Cardiovascular effects stimulants

Relatively selective stimulation of Pi-adrenergic receptors can be achieved with dobutamine. This is a racemic drug of which both isomers activate the Pi-receptor, and in addition the (-) isomer activates ( -receptors whereas the (+) isomer activates p2-receptors the simultaneous activation of ai- and p2-receptors results in no major net effect on peripheral resistance, and thus the overall cardiovascular effects are mediated by Pi-stimulation leading to increases in cardiac contractility and output. Dobutamine is used for the short-term treatment of acute cardiac failure and for diagnostic purposes in stress echocardiography. 

Oppenheimer SM, Gelb A, Girvin JP, Hachinski VC. Cardiovascular effects of human insular cortex stimulation. Neurology 1992 42(9) 1727-1732. 

The effects of the autonomic nervous system on MAP are summarized in Figure 15.4. The parasympathetic system innervates the SA node and the AV node of the heart. The major cardiovascular effect of parasympathetic stimulation, by way of the vagus nerves, is to decrease HR, which decreases CO and MAP. 

Results of in vitro studies suggest an interaction between calcium ions and cyanide in cardiovascular effects (Allen and Smith 1985 Robinson et al. 1985a). It has been demonstrated that exposure to cyanide in metabolically depleted ferret papillary muscle eventually results in elevated intracellular calcium levels, but only after a substantial contracture develops (Allen and Smith 1985). The authors proposed that intracellular calcium may precipitate cell damage and arrhythmias. The mechanism by which calcium levels are raised was not determined. Franchini and Krieger (1993) produced selective denervation of the aortic and carotid bifurcation areas, and confirmed the carotid body chemoreceptor origin of cardiovascular, respiratory and certain behavioral responses to cyanide in rats. Bradycardia and hyperventilation induced by cyanide are typical responses evoked by carotid body chemoreceptor stimulation (Franchini and Krieger 1993). 

Cardiovascular effects are related to both central and peripheral sympathetic stimulation. Initial bradycardia appears to be related to vagal stimulation this is followed by tachycardia and hypertension. Larger doses are directly depressant to the myocardium, and death results from cardiac failure. 

Nausea and vomiting because of CTZ stimulation, which can be minimized by starting with a lower dose. It also causes confusion, hallucinations, delusions and other behavioural effects. Certain cardiovascular effects such as palpitation, postural hypoten-sion, sinus tachycardia and ventricular arrhythmias have also been reported. 

Although ketamine produces direct myocardial depression, it has significant indirect cardiovascular effects through sympathomimetic effects and stimulation of the vasomotor centre. The heart rate and systolic blood pressure increase by 30% and occasionally up to 100%. Owing to the increased cardiac work and myocardial consumption, ketamine adversely affects the balance between myocardial oxygen supply and demand. Consequently, it is not recommended for use as the sole agent in adults with severe cardiovascular disease. However, the same haemodynamic effects, particularly the raised systemic vascular resistance, make the agent particularly suitable for children with cyanotic heart disease. 

Atracurium causes minimal cardiovascular effects except those associated with some histamine release if the drug is given rapidly or in high doses. As with vecuronium, it produces little increase in heart rate in fact, decreases in heart rate have been reported. This is once again thought to be due to the effects of other agents, such as the opiates, or as a result of vagal stimulation. The incidence of histamine release with atracurium is about one-third of that observed after tubocurarine administration. 

Atomoxetine is a selective inhibitor of the norepinephrine reuptake transporter. Its actions, therefore, are mediated by potentiation of norepinephrine levels in noradrenergic synapses. It is used in the treatment of attention deficit disorders (see below). Atomoxetine has surprisingly little cardiovascular effect because it has a clonidine-like effect in the central nervous system to decrease sympathetic outflow while at the same time potentiating the effects of norepinephrine in the periphery. However, it may increase blood pressure in some patients. Norepinephrine reuptake is particularly important in the heart, particularly during sympathetic stimulation, and this... 

In humans, injection or infusion of histamine causes a decrease in systolic and diastolic blood pressure and an increase in heart rate. The blood pressure changes are caused by the direct vasodilator action of histamine on arterioles and precapillary sphincters the increase in heart rate involves both stimulatory actions of histamine on the heart and a reflex tachycardia. Flushing, a sense of warmth, and headache may also occur during histamine administration, consistent with the vasodilation. Vasodilation elicited by small doses of histamine is caused by H -receptor activation and is mediated primarily by release of nitric oxide from the endothelium (see Chapter 19). The decrease in blood pressure is usually accompanied by a reflex tachycardia. Higher doses of histamine activate the H2-mediated cAMP process of vasodilation and direct cardiac stimulation. In humans, the cardiovascular effects of small doses of histamine can usually be antagonized by Hi-receptor antagonists alone. 

The primary drug therapies are psychostimulants which are indicated for both emotional based sleep disorders (i.e., narcolepsy) as well as ADHD. The drugs of choice are Ritalin (methylphenidate), dextroamphetamine or Cylert (pemoline), all CNS stimulants that effect the monoamine systems. The current therapies provide symptomatic relief but the current medications are not without side effects, including abuse potential, cardiovascular effects, insomnia, appetite suppression, head and stomach aches, crying and nervous mannerisms. 

The net cardiovascular effects of atropine in patients with normal hemodynamics are not dramatic tachycardia may occur, but there is little effect on blood pressure. However, the cardiovascular effects of administered direct-acting muscarinic stimulants are easily prevented. 

Adverse cardiovascular effects seen with intravenously infused pressor agents include marked elevations in blood pressure that cause increased cardiac work, which may precipitate cardiac ischemia and failure. Systemically administered Preceptor-stimulant drugs may cause sinus... 

Acute intoxication with amphetamine is associated with tremor, confusion, irritability, hallucinations and paranoid behaviour, hypertension, sweating and occasionally cardiac arrhythmias convulsions and death may occur. The cardiovascular effects of the stimulants may be treated by beta-blockers, or by the combined alpha- and beta-blocker labetalol calcium channel antagonists such as nifedipine may correct the arrhythmias, while intravenous diazepam is of value in attenuating seizures. 

Cardiovascular Effects. No studies were located regarding cardiovascular effects in humans after dermal exposure to acrolein. When applied locally to the eyes of rabbits, acrolein (dose not reported) increased the heart rate (Basu et al. 1971). However, this effect is most likely due to the painful stimulation of the eye. 

Q10 Other bronchodilator agents include nebulized ipratropium. Ipratropium is a muscarinic receptor antagonist that helps to relax bronchial smooth muscle which has contracted via parasympathetic stimulation. The xanthines theophylline and aminophylline (theophylline ethylenediamine) are alternative bronchodilator agents. These agents may act as phosphodiesterase inhibitors and, although they have been used as bronchodilators for many years, adverse CNS, GI and cardiovascular effects may limit their usefulness. 

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