Hivent EM/Hivent DS/Hivent Plus Mechanism of Action

Pharmacology: Hivent EM: Salbutamol is a selective Beta₂ adrenergic agonist which, in therapeutic doses, acts selectively on receptors in the bronchial muscles with little or no effect on the cardiac receptors. Its behavior following inhalation depends on the delivery method used, which determines the proportion of inhaled salbutamol relative to the proportion inadvertently swallowed. Its plasma half-life is from 2 to 7 hours, with the longer value following aerosol inhalation.
Hivent DS: Mechanism of Action: Salbutamol like other β-adrenergic drugs stimulate adenyl cyclase, the enzyme that catalyzes the formation of cyclic-3'-5'-adenosine monosphosphate (cAMP) from adenosine triphosphate (ATP). The cAMP thus formed mediates the cellular responses, resulting in the decreased tone of bronchial smooth muscles.
As with other β₂-adrenergic receptor agonists, Salbutamol binds to β₂-adrenergic receptors with a higher affinity than β₁-receptors. Salbutamol is a selective β₂ adrenoceptor agonist. At therapeutic doses it acts on the β₂-adrenoceptors of bronchial muscle, with little or no action on the β₁-adrenoreceptors of the heart.
Inhaled salbutamol sulfate has a rapid onset of action, providing relief within 5-15 minutes of administration.
In tocolysis, the activation of β₂-receptors results in relaxation of uterine smooth muscle, thus delaying labor.
Hivent Plus: Salbutamol is a direct-acting sympathomimetic agent with predominantly beta-adrenergic activity and a selective action on beta₂ receptors (beta agonist). Beta agonists activate pulmonary receptors that relax bronchial smooth muscles and decrease airway resistance (bronchodilation); they inhibit the release of inflammatory mediators from mast cells and increase ciliary motility. Selective beta receptor agonists have less tendency to produce cardiac stimulation than nonselective beta agonist that stimulates beta receptors in cardiac muscle. Thus, the incidence of cardiac side effects such as tachycardia and more serious arrhythmia is lower, but not absent, in selective beta₂ agonists.
Ipratropium Bromide is a quaternary ammonium compound that acts like atropine to block muscarinic receptors. It is formed by the introduction of an isopropyl group to the N atom of atropine. Ipratropium has relatively lack of effect on the function of ciliated bronchial epithelium, compared with the marked inhibition of ciliary beating and mucociliary clearance produced by atropine. When solutions are inhaled, the actions of Ipratropium are confined almost exclusively to the mouth and airways. Even when administered in amounts many times the recommended dosage, little or no change occurs in heart rate, blood pressure, bladder function, intra ocular pressure or pupillary diameter. Hence, it is administered by inhalation to limit its systemic anticholinergic actions and to reduce bronchoconstriction that is present in some patients with Chronic Obstructive Pulmonary Disease (e.g. chronic bronchitis and emphysema).
Rationale of Combination: The fixed-dose combination of Salbutamol + Ipratropium Bromide, with a sympathomimetic (beta₂ agonist) and parasympatholytic (anticholinergic) properties, respectively produces a greater bronchodilating effect than when either drug is used alone.
Pharmacokinetics: Hivent DS: Metabolism: Hepatic.
Half life: 1.6 hours.
Excretion: Renal (majority of a dose of salbutamol given intravenously, orally or by inhalation is excreted within 72 hours).
Hivent Plus: Salbutamol does not appear to be metabolized in the lungs, therefore its ultimate metabolism and excretion following inhalation depends upon the delivery method used, which determines the proportion of inhaled salbutamol relative to the proportion inadvertently swallowed. It has been suggested that the majority of an inhaled dose is swallowed and absorbed from the gut. It is subject to first-pass metabolism in the liver and possibly in the gut wall; the main metabolite is an inactive sulphate conjugate. The plasma half life of salbutamol has been estimated to range from about 2 to as much as 7 hours. It is rapidly excreted in the urine as metabolites and unchanged drug; there is some excretion in the feces.
Following inhalation, only small amount of ipratropium reaches the systemic circulation. Some is advertently swallowed but it is poorly absorbed from the gastrointestinal tract. Ipratropium and its metabolites are eliminated in the urine and feces.