Aspirin Development, Use, and Toxicity

Questions and Answers

What is the primary mechanism of action of non-selective NSAIDs?

Inhibition of COX 1 and COX 2 enzymes (correct)

Stimulation of COX 2 enzymes

Stimulation of prostaglandin production

Inhibition of leukotriene production

What is the purpose of plotting salicylate levels on a nomogram?

To determine the severity of dehydration

To diagnose NSAID overdose

To monitor liver transaminases

To estimate the toxicity of salicylate ingestion (correct)

What is the common effect of most NSAID overdoses?

Respiratory depression

Cardiac arrhythmias

Mild gastrointestinal upset (correct)

Severe gastrointestinal bleeding

What is the likely effect of altered capillary integrity in cerebral and pulmonary edema?

Prolonged prothrombin time Signup and view all the answers

What is the initial step in managing salicylate intoxication?

Maintain the airway and assist ventilation if necessary Signup and view all the answers

What is the benefit of using antacids in NSAID overdose?

To treat mild GIT upset Signup and view all the answers

What is the primary use of COX 2 inhibitors?

To relieve ulcer pain Signup and view all the answers

What is the treatment for metabolic acidosis in salicylate intoxication?

Intravenous administration of sodium bicarbonate Signup and view all the answers

What laboratory tests are useful in NSAID overdose?

CBC, electrolytes, glucose, BUN, creatinine, liver transaminases, and urinalysis Signup and view all the answers

What is the therapeutic dose of aspirin for treatment?

40-60 mg/kg/d Signup and view all the answers

What is the likely outcome of acute ingestion of 150-200 mg/kg of aspirin?

Mild intoxication Signup and view all the answers

What is the purpose of replacing fluid losses with intravenous crystalloid solutions?

To replace fluid losses due to dehydration Signup and view all the answers

What is the minimum duration for monitoring asymptomatic patients?

6 hours Signup and view all the answers

Is there a specific antidote for most NSAID overdoses?

No, there is no specific antidote for most NSAID overdoses Signup and view all the answers

What is the effect of COX 1 inhibition?

Decreased prostaglandin production Signup and view all the answers

What is the effect of sodium bicarbonate in salicylate intoxication?

It promotes salicylate elimination by the kidneys Signup and view all the answers

What is the characteristic of pulmonary edema in salicylate intoxication?

It is related to alteration in capillary integrity Signup and view all the answers

What is the likely outcome of chronic ingestion of more than 100 mg/kg/d of aspirin for 2 or more days?

Chronic intoxication Signup and view all the answers

What is the mechanism of toxicity for salicylates?

All of the above. Signup and view all the answers

What is the primary cause of respiratory alkalosis in salicylate toxicity?

Decreased carbon dioxide retention in the lungs. Signup and view all the answers

What is the typical range of therapeutic salicylate concentrations in patients with arthritis?

100-300 mg/dL Signup and view all the answers

What salicylate concentration is considered very dangerous, often accompanied by acidosis and altered mental status?

600 mg/L Signup and view all the answers

Which of the following laboratory studies is NOT recommended for evaluating salicylate toxicity?

Complete blood count Signup and view all the answers

What is the primary mechanism by which salicylate toxicity contributes to dehydration?

All of the above. Signup and view all the answers

What is the primary clinical manifestation of salicylate toxicity that leads to respiratory alkalosis?

Hyperventilation Signup and view all the answers

What is the primary mechanism by which salicylate toxicity interrupts glucose and fatty acid metabolism?

Uncoupling of oxidative phosphorylation. Signup and view all the answers

What is the primary treatment for salicylate toxicity?

Supportive care Signup and view all the answers

Which of the following drugs can cause methemoglobinemia and hemolytic anemia?

Primaquine phosphate Signup and view all the answers

What is the primary mechanism of toxicity for chloroquine?

Inhibition of DNA and RNA synthesis Signup and view all the answers

Which of the following is a potential cardiotoxic effect of chloroquine overdose?

Ventricular fibrillation Signup and view all the answers

Which of the following drugs is associated with fatal neutropenia?

Amodiaquine HCl Signup and view all the answers

What is the therapeutic dose of chloroquine phosphate for malaria prophylaxis?

500 mg once a week Signup and view all the answers

Which of the following is NOT a potential side effect of mefloquine?

Hypotension Signup and view all the answers

What is the role of G6PD in red blood cells?

Protection from harmful substances Signup and view all the answers

Which of the following is NOT a sign of severe chloroquine overdose?

Hepatitis Signup and view all the answers

Which of the following drugs is most likely to cause ototoxicity?

Primaquine phosphate Signup and view all the answers

What is a common clinical presentation associated with quinidine toxicity?

Confusion Signup and view all the answers

Which of the following drugs has ganglionic and neuromuscular blocking activity?

Procainamide Signup and view all the answers

What is the toxic dose for procainamide?

5 g Signup and view all the answers

Which of these statements about lidocaine is correct?

It is also an anti-dysrhythmic agent. Signup and view all the answers

What is one potential consequence of quinidine toxicity?

Coma Signup and view all the answers

Which of the following is a metabolite of lidocaine that may contribute to toxicity?

Monoethylglycinexylidide Signup and view all the answers

Encainide was withdrawn from the market primarily due to its association with which issue?

Increased cardiovascular events Signup and view all the answers

What cardiac effect is NOT associated with high doses of anti-dysrhythmic drugs?

Tachycardia Signup and view all the answers

Which condition may arise from an overdose of lidocaine?

Seizures Signup and view all the answers

Study Notes

Aspirin Development and Use

Developed in 1897, aspirin became widely distributed to doctors by 1915, becoming the top drug globally.
Therapeutic concentration for chronic use in arthritis patients is 100-300 mg/L.
Toxic levels exceed 600 mg/L and can cause severe acidosis and altered mental status.

Mechanism of Toxicity

Salicylate toxicity leads to hyperventilation and respiratory alkalosis, increasing blood pH.
Metabolic acidosis can occur from acid buildup (lactate, ketones), leading to dehydration.
Uncoupling of oxidative phosphorylation affects glucose and fatty acid metabolism.
Can cause cerebral and pulmonary edema due to capillary integrity alteration.
Prolonged prothrombin time and altered platelet function are noted.

Treatment for Salicylate Toxicity

Maintain airway and ventilation; supplemental oxygen may be given.
Treat acute manifestations: coma, seizures, hyperthermia, and pulmonary edema.
Administer intravenous sodium bicarbonate to manage metabolic acidosis; prevent pH from falling below 7.4.
Replace fluid and electrolytes lost through vomiting and hyperventilation.
No specific antidote; sodium bicarbonate aids in salicylate elimination.

NSAIDs Overview

NSAIDs are diverse agents used for pain and inflammation management.
Most overdose cases lead to mild gastrointestinal upset.
Non-selective NSAIDs inhibit COX-1 and COX-2, affecting prosaglandin and leukotriene production.
Selective COX-2 inhibitors primarily relieve ulcer pain.

Chloroquine inhibits DNA and RNA synthesis; can cause cardiotoxicity similar to quinidine.
Overdose may lead to severe cardiotoxicity symptoms: sinoatrial arrest, ventricular arrhythmias.
Primaquine and quinacrine can cause hemolytic anemia and methemoglobinemia, especially in patients with G6PD deficiency.
Therapeutic dose for chloroquine in malaria prevention is 500 mg weekly; treatment dose is 2.5 g over 2 days.

Specific Drug Toxicity

Quinidine: 1 g toxic dose, can lead to confusion, sedation, and asystole.
Procainamide: Toxic at 5 g; can cause respiratory arrest and cardiac complications.
Lidocaine: Antidysrhythmic agent; potential toxicity from metabolites.
Encainide withdrawn due to mortality concerns in cardiac dysrhythmia trials.

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Description

Learn about the development and use of aspirin, including its therapeutic concentration and toxic levels, as well as the mechanism of toxicity and its effects on the body.