Cardiac effects

The cardiac effects of the calcium antagonists, ie, slowed rate (negative chronotropy) and decreased contractile force (negative inotropy), are prominent in isolated cardiac preparations. However, in the intact circulation, these effects may be masked by reflex compensatory adjustments to the hypotension that these agents produce. The negative inotropic activity of the calcium antagonists may be a problem in patients having heart failure, where contractility is already depressed, or in patients on concomitant -adrenoceptor blockers where reflex compensatory mechanisms are reduced. 

With regard to epinephrines potential adverse cardiac effects, it is important to remember that in anaphylaxis, the heart is a target organ. Mast cells located between myocardial fibers, in perivascular tissue, and in the arterial intima are activated through IgE and other mechanisms to release chemical mediators of inflammation, including histamine, leukotriene C4, and prostaglandin D2. Coronary artery spasm, myocardial injury, and cardiac dysrhythmias have been documented in some patients before epinephrine has been injected for treatment of anaphylaxis, as well as in patients with anaphylaxis who have not been treated with epinephrine [11, 12]. 

Acute oral LDjgS are available from animal studies (Smyth et al. 1969 Tucker et al. 1982). Following acute oral exposure to trichloroethylene effects noted in humans include cardiac effects (Dhuner et al. 1957 Morreale 1976 Perbellini et al. 1991) and neurological effects (Dhuner et al. 1957 Morreale 1976 ... 

Additional information is needed regarding doses/concentrations that result in cardiac effects and conditions that may make persons more sensitive to these effects. 

Wu S et al. (2001) Cardiac effects of the extract and active components of Radix stephaniae tetrandrae. I. Electrically induced intracellular calcium transient and protein release during the calcium paradox. Life Sci 68(25) 2853-2861... 

Patients with acute hyperkalemia usually require other therapies to manage hyperkalemia until dialysis can be initiated. Patients who present with cardiac abnormalities caused by hyperkalemia should receive calcium gluconate or chloride (1 g intravenously) to reverse the cardiac effects. Temporary measures can be employed to shift extracellular potassium into the intracellular compartment to stabilize cellular membrane effects of excessive serum potassium levels. Such measures include the use of regular insulin (5 to 10 units intravenously) and dextrose (5% to 50% intravenously), or nebulized albuterol (10 to 20 mg). Sodium bicarbonate should not be used to shift extracellular potassium intracellularly in patients with CKD unless severe metabolic acidosis (pH less than 7.2) is present. These measures will decrease serum potassium levels within 30 to 60 minutes after treatment, but potassium must still be removed from the body. Shifting potassium to the intracellular compartment, however, decreases potassium removal by dialysis. Often, multiple dialysis sessions are required to remove potassium that is redistributed from the intracellular space back into the serum. 

In patients who have failed initial therapy (i.e., salvage), liposomal amphotericin products, itraconazole, or the echinocandin caspofungin can be used. Itraconazole has a response rate of approximately 40%.100 Oral itraconazole exhibits erratic absorption the IV formulation is suspended in cyclodextrin, which is eliminated renally, and thus IV itraconazole should be avoided in patients with a creatinine clearance of less than 30 mL/minute (0.29 mL/s m2).103 Itraconazole also has negative inotropic cardiac effects and increases the serum concentrations of medications (e.g., cyclophosphamide, etopo-side, calcineurin inhibitors, and sirolimus). 

Leurs, R., Church, M. K Taglialatela, M. (2002). Hl-antihistamines inverse agonism, anti-inflammatory actions and cardiac effects. Clin. Exp. Allergy 32, 489-98. 

The answer is a. (Hardman, p 436J The most common side effects associated with tricyclic antidepressants are their anti muscarinic effects, which may be evident in over 50% of patients. Clinically, the anti muscarinic effects may manifest as dry mouth, blurred vision, constipation, tachycardia, dizziness, and urinary retention. At therapeutic plasma concentrations, these drugs usually do not cause changes in the EKG Direct cardiac effects of the tricyclic antidepressants are important in over dosage. 

Meek and Eyster (1920) exposed eight mongrel dogs (gender not specified) to phosgene at 80-100 ppm for 30 min. All eight died within 24 h postexposure. Pulmonary edema with some evidence of cardiac effects was observed at necropsy. 

The AEGL-3 was based on the lowest response that induced a marked cardiac effect in the cardiac sensitization test with the dog. This concentration of 80,000 ppm was adjusted by a single intraspecies UF of 3 to protect potentially susceptible individuals. An interspecies UF was not applied, because the... 

The dose of administered epinephrine results in blood levels that may be approximately ten times endogenous levels and is close to the threshold for inducing cardiac effects in the absence of the test chemical. 

The cardiac sensitization test is based on the observation that some halocarbons make the mammalian heart abnormally sensitive to epinephrine, resulting in ectopic beats and/or ventricular fibrillation, which may result in death. Effects are monitored with electrocardiograms (EKG). The dose of administered epinephrine results in blood levels that may be approximately ten times endogenous levels and is close to the threshold for inducing cardiac effects in the absence of the test chemical. 

Rat 200 12.5 min Possible changes in blood enzymes attributed to cardiac effects O Flaherty and Thomas 1982... 

Another unanswered question is the evaluation of the effect on cardiac repolarization of oncologic drugs, for which the thorough QT/QTc study in volunteers cannot be performed [166], In these cases, not only central tendency (i.e. mean QTc increase) and proportion of outliers but also other findings such as syncope, ventricular tachyarrhythmias and other cardiac effects should be more closely defined. 

Baskin SI, Wilkerson G, Blitstein AG, et al. 1987. Cardiac effects of cyanide. Clinical and Experimental Toxicology of Cyanides 62-79. 

Because of their reflex cardiac effect, vasodilators, if used alone in the treatment of hypertension, have not been a successful therapeutic tool. However, the reflex tachycardia and increase in cardiac output can be effectively blocked by the therapeutic association with a sympathetic blocker guanethidine, reserpine, methyldopa, or clonidine. More specifically, blockade of the cardiac beta-adrenergic receptors will also prevent the cardiac response to hydralazine. Thus, the therapeutic combination of hydralazine and propranolol can be successfully employed for effective blood pressure reduction(11). 

Clinically, clonidine has shown great versatility effective in mild, moderate and severe hypertension. The major side effects are drowsiness and dry mouth. Clonidine can be effectively used in combination with a diuretic(32). In addition, a vasodilator (hydralazine) can be usefully added. The brady-cardiac effect of clonidine prevents the reflex tachycardia induced by the vasodilator. 

Cardiac arrhythmia and bradycardia were reported in a man that splashed an unspecified concentration of a phenol-water solution over his face, chest wall, hand, and both arms (Horch et al. 1994). The cardiac effects were noted during the first 6 hours after exposure. The serum levels of phenol in g/L were 11,400 after 1 hour, 17,400 after 4 hours, and 6,000 after 8 hours. 

Cardiac arrhythmia has also been noted in rabbits treated with 2 mL of a 50% phenol solution on a 15-cm2 area (23.8 mg/cm2/kg) (Wexler et al. 1984). Reducing plasma concentrations of phenol by forced diuresis or a longer application time reduced the cardiac effects. 

It has been suggested that phenol exposure results in cardiac effects because it blocks the cardiac sodium channel subtype, with little effect on sodium channels in skeletal muscle (Zamponi et al. 1994). Phenol does not appear to be carcinogenic following oral exposure (NCI 1980), although the chemical combinations that result from benzene and phenol metabolism may contain compounds that do initiate or promote cancer. Metabolites such as hydroquinone and catechol have been demonstrated to be genotoxic and clastogenic. 

Furthermore, by in vitro experiments, it has been verified that stereospecific activation of alprenoxime is organ-specific, occurring in the eye and not systemically. When administered locally to rabbits, marked decreases in intra-ocular pressure were observed, whereas oral administration elicited almost no cardiac effects. Such ketoximes represent promising chemical delivery systems in the treatment of glaucoma However, a major limitation is their poor stability in solution, seemingly due to hydrolysis of the oxime function. 

Nonetheless, a sufficient dose will reduce or temporarily halt peristalsis (Brown and Taylor 1996). Some effects on esophageal peristalsis may be mediated by central mechanisms (Bieger 1984). Atropine reduces the tone and contractions of the ureter and bladder, and has antispasmodic effects on the gallbladder and bile duct. Negligible effects are produced on uterine contractions. Sweat glands are inhibited by atropine, and it can impair thermoregulation, especially in hot environments. Cardiac Effects... 

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