Hypotensive effects

The principal mechanism of the hypotensive effect of diuretics (qv) is salt and fluid depletion, leading to reduction in blood volume (200,240). Acute effects lead to a decrease in cardiac output and an increase in total peripheral resistance. However, during chronic adrninistration, cardiac output and blood volume return toward normal and total peripheral resistance decreases to below pretreatment values. As a result, the blood pressure falls. The usual reduction in blood volume is about 5%. A certain degree of sustained blood volume contraction has to occur before the blood pressure decreases. The usual decrease in blood pressure achieved using a diuretic is about 20/10 mm Hg (2.7/1.3 kPa) (systoHc/diastoHc pressures. 

Figures 2 and 3 illustrate the constant release of pilocarpiae over the seven day treatment period. An initial burst of dmg iato the eye is seen ia the first few hours. This is temporary and the system drops to the rated value ia approximately six hours. The total amount of dmg released ia this transitory period is less than that normally given ia pilocarpiae ophthalmic solutions. The ocular hypotensive effect of these devices is hiUy developed within 2 hours of placement ia the conjunctival sac, and the hypotensive response is maintained throughout the therapy. This system replaces the need for eyedrops apphed four times per day to control iatraocular pressure.

When either drug is administered with diuretics and other hypotensives, an increased hypotensive effect may occur. When labetalol is administered with cimetidine, the effects of labetalol are increased. Halothane increases the effects of labetalol. When carvedilol is administered with the antidiabetic drugs, there is an increased effectiveness of the antidiabetic drugs. There is an increased effectiveness of clonidine when carvedilol is administered with clonidine There is an increased serum level of digoxin when digoxin is administered with carvedilol. 

When two antiarrhythmic dragp are administered concurrently the patient may experience additive effects and is at increased risk for drug toxicity. When quinidine and procainamide are administered with digitalis, tiie risk of digitalis toxicity is increased. Hiarmacologic effects of procainamide may be increased when procainamide is administered with quinidine When quinidine is administered with the barbiturates or cimetidine, quinidine serum levels may be increased. When quinidine is administered with verapamil, there is an increased risk of hypotensive effects. When quinidine is administered with disopyramide, there is an increased risk of increased disopyramide blood levels and/or decreased serum quinidine levels. 

Verapamil may cause an additive hypotensive effect when administered with other antihypertensives, alcohol, or the nitrates. Verapamil increases plasma digoxin levels and may cause bradycardia or CHF. 

If die nitrates are administered witii the antihypertensives, alcohol, calcium channel blockers, or the phe-notiiiazines, there may be an increased hypotensive effect. When nitroglycerin is administered intravenously (IV), die effects of heparin may be decreased. Increased nitrate serum concentrations may occur when the nitrates are administered witii aspirin. 

Make position changes slowly to minimize hypotensive effects. 

D. discontinue use of the calcium channel blocker until die hypotensive effects diminish... 

The hypotensive effects of most antihypertensive dru are increased when administered with diuretics and other antihypertensives. Many dnigp can interact with the antihypertensive drugs and decrease their effectiveness (eg, antidepressants, monoamine oxidase inhibitors, antihistamines, and sympathomimetic bronchodilators). When the ACE inhibitors are administered with the NSAIDs, their antihypertensive effect may be decreased. Absorption of the ACE inhibitors may be decreased when administered with the antacids. Administration of potassium-sparing diuretics or potassium supplements concurrently with the ACE inhibitors may cause hyperkalemia. When the angiotensin II receptor agonists are administered with... 

Older adults are particularly sensitive to the hypotensive effects of nitroprusside. To minimize the hypotensve effects the drug is initially given in lower dosages Older adults require more frequent monitoring during the administration of nitroprusside. 

Additive hypotensive effects occur when the potassium-sparing diuretics are given with alcohol, other... 

The thiazide diuretics are used cautiously in patients with liver or kidney disease, lupus erythematosus (may exacerbate or activate the disease), or diabetes. Additive hypotensive effects occur when the thiazides are given with alcohol, other antihypertensive drugp, or nitrates. 

When asparaginase is administered to a patient witii diabetes, die risk for hyperglycemia is increased a dosage adjustment of die oral antidiabetic drug may be necessary. Glucocorticoids decrease die effectiveness of aldesleukin. When aldesleukin is administered witii antihypertensive drugs, tiiere is an additive hypotensive effect Etoposide may decrease the immune response to live viral vaccines. 

Essential hypertension, whose prevalence is increased nearly two-fold in the diabetic population, may be another source of free-radical activity. The vascular lesions of hypertension can be produced by free-radical reactions (Selwign, 1983). In the recent Kuopio Ischaemic Heart Risk Factor Study in Finnish men, a marked elevation of blood pressure was associated with low levels of both plasma ascorbate and serum selenium (Salonen etal., 1988). A few studies report a hypotensive effect of supplementary ascorbate in patients with hypertension, but the actual changes in both systolic and diastolic pressure after ascorbate were not statistically significant in comparison with placebo (Trout, 1991). 

Fenoldopam does not decrease the incidence of contrast nephropathy.40 Due to its hypotensive effect, it may worsen kidney function. 

Disulfiram works by irreversibly blocking the enzyme aldehyde dehydrogenase, a step in the metabolism of alcohol, resulting in increased blood levels of the toxic metabolite acetaldehyde. As levels of acetaldehyde increase, the patient experiences decreased blood pressure, increased heart rate, chest pain, palpitations, dizziness, flushing, sweating, weakness, nausea and vomiting, headache, shortness of breath, blurred vision, and syncope. These effects are commonly referred to as the disulfiram-ethanol reaction. Their severity increases with the amount of alcohol that is consumed, and they may warrant emergency treatment. Disulfiram is contraindicated in patients who have cardiovascular or cerebrovascular disease, because the hypotensive effects of the disulfiram-alcohol reaction could be fatal in such patients or in combination with antihypertensive medications. Disulfiram is relatively contraindicated in patients with diabetes, hypothyroidism, epilepsy, liver disease, and kidney disease as well as impulsively suicidal patients. 

E Duzman, CC Chen, J Anderson, M Blumenthal, H Twizer. (1982). Diacetyl derivative of nadolol, I. Ocular pharmacology and short-term ocular hypotensive effect in glaucomatous eyes. Arch Ophthalmol 100 1916-1919. 

The answer is b. (Hardman, p 790.) Neuronal uptake is necessary for the hypotensive action of guanethidine. It competes for the norepinephrine storage site and, in time, replaces the natural neurotransmitter. This is the basis of its hypotensive effect. Drugs that prevent reuptake by the neurons, such as cocaine, would destroy the effectiveness of guanethidine... 

MacMillan, L. B., Hein, L., Smith, M. S., Piascik, M. T. and Limbird, L. E. Central hypotensive effects of the alpha2a-adrenergic receptor subtype. Science 273 801-803,1996. 

Potassium-sparing diuretics are weak antihypertensives when used alone but provide an additive hypotensive effect when combined with thiazide or loop diuretics. Moreover, they counteract the potassium- and magnesiumlosing properties and perhaps glucose intolerance caused by other diuretics. 

Acutely, diuretics lower BP by causing diuresis. The reduction in plasma volume and stroke volume associated with diuresis decreases cardiac output and, consequently, BP. The initial drop in cardiac output causes a compensatory increase in peripheral vascular resistance. With chronic diuretic therapy, the extracellular fluid volume and plasma volume return almost to pretreatment levels, and peripheral vascular resistance falls below its pretreatment baseline. The reduction in peripheral vascular resistance is responsible for the long-term hypotensive effects. Thiazides lower BP by mobilizing sodium and water from arteriolar walls, which may contribute to decreased peripheral vascular resistance. 

When diuretics are combined with other antihypertensive agents, an additive hypotensive effect is usually observed because of independent mechanisms of action. Furthermore, many nondiuretic antihypertensive agents induce salt and water retention, which is counteracted by concurrent diuretic use. 

Hydralazine and minoxidil cause direct arteriolar smooth muscle relaxation. Compensatory activation of baroreceptor reflexes results in increased sympathetic outflow from the vasomotor center, producing an increase in heart rate, cardiac output, and renin release. Consequently, the hypotensive effectiveness of direct vasodilators diminishes over time unless the patient is also taking a sympathetic inhibitor and a diuretic. 

Regarding the vasculature, treatment of aortic rings with mtALDH inhibitors attenuated GTN-dependent relaxation, formation of 1,2-GDN and accumulation of cGMP. Moreover, when tolerance was induced by pre-treatment with GTN, generation of 1,2-GDN and cGMP were again decreased, as was the activity of mtALDH. In whole animals, ALDH inhibitors were shown to attenuate the hypotensive effects of GTN in rabbits and rats. 

Under physiological conditions Molsidomine is rapidly converted to SIN-1, mainly by the action of liver esterases [94]. In hepatectomized rats the drug did not show any hypotensive effect, suggesting that the parent compound is inactive and the pharmacological effects are mediated by its metabolites. 

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