Ammonium chloride/chlorpheniramine/dextromethorphan/ephedrine/ipecac/phenylephrine Disease Interactions

Ammonium undergoes hepatic biotransformation to urea. Ammonium toxicity resulting in irregular heart rate, bradycardia, arrhythmia. hyperglycemia, glucosuria, twitching, asterixis, tonic seizures, and calcium- deficient tetany have occurred in patients with hepatic impairment. Therapy with ammonium chloride should be administered cautiously in patients with compromised hepatic function.

Ipecac induces vomiting of gastrointestinal contents that can be aspirated. Therapy with ipecac should not be administered to patients who are less than fully conscious, severely intoxicated, in shock, having seizures, or lack gag reflexes.

Sympathomimetic agents may cause adverse cardiovascular effects, particularly when used in high dosages and/or in susceptible patients. In cardiac tissues, these agents may produce positive chronotropic and inotropic effects via stimulation of beta- 1 adrenergic receptors. Cardiac output, oxygen consumption, and the work of the heart may be increased. In the peripheral vasculature, vasoconstriction may occur via stimulation of alpha-1 adrenergic receptors. Palpitations, tachycardia, arrhythmia, hypertension, reflex bradycardia, coronary occlusion, cerebral vasculitis, myocardial infarction, cardiac arrest, and death have been reported. Some of these agents, particularly ephedra alkaloids (ephedrine, ma huang, phenylpropanolamine), may also predispose patients to hemorrhagic and ischemic stroke. Therapy with sympathomimetic agents should generally be avoided or administered cautiously in patients with sensitivity to sympathomimetic amines, hyperthyroidism, or underlying cardiovascular or cerebrovascular disorders. These agents should not be used in patients with severe coronary artery disease or severe/uncontrolled hypertension.

Ammonium chloride should be used cautiously and under medical supervision in patients with renal impairment as it can result in hyperchloremia and metabolic acidosis. Ammonium chloride should not be administered alone in patients with severe renal impairment experiencing metabolic alkalosis secondary to vomiting of HCl and accompanied by substantial sodium loss. Sodium chloride alone or in combination with ammonium chloride may be necessary to correct the sodium and chloride loss.

Antihistamines often have anticholinergic activity, to which elderly patients are particularly sensitive. Therapy with antihistamines should be administered cautiously, if at all, in patients with preexisting conditions that are likely to be exacerbated by anticholinergic activity, such as urinary retention or obstruction; angle-closure glaucoma, untreated intraocular hypertension, or uncontrolled primary open-angle glaucoma; and gastrointestinal obstructive disorders. Conventional, first-generation antihistamines such as the ethanolamines (bromodiphenhydramine, carbinoxamine, clemastine, dimenhydrinate, diphenhydramine, doxylamine, phenyltoloxamine) tend to exhibit substantial anticholinergic effects. In contrast, the newer, relatively nonsedating antihistamines (e.g., cetirizine, fexofenadine, loratadine) reportedly have low to minimal anticholinergic activity at normally recommended dosages and may be appropriate alternatives.

It has been suggested that the anticholinergic effect of antihistamines may reduce the volume and cause thickening of bronchial secretions, resulting in obstruction of respiratory tract. Some manufacturers and clinicians recommend that therapy with antihistamines be administered cautiously in patients with asthma or chronic obstructive pulmonary disease.

Antihistamines may infrequently cause cardiovascular adverse effects related to their anticholinergic and local anesthetic (quinidine-like) activities. Tachycardia, palpitation, ECG changes, arrhythmias, hypotension, and hypertension have been reported. Although these effects are uncommon and usually limited to overdosage situations, the manufacturers and some clinicians recommend that therapy with antihistamines be administered cautiously in patients with cardiovascular disease, hypertension, and/or hyperthyroidism.

Limited pharmacokinetic data are available for the older, first-generation antihistamines. Many appear to be primarily metabolized by the liver, and both parent drugs and metabolites are excreted in the urine. Patients with renal and/or liver disease may be at greater risk for adverse effects from antihistamines due to drug and metabolite accumulation. Therapy with antihistamines should be administered cautiously in such patients. Lower initial dosages may be appropriate.

Sympathomimetic agents such as ephedrine have the potential for producing clinically significant systemic effects, particularly during prolonged or indiscriminate use. In patients with prostate enlargement, urinary difficulty may develop or worsen due to smooth muscle contraction in the bladder neck via stimulation of alpha-1 adrenergic receptors. Therapy with ephedrine should be administered cautiously in patients with difficulty for urination due to hypertrophy or neoplasm of the prostate. It is important that the recommended dosages are not exceeded.

Ephedrine may produce slight increases in blood glucose concentrations. Therapy with ephedrine should be administered cautiously in patients with diabetes mellitus. Closer monitoring of blood glucose concentrations may be appropriate. It is important that the recommended dosages of ephedrine are not exceeded.

Ipecac may be absorbed if vomiting does not take place. Cardiotoxicity such as tachycardia, hypotension, dyspnea, ECG changes or arrhythmia have occurred. Chronic use to induce vomiting by patients with eating disorders has resulted in myocarditis, cardiac arrest and failure. Therapy with ipecac should be administered cautiously in patients with or predisposition to cardiovascular dysfunction.

Ipecac induced vomiting can increase blood pressure. Vomiting and retching associated with ipecac therapy may increase the risk of hemorrhage in patients with sclerotic or other pathologic changes in blood vessels. Therapy with ipecac should be administered cautiously in patients with altered vascular physiology.

Sympathomimetic agents may cause or worsen urinary difficulty in patients with prostate enlargement due to smooth muscle contraction in the bladder neck via stimulation of alpha-1 adrenergic receptors. Therapy with sympathomimetic agents should be administered cautiously in patients with hypertrophy or neoplasm of the prostate.

Sympathomimetic agents may cause increases in blood glucose concentrations. These effects are usually transient and slight but may be significant with dosages higher than those normally recommended. Therapy with sympathomimetic agents should be administered cautiously in patients with diabetes mellitus. Closer monitoring of blood glucose concentrations may be appropriate.

Sympathomimetic agents can induce transient mydriasis via stimulation of alpha-1 adrenergic receptors. In patients with anatomically narrow angles or narrow-angle glaucoma, pupillary dilation can provoke an acute attack. In patients with other forms of glaucoma, mydriasis may occasionally increase intraocular pressure. Therapy with sympathomimetic agents should be administered cautiously in patients with or predisposed to glaucoma, particularly narrow-angle glaucoma.