The ideal agent for perioperative hypertension and potential cytoprotective effects

Abstract

Perioperative hypertension is primarily due to increased systemic vascular resistance (SVR). Therefore, the major therapeutic approaches are directed at reducing vasoconstriction, using drugs that increase cyclic nucleotides or block calcium entry into vascular smooth muscle. Nitroprusside and other nitric oxide–derived vasodilators affect both the resistance vessels and the vascular capacitance bed. Antihypertensive drugs that affect venous return can have unpredictable effects on blood pressure and calculated SVR. The new intravenous dihydropyridine calcium antagonists have arterial vasodilating actions and are especially promising as new therapeutic approaches for perioperative hypertension. Following coronary bypass–grafting, patients have undergone direct mechanical manipulation of their native grafts, coronary arteries, and internal mammary artery, creating a potential risk for coronary or internal mammary spasm. Calcium antagonists may be an important therapy for perioperative hypertension in such patients. Experimental models have demonstrated that calcium antagonists can attenuate the production of inflammatory mediators and thereby reduce cellular damage following reperfusion. These potential anti–inflammatory drugs may prove to offer additional benefits in the therapy of perioperative hypertension. The potential anti–inflammatory and cytoprotective effects of calcium antagonists may make them the ideal agents for the treatment of acute perioperative hypertension.

Pharmacodynamic, Pharmacokinetic and Clinical Effects of Clevidipine, an Ultrashort‐Acting Calcium Antagonist for Rapid Blood Pressure Control

“…However, â-adrenoceptor antagonists decrease blood pressure at least partly by reducing CO. They do not affect primarily increased SVR, the most common reason for elevated blood pressure during cardiac surgery (35,37,40). A potential drawback of reducing CO is impaired organ perfusion.…”

“…Both GTN and SNP have a pharmacokinetic profile that allows rapid titration to the desired blood pressure level (40). However, these drugs are non-selective vasodilators, they dilate both arteriolar resistance as well as venous capacitance vessels (37,40). The latter effect may compromise venous return and thereby reduce cardiac output (CO) (24).…”

“…Dihydropyridine-type calcium antagonists, like nicardipine, isradipine and nifedipine, have been used successfully to control blood pressure during cardiac surgery (37). Among calcium antagonists, dihydropyridines are highly vasoselective; they dilate precapillary resistance vessels without depressing cardiac contractility (40,51).…”

Pharmacokinetics and tissue distribution of clevidipine and its metabolite in dogs and rats

“…However, subjects with acute, severe hypertension or in the cases of cardiac surgery require intravenous therapy when rapid, controlled blood pressure reduction is necessary and the administration of oral agents is not feasible [2][3][4] . The ideal therapeutic profile for an intravenous antihypertensive agent consists of rapid action, predictability, easy titratability, short duration after discontinuation, and minimal risk of side effects [4][5][6][7] .…”

Evaluation of Electrocardiography After Combined Use of Ondansetron and Diltiazem in Anesthetized Rats

“…7 Diltiazem, an ideal agent used in the treatment of perioperative acute hypertension, is a calcium-channel blocker, which also affects cardiac electrical activity. [8][9][10] Due to this effect, it causes bradycardia and a prolonged PR interval on ECG. 11,12 Since diltiazem used to treat hypertension and ondansetron used to prevent and treat nausea and vomiting cause ECG changes, coadministration of the two drugs in the same individual remains to be studied.…”