Drug-Induced Medical Emergencies

• Drug-induced medical diseases can be due to medical errors but are frequently inevitable.• They can affect virtually all body systems • This talk concentrates on emergency

conditions with special highlight on skin

ANAPHYLAXISTriggers of anaphylaxis:

beta-lactam antibiotics, some NSAIDs and opioids

Cardiac ComplicationsBradycardia/AV blockade : –Beta blockers, Calcium channel blockers and Digoxin

Supraventricular and ventricular tachycardia: – Sympathomimetics and Theophylline

Cardiotoxicity : – cancer chemotherapy

RespiratoryNon-cardiogenic pulmonary edema–Opiates, Sedative-hypnotics, salicylates, Beta

blockers and Calcium-channel blockersBradypnea/hypoventilation–Antidepressants, Antipsychotics and

AntiepilepticsPulmonary Toxicity–Nitrofurantoin

HepatobiliaryDrug-induced liver injury (DILI)• Over 1000 medications and herbal products have been

implicated• DILI can be classified in several ways by clinical

presentation, mechanism of hepatotoxicity (predictable or idiosyncratic) and histological finding (hepatitis, cholestasis or steatosis)

• Withdrawal of the offending drug remains the primary treatment for DILI.

Gastrointestinal

• GIT Hemorrhage• Anti-thrombotics, NSAIDS and Steroids

• C. difficile colitis• Antibiotics

RENAL

• Acute Interstitial Nephritis• Acute Tubular Necrosis• Drug induced thrombotic microangiopathy

(DITMA) • Crystal nephropathy• Acute nephrocalcinosis

NEUROLOGICALSeizures–Sympathomimetics, Antidepressants, Salicylates,

Imipenem, Penicillins and Ciprofloxacin

Coma –Anticholinergics, Antihistamines, Antidepressants,

SSRI, Beta blockers, Calcium channel blockers and Benzodiazepines

Neuroleptic Malignant Syndrome(NMS)–Anti-psychotics

Intracranial Hemorrhage–Anti-thrombotics

METABOLICHypoglycemia – Insulin, OHG, Beta blockers and SalicylatesHyperkalemia – Beta blockers and Cardiac glycosides Hypokalemia – Diuretics, Beta-agonists and TheophyllineRhabdomyolysis – Corticosteroids, Sympathomimetics, Anticholinergics

and Isoniazid

Hematological

Myelosuppression• Anti-thyroid, NSAIDS, antipsychotics, antibiotics

Hemolysis– Immune: Dapson, methyldopa, NSAIDS, ribavirin

and penicillins– Non-immune: interferon, IVIG, lead and copper

Drug Induced Skin Emergencies

–Steven Johnson syndrome and toxic epidermal necrolysis–Urticaria, angioedema–Acute generalized erythematous pustulosis–Drug reaction with eosinophilia and systemic symptoms (DRESS)–Leucocytoclastic vasculitis–Warfarin-induced skin necrosis and heparin induced skin reaction–Staphylococcal scalded skin syndrome

URTICARIA AND ANGIOEDEMA

ACUTE GENERALIZED ERYTHEMATOUS PUSTULOSIS (AGEP)

Commonly occur with penicillins, quinolones and macrolides

DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS)

HYPERSENSITIVITY VASCULITIS (LEUCOCYTOCLASTIC VASCULITIS)

WARFARIN INDUCED SKIN NECROSIS

HEPARIN INDUCED SKIN REACTION

FIXED DRUG ERUPTION (FDE)

STEVENS-JOHNSON SYNDROME & TOXIC EPIDERMAL NECROLYSIS

• TEN & SJS are life-threatening syndromes with an incidence ranging from 0.5 to 7.1 cases per million person per year.• Percentage of skin detachment determines the

classification (10% – 30%)• A prodromal phase of fever and sore throat precede skin

sloughing.• Mucous membranes involvement occur in about 85% of

cases• Additionally, epithelium of gastrointestinal and respiratory

tract may be involved.

IMPLICATED DRUGSHL

A B

1502

& cy

p 2c

19

Prognosis (Score TEN)• Age > 40• History of malignancy• Body surface area detached > 10%• Pulse > 120 b/min• Urea > 10 mmol/L• Glucose > 250 mg/dl• Bicarb < 20 mmol/l

Prompt withdrawal of the culprit drug is the cornerstone of management

• Wound care: the extent of epidermal detachment should be evaluated. Some centers may surgically debride wounds, others may use anti-shear wound care. • Fluid and electrolyte replacement with nutritional

assessment.• Ocular care• Prevention of infection: sterile handling, antiseptic

solutions• Antibiotics are given according to cultures results.

Systemic steroidsResults from EuroSCAR and RegiSCAR studies done on more than 500 patients from France and Germany DON’T support the use of systemic steroids for the treatment of SJS/TEN.

In addition, since steroids are associated with increased risk of sepsis, catabolism and poor wound healing, their use in such cases is contraindicated.

Intravenous immunoglobulins

Data surrounding the use of IVIG in SJS/TEN patients are conflicting.

Cyclosporine A survival benefit for patients treated with cyclosporine (dosed at 3 – 5 mg/kg/day) was noted in RegiSCAR cohort study, however further studies are required to confirm its rule in SJS/TEN.

Tumor necrosis factor inhibitor (Anti-TNF)

• A single infusion of 5 mg/kg of anti-TNF halted the progression of skin detachment and induced rapid re-epithelialization.• Etanercept 50 mg single subcutaneous

injection has been successful in some cases.

Thank you