14)Toxic effects of drugs

Question 1

Toxic affects

Answer 1

Can range from negligible to incredibly severe

Toxic concentration of a drug/it’s metabolites ⇢ can cause cellular necrosis/apoptosis

Question 2

Covalent toxic interactions

Answer 2

• Binding to DNA, proteins, lipids, carbs
• Irreversible binding can be especially toxic

Question 3

Non-Covalent toxic interactions

Answer 3

• Lipid per oxidation ⇢ lipid peroxyl radicals cause a per oxidative cascade, affecting membrane lipid
• ROS generation ⇢ formation of cytotoxic reactive O2 species
• Depletion of glutathione ⇢ glutathione protects cell from oxidative stress
• Cytotoxicity ⇢ Drug causes damage to cells

Question 4

Liver

Answer 4

• Mechanism for hepatotoxicity is exemplified by paracetamol
• When a toxic dose is given ⇢ normal enzymes that metabolise paracetamol are saturated
• Therefore, mixed function oxidases take over + convert paracetamol into active metabolites

Question 5

Kidney

Answer 5

• Nephrotoxicity ⇢ usually caused by normal pharmacological actions of drug
• Eg: NSAIDs cause ischaemic renal failure + sodium & H2O retention = ⇡ pressure in kidney
• Renal tubular cells are exposed to high concs of drugs + metabolites as urine is concentrated

Question 6

Carcinogenesis

Answer 6

• Alteration of DNA
• Immunosuppression ⇢ wide range of cancers develop in immunosuppressed patients
• Hormonal ⇢ Long terms of oestrogen replacement in post menopausal women induces endometrial cancer

Question 7

Pulmotoxicity

Answer 7

• Amiodarone ⇢ can cause pulmonary fibrosis

Question 8

Antidotes

Answer 8

Antidotes negate effects of drugs that have been overdosed

Examples:

• Acetylcysteine ⇢ Used against paracetamol + carbon tetrachloride ⇢ protects liver from damage
• Activated charcoal ⇢ Non-specific poisons
• Glucagon ⇢ used against Beta-blockers + calcium channel blockers
• Glucose ⇢ against insulin reaction

Question 9

Antidotes

Answer 9

Antidotes negate effects of drugs that have been overdosed

Examples:

• Acetylcysteine ⇢ Used against paracetamol + carbon tetrachloride ⇢ protects liver from damage
• Activated charcoal ⇢ Non-specific poisons
• Glucagon ⇢ used against Beta-blockers + calcium channel blockers
• Glucose ⇢ against insulin reaction

Question 10

Complications of opioid abuse

Answer 10

• Permanent lung damage
• Seizures + tremors
• Reduced mental capacity
• Permanent organ damage
• Hypotension