Clinical Pearl Series Edited from Yale-G First Aid: Crush USMLE Step 2CK & Step 3 by Yale Gong, MD, Sr. Medical Advisor at www.medicine.net (Copyrighted)

Basics of Toxicology

Toxicology is the study of the nature, adverse effects, mechanisms, and detection of poisons and the treatment of poisoning. Poisoning is injury or death due to swallowing, inhaling, touching, or injecting various drugs, chemicals, venoms, or gases. Many substances (such as drugs and carbon monoxide) are poisonous only in high concentrations or dosages. Some others (such as cleaners) are dangerous only if ingested.

Guidelines for Evaluation and Management of Poisoning

Early recognition is the key to successful management. First, try to find out the nature of the toxin and the time ingested based on patient’s history and manifestations, and then manage accordingly. If patient’s vital signs are compromised, follow the above emergent principles of “ABC”.

1. Induced vomiting

Ipecac can be used within 1-2 hours after ingestion; it is most useful at home but often too late and unnecessary in the hospital (emergency room). It only decreases absorption by < 30% after 1 hour of ingestion. Furthermore, it takes 15-20 min for the ipecac to work and delays the antidote administration.

2. Gastric lavage

It is best used within 1 hour of ingestion in patients with normal consciousness. It removes 50% of the pills at 1 hour of ingestion, which is useful, and only 15% at 2 hours of ingestion, which is useless.

Both ipecac and lavage are contraindicated with (1) altered mental status (may cause aspiration); (2) ingestion of caustic substances (acids or alkalis, may cause injury of the esophagus and oropharynx).

3. Charcoal

It is harmless and the mainstay of therapy for most patients with 1-2 hours after toxic ingestion or after gastric emptying of the toxin. It works to accelerate the removal of already absorbed toxins. Charcoal administration is not dangerous but is ineffective for hydrocarbon ingestions (such as methanol or ethylene glycol). Cathartics (sorbitol, etc.) are only useful when used in combination with charcoal administration.

4. Whole bowel irrigation

It’s the flushing-out of the GI contents with polyethylene glycol-electrolyte solution by a gastric tube. It has limited indications in large-volume pill ingestions such as iron, lithium, and drug-filled packets seen on an imaging exam.

5. Dialysis

It’s only used under very serious conditions such as hypotension, hyperkalemia, coma, or apnea, especially with renal/hepatic failure compromising removal of toxins from the body.

6. Diuresis

It refers to administration of fluids and diuretics to accelerate urinary excretion of toxins, but may cause more harm such as pulmonary edema (if with heart failure) than benefits.

Summary of Toxicity and Treatment of Commonly Used Drugs

Drug / Toxicity and Treatment

Acyclovir: Renal tube crystal and obstruction, may lead to renal failure. Tx: Large fluid intake.

ACE inhibitors (Captopril, etc.): Cough (#1 common), rash, proteinuria, angioedema, taste changes, hypo-Na, and hyper-K.

Aminoglycosides: Ototoxicity, nephrotoxicity, etc.

Amiodarone: Pulmonary fibrosis (also with bleomycin), arrhythmia (prolonged Q-T as with quinidine), peripheral deposit (skin discolor, photosensitivity), hypo/hyper-thyroidism

Amphotericin: Fever, chills, and nephrotoxicity; Mnemonic: “Ampho-terror”.

Amantadine: Ataxia and livedo reticularis.

Antimuscarinic, anticholinergic agents: Urinary retention, constipation, sedation, orthostatic hypotension, and paralysis. Antidote: Physostigmine.

Antipsychotics: Extrapyramidal symptoms (dystonia, akathisia, and convulsion) —Treat with propranolol or diazepam; neuroleptic malignant syndrome (NMS) —Treat with dantrolene +/- bromocriptine or amantadine; anticholinergic effects—Treat with physostigmine.

Azathioprine: Dose-related diarrhea, liver toxicity, and WBC decrease.

Azidothymidine (AZT): Thrombocytopenia and megaloblastic anemia.

Benzodiazepines (BZD): Psychological and physical dependence; addictive effects with other CNS depressants. Antidote: Flumazenil. Caution: Flumazenil can cause seizures in chronic BZD-dependent patients.

Beta-R-blockers (-olol): Asthma exacerbation, A-V block, CHF, masking of hypoglycemia, and impotence. Antidote: Glucagon.

Bile acid resins: GI upset and malabsorption of lipid-soluble vitamins and medicines.

Ca-blockers: Cardiac depression, peripheral edema, and constipation.

Carbamazepine: Agranulocytosis, aplastic anemia, and induction of p450.

Chloramphenicol: Aplastic anemia and grey baby syndrome.

Clonidine: Severe rebound headache and hypertension.

Clozapine: Agranulocytosis.

Corticosteroids: Mania (acute toxicity), immunosuppression, bone mineral loss, thin skin, and easy bruising, and myopathy (chronic use).

Cisplatin: Nephrotoxicity and acoustic nerve damage.

Colchicine, meclocycline, and lithium: Renal desensitivity to ADH (causing renal DI).

Cyclophosphamide: Myelosuppression and hemorrhagic cystitis.

Cyclosporine: Nephrotoxicity, hyper-K, hypertension, gingival hyperplasia, hirsutism, and tremor.

Doxorubicin: Cardiotoxicity.

Fluoroquinolones (quinolones): Cartilage damage in children.

Fluconazole (-azoles): Inhibits liver p450 enzymes and increases toxicity of other drugs metabolized by p450.

Furosemide: Hypo-K, Hypo-NaCl, ototoxicity, and nephritis.

Gemfibrozil, -statins: Myositis and reversible hepatic enzyme increase.

Halothane: Hepatotoxicity.

Heparin: Bleeding trends, thrombocytopenia, and drug-drug interactions. Antidote: Protamine.

Hydralazine: Orthostatic hypotension and lupus syndrome (also for procainamide).

Isoniazid (INH): B6-deficient neuritis, hepatoxicity (rare), and seizure (overdose). Tx: Stop INH and use B₆.

Iron salts: GI upset and bleeding, hyperglycemia, and “3 Cs” (cardiotoxicity, convulsion, and coma). Antidote: Deferoxamine.

MAOIs: Hypertension crisis with tyramine (in cheese, wine, etc.).

Methyldopa: Hemolysis, lupus syndrome, and sexual dysfunction.

Metronidazole: Disulfiram reaction (with alcohol) and CN₈ toxicity.

Opiates: Respiratory inhibition, miosis (“pinpoint pupils”), and coma. Antidote: Naloxone.

Organophosphate: Salivation, urination, diarrhea, emesis, miosis, diaphoresis, bradycardia, hypoglycemia, bronchospasm, and even respiratory arrest. Antidote: Atropine followed by pralidoxime.

Penicillin: Anaphylaxis. Tx: “ABC”, epinephrine (EP), and antihistamine.

Phenytoin: Diplopia, nystagmus, ataxia, gingival hyperplasia, and hirsutism.

Prazosin: 1^st-dose hypotension and priapism.

Quinidine: Arrhythmia, cinchonism (headache and tinnitus), and thrombocytopenia. Tx: NaHCO₃.

SSRIs: More sexual dysfunction, GI stimulation (nausea/vomiting) and CNS toxicity (headache, insomnia, and tremor) than TCAs. Toxicity increases with coexistent MAOIs or TCAs. Treatment of overdose: Use BZD (lorazepam) for agitation, tremor, or seizures; NaHCO3 for arrhythmia. Avoid serotonergic medications.

TCAs: More serious adverse effects than SSRIs— “3 Cs”: Cardiotoxicity (typical QRS widening in ECG), Convulsion, and Coma; anticholinergic effects (dry mouth, constipation, and urinary retention). Tx: NaHCO₃ is effective in treating arrhythmia (but not increasing excretion of TCAs). Use lorazepam for seizures.

Theophylline: Ventricular arrhythmia, GI upset, hyper-ventilation, convulsion, hypo-K, hypo-Mg, hypo-P, hyper-Ca, and hyperglycemia. Tx: 1. Active charcoal; 2. hemodialysis; lorazepam for convulsion; amiodarone for ventricular arrhythmia. Avoid lidocaine.

Thiazides: Mnemonics— “3 lows 3 highs”: Hypo-K, -Na, and -Cl; Hyper-glycemia, -lipidemia, and -uricemia.

TPA, streptokinase: Bleeding tendency. Antidote: Aminocaproic acid.

Valproic acid: Neural tube defects (congenital) and hepatotoxicity (rare).

Vancomycin: CN8 toxicity, nephrotoxicity, and “red man syndrome” (due to histamine release, not allergy).

Warfarin: Bleeding tendency, teratogen, and drug-drug interactions. Antidote: Vitamin K or FFP (fresh frozen plasma), recovering in 1-2 days.

Basics of Teratology

Teratology is the study of abnormalities of physiological development. It is often thought of as the study of human birth defects, but it is much broader than that. A teratogen is any agent that disturbs normal fetal development and affects subsequent function. The nature of the agent and its timing and duration after conception are all critical factors to affect the fetus.

Summary:  Maternal Drug Use or Disease and Associated Fetal Effects

Maternal drug or disease / Fetal effects 

ACE-Inh: Fetal renal tubular dysplasia, neonatal renal failure, oligohydramnios, IUGR, cranial ossification defect (Def).

Alcohol: Fetal alcohol syndrome--intellectual disability, growth restriction, midfacial hypoplasia, renal-cardiac Def.

Amphetamines: Preterm delivery, preeclampsia, placental abruption, IUGR, fetal demise.

Androgens and derivatives: Female fetal virilization; advanced genital development in male fetuses.

Anesthetics; barbiturates: Respiratory, CNS depression; Vit-K deficiency (Def).

Carbamazepine: Neural tube Def, fingernail hypoplasia, microcephaly, IUGR.

Cocaine: Bowel atresia, Def of the heart, face, limbs, and GU tract, microcephaly, IUGR, cerebral infarctions.

Coumadin derivatives: Nasal hypoplasia, stippled bone epiphyses, IUGR, eye Def.

Cyanotic heart disease: IUGR.

DES (Diethylstilboestrol): Genital clear cell adenocarcinoma, vaginal adenosis, genital Def (both male & female).

Folate antagonists (methotrexate): Increased rate of spontaneous abortion (SAB).

Graves disease: Transient thyrotoxicosis.

Hyperparathyroidism: Hypocalcemia.

ITP: Thrombocytopenia.

Lead: Increased rate of SAB or stillbirths.

Lithium: Congenital heart Def (Ebstein anomaly).

MgSO₄: Respiratory depression.

Myasthenia gravis: Transient neonatal myasthenia.

Organic mercury: Cerebral atrophy, microcephaly, intellectual disability, seizures, blindness.

Sulfonamides: Displaces bilirubin from albumin.

Phenytoin: Dysmorphic facies, IUGR, intellectual disability, heart Def, fingernail Def.

Radiation (<0.05Gy is safe): Microcephaly, intellectual disability.

SLE: Congenital heart block.

Streptomycin and kanamycin: CN-8 (facial nerve) damage and hearing loss.

Tetracycline: Enamel hypoplasia or permanent tooth discoloration.

Thalidomide: Bilateral limb Def, cardiac and GI Def, anotia, microtia.

Trimethadione and paramethadione: Cleft lip or palate, cardiac Def, microcephaly, intellectual disability.

Valproic acid: Neural tube Def or craniofacial Def.

Vit-A (isotretinoin) and derivatives: Increased rate of SAB, thymic agenesis, congenital heart disease, craniofacial Def, cleft lip or palate, intellectual disability.

Warfarin: Nasal hypoplasia and stippled bone epiphyses, IUGR, developmental delay, ophthalmologic Def.