Salicylates overdose/toxicity

Patients with chronic salicylism may present with symptoms clinically similar to those seen in the acute situation. However, some patients with chronic salicylate overdose may present with CNS effects as their primary complaint, and typically have a higher morbidity and mortality than patients with acute salicylate overdose. Chronic salicylism is more often associated with pronounced hyperventilation, dehydration, pulmonary edema, renal failure, coma, seizures, and acidosis. Chronic salicylism patients will have more profound clinical effects at lower serum salicylate levels compared to patients with acute overdoses. Patients have developed toxicity with chronic salicylate serum levels as low as 15mgdl . ... 

Hydration to promote diuresis is recommended in all salicylate overdoses. Urine alkalinization is generally recommended at plasma concentrations above 600 mg 1 1 salicylate, or half that in children and the elderly. Even this, however, has its limits, and hemodialysis at salicylate concentrations of >800 mg l-1 in adults (half in children and the elderly), or regardless of plasma concentration when there are signs of CNS toxicity, is the treatment of choice. 

Pulmonary edema has occurred occasionally with salicylate overdoses. The serum salicylate concentrations are often greater than 45 mg/dL, and the patients have other signs of toxicity, although some cases have been associated with concentrations in the usual therapeutic range. ... 

Council Regulation (EEC) N. 2377/90 as a substance that does not need an MRL level. Gaultheria procumbens should not to be used as flavoring in pet food since salicylates are toxic to dogs and cats. As cats metabolize salicylates much more slowly than other species, they are more likely to be overdosed. Use of methylsalicylate in combination with anticoagulants such as warfarin can result in adverse interactions and bleedings (Chow et al., 1989 Ramanathan, 1995 Tam et al 1995 Yip etal., 1990). 

Changes in plasma pH may also affect the distribution of toxic compounds by altering the proportion of the substance in the nonionized form, which will cause movement of the compound into or out of tissues. This may be of particular importance in the treatment of salicylate poisoning (see chap. 7) and barbiturate poisoning, for instance. Thus, the distribution of phenobarbital, a weak acid (pKa 7.2), shifts between the brain and other tissues and the plasma, with changes in plasma pH (Fig. 3.22). Consequently, the depth of anesthesia varies depending on the amount of phenobarbital in the brain. Alkalosis, which increases plasma pH, causes plasma phenobarbital to become more ionized, alters the equilibrium between plasma and brain, and causes phenobarbital to diffuse back into the plasma (Fig. 3.22). Acidosis will cause the opposite shift in distribution. Administration of bicarbonate is therefore used to treat overdoses of phenobarbital. This treatment will also cause alkaline diuresis and therefore facilitate excretion of phenobarbital into the urine (see below). 

When overdosing occurs, gastric lavage is advised and an alkaline, high urine output state should be maintained (see Chapter 59 Management of the Poisoned Patient). Hyperthermia and electrolyte abnormalities should be treated. In severe toxic reactions, ventilatory assistance may be required. Sodium bicarbonate infusions may be employed to alkalinize the urine, which will increase the amount of salicylate excreted. 

Several drugs, including salicylate (in overdose), alcohol, and possibly some hydrazines and other drugs which are metabolised by acetylation, have saturable elimination kinetics, but the only significant clinical example is phenytoin. With this drug, capacity-limited elimination is complicated further by its low therapeutic index. A 50% increase in the dose of phenytoin can result in a 600% increase in the steady-state blood concentration, and thus expose the patient to potential toxicity. Capacity-limited pathways of elimination lead to plasma concentrations of drugs which can be described by a form of the Michaelis-Menten equation. In such cases, the plasma concentration at steady state is given by... 

Quinine The antimalarial agent quinine is derived from the bark of the cinchona tree along with several other alkaloids and salicylate (aspirin). Many of these agents produce similar toxic features (cinchon-ism) in patients with excessive intake, but only quinine produces blindness. Cinchonism consists of abdominal pain and vomiting, ringing in the ears (tinnitus), and confusion. Visual loss after quinine overdose is due to direct retinal toxicity, although until recently it was believed to be due to spasm of the arterial blood supply to the retina. Treatment is difficult, but limited evidence suggests charcoal hemoperfusion may be beneficial (hemoperfusion is similar to hemodialysis, except in place of a semi-permeable membrane to filter the toxin from the blood, charcoal is used to bind the toxin). 

Antihistamines are present in prescription and nonprescription forms, alone or in combination with analgesics, such as aspirin and acetaminophen. In instances of overdose, a urine drug screen that detects sahcylate, acetaminophen, and the antihistamines is helpful, especially when the source of intoxication is unknown. The detection of either analgesic in the urine of a symptomatic patient should lead to their quantitation in serum to assess their potential toxicity (see sections on Salicylate and Acetaminophen). Quantitation of antihistamines in serum is not useful, because there is a poor correlation between dose, drug level, and degree of toxicity. 

Overdoses greater than 150 mg kg-1 (i.e. 20-40 tablets weighing 325 mg each) cause toxicity, although fatality is related not only to overdose size but also to the patient s general condition children are sensitive to salicylates disproportionately to their body weight, and are also liable to more serious metabolic acidosis. 

Drugs for which concentration assays are clearly unsuited include acute therapies (i.e. not used at steady state), those with extraordinarily short half-times (e.g. injected or intranasal polypeptides) and those for which either treatment is indicated regardless (late acetaminophen/parace-tamol overdoses, see above), or when adverse events are almost automatic and should be monitored in other ways, for example CNS toxicity with salicylates (see above) or liability to bone marrow suppression with cytotoxic agents. Furthermore, the efficacy and tolerability of some drugs are known to be unrelated to circulating concentrations (e.g. penicillin anaphylaxis),... 

The drug itself is not toxic, but a toxic compound, N-acetyl-p-benzoquinonimine, is formed from it as it is broken down by enzymes in the liver. In small amounts this compound can be detoxified and excreted. But in large amounts it overwhelms the detoxification system and the compound begins killing liver tissue. Overdose can be treated by giving the patient activated charcoal, which absorbs the acetaminophen in the patient s stomach and intestines, and by administering A/-acetylcystine, a compound that can deactivate the toxic product of metabolism, see also Acetyl-salicylic Acid Ibuprofen. 

B. Toxicodynamics Toxicodynamics is a term used to denote the injurious effects of toxins, ie, their pharmacodynamics. A knowledge of toxicodynamics can be useful in the diagnosis and management of poisoning. For example, hypertension and tachycardia are typically seen in overdoses with amphetamines, cocaine, and antimuscarinic drugs. Hypotension with bradycardia occurs with overdoses of calcium channel blockers, beta-blockers, and sedative-hypnotics. Hypotension with tachycardia occurs with tricyclic antidepressants, phenothiazines, and theophylline. Hyperthermia is most frequently a result of overdose of drugs with antimuscarinic actions, the salicylates, or sympathomimetics. Hypothermia is more likely to occur with toxic doses of ethanol and other CNS depressants. Increased respiratory rate is often a feature of... 

B. Diflunisal overdose produces toxicity resembling salicylate poisoning (see... 

Drug overdose A report of salicylate intoxication has shown that salicylate absorption and metabolism after a large overdose can be unpredictable and that there is a risk of delayed toxicity [ r ]. 

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