Toxic Substances by Organ System
LIVER TOXICITY
The most critical hepatotoxic agents include acetaminophen (dose-dependent), certain herbal supplements, and idiosyncratic drug reactions that typically occur within the first 6 months of drug initiation. 1
Prescription Drugs
- Acetaminophen: The only common drug causing dose-related hepatotoxicity; maximum daily dose should not exceed 4 grams 1
- Methotrexate: Requires monthly liver function tests for first 3 months, then every 2 months thereafter 1
- Azathioprine: Mandates monthly LFT monitoring for first 3 months, then bimonthly 1
- Hydroxyurea: Associated with hepatotoxicity requiring regular LFT surveillance 1
- Fumaric acid esters: Can cause elevated LFTs and hepatotoxicity 1
Herbal Supplements & Dietary Products
- Aristolochic acid-containing herbs (guang fang ji, chocolate vine/mu tong): Cause tubulointerstitial disease and acute liver injury; no longer sold in US 1, 2
- Turmeric: Associated with alterations in organ blood flow and documented liver injury cases 1, 3
- Thundergod vine (Tripterygium wilfordii): Causes both liver and kidney toxicity 2, 4
- Wormwood (Artemisia herba-alba): Documented hepatotoxicity 2
- St. John's wort (Hypericum perforatum): Can cause liver injury 2
- Kava: Alters renal hemodynamics through cyclooxygenase inhibition 1
- Impila (Callilepis laureola): Nephrotoxic and hepatotoxic 2
Critical caveat: Herbal supplement concentrations vary considerably between manufacturers due to lack of governmental regulation in the United States 1
Foods
- Mushroom poisoning: Requires penicillin G and silymarin treatment; often necessitates liver transplantation as lifesaving option 1
KIDNEY TOXICITY
Living kidney donors and patients with reduced GFR should avoid dietary supplements entirely due to unknown effects on kidney function and potential for direct or indirect nephrotoxicity. 1
Prescription Drugs Requiring Temporary Discontinuation in Acute Illness (GFR <60)
- ACE inhibitors and ARBs: Discontinue during serious intercurrent illness increasing AKI risk 1
- Diuretics: Stop temporarily during acute illness 1
- NSAIDs (naproxen, ibuprofen, etc.): Can cause ulcers, bleeding, and nephrotoxicity; elderly at highest risk 1, 5
- Metformin: Continue if GFR ≥45; review if GFR 30-44; discontinue if GFR <30 1
- Lithium: Requires regular GFR and electrolyte monitoring 1
- Calcineurin inhibitors: Mandate regular GFR monitoring 1
- Digoxin: Temporary discontinuation during acute illness 1
Herbal Supplements & Dietary Products
- Aristolochic acid herbs: Most clearly associated with direct nephrotoxicity causing fibrosing interstitial nephritis; 3-5% incidence of kidney injury 1, 2
- Turmeric: Alters renal blood flow 1, 3
- Kava: Inhibits cyclooxygenase causing altered renal hemodynamics 1
- Horsetail: Potent diuretic comparable to hydrochlorothiazide 25mg daily; can cause hypotension 1
- Ephedra (ma huang): Causes nephrolithiasis; no longer sold in US 1, 2
- Creatine monohydrate: Associated with rhabdomyolysis; interferes with creatinine clearance measurements 1, 2
- Chinese yew extract (Taxus celbica): Nephrotoxic 2
- Morning cypress (Cupressus funebris): Causes kidney injury 2
- Tribulus (Tribulus terrestris): Documented nephrotoxicity 2
- Chlorella, chromium, glucosamine, hydrazine: All associated with kidney injury case reports 2
Vitamins & Minerals (Excessive Doses)
- Vitamin A: Excess intake causes kidney toxicity 2
- Vitamin C: Excessive doses nephrotoxic 2
- Vitamin D: Overdose causes kidney injury 2
Foods
- Djenkol bean: Nephrotoxic 2
- Fish gallbladders (carp, pufferfish): Cause kidney injury 2
- Snake gallbladder: Nephrotoxic 2
- Star fruit: Toxic only in chronic kidney disease patients 2
- Uncooked yam powder/juice: Causes kidney damage 2
Critical monitoring: Patients with GFR <60 should have medication review before using any over-the-counter medicines or nutritional protein supplements 1
HEART TOXICITY
Cocaine, doxorubicin, emetine (in ipecac syrup), and chronic alcohol use represent the most significant cardiotoxic agents, causing arrhythmias, cardiomyopathy, and sudden death. 6
Prescription Drugs
- Doxorubicin and analogs: Cause oxidative stress, calcium homeostasis changes, decreased ATP production, and systemic release of cardiotoxic mediators; doxorubicinol metabolite may be responsible 6
- Sotalol AF: Can cause dangerous abnormal heart rhythms (proarrhythmic); requires hospital initiation with 2+ days cardiac monitoring 7
- Chemotherapy agents: Many have cardiotoxic potential 6
OTC Drugs & Stimulants
- Cocaine: Causes hypertension, arrhythmias, reduced coronary blood flow; sudden death may relate more to hyperthermia and seizures than direct cardiovascular toxicity 6
- Caffeine: Associated with cardiac arrhythmias and tachycardia 4
- Bitter orange: Documented heart toxicity 4
- Energy drinks: Cause tachycardia, arrhythmias, hypertension 4
- Nitric oxide products: Associated with cardiac events 4
Herbal Supplements
- Aconitum species: Severe cardiotoxicity; no longer sold in US 4
- Ephedra species: Cardiac toxicity; banned in US 4
- Don quai (Angelica sinensis): Traditional Chinese medicine herb causing heart problems 4
- Jin bu huan (Lycopodium serratum): Cardiotoxic 4
- Thundergod vine (Tripterygium wilfordii): Causes cardiac toxicity 4
- Ting kung teng (Erycibe henryi): Heart-related problems 4
- Ashwagandha (Withania somnifera): Ayurvedic herb with cardiac toxicity 4
- Blue cohosh (Caulophyllum thalictroides): Cardiotoxic 4
- Yohimbe (Pausinystalia johimbe): Causes hypertension, tachycardia, arrhythmias 4
Substances of Abuse
- Emetine (in ipecac syrup): Cardiotoxicity occurs with chronic exposure in bulimics or amebiasis treatment; mechanisms poorly understood 6
- Chronic alcohol: Causes dilated cardiomyopathy and heart failure; abstinence is only effective treatment 6
Foods
- Licorice: Daily consumption increases blood pressure by 7/4 mmHg; causes hypertension and cardiac problems 1, 4
Critical drug interactions: Sotalol AF taken with drugs that prolong QT interval (phenothiazines, bepridil, tricyclic antidepressants, oral macrolides) dramatically increases risk of dangerous arrhythmias 7
BRAIN TOXICITY
Sedating antihistamines, particularly diphenhydramine, impair driving performance more severely than alcohol at legal intoxication levels, representing significant neurotoxic risk. 1
OTC Medications
- Diphenhydramine (50mg single dose): Greater effect on driving performance than BAC of 0.10%; causes severe sedation and cognitive impairment 1
- Sedating antihistamines: Detrimental effects on cognitive function and driving abilities 1
Prescription Drugs
- Sedatives: Impair brain function and driving abilities 1
- Analgesics: Can affect cognitive performance 1
- Stimulants: Alter brain function 1
- Antihypertensives: May cause cognitive side effects 1
- Tricyclic antidepressants: Affect brain function; interact dangerously with cardiac medications 7
Drug Combinations
- Alcohol + marijuana: Dramatic deterioration in cognitive performance, reaction time, and motor control 1
- Alcohol + medications: Especially dangerous combinations 1
- Multiple sedating medications: Amplified effects, particularly in kidney disease 8
Critical warning: Failure to warn patients about driving impairment from medications has resulted in successful lawsuits against physicians 1
GENERAL PRINCIPLES FOR ALL ORGAN SYSTEMS
Monitoring Requirements
- Obtain complete medication history including all prescription drugs, OTC medications, herbs, dietary supplements, and natural remedies before any treatment 1, 7
- Determine ingredients of non-prescription medications whenever possible 1
- Regular monitoring of organ function (LFTs, renal function, cardiac rhythm) required for potentially toxic agents 1, 7
High-Risk Populations Requiring Extra Caution
- Kidney donors: Should avoid all dietary supplements due to unknown effects on kidney function 1, 3
- Elderly patients: At highest risk for NSAID toxicity (GI, platelet, nephrotoxic effects) 1
- Patients with GFR <60: Require dose adjustments and careful medication review 1
- Pregnant women: Many agents contraindicated; NSAIDs should not be used late in pregnancy 5
- Transplant recipients: 44-51% use dietary supplements without medical consultation; low awareness of toxicity 9
Critical Discontinuation Recommendations
- In acute liver failure: Discontinue all but essential medications when drug hepatotoxicity suspected 1
- Herbal remedies: Should not be used in people with CKD 1
- During acute illness (GFR <60): Temporarily stop nephrotoxic and renally excreted drugs 1
Most important pitfall: Patients frequently fail to disclose supplement use to healthcare providers; 27% of transplant patients obtained information from physicians, but most used supplements without medical consultation 9