Cardiac stimulant drugs

Figure 9.14 A steroid glycoside. Digitoxenin is a cardiac-stimulating drug. It is a steroid glucoside in which a compound with a steroid structure is linked to a-D-glu-copyranose by condensation of the anomeric hydroxyl group on the carbohydrate and the alcohol group at position 5 on the steroid nucleus.

Clinically, it has been confirmed that the drug is an effective bronchodilator with very little cardiovascular activity it does not appear to increase hypoxaemia [439]. A more detailed study [440], comparing salbutamol with isoprenaline and orciprenaline, demonstrated that 200 jug of salbutamol provided effective bronchodilation for at least three hours without detectable cardiac stimulation. Equivalent bronchodilator doses of isoprenaline and orciprenaline were 1000 /ag and 1500 jUg respectively. The bronchial effects of isoprenaline, though initially intense, waned within one hour and cardiac effects were noted. In this trial little objective difference could be detected between salbutamol and orciprenaline at the dose levels used, though most patients expressed preference for salbutamol. 

Thus, it seems that the lack of sympathetic nervous system inhibition produced by the vasodilators, which is advantageous in some ways, can also be a disadvantage in that reflex increases in sympathetic nerve activity will lead to hemodynamic changes that reduce the effectiveness of the drugs. Therefore, the vasodilators are generally inadequate as the sole therapy for hypertension. However, many of the factors that limit the usefulness of the vasodilators can be obviated when they are administered in combination with a -adrenoceptor antagonist, such as propranolol, and a diuretic. Propranolol reduces the cardiac stimulation that occurs in response to increases in sympathetic nervous activity, and the... 

Hydralazine is generally reserved for moderately hypertensive ambulatory patients whose blood pressure is not well controlled either by diuretics or by drugs that interfere with the sympathetic nervous system. It is almost always administered in combination with a diuretic (to prevent Na+ retention) and a p-blocker, such as propranolol (to attenuate the effects of reflex cardiac stimulation and hyperreninemia). The triple combination of a diuretic, -blocker, and hydralazine constitutes a unique hemodynamic approach to the treatment of hypertension, since three of the chief determinants of blood pressure are affected cardiac output (p-blocker). 

The acute effects of psychomotor stimulant overdoses are related to their CNS stimulant properties and may include euphoria, dizziness, tremor, irritability, and insomnia. At higher doses, convulsions and coma may ensue. These drugs are cardiac stimulants and may cause headache, palpitation, cardiac arrhythmias, anginal pain, and either hypotension or hypertension. Dextroamphetamine produces somewhat less cardiac stimulation. Chronic intoxication, in addition to these symptoms, commonly results in weight loss and a psychotic reaction that is often diagnosed as schizophrenia. 

If the therapeutic range of a drug is broad then many substitutions can probably be made. This occurs, for example, with the penicillins. However, if there is a narrow therapeutic range then bioavailability must be carefully considered. Examples of this situation are the use of digoxin (cardiac stimulant) and phenytoin (anticonvulsive). 

Digitoxin and related drugs are used as cardiac stimulants, causing a positive inotropic effect. Thus, they increase the strength and intensity of the contractions and so are used in the treatment of heart failure. Because they slow the electrical conduction between atria and ventricles, they can also be used in the treatment of atrial fibrillation, atrial tachycardia, and atrial flu ter. 

Caffeine is derived by extraction of coffee beans, tea leaves, and kola nuts. It is also prepared synthetically. Much of the caffeine of commerce is a by-product of decaffeinized coffee manufacture. The compound is purified by a series of recrystallizations. Caffeine finds use in medicine and in soft drinks. Caffeine is also available as the hydrobromide and as sodium benzoate, winch is a mixture of caffeine and sodium benzoate, containing 47-50% anhydrous caffeine and 50-53% sodium benzoate. This mixture is more soluble in water than pure caffeine. A number of nonprescription (pain relief) drugs contain caffeine as one of several ingiedients. Caffeine is a known cardiac stimulant and in some persons who consume significant amounts, caffeine can produce ventricular premature beats. 

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... 

In contrast to phenoxybenzamine, phentolamine [fen TOLE a meen] produces a competitive block of ai and a2 receptors. The drug s action lasts for approximately 4 hours after a single administration. Like phenoxybenzamine, it produces postural hypotension and causes epinephrine reversal. Phentolamine had been used in the diagnosis of pheochromocytoma and in other clinical situations associated with excess release of catecholamines. Phentolamine-induced reflex cardiac stimulation and tachycardia are mediated by the baroreceptor reflex and by blocking the a2 receptors of the cardiac sympathetic nerves. The drug can also trigger arrhythmias and anginal pain and is contraindicated in patients with decreased coronary perfusion. 

Catecholamines are sympathomimetic drugs. Dopamine and norepinephrine are used as vasopressors (antihypotensives). Epinephrine is used as a vasoconstrictor, cardiac stimulant, or bronchodilator to counter allergic reaction, anesthesia, and cardiac arrest. It is also an antiglaucoma agent. 

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