6.2 Antimicrobials, Vitamins and Minerals, and Veterinary Products
Key Takeaways
- Isoniazid overdose causes refractory seizures with lactic acidosis by depleting pyridoxal 5'-phosphate and therefore GABA; the antidote is intravenous pyridoxine given gram for gram with the ingested dose, or 5 g empirically in adults.
- Chloroquine and hydroxychloroquine cause rapid cardiovascular collapse with sodium channel blockade, QT prolongation, and hypokalemia; management combines high-dose diazepam, epinephrine, sodium bicarbonate for a wide QRS, and cautious potassium replacement.
- Dapsone and other oxidizing drugs cause methemoglobinemia with hemolysis, and dapsone has a long half-life with enterohepatic recirculation, so multiple-dose activated charcoal is used in addition to methylene blue.
- Fat-soluble vitamins are the dangerous vitamins: acute vitamin A causes intracranial hypertension and desquamation, and vitamin D causes hypercalcemia with kidney injury, while water-soluble vitamins in children's multivitamins are hazardous mainly for their iron content.
- Veterinary products cause human exposures through concentration and formulation differences, with concentrated permethrin spot-on products, ivermectin paste, and pet medications packaged without child-resistant closures as recurring problems.
Most antibiotic exposures reported to poison centers are benign: a toddler who drinks a flavored amoxicillin suspension will have loose stools, not organ failure. A short list of antimicrobials, however, is genuinely lethal in overdose, and the specialist must recognize them immediately.
Isoniazid
Isoniazid inhibits pyridoxine phosphokinase and combines with pyridoxal 5'-phosphate, the obligatory cofactor for glutamic acid decarboxylase. Without that cofactor, GABA synthesis stops.
- Classic triad: refractory seizures, severe metabolic (lactic) acidosis, and coma, often beginning within 30 minutes to 2 hours of ingestion.
- Ingestion of about 1.5 g in an adult has produced toxicity, and doses above roughly 30 mg/kg are frequently convulsant.
- Antidote: intravenous pyridoxine, gram for gram with the amount ingested (5 g empirically in an adult when the dose is unknown; 70 mg/kg up to 5 g in a child), repeated as needed. Benzodiazepines act synergistically because they depend on residual GABA tone.
- Chronic therapeutic use causes hepatitis and peripheral neuropathy, and slow acetylators are at higher risk of neuropathy while rapid acetylators generate more hepatotoxic metabolites.
Chloroquine and Hydroxychloroquine
These 4-aminoquinolines are among the most lethal tablet ingestions in the world. They block cardiac sodium channels and potassium channels and cause direct myocardial depression.
- Presentation: rapid onset (1 to 3 hours) of vomiting, visual blurring, then hypotension, wide QRS, prolonged QT, ventricular dysrhythmias, seizures, and cardiac arrest. Hypokalemia is a marker of severity and results from an intracellular shift.
- Management: early intubation for significant ingestions, high-dose diazepam (classically 2 mg/kg as a load, which is both anticonvulsant and cardioprotective in this poisoning), epinephrine infusion for shock, sodium bicarbonate for a wide QRS, and cautious potassium replacement because correcting the shift too aggressively causes rebound hyperkalemia. Activated charcoal is given if the airway is protected. Dialysis does not help, since the volume of distribution is enormous.
- Quinine shares sodium channel blockade with additional oculotoxicity (irreversible blindness) and is one of the five agents for which multiple-dose activated charcoal is recommended.
Dapsone
Dapsone is a sulfone used for leprosy, dermatitis herpetiformis, and pneumocystis prophylaxis.
- Its hydroxylamine metabolite is a potent oxidant, producing methemoglobinemia together with hemolysis and, later, sulfhemoglobinemia.
- The half-life is long (roughly 30 hours, longer in overdose) with extensive enterohepatic recirculation, so methemoglobinemia relapses after methylene blue wears off.
- Management: methylene blue 1 to 2 mg/kg IV, repeated as needed, plus multiple-dose activated charcoal, which shortens the half-life considerably. Severe hemolysis may require transfusion or exchange transfusion.
Other Antimicrobials
| Agent | Hazard |
|---|---|
| Aminoglycosides | Impair presynaptic acetylcholine release; can worsen neuromuscular blockade in botulism or myasthenia, and are nephrotoxic and ototoxic with accumulation |
| Fluoroquinolones | Seizure threshold lowering, QT prolongation, tendon rupture, and CYP1A2 inhibition that precipitates theophylline and clozapine toxicity |
| Macrolides | QT prolongation and CYP3A4 inhibition, which raises levels of colchicine, statins, and calcium channel blockers |
| Trimethoprim-sulfamethoxazole | Hyperkalemia, methemoglobinemia, and marked warfarin potentiation |
| Penicillins and cephalosporins | Large ingestions cause gastrointestinal upset; massive intravenous doses have caused seizures in kidney failure |
| Antimalarial artemisinins and atovaquone | Generally low acute toxicity |
| Antivirals | Low acute toxicity; nucleoside analogues cause lactic acidosis with chronic use |
Vitamins and Minerals
The reflex assumption that vitamins are harmless is correct for water-soluble vitamins and wrong for fat-soluble vitamins and for anything containing iron.
| Agent | Acute Overdose | Chronic Excess |
|---|---|---|
| Vitamin A | Nausea, vomiting, headache, blurred vision, bulging fontanelle in infants, intracranial hypertension, later skin desquamation | Alopecia, dry skin, bone and joint pain, hepatotoxicity, pseudotumor cerebri; teratogenic (retinoids) |
| Vitamin D | Usually asymptomatic acutely | Hypercalcemia: weakness, polyuria, nephrolithiasis, kidney injury; treat with fluids, then consider bisphosphonate or calcitonin |
| Iron-containing multivitamins | The real danger in pediatric "vitamin" ingestions; see the elemental iron thresholds with the metals | — |
| Niacin | Flushing, pruritus, hypotension | Hepatotoxicity with sustained-release forms |
| Pyridoxine (B6) | Antidote in isoniazid and gyromitrin poisoning | Chronic megadoses cause a sensory peripheral neuropathy |
| Vitamin C | Diarrhea; oxalate load with large doses | Nephrolithiasis |
| Fluoride | Above about 5 mg/kg of fluoride ion: vomiting and abdominal pain; above roughly 15 mg/kg: hypocalcemia, hypomagnesemia, hyperkalemia, dysrhythmias | Dental and skeletal fluorosis |
| Selenium | Garlic odor, vomiting, hypotension; selenious acid (gun bluing) is rapidly fatal | Hair and nail loss, neuropathy |
| Zinc | Gastrointestinal irritation, metal fume fever with inhaled fumes | Copper deficiency and anemia |
| Potassium supplements | Life-threatening hyperkalemia after massive ingestion, especially in kidney disease; consider whole bowel irrigation | — |
Fluoride pearl: calcium is the functional antidote. Milk or an oral calcium-containing product binds fluoride in the gut for small ingestions; intravenous calcium is used for symptomatic hypocalcemia.
Veterinary Products
Veterinary formulations reach humans in three ways: children find the packaging, adults self-treat with animal products, and caregivers dose the wrong family member.
| Product | Human Hazard |
|---|---|
| Concentrated permethrin spot-on products | Sold at 45% to 65% permethrin for dogs. Oral or ocular exposure causes irritation and vomiting; the classic veterinary disaster is applying a dog product to a cat, which cannot glucuronidate it and develops tremor and seizures. Human oral exposures are usually mild, but the concentration warrants irrigation and observation |
| Ivermectin (paste, injectable, pour-on) | Large ingestions, especially of concentrated equine paste, cause vomiting, ataxia, confusion, tremor, hypotension, and coma; treatment is supportive |
| Xylazine | Veterinary alpha-2 agonist, now a common adulterant of illicit fentanyl; causes sedation, bradycardia, and necrotic skin ulcers, and does not respond to naloxone |
| Heartworm and dewormer products (pyrantel, praziquantel, milbemycin) | Low acute human toxicity |
| Animal vaccines | Needle-stick exposures: local reaction and infection risk; modified-live vaccines are a concern for immunocompromised people |
| Veterinary euthanasia solutions (pentobarbital) | Profound coma and respiratory depression after accidental exposure |
| Concentrated flea and tick collars, dips (organophosphate or carbamate) | Cholinergic toxicity by the usual mechanisms |
Packaging pearl: many veterinary products are exempt from child-resistant packaging requirements and are stored in kitchens, garages, and purses rather than medicine cabinets, so they are disproportionately available to toddlers.
Poison Center Case: Seizures in a Tuberculosis Clinic Patient
A 46-year-old on isoniazid for latent tuberculosis is brought in after a witnessed generalized seizure at home; an empty bottle that held sixty 300 mg tablets is found. In the emergency department she seizes again despite 8 mg of intravenous lorazepam. Venous pH is 6.98 with a lactate of 14 mmol/L.
Specialist actions. The CSPI recognizes the isoniazid triad of refractory seizures, profound lactic acidosis, and coma, and calculates the ingested dose as up to 18 g. Recommendation: intravenous pyridoxine 5 g immediately, repeated toward a gram-for-gram match with the ingested dose (up to about 18 g in divided doses) while benzodiazepines continue, because the two work synergistically. The team is warned that phenytoin will not work, that the acidosis will resolve once seizures stop rather than requiring aggressive bicarbonate, and that airway control should precede further dosing. Activated charcoal is given after intubation.
A 24-year-old ingests an unknown number of isoniazid tablets and has three generalized seizures that do not respond to escalating benzodiazepine doses. Venous pH is 7.02 with a lactate of 13 mmol/L. What is the specific antidote and dose approach?
A 34-year-old presents 90 minutes after ingesting about 6 g of hydroxychloroquine. Blood pressure is 76/40, QRS is 128 ms, QTc is 540 ms, and potassium is 2.7 mEq/L. Which management package is most consistent with established practice?
A 3-year-old chewed several adult gummy vitamins. Which single ingredient most often determines whether this exposure needs emergency evaluation?