Reflex tachycardia

Prazosin, a selective a -adrenoceptor antagonist, exerts its antihypertensive effect by blocking the vasoconstrictor action of adrenergic neurotransmitter, norepinephrine, at a -adrenoceptors in the vasculature (200,227,228). Prazosin lowers blood pressure without producing a marked reflex tachycardia. It causes arteriolar and venular vasodilation, but a significant side effect is fluid retention. Prazosin increases HDL cholesterol, decreases LDL cholesterol, and does not cause glucose intolerance. 

Nifedipine, verapamil, and diltiazem are all efficacious in the treatment of mild and moderate hypertension, but nifedipine is more efficacious than diltiazem and verapamil in the control of severe hypertension. Nifedipine does not cause significant reflex tachycardia or orthostatic hypotension. Nifedipine benefits the older and black patients and patients with low PRA. 

Nifedipine (Table 3) is a potent vasodilator that selectively dilates resistance vessels and has fewer effects on venous vessels. It does not cause reflex tachycardia during chronic therapy. Nifedipine is one of the first-line choices for black or elderly patients and patients having concomitant angina pectoris, diabetes, or peripheral vascular diseases. Nifedipine, sublingually, is also suitable for the treatment of hypertensive emergencies. Nifedipine does not impair sexual function or worsen blood Hpid profile. The side effects are flushing, headache, and dizziness. 

Closely monitor heart rate in patients treated with drugs that have negative chronotropic effects (e.g., fi-blockers, verapamil, or diltiazem) or drugs that may cause reflex tachycardia (e.g, nitrates or dihydropyridine CCBs). 

Vasodilators. Hydralazine causes direct relaxation of arteriolar smooth muscle. An important consequence of this vasodilation, however, is reflex tachycardia (T CO). It may also cause sodium retention (T plasma volume). The resulting increase in CO tends to offset effects of the vasodilator. Therefore, these drugs are most effective when administered along with sympathetic agents such as P-adrenergic receptor antagonists, which prevent unwanted compensatory responses by the heart. 

The answer is a. (Hardman, pp 762-764.) Experimentally, nitrates dilate coronary vessels. This occurs in normal subjects, resulting in an overall increase in coronary blood flow. In arteriosclerotic coronaries, the ability to dilate is lost, and the ischemic area may actually have less blood flow under the influence of nitrates. Improvement in the ischemic conditions is the result of decreased myocardial oxygen demand because of a reduction of preload and afterload. Nitrates dilate both arteries and veins and thereby reduce the work of the heart. Should systemic blood pressure fall, a reflex tachycardia will occur. In pure coronary spasm, such as Prinzmetal s angina, the effect of increased coronary blood flow is relevant, while in severe left ventricular hypertrophy with minimal obstruction, the effect on preload and afterload becomes important. 

The answer is a. (Hardman, pp 228-229.) Phentolamine is a non-selective a-adrenergic receptor blocker (i.e., it has affinity for both - and ct2-adrenergic receptor sites). It also has a prominent direct relaxant (musculotropic spasmolytic) effect on arterioles, which results in vasodilation and reflex tachycardia. In addition, phentolamine can block the effects of serotonin and will increase hydrochloric acid and pepsin secretion from the stomach. Phentolamine is used for the short-term control of hypertension in patients with pheochromocytoma (i.e., a type of secondary hypertension) because of the high incidence of tachycardia associated with the compound, it is not used chronically for the treatment of essential hypertension... 

If /1-blockers are ineffective or not tolerated, then monotherapy with a calcium channel antagonist or combination therapy may be instituted. Reflex tachycardia from nitrates can be blunted with /1-blocker therapy, making this a useful combination. Patients with severe angina, rest angina,... 

Adverse effects include postural hypotension with associated CNS symptoms, reflex tachycardia, headaches and flushing, and occasional nausea. Excessive hypotension may result in MI or stroke. Noncardiovascular adverse effects include rash (especially with transdermal nitroglycerin) and methemoglobinemia with high doses given for extended periods. 

In dogs, this compound is a potent, long acting hypotensive which shows reflex tachycardia but no tolerance potential (39). 

Hydralazine is equally effective in the supine and standing positions. The cardiovascular reflexes are intact and no postural hypotension is seen. However, the reflex tachycardia and increase in cardiac output (Figure 1) severely limit the clinical use of this drug. Tachycardia is almost invariably associated with the subjective complaints of severe palpitations (Figure 1). 

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). 

Clinically, clonidine has shown great versatility effective in mild, moderate and severe hypertension. The major side effects are drowsiness and dry mouth. Clonidine can be effectively used in combination with a diuretic(32). In addition, a vasodilator (hydralazine) can be usefully added. The brady-cardiac effect of clonidine prevents the reflex tachycardia induced by the vasodilator. 

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). 

At the start of therapy, unwanted reactions occur frequently in the form of a throbbing headache, probably caused by dilation of cephalic vessels. This effect also exhibits tolerance, even when daily nitrate pauses are kept Excessive dosages give rise to hypotension, reflex tachycardia, and circulatory collapse. 

Indications. Verapamil is used as an antiarrhythmic drug in supraventricular tachyarrhythmias. In atrial flutter or fibrillation, it is effective in reducing ventricular rate by virtue of inhibiting AV-conduction. Verapamil is also employed in the prophylaxis of angina pectoris attacks (p. 308) and the treatment of hypertension (p. 312). Adverse effects Because of verapamil s effects on the sinus node, a drop in blood pressure fails to evoke a reflex tachycardia Heart rate hardly changes bradycardia may even develop. AV-block and myocardial insufficiency can occur. Patients frequently complain of constipation. 

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. 

Doxazosin, also a selective a i-blocker, resembles prazosin in most aspects, but it has a better pharmacokinetic profile, at least for long-term use as in essential hypertension. Owing to its slow onset of action, doxazosin causes far less orthostatic hypotension and reflex tachycardia than prazosin. As a result of its long duration of action, it can be administered once daily in the long-term treatment of essential hypertension. 

In the treatment of hypertension a selective O -adrenoceptor agent is preferable to the older, non-selective (ai - - a2)-blockers. Doxazosin is preferable to prazosin, because it has a slower onset and longer duration of action. It therefore causes less or no reflex tachycardia and orthostatic hypotension. 

Hydralazine and dihydralazine are predominantly arterial vasodilators which cause a reduction in peripheral vascular resistance but also reflex tachycardia and fluid retention. They were used in the treatment of hypertension, in combination with a -blocker and a diuretic. Long-term use of these compounds may cause a condition resembling lupus erythematodes with arthrosis, dermatitis and LE-cells in the blood. This risk is enhanced in women and in patients with a slow acetylator pattern. When combined with the venous vasodilator isosorbide (an organic nitrate) hydralazine was shown to be mildly beneficial in patients with congestive heart failure (V-HEFT I Study). Hydralazine and dihydralazine have been replaced by other therapeutics, both in hypertension treatment and in the management of heart failure. 

Vasodilatation explains both the therapeutic efficacy of the nitrates in angina (see above) and their well-known side-effects, such as headache, facial flush, reflex tachycardia, and (in higher doses) hypotension. 

Fig. 3. Haemodynamic effects of different types of calcium antagonists. Drawn lines nifedipine and other rapidly an short-acting dihydropyridines. Dotted lines verapamil and diltiazem. MAP = mean arterial pressure HR = heart rate CO = cardiac output TPR = total peripheral resistance UE = urinary excretion of Na and H2O. Note the reflex tachycardia, provoked by nifedipine.

Nifedipine -blockers suppress reflex tachycardia (favourable), but enhance the negative inotropic activity. 

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