Cardiac manifestations system

Acute toxicity manifests primarily in the CNS, cardiovascular system, and gastrointestinal system. CNS signs include restlessness, tremor, nervousness, headache, insomnia, tinnitus, confusion, delirium, psychosis, and seizures. Cardiac manifestations of overdose include sinus tachycardia, various dysrhythmias, asystole, and cardiovascular collapse. Other findings include tachypnea, nausea, vomiting, hematemesis, diarrhea, and fever. Case reports also include rhabdomyolysis and pulmonary edema. Laboratory findings include metabolic acidosis, respiratory alkalosis, ketosis, hypokalemia, and hyperglycemia. The estimated lethal dose in adults is 150-200 mg kg whereas doses of 10-15mgkg ... 

Adverse Effects. Digoxin can produce a variety of cardiac and noncardiac adverse effects, but it is usually well tolerated by most patients (Table 14-11). Noncardiac adverse effects frequently involve the central nervous system or gastrointestinal system but also may be nonspeciflc (e.g., fatigue or weakness). Cardiac manifestations include numerous different arrhythmias that are believed to be caused by multiple electrophysio logic effects (see Table 14-11). Cardiac arrhythmias may be the flrst evidence of toxicity in a patient (before any noncardiac symptoms occur). Rhythm disturbances are of particular concern because patients with chronic heart failure are aheady at increased risk for sudden cardiac death presumably owing... 

Most of the signs and symptoms of thyrotoxicosis stem from excessive heat production, increased motor activity, and increased activity of the sympathetic nervous system. Eventually, the increased energy expenditure is often associated with weight loss. Cardiac manifestations include tachycardia and bounding pulses older patients or those with underlying heart disease may exhibit angina, arrhythmias (especially atrial fibrillation), and high-output heart failure. 

Peripheral arterial occlusion can be the initial manifestation of cardiac or systemic disease. At times, patients with chronic stable claudication may experience abrupt shortening of the distance at which claudication occurs, and this may be the only symptomatic evidence of an acute arterial occlusion either by embolization of by thrombus formation on a pre-existing arterial stenosis. The situation is not chronic and stable any more, but acute and unstable. As ischemia becomes more severe, the patient with chronic peripheral arterial disease develops ischemic pain at rest. The pathophysiologic mechanisms and the clinical presentation parallel the evolution of chronic stable angina pectoris to unstable angina and acute coronary syndromes. 

Intoxication results in a characteristic intense, throbbing headache, presumably due to cerebral vasodilation, often associated with dizziness and nausea and occasionally with vomiting and abdominal pain. More severe exposure also causes hypotension, flushing, palpitation, low levels of methemoglobinemia, delirium, and depression of the central nervous system. Aggravation of these symptoms after alcohol ingestion has been observed. On repeated exposure, a tolerance to headache develops but is usually lost after a few days without exposure. At times, persistent tachycardia, diastolic hypertension, and reduced pulse pressure have been observed. On rare occasions, a worker may have an attack of angina pectoris a few days after cessation of repeated exposures, a manifestation of cardiac ischemia. Sudden death due to unheralded cardiac arrest has also been reported under these circumstances. ... 

Action on the CNS depends directly on the dose of administered drug, and can be manifested as fatigue, anxiety, tremors, and even convulsions in relatively high doses. Theophylline acts on the cardiovascular system by displaying positive ionotropic and chronotropic effects on the heart, which, can likely be linked to the elevated influx of calcium ions by modulated cyclic adenosine monophosphate and its action on specific cardiac phosphodiesterases. In the gastrointestinal system, methylxanthines simultaneously stimulate secretion of both gastric juice and digestive enzymes. 

During the 14 day observation period some rabbits (2-8) died after 8-hour exposure to doses of 775-1,550 mg/kg applied directly to shaved skin (3.2 cm, but no deaths occurred in the 388 mg/kg dose group. The author calculated an LD o of 1,116 mg/kg from these data (Duprat and Gradiski 1978). Central nervous system depression was evident, as manifested by stupor. Some animals were weak and anorexic, while others showed signs of dyspnea and cyanosis. The lungs, liver, and kidneys were congested in animals that died. Death was reportedly due to respiratory or cardiac failure. 

The phenomena of systemic cocaine poisoning are largely those of sympathetic stimulation but not as consistently as with epinephrine. The sympathetic stimulation is mainly central (midbrain) but partly peripheral. The chief manifestations of sympathetic stimulation are (1) sensitization to epinephrine (but antagonization to ephedrine) by peripheral action, (2) mydriasis and slight exophthalmos by central and peripheral action, and (3) cardiac acceleration (chiefly central). Other sympathetic symptoms are constriction of the blood vessels, erection of hair, and relaxation of the intestines. High concentrations of cocaine paralyze all smooth muscles. Procaine also produces... 

CNS have the highest demand of all the cells in the body for OXPHOS to provide ATP for normal function. Cardiac and skeletal muscle have the next highest need for OXPHOS, while the endocrine system and skin have lesser requirements for OXPHOS. Thus, as mitochondrial function fails due to deleterious mutations in mtDNA, often the earliest manifestations of such mitochondrial distress is seen in neurological and muscular abnormalities. 

High blood levels after topical application or injection of anesthetics may potentially cause systemic reactions. Toxic effects may appear in the central nervous system (CNS), cardiovascular system, or respiratory system. CNS toxicity appears initially as stimulation and may manifest itself clinically as nervousness, tremors, or convulsions. CNS depression, observed clinically as loss of consciousness and depression of respiration, usually follows. The earliest signs of cardiovascular involvement are hypertension, tachycardia, and, occasionally, cardiac arrhythmias. Late cardiovascular signs are hypotension, absent pulse, and weak or absent heartbeat. The effects on the cardiovascular system can develop either simultaneously with CNS depression or alone. If allowed to continue, such cardiac depression and resultant peripheral vasodilation are followed by secondary respiratory failure. 

Therapy for SEE is both complex and, in many instances, disappointing for both patient and practitioner. Management of the systemic signs and symptoms may not improve the ocular manifestations of the disease. The most common therapy for the arthritic and cardiac complications is NSAID use. Hydroxychloroquine and chloroquine are particularly effective in treating the discoid rash associated with the disease. In some cases oral steroids are used either alone or in combination with other immunosuppressive agents. Methotrexate can effectively reduce the need for systemic steroids in the treatment of mild to moderate SEE. Cyclophosphamide and... 

Type 2 is the juvenile haemochromatosis. This rare form of iron storage can be differentiated from type 1 by an earlier onset of clinical symptoms. It becomes manifest prior to the age of 30. Both sexes are affected equally. The gene defect is localized on chromosome Iq (A. RoETToetal., 1999). Compared to type 1, cardiomyopathy and hypogonadism are more frequent, the course of disease is more severe and cardiac-induced death is more common. HFE mutations are absent, and there is no association with the HLA system. This form of HC has an autosomal recessive inheritance, (s. tab. 31.17)... 

The exact mechanism of this peripheral adrenergic neuron blocking agent is not well defined. Reserpine administration results in depleted stores of norepinephrine, dopamine, and serotonin in multiple organs. The decreased peripheral resistance and cardiac output that results is manifested as a decrease in blood pressure. A central nervous system (CNS) effect may also play a role in decreasing blood... 

Functional renal insufficiency is manifested as increases in serum creatinine and blood urea nitrogen. As cardiac output and renal blood flow decline, renal perfusion is maintained by the vasoconstrictor effect of angiotensin II on the efferent arteriole. Patients most dependent on this system for maintenance of renal perfusion (and therefore most likely to develop functional renal insufficiency with ACE inhibitors) are those with severe heart failure, hypotension, hyponatremia, volume depletion, and concomitant use of NSAIDs. - Sodium depletion (usually secondary to diuretic therapy) is the most important factor in the development of functional renal insufficiency with ACE inhibitor therapy. Renal insufficiency therefore can be minimized in many cases by reduction in diuretic dosage or liberalization of sodium intake. In some patients, the serum creatinine concentration will return to baseline levels without a reduction in ACE inhibitor dose. Since renal dysfunction with ACE inhibitors is secondary to alterations in renal hemodynamics, it is almost always reversible on discontinuation of the drug. ... 

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