Muscle negative inotropic effects

Q69 At therapeutic doses the occurrence of o negative inotropic effect v/ith omlodipine is rarely seen. Amlodipine has greater selectivity for vascular smooth muscle than for myocardium. 

Amlodipine is a calcium-channel blocker that blocks the intracellular movement of calcium ions and hence slows the contractility of the myocardium and relaxes the vascular smooth muscle. The negative inotropic effects are rarely seen at therapeutic doses since amlodipine has a greater selectivity for vascular smooth muscle than for the myocardium. 

Halothane exerts a pronounced hypotensive effect, to which a negative inotropic effect contributes. Enflurane and isoflurane cause less circulatory depression. Halothane sensitizes the myocardium to catecholamines (caution serious tachyarrhythmias or ventricular fibrillation may accompany use of catecholamines as antihypotensives or toco-lytics). This effect is much less pronounced with enflurane and isoflurane. Unlike halothane, enflurane and isoflurane have a muscle-relaxant effect that is additive with that of nondepolarizing neuromuscular blockers. 

As propafenone exerts both beta blockade and a (dose-related) negative inotropic effect on cardiac muscle, fully compensate patients with CHF before receiving propafenone. If CHF worsens, discontinue propafenone unless CHF is due to the cardiac arrhythmia and, if indicated, restart at a lower dosage only after adequate cardiac compensation has been established. 

Most of the haemodynamic effects of opioids are related to decreased central sympathetic outflow, specific vagal effects or, in the case of morphine and pethidine, histamine release. Fentanyl and its analogues do not cause histamine release. All opioids, with the exception of pethidine, produce bradycardia by actions on the afferent fibres of the vagus and the nucleus tractus solitarius and nucleus commissuralis, which have very high densities of opioid receptors. Pethidine often produces tachycardia, possibly due to its structural similarity to atropine. In isolated heart or heart-muscle preparations, opioids produce a dose-related negative inotropic effect, but only at concentrations 100 to several thousand times those found clinically. 

Effects on respiration are similar to those of thiopental at usual anesthetic doses. However, propofol causes a marked decrease in systemic blood pressure during induction of anesthesia, primarily through decreased peripheral resistance. In addition, propofol has greater negative inotropic effects on the heart than etomidate and thiopental. Apnea and pain at the site of injection are common adverse effects of bolus administration. Muscle movements, hypotonus, and (rarely) tremors have also been reported following its use. Clinical infections due to bacterial contamination of the propofol emulsion have led to the addition of antimicrobial adjuvants (eg, ethylenediaminetetraacetic acid and metabisulfite). 

Ugur, M., and Turan, B. 2001. Adenosine triphosphate alters the selenite-induced contracture and negative inotropic effect on cardiac muscle contractions. Biol. Trace Elem. Res. 79 235-245. 

Benzothiazepines Diltiazem [dil TYE a zem] is the only member of this class that is currently approved in the United States. Like verapamil, diltiazem affects both cardiac and vascular smooth-muscle cells however, it has a less pronounced negative inotropic effect on the heart than does verapamil. Diltiazem has a favorable side-effect profile. 

Kataoka et al. (1994) studied the negative inotropic effects of sevoflurane, isoflurane, enflurane and halothane in canine blood-perfused papillary muscles. 

Viscum contain lectins that are cytotoxic by inhibiting protein synthesis on the ribosomal level in a manner similar to the toxalbumins ricin and abrin. Viscotoxin and phoratoxin are cardiac toxins and vasoconstrictors. Both produced reflex bradycardia, negative inotropic effects, and, in high doses, vasoconstriction of skin and skeletal muscle vessels in animals. 

In the dihydropyridine class it is also evident that the ester functions at C3 and of the 1,4-dihydropyridine ring are an important determinant of activity. Rodenkirchen et al (47), studying a limited series of compounds producing negative inotropic effects in cardiac muscle, suggested that activity decreases with increasing size of lipophilicity of the ester function. However, other studies (.48,4,9) have shown that bulky ester substitutions maintain or even increase activity in smooth muscle preparations (Table 2). 

Nifedipine given intravenously increases forearm blood flow with little effect on venous pooling this indicates a selective dilation of arterial resistance vessels. The decrease in arterial blood pressure elicits sympathetic reflexes, with resulting tachycardia and positive inotropy. Nifedipine also has direct negative inotropic effects in vitro. However, nifedipine relaxes vascular smooth muscle at significantly lower concentrations than those required for prominent direct effects on the heart. Thus, arteriolar resistance and blood pressure are lowered, contractility and segmental ventricular function are improved, and heart rate and cardiac output are increased modestly. After oral administration of nifedipine, arterial dilation increases peripheral blood flow venous tone does not change. 

Acetylcholine (ACh) decreases the rate of firing of the sinoatrial (SA) node (negative chronotropic effect) and the rate of conduction through the atrioventricular (AV) node and ventricular conduction system (negative dromotropic effect), resulting in bradycardia. The force of contraction of the heart muscle is also reduced (negative inotropic effect), resulting in decreased ejection fraction and decreased cardiac output. 

CARDIOVASCULAR SYSTEM ACh has four primary effects on the cardiovascular system vasodilation, a decrease in cardiac rate (the negative chronotropic effect), a decrease in the rate of conduction in the specialized tissues of the SA and atrioventricular (AV) nodes (the negative dromotropic effect), and a decrease in the force of cardiac contraction (the negative inotropic effect). The last effect is of lesser significance in ventricular than in atrial muscle. Certain of the above responses can be obscured by baroreceptor and other reflexes that dampen or counteract the direct responses to ACh. 

All channel blockers relax arterial smooth muscle they have little effect on most venous beds and hence do not affect cardiac preload significantly. In cardiac muscle, Ca + channel blockers can produce a negative inotropic effect. Although true for all classes of Ca channel blockers, the marked peripheral vasodilation seen with the dihydropyridines is accompanied by a robust baroreflex-mediated increase in sympathetic tone that overcomes the negative inotropic effect. 

Green and Nacy, 1993 Nussler and Billiar, 1993 Vane era/., 1994). Induction of iNOS can have potent toxic autocrine effects. Induction of iNOS in endothelial cells may result in endothelial damage (Estrada et al., 1992). In myocardial cells it may cause negative inotropic effects (Evans et al., 1992). It may cause apoptosis in macrophages (Albina et al., 1993) and inhibit cellular respiration in vascular smooth muscle cells (Geng et al., 1992). 

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