Congestive heart failure toxicity

The Class I agents have many similar side effects and toxicities. The anticholinergic side effects include dry mouth, constipation, and urinary hesitancy and retention. Common gastrointestinal (GI) side effects include nausea, vomiting, diarrhea, and anorexia. Cardiovascular adverse effects are hypotension, tachycardia, arrhythmias, and myocardial depression, especially in patients with congestive heart failure. Common central nervous system (CNS) side effects are headache, dizziness, mental confusion, hallucinations, CNS stimulation, paraesthesias, and convulsions. 

Cardiotoxicity is a serious, rare adverse effect of mitox-antrone. The incidence of congestive heart failure was 0.15% in patients with normal left ventricular ejection fraction and 2.18% in those who had asymptomatic left ventricular ejection fraction of less than 50% at baseline.46 Therefore, mitoxantrone should not be used in patients with baseline cardiomyopathy, even if asymptomatic. The risk of cardiotoxicity is dose-related. The maximum lifetime dose of mitoxantrone is 140 mg/m2, or about 3 years of MS therapy. The use of cyclooxygenase-2 inhibitors should be avoided in patients receiving mitoxantrone because of a potential for worsening cardiac toxicity.46... 

Suggested Alternatives for Differential Diagnosis Acute respiratory distress syndrome, congestive heart failure, pulmonary edema, AIDS, pneumonia, cardiogenic shock, septic shock, phosgene toxicity, phosphine toxicity, salicylate toxicity with pulmonary edema, influenza, plague, tularemia, and anthrax. 

Adverse effects include myelosuppression, alopecia and gastrointestinal disturbances. Most important is the dose related cardiac toxicity which is cumulative and can become manifest by congestive heart failure weeks or moths after termination... 

The major toxic reactions to disopyramide administration include hypotension, congestive heart failure, and conduction disturbances. These effects are the result of disopyramide s ability to depress myocardial contractility and myocardial conduction. Although disopyramide initially may produce ventricular tachyarrhythmias or ventricular fibrillation in some patients, the incidence of disopyramide-induced syncope in long-term therapy is not known. Most other toxic reactions (e.g., dry mouth, blurred vision, constipation) can be attributed to the anticholinergic properties of the drug. 

These salts should always be given with substantial amounts of water otherwise the patient may be purged at the expense of body water, resulting in dehydration. Sodium-containing laxatives should not be used in patients with congestive heart failure, since the patient may absorb excessive sodium. Similarly, in cases of renal failure, magnesium or phosphate-containing products should not be used, since the loss of a renal clearance of these ions may result in cumulative toxic levels despite their minimal absorption. 

A toxicity that is unique to cyclophosphamide and ifosfamide is cystitis. Dysuria and decreased urinary frequency are the most common symptoms. Rarely, fibrosis and a permanently decreased bladder capacity may ensue. The risk of development of carcinoma of the bladder also is increased. Large intravenous doses have resulted in impairment of renal water excretion, hyponatremia, and increased urine osmolarity and have been associated with hemorrhagic subendocardial necrosis, arrhythmias, and congestive heart failure. Interstitial pulmonary fibrosis may also result from chronic treatment. Other effects of chronic drug treatment include infertility, amenorrhea, and possible mutagenesis and carcinogenesis. 

Toxic reactions appear as blood dyscrasias, including aplastic anemia, agranulocytosis, thrombocytopenia, leukopenia, leukocytosis, eosinophilia, cardiovascular disturbances, such as congestive heart failure (CHF), hypotension or hypertension, thrombophlebitis, arrhythmias, and dermatologic effects, such as rash, urticaria, pruritus, photosensitivity. 

As noted earlier, lithium is contraindicated in patients with unstable congestive heart failure or the sick sinus node syndrome ( 307, 328). In older patients or those with prior cardiac histories, a pretreatment ECG should be obtained. Except for the potential adverse interactions with diuretics, the concomitant use of other cardiac drugs is generally safe. Because verapamil may lower serum levels of lithium, however, more careful monitoring may be required to assure continued therapeutic effects (329). Some data also indicate that verapamil may predispose to lithium neurotoxicity. Conversely, increased lithium levels leading to toxicity has occurred with methyidopa and enalapril. When antihypertensive therapy is necessary, b-blockers are a reasonable choice when lithium is coadministered. 

Metformin Obscure Reduced hepatic and renal gluconeogenesis Decreased endogenous glucose production Type 2 diabetes Oral maximal plasma concentration in 2-3 h Toxicity Gastrointestinal symptoms, lactic acidosis (rare) cannot use if impaired renal/hepatic function congestive heart failure (CHF), hypoxic/acidotic states, alcoholism... 

Nerium indicum Mill. Jia Zhu Tao (Indian oleander) (leaf, stem, flower, root) Oleandrin (toxic), oleandrose, neriodorin, nerioderin, karabin, scopoletin, scopoline, neriodin, ursolic acid, adynerin 33>45° Treats psychosis, congestive heart failure, analgesic, emmenagogue. 

China Nerium indicum L. Oleandrin (toxic), oleandrose.33 Treat psychosis, congestive heart failure, analgesic, emmenagogue. 

Roberge RJ, Sorensen T. Congestive heart failure and toxic digoxin levels role of cholestyramine. Vet Hum Toxicol 2000 42(3) 172-3. 

When the heart can no longer pump an adequate supply of blood to meet the metabolic needs of the tissues or in relation to venous return, cardiac failure may ensue. The causes of cardiac failure are complex, but stem from mechanical abnormalities (e.g., pericardial tamponade), myocardial failure (e.g., cardiomyopathy and inflammation), and arrhythmias. In high-output failure, the cardiac output, which may be normal or even higher than normal, is not sufficient to meet the metabolic requirement of the body. Cardiac failure may predispose a patient to congestive heart failure, which is a state of circulatory congestion. Toxic injury, caused by agents such as doxorubicin, the alkaloid emetine in ipecac syrup, cocaine, or ethyl alcohol, is another way by which the functional integrity of the heart may also be compromised. 

Toxicities included an infusion reaction consisting of fever, chills, pain, asthenia, nausea, and vomiting. This syndrome was typically observed after the initial infusion, was self-limited, and frequently did not recur with subsequent infusions. The most serious toxicity was cardiac dysfunction, defined as clinical findings of congestive heart failure and/or subclinical declines in cardiac ejection fraction, which was seen in 5% of patients. Cardiotoxicity was unanticipated, as it had not been detected in previous studies. The mechanism for this effect is unclear, but is likely related to trastuzumab s antiproferative effect on HER2-mediated homeostasis and response to injury. 

Adverse effects Amiodarone shows a variety of toxic effects. After long-term use, more than one half of the patients receiving the drug show side effects sufficiently severe to prompt its discontinuation. Some of the more common effects include interstitial pulmonary fibrosis, gastrointestinal tract intolerance, tremor, ataxia, dizziness, hyper- or hypothyroidism, liver toxicity, photosensitivity, neuropathy, muscle weakness, and blue skin discoloration caused by iodine accumulation in the skin. As noted earlier (see p. 166) recent clinical trials have shown that amiodarone did not reduce incidence of sudden death or prolong survival in patient with congestive heart failure (CHF). 

Emetine [EM e teen] and dehydroemetine [de hye dro EM e teen] are alternate agents for the treatment of amebiasis. They inhibit protein synthesis by blocking chain elongation1. Intramuscular injection is the preferred route. Emetine is concentrated in the liver where it persists for a month after a single dose. It is slowly metabolized and excreted and can accumulate. Its ty2 is 5 days. The use of these ipecac alkaloids is limited by their toxicities. Dehydroemetine is probably less toxic than emetine. Close clinical observation is necessary when these drugs are used. Among the untoward effects are pain at the site of injection, transient nausea, cardiotoxicity (e.g., arrhythmias, congestive heart failure), neuromuscular weakness, dizziness, and rashes. 

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