Pharmaceutical Toxicology

Summary

This lecture on pharmaceutical toxicology provides an in-depth examination of various substances, including salicylates, paracetamol, sulphonamides, and insulin. It discusses their chemical properties, therapeutic uses, mechanisms of action, clinical features of poisoning, and treatment protocols. Key points include the acute and chronic effects of salicylate poisoning, the staged symptoms of paracetamol toxicity, and the adverse reactions associated with sulphonamides. Additionally, it highlights the critical management strategies for insulin overdose, emphasizing the importance of prompt treatment and monitoring. The lecture serves as a comprehensive guide for understanding toxicological challenges in pharmaceuticals.

Takeaways

• 😀 Salicylates, derivatives of salicylic acid, include acetylsalicylic acid (aspirin), sodium salicylate, and methyl salicylate, each with distinct properties and uses.
• 😀 Acetylsalicylic acid is an odorless white crystalline powder known for its unpleasant taste and is used in various therapeutic forms.
• 😀 Salicylates are utilized as antibiotics and analgesics, particularly in treating rheumatoid arthritis and preventing cerebrovascular events.
• 😀 Acute salicylate poisoning presents with symptoms such as nausea, vomiting, tinnitus, hyperventilation, and can lead to severe complications like metabolic acidosis.
• 😀 Chronic salicylate poisoning, or salicylism, can cause confusion, agitation, lethargy, and may mimic sepsis, leading to multi-organ failure.
• 😀 Paracetamol (acetaminophen) poisoning has a staged progression, with symptoms ranging from initial nausea to severe hepatic necrosis if untreated.
• 😀 Management of paracetamol poisoning includes stomach wash, activated charcoal, and specific antidotes like N-acetylcysteine.
• 😀 Sulphonamides, classified as anti-infective agents, are used primarily as antibacterials and can cause severe hypersensitivity reactions and hematologic symptoms.
• 😀 Insulin regulates carbohydrate and fat metabolism, with overdose leading to significant CNS symptoms, including confusion, seizures, and potentially coma.
• 😀 Treatment for insulin poisoning involves administering glucose, with dosages varying based on the method of delivery (oral vs. intravenous).

Q & A

What are salicylates and what are some common forms?

Salicylates are derivatives of salicylic acid, including acetylsalicylic acid (aspirin), sodium salicylate, and methyl salicylate. They are available in various forms such as tablets, capsules, powders, liquid preparations, rectal suppositories, and topical applications.

What is the primary mode of action of salicylates?

Salicylates stimulate the respiratory center in the brainstem, leading to hyperventilation and respiratory alkalosis. They also interfere with the Krebs cycle, inhibit ATP production, and increase lactate production, resulting in ketosis and metabolic acidosis.

What are the early symptoms of acute salicylate poisoning?

Early symptoms include nausea, vomiting, sweating, tinnitus, vertigo, and hyperventilation due to respiratory alkalosis.

What are the stages of acute paracetamol poisoning?

Acute paracetamol poisoning is divided into four stages: Stage 1 (0.5 to 24 hours) includes anorexia and vomiting; Stage 2 (24 to 72 hours) is relatively symptom-free but may show right upper quadrant pain; Stage 3 (72 to 96 hours) features hepatic necrosis, jaundice, and coagulation defects; Stage 4 (4 days to 2 weeks) is recovery if the patient survives Stage 3.

What is the treatment for paracetamol poisoning?

Treatment includes stomach wash if within 1 hour of ingestion, administration of activated charcoal, supportive measures like dextrose for hypoglycemia, fresh frozen plasma for bleeding, and mannitol for cerebral edema. The antidote for paracetamol poisoning is N-acetylcysteine.

What are the clinical features associated with sulphonamides?

Clinical features of sulphonamide poisoning include hypersensitivity reactions (anaphylaxis, rashes), renal issues (crystaluria), hematological symptoms (agranulocytosis, thrombocytopenia), and neurological symptoms (headaches, insomnia).

What are the main clinical features of insulin poisoning?

Insulin poisoning can cause gastrointestinal symptoms like vomiting and CNS symptoms such as anxiety, confusion, seizures, and coma. Physical symptoms include tachycardia, hypotension, and profuse sweating.

How should hypoglycemia be treated in cases of insulin poisoning?

Treatment includes administering glucose, either orally (10 to 20 grams) or intravenously (50 mL of 50% glucose). Continuous infusion of 10% glucose should be given until the patient improves.

What autopsy findings are associated with salicylate poisoning?

Autopsy findings in salicylate poisoning may include erosion of the gastric mucosa, altered blood in the stomach, pulmonary and cerebral edema, and presence of tablets in various organs.

What can chronic paracetamol poisoning lead to?

Chronic paracetamol poisoning can lead to toxic hepatitis, particularly in individuals consuming large doses over time, such as alcoholics or those taking other medications that deplete glutathione.