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Decongestants (Toxicity)


Imidazoline Decongestants

The imidazoline derivatives, oxymetazoline, xylometazoline, tetrahydrozoline, and naphazoline, are found in topical ophthalmic and nasal decongestants available OTC. They are generally used as topical vasoconstrictors in the nose and eyes for temporary relief of nasal congestion due to colds, hay fever or other upper respiratory allergies, or sinusitis.

Imidazolines are sympathomimetic agents, with primary effects on α-adrenergic receptors and little if any effect on β-adrenergic receptors. Oxymetazoline is readily absorbed orally. Effects on α-receptors from systemically absorbed oxymetazoline hydrochloride may persist for up to 7 hr after a single dose. The elimination half-life in people is 5–8 hr. It is excreted unchanged both by the kidneys (30%) and in feces (10%).

In dogs, signs of intoxication may include vomiting, bradycardia, cardiac arrhythmias, poor capillary refill time, hypotension or hypertension, panting, increased upper respiratory sounds, depression, weakness, collapse, nervousness, hyperactivity, or shaking. These signs usually appear within 30 min to 4 hr after exposure. In general, imidazoline decongestant exposure may affect the GI, cardiopulmonary, and nervous systems.

Decontamination (induction of emesis and administration of activated charcoal) may not be practical because of the rapid absorption and onset of clinical signs. Heart rate and rhythm and blood pressure should be assessed, and an ECG obtained if needed. IV fluids should be given, along with atropine at 0.02 mg/kg, IV, if bradycardia is present. Diazepam (0.25–0.5 mg/kg, IV) can be given if CNS signs (eg, apprehension, shaking) are present. Serum electrolytes (ie, potassium, sodium, chloride) should be assessed and corrected as needed. Yohimbine, a specific α2-adrenergic antagonist, can also be used at 0.1 mg/kg, IV, and repeated in 2–3 hr if needed. If yohimbine is not available, atipamezole can be used at 50 mcg/kg, one-fourth IV and the rest IM; it can be repeated in 30–60 min if there is no improvement.


Phenylephrine is a sympathomimetic amine with mainly an α1-adrenergic receptor agonist effect, available OTC as a decongestant in oral formulations (5–10 mg tablets), nasal sprays, or eye drops (0.25%–1%). It has poor oral bioavailability (38%) in people because of a significant first-pass effect and extensive metabolism by monoamine oxidases in the GI tract and liver. The oral LD50 in rats and mice is 350 mg/kg and 120 mg/kg, respectively. The half-life is 2–3 hr. CNS stimulation, agitation, nervousness, and hypertension are possible but less frequent with phenylephrine than with pseudoephedrine. Treatment is mainly symptomatic care and is similar to that for pseudoephedrine toxicosis (see below).

Pseudoephedrine and Ephedrine

Pseudoephedrine is a sympathomimetic drug found naturally in plants of the genus Ephedra. Several states in the USA have limited the availability and use of pseudoephedrine as an OTC decongestant because of its use as a precursor in illegal amphetamine synthesis. It is being replaced with other decongestants such as phenylephrine.

Pseudoephedrine is a stereoisomer of ephedrine and is available as the hydrochloride or sulfate salt. Both ephedrine and pseudoephedrine have α- and β-adrenergic agonist effects. The pharmacologic effects of the drugs are due to direct stimulation of adrenergic receptors and the release of norepinephrine.

In people, pseudoephedrine is rapidly absorbed orally. The onset of action is 15–30 min, with peak effects within 30–60 min. With extended-release preparations (12–24 hr), onset of clinical signs can be delayed (2–8 hr) and duration of clinical signs can be longer than with regular preparations. It is incompletely metabolized in the liver. Approximately 90% of the drug is eliminated through the kidneys. Renal excretion is accelerated in acidic urine. Elimination half-life varies between 2–21 hr, depending on urinary pH.

Pseudoephedrine and ephedrine overdose can result in mainly sympathomimetic effects, including agitation, hyperactivity, mydriasis, tachycardia, hypertension, sinus arrhythmias, anxiety, tremors, hyperthermia, head bobbing, hiding, and vomiting. Clinical signs can be seen at dosages of 5–6 mg/kg, and death may occur at 10–12 mg/kg.

Treatment of pseudoephedrine toxicosis consists of decontamination, controlling the CNS and cardiovascular effects, and supportive care. Vomiting should be induced only in asymptomatic patients, followed by administration of activated charcoal with a cathartic. If the animal's condition contraindicates induction of emesis, a gastric lavage with a cuffed endotracheal tube should be performed. Hyperactivity, nervousness, or seizures can be controlled with acepromazine (0.05–1 mg/kg, IM, IV, or SC), chlorpromazine (0.5–1 mg/kg, IV), phenobarbital (3–4 mg/kg, IV), or pentobarbital to effect. Diazepam should be avoided, because it can exaggerate hyperactivity. Phenothiazines should be used with caution because they can lower the seizure threshold, lower blood pressure, and cause bizarre behavioral changes. Tachycardia can be controlled with propranolol at 0.02–0.04 mg/kg, IV, repeated if needed, or with esmolol at 0.2–0.5 mg/kg, given slowly IV or as a constant-rate infusion at 25–200 mcg/kg/min. IV fluids should be given. Acidifying the urine with ammonium chloride (50 mg/kg, PO, qid) or ascorbic acid (20–30 mg/kg, IM or IV, tid) may enhance urinary excretion of pseudoephedrine. Acid-base status should be monitored if ammonium chloride or ascorbic acid is given. Electrolytes, heart rate and rhythm, and blood pressure should be monitored. Excessive trembling or shaking can cause myoglobinuria; if this occurs, kidney function should be monitored. Significant and persistent hyperthermia due to severe hyperactivity and CNS excitation could result in disseminated intravascular coagulation. Clinical signs of toxicosis can last 1–4 days. The presence of pseudoephedrine in urine can support the diagnosis.

Last full review/revision August 2014 by Safdar A. Khan, DVM, MS, PhD, DABVT

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