Hepatotoxicity of Drugs

Question 1

Adverse Drug Reactions

Answer 1

Type A (Augmented)- due to pharmacological effects of drug, predictable, related to dose.

Type B( Idiosyncratic)- not due to pharmacological effects, not predictable, not related to dose, can be due to allergic reaction, and metabolic activation to toxic intermediates

Question 2

Cell Damage

Answer 2

Can be covalent or noncovalent
Covalent:
1) bind to cellular macromolecules
2) bind to DNA
3) bind to protein
Noncovalent:
1) lipid peroxidation via a chain reaction
2) depletion of GSH
3) generation of cytotoxic reactive oxygen species

Question 3

Drugs known to cause liver cell damage/ death

Answer 3

Amphetamine-potent central nervous system (CNS) stimulant
Bromobenzene- no medical use
Iproniazid- non-selective, irreversible monoamine oxidase inhibitor (MAOI)
Isoflurane- general anesthetic
Isoniazid- antibiotic used for the treatment of tuberculosis
Lamotrigine- anticonvulsant drug
Methotrexate- treat certain types of cancer of the breast, skin, head and neck, or lung
Paracetamol
Troglitazone- antidiabetic and anti-inflammatory drug

Question 4

Drugs that cause cholestasis (Impairment of hepatocellular bile excretion)

Answer 4

Amoxicillin-clavulanic acid- antibiotics
Anabolic steroids
Cholesterol-lowering “Statins”
Chlorpromazine- antipsychotic
Erythromycin- antibiotics
Fluoroquinolones- antibiotics
Irbesartan- hypertensive medication
Oxypenicillins- antibiotics
Tamoxifen- treat breast cancer
Terbinafine- antifungal medication
Terfenadine- antihistamine