Negative chronotropic effect

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). 

Figure 14.1 Effect of autonomic nervous system stimulation on action potentials of the sinoatrial (SA) node. A normal action potential generated by the SA node under resting conditions is represented by the solid line the positive chronotropic effect (increased heart rate) of norepinephrine released from sympathetic nerve fibers is illustrated by the short dashed line and the negative chronotropic effect (decreased heart rate) of acetylcholine released from parasympathetic nerve fibers is illustrated by the long dashed line.

More recently, the clavulones (not specified which ones) [134] were described to have potent effects on the spontaneous beating rate of cultured myocardial cells from fetal mouse hearts. At a concentration of 0.45 pM, clavulone had positive chronotropic action on these cells however, the character of this effect clearly differed from the positive ionotropic and negative chronotropic effects of the steroid glycoside ouabain or the drug Bay K 8644. Hence, these results suggest that the clavulones may possess a new mechanism of action in this assay system. 

Verapamil must be used with extreme caution or not at all in patients who are receiving p-adrenoceptor blocking agents. Normally, the negative chronotropic effect of verapamil will in part be overcome by an increase in reflex sympathetic tone. The latter is be prevented by simultaneous administration of a p-adrenoceptor blocking agent, which exaggerates the depressant effects of... 

C) Inhibition of a GABA-mediated negative chronotropic effect at the heart... 

Beta blockers bind to beta-1 receptors on the myocardium and block the effects of norepinephrine and epinephrine (see Chapter 20). These drugs therefore normalize sympathetic stimulation of the heart and help reduce heart rate (negative chronotropic effect) and myocardial contraction force (negative inotropic effect). Beta blockers may also prevent angina by stabilizing cardiac workload, and they may prevent certain arrhythmias by stabilizing heart rate.40 These additional properties can be useful to patients with heart failure who also have other cardiac symptoms. 

Compared with other CCBs, mibefradil was found to have more negative chronotropic effects, with a significant incidence of dose-dependent first-degree AV block and sinus bradycardia. No effect on QT intervals was detected in the phase III studies. 

The ability to examine a drug effect over its full range of intensities for example, it would be impossible in the intact organism to follow negative chronotropic effects to the point of cardiac arrest. 

BACLOFEN, TIZANIDINE 1. ANAESTHETICS - general 2. ANTICANCER AND IMMUNOMODULATING DRUGS - IL-2 3. ANTIDEPRESSANTS - MAOIs 4. ANTI HYPERTENSIVES AND HEART FAILURE DRUGS 5. ANTI-PSYCHOTICS 6. ANXIOLYTICS AND HYPNOTICS 7. BETA-BLOCKERS 8. CALCIUM CHANNEL BLOCKERS 9. DIURETICS 10. NITRATES 11. PERIPHERAL VASODILATORS-moxisylyte (thymoxamine) 12. POTASSIUM CHANNEL ACTIVATORS t hypotensive effect Additive hypotensive effect. Tizanidine also has a negative chronotropic effect and may cause additive bradycardia with beta-blockers and calcium channel blockers Monitor BP at least weekly until stable. Warn patients to report symptoms of hypotension (light-headedness, dizziness on standing, etc.)... 

BACLOFEN, TIZANIDINE ANAESTHETICS - GENERAL t hypotensive effect Additive hypotensive effect. Tizanidine also has a negative chronotropic effect and may cause additive bradycardia with beta-blockers and calcium channel blockers Monitor BP closely, especially during induction of anaesthesia... 

The differences between their clinical effects can be explained in part by their binding to different parts of the L-type calcium channel. All members of the group are vasodilators, and some have negative cardiac inotropic action and negative chronotropic effect via pacemaker cells and depress conducting tissue. The attributes of individual drugs are described below. 

A comparison of the cardiotoxicity of the two stereoisomers of ropivacaine and bupivacaine on the isolated heart showed that both compounds had negative inotropic and negative chronotropic effects irrespective of the stereoisomer used, but bupivacaine had greater effects compared with ropivacaine at equal concentrations (16). Atrioventricular conduction time showed stereoselectivity for bupivacaine at clinical concentrations the R(-b) isomer had a greater effect in lengthening atrioventricular... 

Negative inotropic effect Negative chronotropic effect Bradycardia... 

Class IV (diltiazem, verapamil) i AV conduction Negative inotropic effect Negative chronotropic effect Bradycardia Ca + channel blockade... 

Pharmacological investigations using a particular valepotriate fraction called Vpt2 extracted from the roots of V. officinalis (L.) have shown antiar-rhythmic activity and ability to dilate coronary arteries in experimental animals. Moderate positive inotropic and a negative chronotropic effect were also observed. Vpt2 contains valtratum (50%), valeridine (25%), and valechlorin (3%), with trace amounts of acevaltrate, dihydrovaltratum, and epi-7-desacetyl-isovaltrate (36). 

Adenosine Negative chronotropic effect Hypersensitivity Effect on sinus node of denervated heart Life-threatening asystole (>0.5 min) may occur if used to treat supraventricular arrhythmia or stress testing... 

Acetylcholine Negative chronotropic effect Hypersensitivity Effect on sinus node of denervated heart ... 

Isradipine also produces the typical peripheral vasodilation seen with other dihydropyridines, but because of its inhibitory effect on the SA node, little or no rise in heart rate is seen. This inhibitory effect does not extend to the cardiac myocytes, however, because no cardiodepressant effect is seen. Despite the negative chronotropic effect,... 

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