- ADR — परिभाषा और महत्व
- ADR के प्रकार
- Presentation — symptom-wise
- Pathophysiology & common culprits
- Investigations & monitoring
- Management — symptom-wise (meds & doses)
- Emergency protocol — Anaphylaxis & Airway
- SJS/TEN care
- Reporting / Pharmacovigilance
- Prevention & Patient counselling
- Appendix — Checklists & Templates
- External authoritative references
ADR — परिभाषा और महत्व
Adverse Drug Reaction (ADR) वह कोई भी हानिकारक और अनपेक्षित प्रतिक्रिया है जो दवा के सामान्य चिकित्सीय dose पर होती है। ADRs अस्पताल में भर्ती, रोग का बिगड़ना, दीर्घकालिक morbidities और public health alerts का कारण बन सकती हैं। Pharmacovigilance systems (WHO, national programs) ADR surveillance का आधार हैं। [NCBI / WHO resources]
ADR के प्रकार (clinically उपयोगी वर्गीकरण)
- Type A (Dose-related): predictable — eg. bleeding with anticoagulants.
- Type B (Idiosyncratic/allergic): unpredictable — eg. penicillin anaphylaxis, SJS/TEN.
- Type C: chronic use related (eg. steroid osteoporosis).
- Type D: delayed (eg. secondary malignancies post-chemotherapy).
- Type E: withdrawal reactions (eg. benzodiazepine withdrawal).
- Type F: failure of therapy (drug interactions leading to reduced efficacy).
Causality assessment: Naranjo scale, WHO-UMC are helpful tools to support reporting and assessment.
Presentation — organ/system-wise (पहचान)
| Organ system | Clinical features / timeline | Common culprit drugs (examples) |
|---|---|---|
| Cutaneous | Rash, urticaria, maculopapular eruption, blistering (days-weeks) | Antibiotics (penicillins, sulfonamides), anticonvulsants |
| Anaphylaxis | Minutes—hours: hypotension, bronchospasm, angioedema | Beta-lactams, NSAIDs, contrast media, monoclonal antibodies |
| SJS/TEN | 1–3 weeks: mucosal erosions, painful blistering | Anticonvulsants (carbamazepine), allopurinol, sulfonamides |
| Hepatic | Elevated transaminases, jaundice (days–months) | Antitubercular drugs, some antibiotics, statins |
| Renal | AKI/Interstitial nephritis, oliguria | NSAIDs, PPIs, some antibiotics |
| Hematologic | Agranulocytosis, hemolysis, thrombocytopenia | Antithyroid drugs, some antibiotics, anticonvulsants |
| CNS | Seizures, delirium, extrapyramidal symptoms | Antipsychotics, certain antivirals/antibiotics |
विशेष रूप से DRESS (rash + fever + organ involvement) को high suspicion से देखें।
Pathophysiology & common culprits
ADR mechanisms में शामिल हैं: IgE-mediated immediate hypersensitivity, T-cell mediated delayed reactions (eg. SJS/TEN), metabolic/toxic accumulation (liver/renal), direct pharmacologic toxicity और genetic predisposition (eg. HLA alleles)।
Known high-risk drug examples: beta-lactams, sulfonamides, anticonvulsants (carbamazepine, lamotrigine), allopurinol, NSAIDs, contrast agents, certain antiretrovirals and chemotherapeutics.
Investigations & monitoring — targeted approach
Investigations should correspond to the suspected organ involvement:
- Basic: CBC with differential, LFTs (ALT, AST, ALP, bilirubin), KFT (creatinine, electrolytes), glucose, urinalysis.
- Dermatologic: Photo documentation, skin biopsy if severe or diagnostic doubt.
- Anaphylaxis: Treat clinically; consider serum tryptase 1–3h post event for retrospective confirmation (do not delay treatment).
- Hepatotoxicity: Viral hepatitis screen where indicated; trend LFTs.
- Renal: Urinalysis, urine eosinophils (if available), renal consult for interstitial nephritis.
- Drug levels: for narrow therapeutic index drugs (eg. digoxin, lithium, anticonvulsants) per protocol.
Management — symptom-wise practical guide (adult typical doses)
मेरे नीचे दिए गए उपाय सामान्य adult guidance हैं — हर मरीज के लिए weight/renal/hepatic status के अनुसार adjust करें और स्थानीय प्रोटोकॉल follow करें।
| Presentation | Immediate steps | Medication / typical adult dose |
|---|---|---|
| Urticaria / Itchy rash | Stop suspect drug; monitor progression | Second-gen antihistamine: Cetirizine 10 mg PO once daily or Loratadine 10 mg PO. If severe pruritus: Diphenhydramine 25–50 mg at night (sedation cautions). |
| Angioedema (no airway compromise) | Stop drug; observe airway closely | Antihistamines + consider short steroid course: Prednisone 30–40 mg PO single dose or short course (clinician decision). |
| Anaphylaxis | Immediate ABCs; IM epinephrine; call emergency | IM epinephrine 1:1000 (1 mg/mL): Adult 0.3–0.5 mg IM (anterolateral thigh); repeat every 5 minutes if no adequate response. Give oxygen, IV fluids (crystalloid bolus 500–1000 mL adult), prepare for airway/advanced care. Adjuncts: chlorpheniramine 10 mg IV, famotidine 20 mg IV, hydrocortisone 100–200 mg IV — adjuncts only, not a substitute for epinephrine. (See Resuscitation Council / WHO guidance). |
| SJS / TEN | Immediate drug cessation; urgent ICU/burn unit admission | Supportive care: fluid/electrolyte balance, wound management (non-adhesive dressings), infection prevention, analgesia, ophthalmology consult. Specialist therapies (IVIG, cyclosporine) discuss with derm/ICU — evidence mixed. |
| Drug-induced liver injury | Stop drug; monitor LFTs; hepatology referral if severe | Supportive care; N-acetylcysteine for paracetamol toxicity (per protocol); specific antidotes per drug. |
| Acute interstitial nephritis | Stop offending drug; nephrology consult | Supportive; corticosteroids in selected cases after specialist discussion. |
| Hematologic (eg. agranulocytosis) | Stop drug; urgent hematology consult | G-CSF may be required; transfusion support and infection precautions as indicated. |
Pediatric dosing is weight-based; always consult pediatric formularies. Adjust for renal/hepatic impairment.
Emergency protocol — Anaphylaxis & airway (step-by-step)
संदेह होने पर तुरंत प्रबंध करें; clinical diagnosis पर treatment delay न करें।
Immediate actions (seconds—minutes)
- Call for help/activate emergency response.
- Give IM epinephrine into anterolateral thigh (adult 0.3–0.5 mg of 1 mg/mL). Repeat every 5 min if necessary.
- Position supine with legs elevated if hypotensive (unless respiratory distress prevents).
- High-flow oxygen 10–15 L/min, establish IV access, give rapid crystalloid bolus for hypotension (500–1000 mL adults; 20 mL/kg children).
- Adjuncts: H1 antihistamine (chlorpheniramine 10 mg IV), H2 blocker (famotidine/ranitidine where available), steroid (hydrocortisone 100–200 mg IV) — adjuncts only.
- Prepare for airway: early anaesthesia/ENT involvement for progressive angioedema/stridor; have difficult airway kit and cricothyrotomy equipment available in worst case.
Refractory anaphylaxis
If persistent hypotension despite initial measures, consider IV epinephrine infusion in ICU (experienced clinicians) and vasopressor support; glucagon IV if patient on beta-blocker causing refractory hypotension.
For detailed algorithms see: Resuscitation Council UK — Anaphylaxis and WHO/CDC resources linked in references.
SJS / TEN — Early recognition & inpatient care
SJS/TEN range: SJS (<10% BSA), SJS-TEN overlap (10–30%), TEN (>30%). Clinical features: prodrome (fever, malaise), painful erythema, widespread blistering, mucosal erosions (oral, ocular, genital).
- Immediate cessation of suspected drug and admission to specialist centre (ICU/burn unit).
- Supportive management: fluid & electrolyte balance, non-adhesive dressings, wound care, infection surveillance, pain control and nutritional support.
- Early ophthalmology for ocular involvement; long-term ocular morbidity risk.
- Consider biopsy for diagnosis; discuss immunomodulatory therapy (IVIG/cyclosporine) with dermatology — evidence variable.
NHS and NCBI reviews: follow those specialist protocols (links below).
Reporting / Pharmacovigilance — क्यों और कैसे
Serious, unexpected, or new ADRs should be reported to national pharmacovigilance systems to detect safety signals and protect public health.
- India: PvPI / ADR India
- WHO: WHO — Pharmacovigilance
- USA: FDA — MedWatch
Reporting template example (use in notes / ADR form):
Patient: [age/sex]
Suspected drug(s): [name, dose, route, start date, batch if known]
Onset of symptoms: [date/time]
Description: [rash / airway compromise / organ involvement]
Investigations done: [labs/images]
Treatment given: [drug/dose/time]
Outcome: [recovered / ongoing / escalated]
Reporter: [name, contact]
Prevention, prescribing safety & patient counselling
- Medication reconciliation at each visit and avoidance of unnecessary polypharmacy.
- Obtain allergy history and prior ADRs before prescribing; provide patient an allergy/ADR card.
- Consider genetic testing where indicated (eg. HLA-B*1502 screening before carbamazepine in high-risk populations).
- Educate patients to report rash, breathing difficulty, swelling, jaundice or dark urine immediately.
- For known severe allergic reaction history, use alternative non-cross reactive drugs and allergy/immunology referral for testing where appropriate.
Appendix — Quick checklists & clinician templates
Immediate Anaphylaxis Checklist (print & keep in ED)
- Call for help / emergency response.
- IM epinephrine 0.3–0.5 mg adult IM into anterolateral thigh; repeat q5 min.
- Oxygen, establish IV access, crystalloid bolus for hypotension.
- Administer adjuncts (antihistamine, steroid) after epinephrine—but do not delay epinephrine.
- Prepare for airway management; early ICU transfer as needed.
Documentation & Handover template (SBAR)
S: Situation — suspected ADR: [describe]
B: Background — drug history, comorbidities, allergies
A: Assessment — vitals, organ systems involved, treatments given
R: Recommendation — admit/observe/ICU, consult services, monitoring plan
Printable one-page clinician checklist — copy the above and print for ED crash cart.
External authoritative references (direct links)
- WHO — Pharmacovigilance
- CDC — Centers for Disease Control and Prevention (search drug safety / anaphylaxis)
- NHS — Stevens-Johnson syndrome (SJS) information
- FDA — MedWatch (Adverse event reporting)
- NCBI / StatPearls — Adverse Drug Reactions overview
- Resuscitation Council UK — Anaphylaxis guidance
- MedlinePlus — Drug information (consumer)