Overdoses of aspirin

Aspirin is generally low in toxicity and produces comparatively little tolerance and no addiction. However, its effects are not entirely benign, especially in certain medical conditions. Acute overdose of aspirin is fatal in doses of 10 to 30 mg, although some high doses have been reported... 

Impairment of mitochondrial jj-oxidation leads to accumulation of fat, resulting in steatosis. Examples are various tetracycline derivatives, valproic acid (used to treat seizures) and overdoses of aspirin [64—66]. Certain NSAIDs such as ibuprofen, ketoprofen and naproxen also have the ability to inhibit jj-oxidation [67-69]. 

As with paracetamol, overdoses of aspirin are unfortunately taken by people as a means of suicide, although the amount that has to be taken for a fatal dose is greater than for paracetamol. There are probably several hundred deaths per year from aspirin overdose worldwide, and in a recent year 10,000 calls to Poison Control Centers relating to aspirin overdose were reported in the USA. 

Apart from the symptoms, how would a doctor know that someone had taken an overdose of aspirin As already described, there are simple tests that can be done on urine to find out if someone suspected of an overdose has taken any of the common drugs. After the drug taken is known, it is important to measure the level of the drug in the blood to find out the likely dose and therefore the necessary treatment (see... 

Screening for salicylates Overdoses of aspirin and other mild analgesics are extremely common. Salicylate is commonly detected in urine by the classical violet iron(III)-salicylate chelate formation. 

This patient had ingested a large quantity of aspirin resulting in the classic findings of a salicylate overdose a centrally mediated respiratory alkalosis with a concurrent anion gap metabolic acidosis. 

Example In an overdose case where evidence was available for the ingestion of Percodan (a mixture of several common drugs) the isobutane-CI mass spectrum of the gastric extract was obtained (Fig. 7.8). [29] All drugs give rise to an [Mh-H] ion. Due to the low exothermicity of protonation by the tert-C Hi) ion, most [Mh-H]" ions do not show fragmentation. Solely that of aspirin shows intense... 

The major consequence of aspirin overdose, which often occurs in children, results from actions on respira-... 

The therapeutic blood level is greater than 150 mg L-1 but symptoms of toxicity occur at blood levels of around 300 mg L-1. Therefore, knowledge of the blood level is important, particularly when aspirin is given in repeated doses. In children, therapeutic overdosage is responsible for the majority of fatalities from aspirin. When an overdose is suspected, measurement of the plasma level on two or more occasions will allow an estimate to be made of the severity of the overdose and whether the plasma level has reached its maximum. For interpretation of the blood level, the Done nomogram can be used. An overdose of 50 to 300 mg tablets in adults will give rise to moderate to severe toxicity and a blood level of 500 to 750 mg L-1 at 12 hours. The blood level must be interpreted with caution, however, because... 

For example, aspirin should be avoided in patients with ulceration and patients taking anticoagulation medications. It is possible that misuse or overdose of OTC products may develop into many medical problems. For example, improper use of antacids (e.g., aluminum hydroxide) causes constipation. 

Codeine Phosphate The presence of aspirin along with codeine, even at a low moisture level, leads to acetylation of codeine phosphate in solid dose forms and is incompatible.36 Codeine sulfate solutions are more stable than phosphate salts.37 Drug dependence and withdrawal resemble that of opioid analgesics. Overdose causes acute intoxication in children, as accidental or deliberate ingestion of cough preparations containing codeine.38... 

N-Acetylcysteine is useful in which of the following drug overdoses a aspirin... 

Overdose. A moderate overdose (plasma salicylate 500-750 mg/1) will cause nausea, vomiting, epigastric discomfort, tinnitus, deafness, sweating, pyrexia, restlessness, tachypnoea and hypokalaemia. A large overdose (plasma salicylate > 750 mg/1) may result in pulmonary oedema, convulsions and coma, with severe dehydration and ketosis. Bleeding is unusual, despite the antiplatelet effect of aspirin. 

Enteric coating reduces the rate of absorption of aspirin. In cases of severe overdosage this can cause difficulties in diagnosis and treatment, since early plasma salicylate measurements are unreliable, maximum blood concentrations sometimes not being reached until 60 or 70 hours after overdose (94,95). Another complication of the use of enteric-coated aspirin is the risk of gastric outlet obstruction and the resulting accumulation of tablets because of subclinical pyloric stenosis. 

Recommendations for sodium bicarbonate vary (from class 1 to class in) depending on the clinical situation. Sodium bicarbonate use is acceptable for patients with known, preexisting hyperkalemia (class 1), preexisting bicarbonate-responsive acidosis (class 11a), overdoses of tricychc antidepressants (class 11a), and to aUcalinize the urine in aspirin and other drug overdoses (class 11a). In addition, sodium bicarbonate may be of benefit in intubated and ventilated patients with along arrest interval (class 11b). Sodium bicarbonate may be harmful in hypercarbic acidosis, and patients with this condition should not receive it (class IH). 

In an overdose situation, the elimination of aspirin follows zero-order kinetics. This means that... 

Answer E. Back to basic principles. Zero-order elimination means that plasma levels of a drug decrease linearly with time. This occurs with ASA at toxic doses, with phenytoin at high therapeutic doses, and with ethanol at all doses. Enzymes that metabolize ASA are saturated at high plasma levels —> constant rate of metabolism = zero-order kinetics. Remember that application of the Henderson-Hasselbalch principle can be important in drug overdose situations. In the case of aspirin, a weak acid, urinary alkalinization favors ionization of the drug —>4 tubular reabsorption —>T renal elimination. 

Care needs to be taken when combining naproxen with other medications. Known adverse drug interactions can occur with aspirin, methotrexate, ACE inhibitors (for high blood pressure), furosemide, lithium, and warfarin (a blood thinner). An overdose of naproxen may cause dizziness, drowsiness, and gastrointestinal problems. High blood pressure, kidney failure, and coma may occur, but are rare. 

Acetaminophen (Tylenol) Mechanism not yet clear. Weak inhibitor of prostaglandin synthesis. Analgesic antipyretic effects equal those of aspirin. Anti-inflammatory effects much weaker. Mild to moderate pain and fever. Preferred over aspirin in children because it is less likely to cause Reye s Syndrome. Does not cause Gl upset or bleeding. Rash, occasionally with fever. Overdose may cause severe hepatic necrosis leading to coma and death. 

Inappropriate blood clotting can be very dangerous, as mentioned above. In Box 14 we examine one form of intervention, with warfarin, to damp down the clotting response, but that is relatively drastic in view of the potential risks of overdose, and a more routine and less severe intervention is a daily dose of aspirin, often prescribed for men beyond middle age. As explained in Topic 49, aspirin is a COX... 

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