Cardiovascular system cardiac actions

Cocaine can have marked effects on the heart and cardiovascular system. Adverse actions may include myocardial ischemia, cardiac arrhythmias, cardiotoxicity, hypertensive effects, cerebrovascular events, and a hyperco-agulable state (24,40). By 1997 more than 250 cases of myocardial infarction related to the recreational use of cocaine had been documented in the literature (41). Although less common, aortic dissection related to use of cocaine-free base ("crackcocaine") has also been documented (42). Seizures also can be associated with cocaine use (43). 

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 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. 

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. 

Cardiovascular System. Atropine is sometimes used to block the effects of the vagus nerve (cranial nerve X) on the myocardium. Release of acetylcholine from vagal efferent fibers slows heart rate and the conduction of the cardiac action potential throughout the myocardium. Atropine reverses the effects of excessive vagal discharge and is used to treat the symptomatic bradycardia that may accompany myocardial infarction.4 Atropine may also be useful in treating other cardiac arrhythmias such as atrioventricular nodal block and ventricular asystole. 

For example, because an adequate dose of hydralazine causes a significant decrease in peripheral vascular resistance, there will initially be a drop in mean arterial blood pressure, evoking a strong response in the form of compensatory tachycardia and salt and water retention (Figure 11-5). The result is an increase in cardiac output that is capable of almost completely reversing the effect of hydralazine. The addition of a B-blocker prevents the tachycardia addition of a diuretic (eg, hydrochlorothiazide) prevents the salt and water retention. In effect, all three drugs increase the sensitivity of the cardiovascular system to each other s actions. 

The most serious toxic effects of cocaine involve changes in the cardiovascular system. These include cardiac arrhythmias, myocardial ischaemia and infarction, and cerebrovascular spasm, all of which can be largely explained by the facilitation of the action of catecholamines on the cardiovascular system. Another explanation of the cardiotoxicity of cocaine lies in the direct vasoconstrictive properties of its major metabolite, norcocaine. It seems likely... 

Cocaine also blocks the reuptake of norepinephrine in the PNS the combination of central and peripheral actions leads to a high probability of toxicity. The cardiovascular system is particularly sensitive to the actions of cocaine, and cardiac arrhythmias, marked increases in blood pressure, cerebral hemorrhage, myocardial ischemia, and outright heart failure are not uncommon with cocaine use. Even young, otherwise healthy individuals with normal coronary and cerebral arteries have died suddenly after cocaine use from cerebral hemorrhage or ventricular fibrillation. There have been several deaths of famous athletes attributed to cocaine cardiotoxicity. These cardiotoxic effects may be related to increased intracellular calcium levels and involve both cardiac and vascular actions of the drug. 

The hemodynamic effects of compounds supposed to affect the cardiovascular system are evaluated by measuring preload and afterload of the heart, contractility, heart rate, cardiac output and peripheral or coronary flow. To measure these cardiovascular parameters accurately, the use of larger animals such as dogs or pigs is necessary. This experimental model allows the classification of test drugs according to their action as having ... 

The adverse effects of most serious concern relate to the cardiovascular system and seizure threshold. Actions on the adrenergic and cholinergic systems probably contribute to both hypotensive and direct cardiac effects, including alterations in heart rate, quinidine-like delays in conduction, and reduced myocardial contractility. The seizure threshold is lowered, increasing the frequency of epileptic seizures. All of these adverse effects can occur at therapeutic dosages in susceptible populations, such as elderly people, children, and people with cardiac problems or epilepsy, but are also a major cause of morbidity and mortality in accidental or intentional overdosage. Doses in excess of 500 mg can be seriously toxic, and death is fairly common when doses of 2 g or more are taken. 

Cardiovascular system. Both caffeine and theophylline directly stimulate the myocardium and cause increased cardiac output, tachycardia and sometimes ectopic beats and palpitations. This effect occurs almost at once after i.v. injection and lasts half an hour. Theophylline contributes usefuUy to the relief of acute left ventricular failure. There is peripheral (but not cerebral) vasodilatation due to a direct action of the drugs on the blood vessels, but stimulation of the vasomotor centre tends to counter this. Changes in the blood pressure are therefore somewhat unpredictable, but caffeine 250 mg (single dose) usually causes a transient rise of blood pressure of about 14/10 mmHg in occasional coffee drinkers (but has no additional effect in habitual drinkers) this effect can be used advantageously in patients with autonomic nervous system failure who experience postprandial hypotension (2 cups of coffee with breakfast may suffice for the day). In occasional coffee drinkers 2 cups of coffee (about 160 mg caffeine) per day raise blood pressure by 5/4 mmHg. Increased coronary artery blood flow may occur but increased cardiac work counterbalances this in angina pectoris. 

Reduction of portal pressure. Vasopressin (anti-duiretic hormone, see p. 711), in addition to its action on the renal collecting ducts (through receptors), constricts smooth muscle (Vj receptors) in the cardiovascular system (hence its name), and particularly in splanchnic blood vessels, so reducing blood flow in the portal venous system. Unfortunately, coronary vasoconstriction can also occur, and treatment has to be withdrawn from 20% of patients because of myocardial ischaemia. Glyceryl trinitrate (transdermally, sublingually, or intravenously) reduces the cardiac risk and, advantageously, further reduces portal venous resistance and pressure. 

Marches C, ed Ambulatory monitoring Cardiovascular system and allied applications. ISBN 0-89838-642-X. Kupper W, MacAlpin RN, Bleifeld W, eds Coronary tone in ischemic heart disease. ISBN 0-89838-646-2. Sperelakis N, Caulfield JB, eds Calcium antagonists Mechanisms of action on cardiac muscle and vascular smooth muscle. ISBN 0-89838-655-1. 

A number of mechanisms has been postulated to explain the effects of Cd on the cardiovascular system, e.g. interference with catecholamine metabolism (inhibition of MAO-activity), direct action on vascular walls changing peripheral compliance or modifying responses to endogeneous pressor substances, modification of cardiac performance and involvement of the renin-angiotensin-aldosteron system, possibly triggered by changes in sodium reabsorption. 

---