardial ischemia and Na+ and water retention. These undesirable effects can be controlled by concurrent therapy with a (3-blocker and a diuretic. 

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). 

Diazoxide is similar chemically to the thiazide diuretics but has no diuretic activity. It is bound extensively to serum albumin and to vascular tissue. Diazoxide is partially metabolized its metabolic pathways are not well characterized. The remainder is excreted unchanged. Its half-life is approximately 24 hours, but the relationship between blood concentration and hypotensive action is not well established. The blood pressure-lowering effect after a rapid injection is established within 5 minutes and lasts for 4-12 hours. 

In contrast to the structurally related thiazide diuretics, diazoxide causes renal salt and water retention. However, because the drug is used for short periods only, this is rarely a problem. 

All sulfonamides, including antimicrobial sulfas, diuretics, diazoxide, and the sulfonylurea hypoglycemic agents, have been considered to be partially cross-allergenic. Flowever, evidence for this is not extensive. The most common adverse effects are fever, skin rashes, exfoliative dermatitis, photosensitivity, urticaria, nausea, vomiting, diarrhea, and difficulties referable to the urinary tract (see below). Stevens-Johnson syndrome, although relatively uncommon (ie, < 1% of treatment courses), is a particularly serious and potentially fatal type of skin and mucous membrane eruption associated with sulfonamide use. Other unwanted effects include stomatitis, conjunctivitis, arthritis, hematopoietic disturbances (see below), hepatitis, and, rarely, polyarteritis nodosa and psychosis. 

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. 

AMP is related to certain mental diseases and may be involved in the action of tranquilizers and antidepressant drugs (60). Whether the ability of diuretic agents such as ethacrynic acid and chlorthalidone to inhibit the enzyme in kidney (68) is related to their diuretic action is also not known. It has been suggested that inhibition of diesterase by diazoxide (59) may explain the hyperglycemic activity of this agent. Several materials are known to activate the enzyme. Imidazole produces strong activation of the enzyme from mammalian tissues (36, 38, 42) but not from E. coli (41). It has been reported (61) that insulin activates the beef heart enzyme in vitro, but it is not known if this has relevance... 

The electronic structures of hydrochlorothiazide 146 and related substances have been determined by the complete neglect of differential overlap (CNDO/2) method (83AF688). The calculation confirms that the diuretic thiazides are electron-accepting, whereas diazoxide 147, a non-... 

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