Cardiac Activity Additional heart rate

The QT interval is a dynamic physiological variable depending on multiple factors such as cardiac cycle length (heart rate), autonomic nervous system activity, age, gender, plasma electrolyte concentrations, genetic variations in ion channels involved in cardiac repolarization. In addition, circadian and seasonal variations of the QT interval have been described [93]. 

Some P-adrenoceptor blockers have intrinsic sympathomimetic activity (ISA) or partial agonist activity (PAA). They activate P-adrenoceptors before blocking them. Theoretically, patients taking P-adrenoceptor blockers with ISA should not have cold extremities because the dmg produces minimal decreases in peripheral blood flow (smaller increases in resistance). In addition, these agents should produce minimal depression of heart rate and cardiac output, either at rest or during exercise (36). 

SNRIs have many of the serotonergic adverse effects associated with SSRIs. In addition, SNRIs may also have noradrenergic effects, including increased blood pressure and heart rate, and CNS activation, such as insomnia, anxiety, and agitation. The hemodynamic effects of SNRIs tend not to be problematic in most patients. A dose-related increase in blood pressure has been seen more commonly with the immediate-release form of venlafaxine than with other SNRIs. Likewise, there are more reports of cardiac toxicity with venlafaxine overdose than with either the other SNRIs or SSRIs. Duloxetine is rarely associated with hepatic toxicity in patients with a history of liver damage. All the SNRIs have been associated with a discontinuation syndrome resembling that seen with SSRI discontinuation. 

Additionally, cardiac function can also be modulated by centrally-located H3-receptors. The intracerebroventricular administration of (R)a-methylhistamine in conscious animals is associated with a marked reduction of the heart rate, an effect which is antagonised by thioperamide (McLeod et al., 1991). The peripheral administration of ipratropium, a muscarinic antagonist which does not cross the blood-brain barrier, prevents such inhibition, demonstrating that the activation of centrally-located histamine H3-receptors leads to an increase in the vagal tone to the heart, rather than to a facilitatory effect on the sympathetic efferent fibers. 

Beta-adrenergic blockers have been used extensively to decrease blood pressure and are a mainstay of antihypertensive therapy in many patients.4,81 Beta blockers exert their primary effect on the heart, where they decrease heart rate and force myocardial contraction. In hypertensive patients, these drugs lower blood pressure by slowing down the heart and reducing cardiac output. This statement, however, is probably an oversimplification of how beta blockers produce an antihypertensive effect. In addition to their direct effect on the myocardium, beta blockers also produce a general decrease in sympathetic tone.19,39 Although their exact effects on sympathetic activity remain to be determined, beta blockers may decrease sympathetic activi-... 

In addition to its effects on cardiac contractility, digitalis has a direct inhibitory effect on sympathetic nervous system activity.37,60 This effect is beneficial because it decreases stress on the failing heart by decreasing excessive sympathetic stimulation of the heart and peripheral vasculature2. Therapeutic levels of digitalis likewise stabilize heart rate and slow impulse conduc-... 

Increased sympathetic activity Baroreceptors sense a decrease in blood pressure, and trigger activation of p-adrenergic receptors in the heart. This results in an increase in heart rate and a greater force of contraction of the heart muscle (Figure 16.4). In addition, vasoconstriction (ai-mediated) enhances venous return and increases cardiac preload. These compensatory responses increase the work of the heart and, therefore, can contribute to the further decline in cardiac function. 

Quinidine, the d-isomer of quinine, has been used in horses since 1924 (Roos 1924) and has a wide variety of properties. It is currently the drug of choice for the treatment of atrial fibrillation (AF) in horses but can be used for the treatment of a variety of re-entrant and ectopic arrhythmias. Quinidine affects heart rate, cardiac rhythm and vascular tone by a range of mechanisms and also produces a variety of non-cardiac effects. In addition to the class la activity, which prolongs the effective refractory period, the drug is vagolytic as a result of its antimuscarinic properties. 

The immediate treatment for nerve agent intoxication is intravenous injection of 2 mg atropine sulfate (intramuscular injection should be considered if the patient is hypoxic and ventilation cannot be initiated, as there is a risk of ventricular fibrillation). This should be followed by additional injections of atropine at 10-15 min intervals, continuing until bradycardia has been reversed (e.g., until the heart rate is at 90 beats per minute). If breathing has stopped, a mechanical respirator should be used to ventilate the patient. Mouth-to-mouth resuscitation should not be attempted. If possible, oxygen or oxygen-enriched air should be used for ventilation. If possible, cardiac activity should be monitored. 

Common side effects of dexmedetomidine include hypotension and bradycardia, attributed to decreased catecholamine release mediated by activation of receptors. Nausea and dry mouth also are common. At higher drug concentrations, the subtype is activated, resulting in hypertension and a further decrease in heart rate and cardiac output. Dexmedetomidine produces sedation and analgesia with minimal respiratory depression. Sedation produced by dexmedetomidine is noted to be more akin to natural sleep, with patients relatively easy to arouse. However, dexmedetomidine does not appear to provide reliable arrmesia and additional agents may be needed if lack of recall is desirable. 

I. Pharmacology. Bretylium is a quaternary ammonium compound that is an effective type III antifibrillatory dmg and also suppresses ventricular ectopic activity. It increases the threshold for ventricular fibrillation and reduces the disparity in action potential duration between nonnal and ischemic tissue, which is believed to abolish boundary currents responsible for reentrant arrhythmias. Its pharmacologic actions are complex. Initially, norepinephrine is released from sympathetic neurons this is followed by a block of further norepinephrine release. In addition, norepinephrine uptake is inhibited at adrenergic neurons. The result is a transient increase in heart rate, blood pressure, and cardiac output that may last from a few minutes to 1 hour. Subsequent adrenergic blockade produces vasodilation, which may result in hypotension. 

These animal studies should indicate to the pharmacist that blood flow can, under certain circumstances, be an important patient variable that may affect the absorption of drugs. Patients in heart failure would generally be expected to have a decreased cardiac output and, therefore, a decreased splanchnic blood flow. This could lead to a decreased rate of absorption for drugs when the blood flow rates in Eq. (7) become rate-limiting. In addition, redistribution of cardiac output during cardiac failure may lead to splanchnic vasoconstriction in patients [57], Other disease states and physical activity can also decrease blood flow to the GIT [2 4], Thus, the pharmacist must be aware of the possible effect of blood flow rate, especially alterations in the rate, on the availability of drugs. 

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