Cardiac function depression

Death from overdose of barbiturates may occur and is more likely when more than 10 times the hypnotic dose is ingested. The barbiturates with high lipid solubility and short half-lives are the most toxic. Thus the lethal dose of phenobarbital is 6—10 g, whereas that of secobarbital, pentobarbital, or amo-barbital is 2-3 g. Symptoms of barbiturate poisoning include CNS depression, coma, depressed reflex activity, a positive Babinski reflex, contracted pupils (with hypoxia there may be paralytic dilation), altered respiration, hypothermia, depressed cardiac function, hypotension, shock, pulmonary complications, and renal failure. 

Reduced lean body mass Reduced muscle strength Reduced exercise performance Thin, dry skin cool peripheries poor venous access Depressed affect, labile emotions Impaired cardiac function... 

It has been proposed that NO mediates the myocardial depression associated with sepsis (F6, L14). NO synthesis induced by endotoxin blunts beta-adrenergic responsiveness (B2). In vivo, the use of NO synthase inhibitors led to conflicting results (M26), with a general decreased cardiac output and oxygen delivery being observed. NO synthase inhibition improved left ventricular contractility in endo-toxemic pigs but also increased ventricular afterloads, which ultimately is detrimental to cardiac function (H20). Possible sources of NO in the heart may be the vascular cells, the endothelial cells, and the cardiac myocytes (P6). 

It is this reduction in preload that, in some cases, is beneficial to patients experiencing heart failure or hypertension. Unlike a healthy heart, a failing heart is unable to pump all of the blood returned to it. Instead, the blood dams up and overfills the chambers of the heart. This results in congestion and increased pressures in the heart and venous system and the formation of peripheral edema. Because the failing heart is operating on the flat portion of a depressed cardiac function curve (see Figure 14.2), treatment with diuretics will relieve the congestion and edema, but have little effect on stroke volume and cardiac output. 

The symptoms of overdose are to some extent predictable from the antimuscarinic and adrenolytic activity of these drugs. Excitement and restlessness, sometimes associated with seizures, and rapidly followed by coma, depressed respiration, hypoxia, hypotension and hypothermia are clear signs of TCA overdose. Tachycardia and arrhythmias lead to diminished cardiac function and thus to reduced cerebral perfusion, which exacerbates the central toxic effects. It is generally accepted that dialysis and forced diuresis are useless in counteracting the toxicity, but activated charcoal may reduce the absorption of any unabsorbed drug. The risk of cardiac arrhythmias may extend for several days after the patient has recovered from a TCA overdose. 

Although myocardial depression is not a problem in patients with normal cardiac function, in patients with compromised myocardial function, quinidine may depress cardiac contractility sufficiently to result in a de-... 

Disopyramide directly depresses myocardial contractility. The negative inotropic effect may be detrimental in patients with compromised cardiac function. Some patients develop overt congestive heart failure. At usual therapeutic doses, depression of myocardial function is not a problem in most patients with normal ventricular function. 

The potential for depression of cardiac function is thus usually offset by afterload reduction, especially in the case of nifedipine, which actually has the most marked negative inotropic effect. 

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. 

Adverse effects. Despite these benefits, intrathecal baclofen is associated with a number of potential complications. Primary among these is the possibility of a disruption in the delivery system that is, a pump malfunction or a problem with the delivery catheter can occur.42,60,67,69 In particular, the catheter can become obstructed, or the tip of the catheter can become displaced so that baclofen is not delivered into the correct area of the subarachnoid space. Increased drug delivery due to a pump malfunction could cause overdose and lead to respiratory depression, decreased cardiac function, and coma.40 Conversely, abruptly... 

The rationale for vasodilation in the management of congestive heart failure is based on the increased arteriolar vasotone that occurs. This initiates a vicious circle in which cardiac function is further depressed by an increase in afterload and in resistance to ejection (Figure 35.9). 

Volkcrs AC, Tulen JH, van den Broek WW, Bruyn JA, Passchier J, Pepplinkhuizen L (2004) Effects of imipramine, fluvoxamine and depressive mood on autonomic cardiac functioning in major depressive disorder. Pharmacopsychiatry 37 18-25... 

Kelling et al. (1987) assessed the effects of 2,3,7,8-TCDD on cardiac function tests in male Sprague-Dawley rats 7 days after single oral doses of 6.25, 25, or 100 g/kg. At 100 g/kg (near-lethal dose), an increased sensitivity to the inotropic (left atrium) and chronotropic (right atrium) effects of isoproterenol were observed. Three daily oral doses of 40 g/kg caused decreased heart rate, depressed blood pressure, and increased myocardial peroxidase activity in rats (Hermansky et al. 1988). All of these effects may have been secondary to the modulation of adenylate cyclase activity at -adrenergenic receptors as a result of hypothyroidism (Hermansky et al. 1987). 

Sodium selenite, at nanomolar concentrations, improved the depressed cardiac performance of the isolated heart subjected to ischemia/reperfusion injury. As ischemia/reperfusion-mediated cardiac function has been reported to occur mainly due to the development of oxidative stress and intracellular Ca2+ overload (Bolli and Marban 1999), it is likely that selenium could protect the heart... 

Adverse effects Verapamil and diltiazem have negative inotropic properties and therefore may be contraindicated in patients with preexisting depressed cardiac function. Both drugs can also cause a decrease in blood pressure caused by peripheral vasodilation. 

Verapamil [ver AP a mill] slows cardiac conduction directly and thus decreases heart rate and oxygen demand. Verapamil causes greater negative inotropic effects than does nifedipine, but it is a weaker vasodilator. Verapamil is contraindicated in patients with preexisting depressed cardiac function or AV conduction abnormalities. It also causes constipation. Verapamil should be used with caution in digitalized patients, since it increases digoxin levels (see p. 160). 

As many as 20% of patients taking adequate doses of a tricyclic antidepressant experience marked postural hypotension. This effect is not consistently correlated with plasma concentrations and tolerance does not develop during treatment (35-37). The mechanism for this effect is uncertain it has been attributed to a peripheral antiadrenergic action, to a myocardial depressant effect, and to an action mediated by alpha-adrenoceptors in the central nervous system (38). Studies of left ventricular function in man are conflicting. One study of systolic time intervals showed a decrement in left ventricular function with therapeutic doses (39), while two in which cardiac function was observed directly during cardiac catheterization after overdosage showed no evidence of impaired myocardial efficiency, whereas the hypotension persisted after left ventricular filling pressures and cardiac output had returned to normal (40,41). 

Cohen LS, Wechsler AS, Mitchell JH,GlickG, Depression of cardiac function by streptomycin and other antimicrobial agents. Am J Cardiol, 1970,26 505-11. 

Systemic Monitor renal function, magnesium levels, EKG for cardiac function. Test patellar reflex or knee jerk reflexes before giving repeat parenteral doses (used as indication of CNS depression suppressed reflex may be sign of impending respiratory arrest). Patellar reflex must be present, respiratory rate greater than 16/min before each parenteral dose. Provide seizure precautions. 

Highly lipid-soluble, rapid-onset, and short-acting barbiturate used mainly for induction. Depresses respiratory and cardiac function but does not increase cerebral blood flow. Rapid recovery associated with redistribution from CNS to peripheral tissues, but liver metabolism required for elimination. 

Fentanyl and its derivatives decrease the heart rate and can mildly decrease BR However, these drugs do not release histamine and, in general, provide a marked degree of cardiovascular stability. Direct depressant effects on the myocardium are minimal. For this reason, high doses of fentanyl or sufentanil are commonly used as the primary anesthetic for patients undergoing cardiovascular surgery or for patients with poor cardiac function. 

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