Cardiovascular system cardiac effects

Figure 15.4 Effects of the autonomic nervous system on mean arterial pressure. The baroreceptors, chemoreceptors, and low-pressure receptors provide neural input to the vasomotor center in the brainstem. The vasomotor center integrates this input and determines the degree of discharge by the sympathetic and parasympathetic nervous systems to the cardiovascular system. Cardiac output and total peripheral resistance are adjusted so as to maintain mean arterial pressure within the normal range.

Adverse Effects. Quinine is associated with many adverse effects involving several primary organ systems. This drug may produce disturbances in the CNS (headache, visual disturbances, ringing in the ears), gastrointestinal system (nausea, vomiting, abdominal pain), and cardiovascular system (cardiac arrhythmias). Problems with hypersensitivity, blood disorders, liver dysfunction, and hypoglycemia may also occur in some individuals. 

Despite conflicting results, enflurane is generally considered to have httle effect on the cardiovascular system. Cardiac output was mildly influenced in healthy men and the negative inotropic effects of enflurane (2) were more pronounced in patients with congestive heart failure (3). Myocardial damage was suggested to be an unhkely comphcation of enflurane anesthesia, even in patients with ischemic heart disease (4). 

Ca2+ is an important intracellular second messenger that controls cellular functions including muscle contraction in smooth and cardiac muscle. Ca2+ channel blockers inhibit depolarization-induced Ca2+ entry into muscle cells in the cardiovascular system causing a decrease in blood pressure, decreased cardiac contractility, and antiarrhythmic effects. Therefore, these drugs are used clinically to treat hypertension, myocardial ischemia, and cardiac arrhythmias. 

Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) are members of a family of so-called natriuretic peptides, synthesized predominantly in the cardiac atrium, ventricle, and vascular endothelial cells, respectively (G13, Y2). ANP is a 28-amino-acid polypeptide hormone released into the circulation in response to atrial stretch (L3). ANP acts (Fig. 8) on the kidney to increase sodium excretion and glomerular filtration rate (GFR), to antagonize renal vasoconstriction, and to inhibit renin secretion (Ml). In the cardiovascular system, ANP antagonizes vasoconstriction and shifts fluid from the intravascular to the interstitial compartment (G14). In the adrenal cortex, ANP is a powerful inhibitor of aldosterone synthesis (E6, N3). At the hypothalamic level, ANP inhibits vasopressin secretion (S3). It has been shown that some of the effects of ANP are mediated via a newly discovered hormone, called adreno-medullin, controlling fluid and electrolyte homeostasis (S8). The diuretic and blood pressure-lowering effect of ANP may be partially due to adrenomedullin (V5). 

One of the pollutants known to interfere with cardiovascular development is 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD). TCDD is a persistent, bioaccumulative environmental contaminant, as well as a potent developmental toxicant and human carcinogen [30]. Piscine, avian, and mammalian cardiovascular systems are sensitive to TCDD toxicity, with effects including cardiac enlargement, edema, and several dysfunctions. In zebrafish embryos, these effects include areduction in cardiomyocyte number at 48 hpf, decreased heart size, altered vascular remodeling, pericardial edema, and decreased ventricular contraction culminating in ventricular standstill [31-34]. 

Action on the CNS depends directly on the dose of administered drug, and can be manifested as fatigue, anxiety, tremors, and even convulsions in relatively high doses. Theophylline acts on the cardiovascular system by displaying positive ionotropic and chronotropic effects on the heart, which, can likely be linked to the elevated influx of calcium ions by modulated cyclic adenosine monophosphate and its action on specific cardiac phosphodiesterases. In the gastrointestinal system, methylxanthines simultaneously stimulate secretion of both gastric juice and digestive enzymes. 

The triazolopyridine trazodone does not have an appreciable effect on the re-uptake of the neurotrans-mittors dopamine or noradrenaline. It is a weak inhibitor of serotonin re-uptake but is a potent antagonist of the serotonin 5-HT2 receptor. Clinical experience has shown unpredictable efficacy. Trazodone has little antimuscarinic activity and has little if any action on cardiac conduction. Like mianserin it can therefore safely be used in patients for which anticholinergics are contraindicated and there are no absolute contraindications for patients with concomitant diseases of the cardiovascular system. 

The most important actions of the (3-blocking drugs are on the cardiovascular system. -Blockers decrease heart rate, myocardial contractility, cardiac output, and conduction velocity within the heart. These effects are most pronounced when sympathetic activity is high or when the heart is stimulated by circulating agonists. 

The actions of anticholinesterase agents on the cardiovascular system are complex. The primary effect produced by potentiation of vagal stimulation is bradycardia with a consequent decrease in cardiac output and blood pressure. However, potentiation of both parasympathetic and sympathetic ganglionic transmis-... 

The effects of nicotine on the cardiovascular system mimic those seen after activation of the sympathoadrenal system, and they are principally the result of a release of epinephrine and norepinephrine from the adrenal medulla and adrenergic nerve terminals. These effects include a positive inotropic and chronotropic effect on the myocardium as well as an increase in cardiac output. In addition, both systohc and diastolic blood pressures are increased secondary to stimulation of the sympathoadrenal system. These effects are the end result of a summation of adrenergic and chohnergic stimulation. 

The effects of phenytoin on the cardiovascular system vary with the dose, the mode and rate of administration, and any cardiovascular pathology. Rapid administration can produce transient hypotension that is the combined result of peripheral vasodilation and depression of myocardial contractility. These effects are due to direct actions of phenytoin on the vascular bed and ventricular myocardium. If large doses are given slowly, dose-related decreases in left ventricular force, rate of force development, and cardiac output can be observed, along with an increase in left ventricular end-diastolic pressure. 

VIP exerts significant effects on the cardiovascular system. It produces marked vasodilation in most vascular beds and in this regard is more potent on a molar basis than acetylcholine. In the heart, VIP causes coronary vasodilation and exerts positive inotropic and chronotropic effects. It may thus participate in the regulation of coronary blood flow, cardiac contraction, and heart rate. 

Cardiovascular system Decreased peripheral vascular resistance increased heart rate, stroke volume, cardiac output, pulse pressure high-output heart failure increased inotropic and chronotropic effects arrhythmias angina Increased peripheral vascular resistance decreased heart rate, stroke volume, cardiac output, pulse pressure low-output heart failure ECG bradycardia, prolonged PR interval, flat T wave, low voltage pericardial effusion... 

For many drugs, at least part of the toxic effect may be different from the therapeutic action. For example, intoxication with drugs that have atropine-like effects (eg, tricyclic antidepressants) reduces sweating, making it more difficult to dissipate heat. In tricyclic antidepressant intoxication, there may also be increased muscular activity or seizures the body s production of heat is thus enhanced, and lethal hyperpyrexia may result. Overdoses of drugs that depress the cardiovascular system, eg, 13 blockers or calcium channel blockers, can profoundly alter not only cardiac function but all functions that are dependent on blood flow. These include renal and hepatic elimination of the toxin and any other drugs that may be given. 

As for the cardiovascular system, the cardioprotective effects of selective H3-receptor agonists, demonstrated in models of protracted myocardial ischemia (Imamura et al., 1994, 1995, 1996a Hatta et al., 1996, 1997), could be predictive of beneficial effects in coronaropatic patients. Hence, the attenuation of carrier-mediated noradrenaline release in hypoxic and/or ischemic myocardium by H3-agonists would limit the sympathetic overactivity and the associated incidence of ventricular arrhythmias and angina, as well as the increase of metabolic demand by the myocardium, thus preventing further damage and cardiac failure. 

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