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[General pathology](https://durgical.com/en/general-pathology/) · [Environmental pathology](https://durgical.com/en/general-pathology/#a-environment)

# Injury by therapeutic drugs: the classic examples

- Topic

Medicines can injure tissue through their predictable toxicity or through rare immune or genetic reactions; some cases are exam classics.

Updated 2026-11-01

## Key points

- Acetaminophen: NAPQI and glutathione depletion; zone 3 necrosis; N-acetylcysteine restores glutathione.
- SJS/TEN: mucosal involvement and skin detachment; carbamazepine, lamotrigine, allopurinol, sulfonamides.
- Doxorubicin: dilated cardiomyopathy; bleomycin and amiodarone: pulmonary fibrosis.
- Aminoglycosides: nephrotoxicity and ototoxicity.
- Alcohol and other CYP2E1 inducers make acetaminophen injury worse.

## What it is

Adverse drug reactions are a frequent cause of hospital admission. They are either predictable (they depend on the amount and on a known toxic metabolite) or idiosyncratic (rare, linked to the immune system or to the patient's genes, such as certain HLA types). Knowing the classic drug–organ pairs helps recognise the injury early.

## Step by step

- The drug is absorbed and, in the liver, phase I enzymes (cytochrome P450) may turn it into a reactive metabolite.
- Phase II conjugation (glucuronide, sulfate, glutathione) normally neutralises that metabolite.
- When the system is saturated or glutathione runs out, the metabolite binds proteins and causes oxidative stress.
- The cell dies by necrosis in the zone where the enzyme is most active (zone 3 of the liver for acetaminophen).
- In idiosyncratic reactions the drug or its metabolite modifies proteins and is presented as an antigen.
- T cells attack the skin, liver or kidney: SJS/TEN, DRESS, interstitial nephritis or immune hepatitis.

## Classic drug injuries to know

| Injury | Typical drugs | Mechanism |
| --- | --- | --- |
| [Centrilobular liver necrosis](https://durgical.com/en/conditions/acetaminophen-toxicity/) | Acetaminophen in overdose | NAPQI exceeds glutathione; antidote N-acetylcysteine |
| [Drug-induced hepatitis](https://durgical.com/en/conditions/drug-induced-liver-injury/) | Isoniazid, valproic acid, amiodarone, methotrexate | Toxic metabolites or immune reaction; methotrexate leads to fibrosis |
| [SJS / toxic epidermal necrolysis](https://durgical.com/en/conditions/stevens-johnson-syndrome-and-toxic-epidermal-necrolysis/) | Carbamazepine, lamotrigine, phenytoin, allopurinol, sulfonamides | Cytotoxic T cells kill keratinocytes; risk HLA such as HLA-B*15:02 |
| [DRESS](https://durgical.com/en/conditions/cutaneous-drug-reactions-and-dress/) | Antiseizure drugs, allopurinol, some antibiotics | Delayed T-cell reaction with eosinophilia and organ involvement |
| [Acute tubular necrosis](https://durgical.com/en/conditions/acute-kidney-injury/) | Aminoglycosides, cisplatin, amphotericin B, iodinated contrast | Direct toxicity to the proximal tubule |
| [Acute interstitial nephritis](https://durgical.com/en/conditions/acute-interstitial-nephritis/) | Penicillins, NSAIDs, proton pump inhibitors | Type IV hypersensitivity in the interstitium |
| [Cardiomyopathy](https://durgical.com/en/conditions/dilated-cardiomyopathy/) | Doxorubicin and other anthracyclines | Free radicals damage cardiac myocytes; cumulative effect |
| [Pulmonary fibrosis](https://durgical.com/en/conditions/interstitial-lung-disease/) | Bleomycin, amiodarone, methotrexate, nitrofurantoin | Oxidative injury and chronic inflammation |
| [Peptic ulcer and bleeding](https://durgical.com/en/conditions/peptic-ulcer-disease/) | NSAIDs, aspirin | Loss of protective prostaglandins in the mucosa |
| [Heparin-induced thrombocytopenia](https://durgical.com/en/conditions/heparin-induced-thrombocytopenia/) | Heparin | IgG antibodies against heparin–PF4 activate platelets: thrombosis |

## Clinical notes

- A careful medication history, including herbal products, is part of the work-up of every unexplained hepatitis or rash.
- Genetic testing for HLA-B*15:02 before carbamazepine is recommended in people of Asian ancestry at risk.

## Memory aid

Predictable injury follows the amount and the metabolite; idiosyncratic injury follows the patient's genes and T cells.

## Test yourself

Think of the answer, then tap the question to see it.

## Why does acetaminophen overdose damage the area around the central vein of the liver lobule first?

Zone 3 has the most CYP2E1 and the least oxygen; there NAPQI forms and, once glutathione is used up, binds and kills hepatocytes.

## Which HLA allele raises the risk of carbamazepine-induced SJS/TEN in people of Asian ancestry?

HLA-B*15:02.

## Which chemotherapy drug is classically linked to cumulative dilated cardiomyopathy?

Doxorubicin (and the other anthracyclines), through free radical injury to cardiac myocytes.

## What is the mechanism of heparin-induced thrombocytopenia?

IgG antibodies bind heparin–platelet factor 4 complexes and activate platelets, so the count falls while the risk of thrombosis rises.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/general-pathology/injury-by-therapeutic-drugs-the-classic-examples/)

## Related

- [Chemical (toxic) cell injury: direct and after metabolism](https://durgical.com/en/general-pathology/chemical-cell-injury-direct-and-after-metabolism/)
- [Oxidative stress and free-radical injury](https://durgical.com/en/general-pathology/oxidative-stress-and-free-radical-injury/)
- [Patterns of necrosis: coagulative, liquefactive, caseous, fat, fibrinoid, gangrenous](https://durgical.com/en/general-pathology/patterns-of-necrosis-coagulative-liquefactive-caseous-fat-fibrinoid-gangrenous/)
- [Apoptosis: the intrinsic and extrinsic pathways](https://durgical.com/en/general-pathology/apoptosis-the-intrinsic-and-extrinsic-pathways/)

## Related conditions

- [Acetaminophen toxicity](https://durgical.com/en/conditions/acetaminophen-toxicity/)
- [Stevens–Johnson syndrome and toxic epidermal necrolysis](https://durgical.com/en/conditions/stevens-johnson-syndrome-and-toxic-epidermal-necrolysis/)
- [Cutaneous drug reactions and DRESS](https://durgical.com/en/conditions/cutaneous-drug-reactions-and-dress/)
- [Drug-induced liver injury](https://durgical.com/en/conditions/drug-induced-liver-injury/)
- [Acute interstitial nephritis](https://durgical.com/en/conditions/acute-interstitial-nephritis/)
- [Heparin-induced thrombocytopenia](https://durgical.com/en/conditions/heparin-induced-thrombocytopenia/)
- [Neutropenia and drug-induced agranulocytosis](https://durgical.com/en/conditions/neutropenia-and-drug-induced-agranulocytosis/)
- [Renal papillary necrosis](https://durgical.com/en/conditions/renal-papillary-necrosis/)
- [Aplastic anaemia](https://durgical.com/en/conditions/aplastic-anaemia/)
- [Isoniazid toxicity](https://durgical.com/en/conditions/isoniazid-toxicity/)
- [Salicylate (aspirin) toxicity](https://durgical.com/en/conditions/salicylate-toxicity/)
- [Peptic ulcer disease](https://durgical.com/en/conditions/peptic-ulcer-disease/)

## Elsewhere in DurgiPedia

- [Acetaminophen metabolism and NAPQI](https://durgical.com/en/biochemistry/topics/acetaminophen-metabolism-and-napqi/)
- [NAPQI (N-acetyl-p-benzoquinone imine)](https://durgical.com/en/biochemistry/molecules/napqi/)
- [Glutathione (GSH)](https://durgical.com/en/biochemistry/molecules/glutathione/)
- [Cytochrome P450 system](https://durgical.com/en/biochemistry/topics/cytochrome-p450-system/)
- [Xenobiotic biotransformation: phases I, II and III](https://durgical.com/en/biochemistry/topics/xenobiotic-biotransformation-phases-i-ii-and-iii/)
- [Type IV hypersensitivity (delayed, T cells)](https://durgical.com/en/immunology/type-iv-hypersensitivity/)
- [Latex and drug allergy](https://durgical.com/en/immunology/latex-and-drug-allergy/)
- [Liver: lobule, acinus, hepatocytes, sinusoids, Kupffer cells](https://durgical.com/en/histology/liver-lobule-acinus-hepatocytes-sinusoids-kupffer-cells/)

## In Pharmacology

- [Paracetamol](https://durgical.com/en/pharmacology/paracetamol/)
- [Acetylcysteine](https://durgical.com/en/pharmacology/acetylcysteine/)
- [Carbamazepine](https://durgical.com/en/pharmacology/carbamazepine/)
- [Lamotrigine](https://durgical.com/en/pharmacology/lamotrigine/)
- [Phenytoin](https://durgical.com/en/pharmacology/phenytoin/)
- [Doxorubicin](https://durgical.com/en/pharmacology/doxorubicin/)
- [Bleomycin](https://durgical.com/en/pharmacology/bleomycin/)
- [Gentamicin](https://durgical.com/en/pharmacology/gentamicin/)
- [Cisplatin](https://durgical.com/en/pharmacology/cisplatin/)
- [Methotrexate](https://durgical.com/en/pharmacology/methotrexate/)

[← All of general pathology](https://durgical.com/en/general-pathology/)

Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.

Sources: [Acetaminophen overdose: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/002598.htm) (MedlinePlus, US National Library of Medicine, 2026); [Stevens-Johnson syndrome/toxic epidermal necrolysis: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/stevens-johnson-syndrome-toxic-epidermal-necrolysis/) (MedlinePlus, US National Library of Medicine, 2026).

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/injury-by-therapeutic-drugs-the-classic-examples/