Drug Reactions Flashcards
Skin is a common target for idiosyncratic reactions. What does this word mean?
Idiosyncratic (also known as type B reactions) = drug reactions that occur rarely and unpredictably amongst the population.
How does a drug reaction in the skin present?
They can mimic a wide variety of other skin diseases – these can be mild e.g. rash, or life threatening, e.g. toxic epidermal necrolysis. Also note that if a patient experiences a mild reaction to a drug, if the take that drug again the reaction can escalate in severity.
What are the four types of immunologically mediated reaction?
Give an example of each.
What is significant about the dose?
Type I. Anaphylactic reactions, e.g. urticaria
Type II. Cytotoxic reactions, e.g. pemphigus & pemphigoid
Type III. Immune complex-mediated reactions, e.g. purpura/rash
Type IV. Cell-mediated delayed hypersensitivity reactions, e.g. T-cell mediated. Erythema/rash
NB – these reactions are not dose-dependent.
What are some types of non-immunologically mediated reaction?
What is significant about the dose?
- Eczema
- Drug-induced alopecia
- Phototoxicity
- Skin erosion or atrophy from topically applied 5-fluorouracil or steroids
- Psoriasis
- Pigmentation
- Cheilitis, xerosis
NB – these reactions can be dose dependent.
Are immunologically or non-immunologically mediated reactions dose dependent?
Immunologically mediated reactions are not dose-dependent
Non-immunologically mediated reactions can be dose dependent
What are some risk factors for development of drug eruptions?
- Age - young adults>infants/elderly
- Gender - females>males
- Genetics
- Concomitant disease - viral infections (HIV/EBV/CMV); cystic fibrosis
- Immune status - previous drug reaction or positive skin test
- Chemistry - Β-lactam compounds, NSAIDs, high molecular weight/hapten-forming drugs
- Route - topical v oral/systemic
- Dose
What is the most common form of drug eruption?
- How does it appear?
- What type of hypersensitivity reaction?
- Mild or severe?
- Mucous membranes?
- Other symptoms?
- Onset?
- Progression?
Exanthematous (morbilliform) drug eruption
- Characterised by a diffuse and symmetric eruption of erythematous macules or small papules
- Idiosyncratic, T-cell mediated delayed type hypersensitivity (Type IV) reaction
- Usually mild & self limiting
- Mucous membranes usually spared
- Pruritus (itch) is common
- Mild fever is common
- Onset is 4-21 days after first taking drug
- Can progress to a severe life-threatening reaction
What are some indicators of a potential severe reaction?
- Involvement of mucous membrane and face.
- Facial oedema & erythema
- Widespread confluent erythema
- Fever (>38.5⁰C)
- Blisters, purpura, necrosis
- Lymphadenopathy, arthalgia
- Shortness of breath, wheezing
Urticarial drug reaction
- What type of hypersensitivity?
- Which drugs?
- Mechanism?
These are usually an immediate IgE mediated hypersensitivity reaction (type I) after rechallenge with a drug, e.g. β-lactam antibiotics, carbazepine, many other drugs.
Either that, or direct release of inflammatory mediators from Mast cells on first exposure (aspirin, opiates, NSAIDs, muscle relaxants, vancomycin, quinolones).
Pustular drug reactions
- Which drugs?
- What other type?
Acne can be caused by glucocorticoids (anabolic steroids), androgens, lithium, isoniazid, phenytoin.
Acute generalised exanthematous pustulosis (AGEP) are rare and can be caused by antibiotics, calcium channel blockers, antimalarials.
Fixed drug eruptions
- What do the lesions look like?
- Where do they occur?
- Why are they fixed?
- Well demarcated round/ovoid plaques – looks like a large red evenly pigmented lesion
- Red, painful
- Hands, genitalia, lips, occasionally oral mucosa
- Resolves with persistent pigmentation when the drug is stopped
- Can re-occur on the same site on re-exposure to the drug
- Usually mild when restricted to a single lesion
What are the differences in symptoms between acute and chronic drug reactions?
Acute – skin toxicity, systemic toxicity, photodegeneration.
Chronic – pigmentation, photoageing, photocarcinogenesis.
What is a phototoxic drug reaction?
Non-immunological mediated skin reaction which will arise in any individual providing there is enough photo-reactive drug and the appropriate wavelength of light.
Waveband of concern is usually UVA/Visible. Can occur indoors through window glass.
What are the major patterns of cutaneous phototoxicity?
- Immediate prickling with delayed erythema and pigmentation - chlorpromazine, amiodarone
- Exaggerated sunburn - quinine, thiazides, DCMT
- Exposed telangiectasia - calcium channel antagonists
- Delayed 3-5 days erythema and pigmentation - psoralens
- Increased skin fragility - nalidixic acid, tetracycline naproxen, amiodarone
What is the major drug category associated with phototoxic drug reactions?
Thiazides
