3.5 Cough and Cold Products, Antihistamines, Muscle Relaxants, and Local Anesthetics
Key Takeaways
- Dextromethorphan blocks NMDA receptors at abuse doses, producing a dose-dependent progression from euphoria and ataxia to dissociation, and it contributes to serotonin toxicity when combined with monoamine oxidase inhibitors or serotonin reuptake inhibitors.
- Imidazoline decongestants such as tetrahydrozoline and oxymetazoline act like clonidine in young children, causing lethargy, miosis, bradycardia, and apnea after only a swallow of eye or nose drops.
- Diphenhydramine and other first-generation antihistamines cause an antimuscarinic toxidrome, and at higher doses they block cardiac sodium channels (wide QRS) and potassium channels (prolonged QT), with seizures a prominent feature in massive ingestion.
- Carisoprodol is metabolized to meprobamate and produces prolonged coma with cyclic fluctuation, while baclofen causes coma with brainstem depression that can mimic brain death and a severe withdrawal syndrome after abrupt discontinuation, especially intrathecal.
- Benzocaine and other topical anesthetics cause methemoglobinemia, and systemic local anesthetic toxicity presents with perioral tingling and agitation progressing to seizures and cardiac arrest treated with intravenous lipid emulsion.
These products share three features that generate poison center calls: they are everywhere, they are usually combination formulations, and the pediatric formulations taste good. The official topic list names cough and cold preparations, antihistamines, imidazoline decongestants, skeletal muscle relaxants, local anesthetics, topicals, and antiseptics, and each has a distinct signature.
Dextromethorphan
Dextromethorphan is a morphinan antitussive with essentially no mu agonist activity at label doses. Its active metabolite dextrorphan is a non-competitive NMDA receptor antagonist, and dextromethorphan also inhibits serotonin reuptake.
| Approximate Dose | Effects |
|---|---|
| 1 to 2 mg/kg | Therapeutic antitussive effect |
| 2 to 4 mg/kg | Mild stimulation, euphoria, restlessness |
| 4 to 7 mg/kg | Hallucinations, ataxia, nystagmus, vomiting |
| 7 to 15 mg/kg | Dissociation, agitation, tachycardia, hypertension, mydriasis |
| Above 15 mg/kg | Deep dissociation, coma, respiratory depression |
Clinical pearls. Adolescents dose by the bottle, so the co-formulated acetaminophen, antihistamine, or decongestant often matters more than the dextromethorphan. Nystagmus with an alert but dissociated adolescent is a useful clue. Naloxone has been reported to reverse some cases inconsistently; management is supportive with benzodiazepines for agitation. Combination with a monoamine oxidase inhibitor is the classic lethal interaction, and combination with a serotonin reuptake inhibitor can produce serotonin toxicity. CYP2D6 poor metabolizers reach higher concentrations from ordinary doses.
Imidazoline Decongestants
Tetrahydrozoline (ophthalmic), oxymetazoline and xylometazoline (nasal), and naphazoline are central alpha-2 agonists when absorbed systemically, which makes them behave like clonidine in a small child.
- A swallow of an eye drop bottle by a toddler can cause lethargy or coma, miosis, bradycardia, hypothermia, hypotension, and apnea, typically within 30 to 60 minutes.
- Because the presentation mimics an opioid exposure, naloxone is often tried; the response is variable.
- Management is airway support, atropine for symptomatic bradycardia, and observation for 4 to 6 hours after even a small exposure in a young child, with hospital referral for any symptoms.
First-Generation Antihistamines
Diphenhydramine, doxylamine, chlorpheniramine, hydroxyzine, and cyproheptadine block central and peripheral muscarinic receptors in addition to H1 receptors.
- Threshold: antimuscarinic effects are expected above about 7.5 mg/kg of diphenhydramine; seizures, wide QRS, and dysrhythmias appear in massive ingestions (commonly above 15 to 25 mg/kg).
- Findings: agitated delirium with mumbling speech and picking movements, mydriasis, dry flushed skin, hyperthermia, urinary retention, decreased bowel sounds, sinus tachycardia.
- Cardiac: sodium channel blockade widens the QRS (treat with sodium bicarbonate) and potassium channel blockade prolongs the QT.
- Rhabdomyolysis is common after prolonged agitation; doxylamine is particularly associated with it.
- Physostigmine may be used for pure antimuscarinic delirium, but it is contraindicated when the QRS is widened or a cyclic antidepressant is suspected.
Promethazine deserves separate mention: it is a phenothiazine, so overdose adds alpha-1 blockade with orthostatic hypotension and dystonic reactions, and extravasation of the intravenous formulation causes severe tissue injury.
Skeletal Muscle Relaxants
| Agent | Mechanism and Overdose Picture | Management Notes |
|---|---|---|
| Carisoprodol | Metabolized to meprobamate; sedation, myoclonus, and prolonged coma that may fluctuate cyclically | Supportive care; prolonged observation; meprobamate can form gastric concretions |
| Cyclobenzaprine | Tricyclic-related; antimuscarinic findings, sedation, tachycardia; contributes to serotonin toxicity | Benzodiazepines; ECG monitoring; avoid physostigmine if QRS widened |
| Baclofen | GABA-B agonist; coma with absent brainstem reflexes that can mimic brain death, seizures despite being a GABA agonist, bradycardia, hypothermia | Supportive care with mechanical ventilation; recovery is usually complete; abrupt withdrawal, especially from an intrathecal pump, causes fever, rigidity, and autonomic instability treated by restarting baclofen and giving benzodiazepines |
| Tizanidine | Central alpha-2 agonist | Clonidine-like sedation, bradycardia, hypotension |
| Metaxalone, methocarbamol, chlorzoxazone | Sedation, nausea; relatively low toxicity alone | Supportive care |
Local Anesthetics and Topical Products
Methemoglobinemia
Benzocaine (teething gels, throat sprays, mucosal anesthetics) and prilocaine are the classic causes. Infants are especially vulnerable because fetal hemoglobin oxidizes more readily and methemoglobin reductase activity is lower.
- Suspect it when cyanosis does not improve with oxygen, pulse oximetry sits near 85%, arterial oxygen tension is normal, and blood is chocolate brown.
- Treat significant cases with methylene blue 1 to 2 mg/kg IV, remembering the cautions in glucose-6-phosphate dehydrogenase deficiency and with serotonergic drugs.
Systemic Local Anesthetic Toxicity
Lidocaine, bupivacaine, and related agents block sodium channels in nerve and myocardium.
- Progression: perioral numbness, metallic taste, tinnitus, agitation, then seizures, then wide-complex dysrhythmias and cardiac arrest.
- Bupivacaine is the most cardiotoxic and the most resistant to resuscitation.
- Treatment: benzodiazepines for seizures, avoidance of further sodium channel blockers, and 20% intravenous lipid emulsion 1.5 mL/kg bolus followed by 0.25 mL/kg/min for cardiovascular toxicity.
- Oral ingestion of viscous lidocaine by children has caused seizures at roughly 6 mg/kg and above.
Antiseptics and Miscellaneous Topicals
| Product | Concern |
|---|---|
| Iodine and povidone-iodine | Concentrated iodine is corrosive; povidone-iodine is largely irritant, but large exposures in neonates can affect thyroid function |
| Phenol and pine oil disinfectants | Mucosal burns, central nervous system depression; phenol causes painless white skin burns and rapid systemic absorption |
| Hydrogen peroxide | 3% causes foaming and irritation; concentrated 35% "food grade" solutions cause caustic injury and life-threatening oxygen gas embolism |
| Camphor and methyl salicylate rubs | Seizures and salicylate toxicity, respectively; both are covered in detail with the pediatric high-risk agents |
| Mercurochrome-type antiseptics | Largely historical; organic mercury content |
Triage Anchors for This Group
- Read the whole label. A single cold caplet may contain four drugs, and the acetaminophen is usually the one that determines management.
- Weight-based thresholds matter most for diphenhydramine and dextromethorphan, while imidazoline drops and benzocaine are hazardous by product rather than by dose in small children.
- Get an ECG for any significant antihistamine, cyclobenzaprine, or local anesthetic exposure.
- Observe for 4 to 6 hours for immediate-release products, longer for sustained-release antihistamine-decongestant combinations and for carisoprodol or baclofen.
A 2-year-old swallows an unknown amount from a bottle of over-the-counter redness-relief eye drops containing tetrahydrozoline. Two hours later he is difficult to rouse with pinpoint pupils, a heart rate of 62, and periodic pauses in breathing. What explains this presentation?
A 16-year-old who drank two bottles of a combination cough syrup is dissociated with nystagmus, a heart rate of 118, and mydriasis. Which management step is the highest priority?
A 44-year-old is found comatose with absent corneal and gag reflexes, flaccid tone, bradycardia, and hypothermia after ingesting a large quantity of his prescription muscle relaxant. Which agent most characteristically mimics brain death in overdose, with full recovery expected after supportive care?