Vasodilation ACE inhibitors

Develop a medication regimen to slow the progression of HF with the use of neurohormonal blockers such as vasodilators (ACE inhibitors, ARBs, or hydralazine/ isosorbide dinitrate), P-blockers, and aldosterone antagonists. Utilize digoxin if the patient remains symptomatic despite optimization of the above therapies. 

Drug Interactions Other antihypertensive agents Carbamazepine (vasodilators, ACE inhibitors, Rifampin diuretics, and beta-blockers) Phenobarbital Digoxin Cyclosporine Disopyramide Theophylline Flecainide Inhalation anesthetics Quinidine Neuromuscular blocking agents Cimetidine Lithium ... 

Other antihypertensive agents (vasodilators, ACE inhibitors, diuretics, and beta-blockers)... 

ANTI HYPERTENSIVE VASODILATORS, ACE INHIBITORS, ANGIOTENSIN II RECEPTOR BLOCKERS, AND CALCIUM CHANNEL BLOCKERS ... 

Describe the beneficial effects of diuretics, vasodilators. ACE inhibitors, and other drugs that lack positive inotropic effects in congestive heart failure. 

ACE inhibitors can be administered with diuretics (qv), cardiac glycosides, -adrenoceptor blockers, and calcium channel blockers. Clinical trials indicate they are generally free from serious side effects. The effectiveness of enalapril, another ACE inhibitor, in preventing patient mortaUty in severe (Class IV) heart failure was investigated. In combination with conventional dmgs such as vasodilators and diuretics, a 40% reduction in mortaUty was observed after six months of treatment using 2.5—40 mg/d of enalapril (141). However, patients complain of cough, and occasionally rash and taste disturbances can occur. 

Angiotensin-converting enzyme (ACE) inhibitors. ACE inhibitors not only cause vasodilation (1 TPR), but also inhibit the aldosterone response to net sodium loss. Normally, aldosterone, which enhances reabsorption of sodium in the kidney, would oppose diuretic-induced sodium loss. Therefore, coadministration of ACE inhibitors would enhance the efficacy of diuretic drugs. 

I to angiotensin II, a potent vasoconstrictor and stimulator of aldosterone secretion. ACE inhibitors also block the degradation of bradykinin and stimulate the synthesis of other vasodilating substances including prostaglandin E2 and prostacyclin. The fact that ACE inhibitors lower BP in patients with normal plasma renin activity suggests that bradykinin and perhaps tissue production of ACE are important in hypertension. 

Starting doses of ACE inhibitors should be low with slow dose titration. Acute hypotension may occur at the onset of ACE inhibitor therapy, especially in patients who are sodium- or volume-depleted, in heart failure exacerbation, very elderly, or on concurrent vasodilators or diuretics. Patients with these risk factors should start with half the normal dose followed by slow dose titration (e.g., 6-week intervals). 

Treatment with a diuretic and an ACE inhibitor is usually very effective. ACE inhibition may be preferable to the use of a receptor antagonist since the inhibition has a dual effect on vasodilation it decreases the concentration of angiotensin II, which is a vasoconstrictor, but increases that of bradykiitin, which is a vasodilator (see Eigure 22.16). 

Figure 22.16 Regulation of vasoconstriction/vasodilation by angiotensin-II and bradykinin. The mechanism by which angiotensin-II stimulates vasoconstriction is shown in Figure 22.15. Angiotensin-converting enzyme is also responsible for bradykinin inactivation. Bradykinin stimulates endothelial cells to produce and secrete nitric oxide and prostacyclin, both of which are vasodilators. Consequently the effect of an ACE inhibitor is to decrease the concentration of angiotensin-II, which lowers blood pressure, and to increase the concentration of bradykinin, which also lowers blood pressure.

Counter-regulation in acute hypotension due to vasodilators (B). Increased sympathetic drive raises heart rate (reflex tachycardia) and cardiac output and thus helps to elevate blood pressure. Patients experience palpitations. Activation of the renin-angioten-sin-aidosterone (RAA) system serves to increase blood volume, hence cardiac output. Fluid retention leads to an increase in body weight and, possibly, edemas. These counter-regulatory processes are susceptible to pharmacological inhibition ( 3-blockers, ACE inhibitors, ATI-antagonists, diuretics). 

Individual vasodilators. Nitrates (p. 120) Ca -antagonists (p. 122). ai-antagonists (p. 90), ACE-inhibitors, ATI -antagonists (p. 124) and sodium nitro-prusside (p. 120) are discussed elsewhere. 

In multidrug therapy, it is necessary to consider which agents rationally complement each other. A p-blocker (bradycardia, cardiodepression due to sympathetic blockade) can be effectively combined with nifedipine (reflex tachycardia), but obviously not with verapamil (bradycardia, cardiodepression). Monotherapy with ACE inhibitors (p. 124) produces an adequate reduction of blood pressure in 50% of patients the response rate is increased to 90% by combination with a (thiazide) diuretic. When vasodilators such as dihydralazine or minoxidil (p. 118) are given, p-blockers would serve to prevent reflex tachycardia, and diuretics to counteract fluid retention. 

Advise patients that initiation of treatment and (to a lesser extent) dosage increases may be associated with transient symptoms of dizziness or lightheadedness (and rarely syncope) within the first hour after dosing. Thus, during these periods, avoid situations such as driving or hazardous tasks, where symptoms could result in injury. In addition, vasodilatory symptoms often do not require treatment, but it may be useful to separate the time of dosing of carvedilol from that of the ACE inhibitor or to temporarily reduce the dose of the ACE inhibitor. Do not increase the dose of carvedilol until symptoms of worsening heart failure or vasodilation have been established. 

Congestive heart failure treatment may be improved by cautiously adding a /3-blocker to conventional management with ACE-inhibitors and diuretics. Bisoprolol and carvedilol are the preferable /3-blockers, since their beneficial effect has been convincngly demonstrated in appropriate clinical trials. Bisoprolol is a highly selective /8i-blocker. Carvedilol has additional properties to its /8-receptor blocking activity, such as a weak vasodilator component and anti-oxidant activity. The beneficial effect is very likely to be caused by /8i-adrenoceptor blockade. 

ACE-inhibition will cause a reduction of cardiac afterload and preload in patients with heart failure. In addition, the ACE-inhibitors exert a favourable effect on the neuro-endocrine activation process associated with chronic heart failure. They are more effective than classic vasodilators such as hydralazine and isosorbide, which do not influence these neuroendocrine mechanisms in a favourable manner. 

In summary, black hypertensive patients respond well to thiazide diuretics, CCB, vasodilators like prazosin, doxazosin or the vasodilating /3-blocker la-betalol. It is suggested that in black hypertensive patients a thiazide diuretic should be routinely added when a /3-blocker or an ACE inhibitor is used. This above information is summarized in Table 10. 

Eurther refinement of this basic understanding followed. Eirst of aU, ACE inhibitors not only block the conversion of angiotensin I to angiotensin II they also block the breakdown of bradykinin. Kinins are vasodilators and serve as part of the yin-yang of the vas-... 

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