USMLE (Subject) / Pharmacology - Toxicities and side effects (Lesson)

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  • Specific toxicity treatments - AChE inhibitors, organophosphates Atropine > pralidoxime
  • Specific toxicity treatments - Antimuscarinic, anticholinergic agents Physostigmine, control hyperthermia
  • Specific toxicity treatments - β-blockers Atropine, glucagon
  • Copper Penicillamine, trientine
  • Cyanide Nitrate + thiosulfate, hydroxocobalamin
  • Iron poisoning Clinical features:- Initially hemorrhagic gastroenteritis, shock symptoms- In case patient survives: symptom-free interval afer 6 hours- Causes dark-colored stools- 1-2 days later: Risk of renal and liver failure, unconsciousness, and respiratory depression Diagnostics: - Anion gap metabolic acidosis- Radiopaque pills on abdominal x-ray Treatment:- Antidote: Deferoxamine- Whole bowel irrigation
  • Lead poisoning Sources of exposure:- Battery manufacturing, metallurgy, corrosion inhibition- Gun range- Tableware containing lead Risk factors:- Home built before 1978- Pica or mouthing behaviors (eg, infants, developmental delay)- Sibling with lead poisoning- Low socioeconomic status- Immigrant or international adoptee Clinical features:- May be asymptomatic- Abdominal pain/constipation- Cognitive impairment/behavioral problems- Encephalopathy- Paralysis of the radial or peroneal nerve (wrist/foot drop)- Symptoms of anemia- Kidneys: Nephropathy, renal cell carcinoma- Purple-bluish line on the gums (lead line or Burton line) Management:- Obtain a venous sample (if screening performed by capillary sample)- Environmental surveillance (identify & remove lead sources)- Notify public health department- Nutritional counseling- Chelation therapy if lead level ≥ 45 µg/dL (children) or ≥ 50/80 µg/dL (symptomatic/asymptomatic adults)→ Oral succimer with/without IV/IM EDTA
  • Mercury Dimercaprol, succimer
  • Methanol, ethylene glycol (antifreeze) Fomepizole > ethanol, dialysis Methanol ingestion:- Visual blurring, central scotomata- Afferent pupillary defect- Altered mentation- High osmolar gap, increased anion gap metabolic acidosis Ethylene glycol ingestion:- Flank pain- Hematuria, oliguria- Cranial nerve palsies, tetany- Calcium oxalate crystals in urine
  • Methemoglobin Methylene blue, vitamine C (reducing agent)
  • Specific toxicity treatments - Salicylates NaHCO3 (alkalinize urine), dialysis
  • Specific toxicity treatments - TCAs NaHCO3 (stabilizes cardiac cell membrane)
  • Coronary vasospasm - Cocaine- Amphetamines- Sumatriptan- Ergot alkaloids
  • Cutaneous flushing - Nitrates- Vancomycin- Adenosine- Niacin- Ca2+ channel blockers- Echinocandins Red man syndrome – rate-dependent infusion reaction to vancomycin causing widespread pruritic erythema. Manage with diphenhydramine, slower infusion rate.
  • Dilated cardiomyopathy - Anthracyclins (eg, doxorubicin, daunorubicin) - Prevent with dexrazoxane
  • Torsades de pointes Agents that prolong QT interval:- Antiarrhythmics class Ia, III- Antibiotics (eg, macrolides)- Antipsychotics (eg, haloperidol)- Antidepressants (eg, TCAs)- Antiemetics (eg, ondansetron)
  • Diabetes insipidus - Lithium- Demeclocycline (semisynthetic tetracycline derivative)
  • Hyperglycemia - Tacrolimus- Protease inhibitors- Niacin- HCTZ- Corticosteroids
  • Hyperthyroidism - Lithium- Amiodarone
  • Hypothyroidism - Lithium- Amiodarone- Sulfonamides
  • SIADH - Carbamazepine- Cyclophosphamie- SSRIs
  • Acute cholestatic hepatitis, jaundice - Macrolides (eg, erythromycin)
  • Diarrhea - Acamprosate (to treat alcohol dependence)- Antidiabetic agents (acarbose, metformin, pramlintide)- Colchicine- Cholinesterase inhibitors - Lipid-lowering agents (eg, ezetimibe, orlistat)- Macrolides (eg, erythromycin)- Quinidine- SSRIs
  • Focal to massive hepatic necrosis - Acetaminophen- Valproic acid- Halothane- Amanita phalloides (death cap mushroom)
  • Hepatitis - Rifampin- Isoniazid- Pyrazinamide- Statins- Fibrates
  • Pancreatitis - Didanosine (NRTI)- Corticosteroids- Alcohol- Valproic acid- Azathioprine- Diuretics (furosemide, HCTZ)
  • Pill-induced esophagitis - Bisphosphonates- Ferrous sulfate- NSAIDs- Potassium chloride- Tetracyclines
  • Pseudomembranous colitis - Ampicillin- Cephalosporins- Clindamycin- Fluoroquinolones
  • Agranulocytosis - Clozapine- Carbamazepine- Propylthiouracil- Methimazole- Colchicine- Ganciclovir
  • Aplastic anemia - Carbamazepine- Methimazole- Propylthiouracil- NSAIDs- Benzene- Chloramphenicol
  • Direct Coombs-positive hemolytic anemia - Penicillin- Methyldopa- Cephalosporins
  • Drug reaction with eosinophilia and systemic symptoms - Allopurinol- Anticonvulsants- Antibiotics- Sulfa drugs DRESS is a potentially fatal delayed hypersensitivity reaction. Latency period (2-8 weeks) followed by fever, morbilliform skin rash, and frequent multiorgan involvement.- Treatment: withdrawal of offending drug, corticosteroids
  • Hemolysis in G6PD deficiency - Isoniazid- Sulfonamides- Dapsone- Primaquine- Aspirin- Ibuprofen- Nitrofurantoin
  • Megaloblastic anemia - Hydroxyurea- Phenytoin- Methotrexate- Sulfa drugs
  • Thrombocytopenia - Heparin- Vancomycin- Linezolid
  • Thrombotic complications - Combined oral contraceptives- Hormone replacement therapy- SERMs (eg, tamoxifen, raloxifene, clomiphene)
  • Drug-induced lupus - Phenytoin- Hydralazine- α-methyldopa- Isoniazid- Sulfa drugs- Procainamide- Etanercept
  • Fat redistribution - Protease inhibitors- Glucocorticoids
  • Gingival hyperplasia - Cyclosporine- Phenytoin- Ca2+ channel blockers
  • Hyperuricemia (gout) - Pyrazinamide- Thiazides- Furosemide- Niacin- Cyclosporine
  • Myopathy - Statins- Fibrates- Niacin- Colchicine- Daptomycin- Hydroxychloroquine- Interferon-α- Penicillamine- Glucocorticoids
  • Osteoporosis - Corticosteroids- Depot medroxyprogesterone acetate- GnRH agonists- Aromatase inhibitors- Anticonvulsants- Heparin- PPIs
  • Rash (Stevens-Johnson syndrome) - Anti-epileptic drugs (especially lamotrigine)- Allopurinol- Sulfa drugs- Penicillin
  • Teeth discoloration Tetracyclines
  • Cinchonism Quinidine, quinine - Can present with tinnitus, hearing/vision loss, psychosis, and cognitive impairment
  • Parkinson-like syndrome - Antipsychotics- Metoclopramide- Reserpine (VMAT inhibitor)
  • Peripheral neuropathy - Phenytoin - Vincristine
  • Pseudotumor cerebri - Vitamin A- Tetracyclines- Growth hormones
  • Seizures - Buproprion- Isoniazid (vitamin B6 deficiency)- Imipenem/cilastatin- Tramadol- Enflurane
  • Visual disturbance - Topiramate (blurred vision/diplopia, haloes)- Digoxin (yellow-tinged vision)- Isoniazid (optic neuropathy/color vision changes)- Vigabatrin (bilateral visual field defects)- PDE-5 inhibitors (blue-tinged vision)- Ethambutol (color vision changes)

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