asmalin broncho?

Answer 1

DESCRIPTION

The active component of Albuterol Inhalation Aerosol is albuterol, USP racemic (alpha1-((Ttert-butylamino)methyl)-4-hydroxy-M-xylene-alpha,alpha,-diol), a relatively selective beta2-adrenergic bronchodilator.

Albuterol is the official generic name in the United States. The World Health Organization recommended name for the drug is salbutamol. The molecular weight of albuterol is 239.3, and the empirical formula is C13H21NO3. Albuterol is a white to off-white crystalline solid. It is soluble in ethanol, sparingly soluble in water, and very soluble in chloroform.

ACTIONS/CLINICAL PHARMACOLOGY

In Vitro studies and In Vivo pharmacologic studies have demonstrated that albuterol has a preferential effect on beta2-adrenergic receptors compared with isoproterenol. While it is recognized that beta2-adrenergic receptors are thepredominant receptors in bronchial smooth muscle, recent data indicate that there is a population of beta2-receptors in the human heart existing in a concentration between 10-50%. The precise function of these, however, is not yet established. The pharmacologic effects of beta-adrenergic agonist drugs, including albuterol, are at least in part attributable to stimulation through beta-adrenergic receptors of intracellular adenyl cyclase, the enzyme which catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3', 5' adenosine monophosphate (c-AMP). Increased c-AMP levels are associated with relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells. Albuterol has been shown in most controlled clinical trials to have more effect on the respiratory tract, in the form of bronchial smooth muscle relaxation, than isoproterenol at comparable doses while producing fewer cardiovascular effects. Controlled clinical studies and other clinical experience have shown that inhaled albuterol, like other beta-adrenergic agonist drugs, can produce a significant cardiovascular effect in some patients, as measured by pulse rate, blood pressure, symptoms, and/or ECG changes.

Albuterol is longer acting than isoproterenol by any route of administration in most patients because it is not a substrate for the cellular uptake processes for catecholamines nor for catechol-O-methyl transferase.

Because of its gradual absorption from the bronchi, systemic levels of albuterol are low after inhalation of recommended doses. Studies undertaken with four subjects administered tritiated albuterol, resulted in maximum plasma concentrations occurring within 2 to 4 hours. Due to the sensitivity of the assay method, the metabolic rate and half-life of elimination of albuterol in plasma could not be determined. However, urinary excretion provided data indicating that albuterol has an elimination half-life of 3.8 hours. Approximately 72% of the inhaled dose is excreted within 24 hours in the urine, and consists of 28% of unchanged drug and 44% as metabolite.

Results of animal studies show that albuterol does not pass the blood-brain barrier.

Recent studies in laboratory animals (minipigs, rodents, and dogs) recorded the occurrence of cardiac arrhythmias and sudden death (with histologic evidence of myocardial necrosis) when beta-agonists and methylxanthines were administered concurrently. The significance of these findings when applied to humans is currently unknown.

The effects of rising doses of albuterol and isoproterenol aerosols were studied in volunteers and asthmatic patients. Results in normal volunteers indicated that albuterol is 1/2 to 1/4 as active as isoproterenol in producing increases in heart rate. In asthmatic patients similar cardiovascular differentiation between the two drugs was also seen.

INDICATIONS AND USAGE

Albuterol Inhalation Aerosol is indicated for the prevention and relief of bronchospasm in patients with reversible obstructive airway disease, and for the prevention of exercise-induced bronchospasm.

In controlled clinical trials the onset of improvement in pulmonary function was within 15 minutes, as determined by both maximal midexpiratory flow rate (MMEF) and FEV1. MMEF measurements also showed that near maximum improvement in pulmonary function generally occurs within 60 to 90 minutes following 2 inhalations of albuterol and that clinically significant improvement generally continues for 3 to 4 hours in most patients. In clinical trials, some patients with asthma showed a therapeutic response (defined by maintaining FEV1 values 15% or more above baseline) which was still apparent at 6 hours. Continued effectiveness of albuterol was demonstrated over a 13-week period in these same trials.

In clinical studies, 2 inhalations of albuterol taken approximately 15 minutes prior to exercise prevented exercise-induced bronchospasm, as demonstrated by the maintenance of FEV1 within 80 percent of baseline values in the majority of patients. One of these studies also evaluated the duration of the prophylactic effect to repeated exercise challenges, which was evident at 4 hours in the majority of patients, and at 6 hours in approximately one third of the patients.

CONTRAINDICATIONS

Albuterol Inhalation Aerosol is contraindicated in patients with a history of hypersensitivity to any of its components.

WARNINGS

As with other inhaled beta-adrenergic agonists, Albuterol Inhalation Aerosol can produce paradoxical bronchospasm that can be life-threatening. If it occurs the preparation should be discontinued immediately and alternative therapy instituted.

Fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. The exact cause of death is unknown, but cardiac arrest following the unexpected development of a severe acute asthmatic crisis and subsequent hypoxia is suspected. Immediate hypersensitivity reactions may occur after administration of albuterol inhalation aerosol, as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, anaphylaxis, and oropharyngeal edema.

The contents of Albuterol Inhalation Aerosol are under pressure. Do not puncture. Do not use or store near heat or open flame. Exposure to temperatures above 120 deg F may cause bursting. Never throw container into fire or incinerator. Keep out of reach of children.

PRECAUTIONS

GENERAL: Albuterol, as with all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension; in patients with convulsive disorders, hyperthyroidism, or diabetes mellitus; and in patients who are unusually responsive to sympathomimetic amines.

Large doses of intravenous albuterol have been reported to aggravate preexisting diabetes and ketoacidosis. Additionally, beta-agonists, including albuterol, when given intravenously may cause a decrease in serum potassium, possibly through intracellular shunting. The relevance of this observation to the use of Albuterol Inhalation Aerosol is unknown, since the aerosol dose is much lower than the doses given intravenously.

Although there have been no reports concerning the use of Albuterol Inhalation Aerosol during labor and delivery, it has been reported that high doses of albuterol administered intravenously inhibit uterine contractions. Although this effect is extremely unlikely as a consequence of aerosol use, it should be kept in mind.

INFORMATION FOR PATIENTS: The action of Albuterol Inhalation Aerosol may last up to six hours and therefore it should not be used more frequently than recommended. Increasing the number or frequency of doses without consulting your physician can be dangerous. If recommended dosage does not provide relief of symptoms or symptoms become worse, seek immediate medical attention. While taking Albuterol Inhalation Aerosol, other inhaled medicines should not be used unless prescribed.

DRUG INTERACTIONS: Other sympathomimetic aerosol bronchodilators should not be used concomitantly with albuterol. If additional adrenergic drugs are to be administered by any route, they should be used with caution to avoid deleterious cardiovascular effects.

Albuterol should be administered with caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants, since the action of albuterol on the vascular system may be potentiated.

Beta-receptor blocking agents and albuterol inhibit the effect of each other.

CARCINOGENESIS, MUTAGENESIS, AND IMPAIRMENT OF FERTILITY: In a 2 year study in the rat, albuterol sulfate caused a significant dose-related increase in the incidence of benign leiomyomas of the mesovarium at doses corresponding to 111, 555, and 2,800 times the maximum human inhalational dose. In another study this effect was blocked by the coadministration of propranolol. The relevance of these findings to humans is not known. An 18-month study in mice revealed no evidence of tumorigenicity. Studies with albuterol revealed no evidence of mutagenesis. Reproduction studies in rats revealed no evidence of impaired fertility.

TERATOGENIC EFFECTS -- PREGNANCY CATEGORY C: Albuterol has been shown to be teratogenic in mice when given in doses corresponding to 14 times the human dose. There are no adequate and well-controlled studies in pregnant women. Albuterol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. A reproduction study in CD-1 mice with albuterol (0.025, 0.25, and 2.5 mg/kg, corresponding to 1.4, 14, and 140 times the maximum human inhalational dose) showed cleft palate formation in 5 of 111 (4.5%) fetuses at 0.25 mg/kg and in 10 of 108 (9.3%) fetuses at 2.5 mg/kg. None were observed at 0.025 mg/kg. Cleft palate also occurred in 22 of 72 (30.5%) fetuses treated with 2.5 mg/kg isoproterenol (positive control). A reproduction study in Stride Dutch rabbits revealed cranioschisis in 7 of 19 (37%) fetuses at 50 mg/kg, corresponding to 2,800 times the maximum human inhalational dose of albuterol. During marketing, various congenital anomalies, including cleft palate and limb defects, have been reported in the offspring of patients being treated with albuterol. Some of the mothers were taking multiple medications during their pregnancies. Because no consistent pattern of defects can be discerned, a relationship between albuterol use and congenital anomalies cannot be established.

NURSING MOTHERS: It is not known whether this drug is excreted in human milk. Because of the potential for tumorigenicity shown for albuterol in animal studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

PEDIATRIC USE: Safety and effectiveness in children below the age of 12 years have not been established.

DRUG INTERACTIONS

Other sympathomimetic aerosol bronchodilators should not be used concomitantly with albuterol. If additional adrenergic drugs are to be administered by any route, they should be used with caution to avoid deleterious cardiovascular effects.

Albuterol should be administered with caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants, since the action of albuterol on the vascular system may be potentiated.

Answer 2

1

Answer 3

2