Hydroxy Compound Disease Interactions

A variety of abnormal thinking and behavior changes have been reported to occur in association with the use of most anxiolytics, sedatives and hypnotics. Some of these changes include decreased inhibition, aggressiveness, agitation, and hallucinations. These drugs can cause or exacerbate mental depression and cause suicidal behavior and ideation. Therapy with these drugs should be administered cautiously in patients with a history of depression or other psychiatric disorders. Patients should be monitored for any changes in mood or behavior. It may be prudent to refrain from dispensing large quantities of medication to these patients.

Hydroxyzine is contraindicated in patients with a QT prolonged interval. Cases of QT prolongation and Torsade de Pointes have been reported during postmarketing studies. Most of the cases reported occurred in patients with other risk factors for QT prolongation, such as preexisting heart disease, electrolyte imbalances or arrhythmogenic drug use. Therefore, hydroxyzine should be used with caution in patients with risk factors for QT prolongation, congenital long QT syndrome, family history of long QT syndrome or other predisposing conditions, as well as myocardial infarction, uncompensated heart failure, and bradyarrhythmias.

Methylxanthines are known to stimulate peptic acid secretion. Therapy with products containing methylxanthines should be administered with extreme caution in patients with active peptic ulcer disease. Some manufacturers consider their use to be contraindicated under such circumstance.

The metabolites of theophylline, which are generally undetectable in patients with normal renal function, may accumulate in patients with renal impairment and contribute to the toxicity of theophylline. In addition, the plasma protein binding of theophylline may be significantly decreased in renal impairment, resulting in elevated free drug concentrations and further increasing the risk of toxicity. Therapy with theophyllines should be administered cautiously in patients with impaired renal function. Dosage adjustments and more intensive monitoring of serum theophylline concentrations may be required.

The use of theophyllines is considered by some manufacturers to be contraindicated in patients with underlying seizure disorders unless they are receiving adequate anticonvulsant therapy. Theophyllines may cause seizures, which have generally been associated with toxic drug levels but have also been reported at therapeutic concentrations in patients with head trauma or cerebral infarct. If theophylline therapy is administered in patients with these or other risk factors for seizures, serum drug levels should be monitored closely and maintained in the low therapeutic range. Intractable seizures and death have been reported during acute theophylline toxicity.

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.

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.

Some hypnotic drugs can have an anticholinergic effect and should be used with caution in patients with glaucoma, and trouble urinating due to retention or enlarged prostate.

In general, anxiolytics, sedatives and hypnotics are extensively metabolized by the liver. Their plasma clearance may be decreased and their half-life prolonged in patients with impaired hepatic function. Therapy with these drugs should be administered cautiously in patients with liver disease (some are not recommended in severe liver impairment), and the dosage should be adjusted accordingly. Laboratory testing is recommended prior and during treatment.

Some anxiolytics, sedatives and hypnotics are extensively metabolized by the liver, and excreted in the urine. Patients with impaired renal and/or hepatic function may be at greater risk for adverse effects, including central nervous system and respiratory depression, due to drug and metabolite accumulation. Therapy with these drugs should be administered cautiously in such patients, with careful dose selection usually starting at the low end of the dosing range.

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.

Methylxanthines increase gastric acidity and may also relax lower esophageal sphincter, which can lead to gastric reflux into the esophagus. Therapy with products containing methylxanthines should be administered cautiously in patients with significant gastroesophageal reflux.

Theophylline is removed by hemodialysis. Doses should either be scheduled for administration after dialysis or supplemental doses be given after dialysis.

Certain conditions have been identified as causes of reduced theophylline clearance. They include age (neonates and infants < 1 year as well as elderly patients > 60 years) and the following concurrent diseases: acute pulmonary edema; decompensated heart failure; cor pulmonale; fever (>= 102 degrees for 24 hours or more, or lesser temperature elevations for longer periods); influenza; untreated or uncontrolled hypothyroidism; liver disease, cirrhosis or acute hepatitis; reduced renal function in infants < 3 months of age; sepsis with multi-organ failure; and shock. Therapy with theophyllines should be administered cautiously in patients presenting with one or more of these risk factors, and the dosage should be appropriately reduced to prevent toxicity. More intensive monitoring of serum theophylline concentrations may be required. Toxicity is most likely to occur when levels exceed 20 mcg/mL. Severe cases, sometimes without previous warning, have led to cardiac arrhythmias, intractable seizures, and death.

The use of theophyllines is associated with an increase in heart rate which may progress to supraventricular tachycardia or ventricular arrhythmia at high serum drug concentrations. Appearance of cardiac adverse effects is generally an indication of theophylline toxicity, although patients with a history of tachyarrhythmias may be more susceptible to the chronotropic effect of these drugs. Therapy with theophyllines should be administered cautiously in such patients. Caution is also advised in patients with hypertension, hyperthyroidism, angina pectoris, or recent myocardial infarction, since high dosages of the drugs are associated with positive inotropic as well as chronotropic effects. Clinical monitoring of serum drug concentrations is recommended to prevent toxicity.

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.