Drug Reactions

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Drug  reactions  can  be  classified  in  many  ways.  One  useful  approach  is  to  separate  predictable  reactions occurring in normal patients from unpredictable reactions occurring in susceptible patients. 

Predictable adverse reactions

  • Over dosage (wrong dosage or defect in drug metabolism)
  • Side effects (sleepiness from antihistamines)
  • Indirect effects (antibiotics changing normal flora)
  • Drug interactions (altered metabolism of drugs; most commonly involving the cytochrome P-450 enzymes)

Unpredictable adverse reactions 

  • Allergic  reaction  (drug  allergy  or  hypersensitivity;  immunologic  reaction  to  drug; requires previous exposure or cross-reaction)
  • Pseudo allergic reaction (non-immunologic activation of mast cells).
  • Idiosyncratic  reaction  (unexplained  reaction,  not  related  to  mechanism  of  action, without known or suspected immunologic mechanism).

Note: 80% of allergic and pseudo allergic drug reactions are caused by Beta-lactam antibiotics, aspirin, NSAIDs, and Sulfonamides

Fixed Drug Eruption (FDE)

It is a cutaneous drug reaction that recurs at the same site with repeated exposure to the agent. 

Clinical presentation 

  • Typically, red-brown patch or plaque
  • Occasionally may be bullous
  • common sites are genitalia, palms, and soles, as well as mucosa
  • Often multiple. Starts with edematous papule or plaque later becomes darker
  • Resolves with post-inflammatory hyperpigmentation

Note:  When confronted with hyper pigmented macule on genitalia, always think of Fixed Drug Eruption

Non-pharmacological Treatment 

Avoidance of triggering drug;

Pharmacological Treatment 

A:  hydrocortisone (IV) 200mg 12hourly for 24hours 

AND 

B: betamethasone valerate cream (topical) 12hourly for 2weeks 

OR 

D: clobetasol propionate cream/ointment (topical) 0.05% 12hourly for 2- 4weeks

Stevens Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)

It is a life-threatening condition caused by reaction to drugs e.g. sulphur containing drugs. It causes  the skin to blister and peel off. Less than 10% of body surface area involved. Is referred to as SJS.  SJS  progresses  to  Toxic  Epidermal  Necrolysis  (TEN)  with  involvement  of  more  than  2  mucosal  surfaces. 

Clinical presentation 

  • Patients usually have prodromal with fever, malaise, and arthralgia’s
  • Erosions, hemorrhage and crusts on lips, and erosions in mouth covered by necrotic white pseudo membrane
  • Involvement of the eyes: Erosive conjunctivitis, can lead to scarring
  • Involvement of genitalia with painful erosions
  • Sudden appearance of diffuse macules or diffuse erythema,
  • Early sites of cutaneous involvement are the presternal region of the trunk and the face, but also the palms and soles.
  • Then prompt progression with widespread erythema and peeling of skin; skin lies in sheets and folds on the bedding.

Pharmacological Treatment 

  • Identify and discontinue potential offending medications/drugs.
  • Transfer patient to intensive care unit or critical care unit or burn unit.
  • Wound care
  • Keep warm
  • Monitor fluid input and output –urine output 0.5-ml/kg/hour. Monitor electrolytes.
  • Consultations – Ophthalmologist, Physician, Dermatologist

SCORTEN SCORE for determining prognosis of patient 

  • Age >40years
  • Malignancy
  • Total body surface area affected >10%

Calculate SCORTEN on days 1 & 3 of hospital stay

Pharmacological Treatment 

A: hydrocortisone (IV) 200mg 12hourly for 48hours 

AND 

A: prednisolone (PO) 1–2mg/kg 24hourly for 5–7days 

Antibiotics in case of infection (as for treatment of sepsis) 

Note:   

  • Topical sulfur containing medications should be avoided.
  • Systemic corticosteroids, if employed, should be used early to attempt to abort the immunologic reaction (first 24 hours).