DESCRIPTION
Ambroxol-Ambroxol is a secretolytic agent used in the treatment of respiratory diseases associated with viscid or excessive mucus. It is the active ingredient of Mucosolvan, Lasolvan or Mucoangin. The substance is a mucoactive drug with several properties including secretolytic and secretomotoric actions that restore the physiological clearance mechanisms of the respiratory tract which play an important role in the body’s natural defence mechanisms. It stimulates synthesis and release of surfactant by type II pneumocytes. Surfactants acts as an anti-glue factor by reducing the adhesion of mucus to the bronchial wall, in improving its transport and in providing protection against infection and irritating agents.Terbutaline-A selective beta-2 adrenergic agonist used as a bronchodilator and tocolytic.Guaiphenesin -An expectorant that also has some muscle relaxing action. It is used in many cough preparations.
CATEGORIES
Ambroxol-Expectorants,Terbutaline-Sympathomimetics Adrenergic beta-2 Receptor Agonists,Bronchodilator Agents,Tocolytic Agents.Guaiphenesin -Expectorants.
CHEMICAL FORMULA
Ambroxol Hcl-C13H19Br2ClN2O,Terbutaline Sulphate -C12H21NO7S. Guaiphenesin -C10H14O4.
COMPOSITION
Ambroxol Hcl 15 mg + Terbutaline sulphate 1.25 mg + Guaiphenesin 50 mg
INDICATION
Ambroxol-Ambroxol is indicated as “secretolytic therapy in bronchopulmonary diseases associated with abnormal mucus secretion and impaired mucus transport. It promotes mucus clearance, facilitates expectoration and eases productive cough, allowing patients to breathe freely and deeply.Terbutaline-For the prevention and reversal of bronchospasm in patients 12 years of age and older with reversible, obstructive airway disease, as well as symptomatic management of reversible bronchospasm associated with bronchitis and emphysema. Also used acute IV and sub-Q therapy in selected women to inhibit uterine contractions in preterm labor (tocolysis) and prolong gestation when beneficial.Guaiphenesin -Used to assist the expectoration of phlegm from the airways in acute respiratory tract infections.
PHARMACODYNAMICS
Terbutaline-Terbutaline is a relatively selective beta2-adrenergic bronchodilator that has little or no effect on alpha-adrenergic receptors. The drug has exerts a preferential effect on beta2-adrenergic receptors but stimulates beta-adrenergic receptors less selectively than relatively selective beta2-agonists. Terbutaline appears to have a greater stimulating effect on beta-receptors of the bronchial, vascular, and uterine smooth muscles (beta2 receptors) than on the beta-receptors of the heart (beta1 receptors). This drug relaxes smooth muscle and inhibits uterine contractions, but may also cause some cardiostimulatory effects and CNS stimulation.Guaiphenesin -Guaifenesin is an expectorant which increases the output of phlegm (sputum) and bronchial secretions by reducing adhesiveness and surface tension. The increased flow of less viscous secretions promotes ciliary action and changes a dry, unproductive cough to one that is more productive and less frequent. By reducing the viscosity and adhesiveness of secretions, guaifenesin increases the efficacy of the mucociliary
MECHANISM
in removing accumulated secretions from the upper and lower airway.
MECHANISM
Ambroxol-Ambroxol is a mucolytic agent. Excessive Nitric oxide (NO) is associated with inflammatory and some other disturbances of airways function. NO enhances the activation of soluble guanylate cyclase and cGMP accumulation. Ambroxol has been shown to inhibit the NO-dependent activation of soluble guanylate cyclase. It is also possible that the inhibition of NO-dependent activation of soluble guanylate cyclase can suppress the excessive mucus secretion, therefore it lowers the phlegm viscosity and improves the mucociliary transport of bronchial secretions. Terbutaline-The pharmacologic effects of terbutaline are at least in part attributable to stimulation through beta-adrenergic receptors of intracellular adenyl cyclase, the enzyme that 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. Guaiphenesin -Guaifenesin may act as an irritant to gastric vagal receptors, and recruit efferent parasympathetic reflexes that cause glandular exocytosis of a less viscous mucus mixture. Cough may be provoked. This combination may flush tenacious, congealed mucopurulent material from obstructed small airways and lead to a temporary improvement in dyspnea or the work of breathing.
ABSORPTION
Ambroxol-Rapid and almost complete.Terbutaline-Approximately 30-50% if administered orally and well absorbed subcutaneously. Guaiphenesin -Rapidly absorbed from the GI tract.
METABOLISM
Guaiphenesin -Rapidly hydrolyzed (60% within seven hours) and then excreted in the urine, with beta-(2-methoxyphenoxy)-lactic acid as its major urinary metabolite.
ELIMINATION
Terbutaline-About 90% of the drug was excreted in the urine at 96 hours after subcutaneous administration, with about 60% of this being unchanged drug. It appears that the sulfate conjugate is a major metabolite of terbutaline and urinary excretion is the primary route of elimination.
HALF LIFE
Ambroxol-7-12 hours.Terbutaline-5.5-5.9 hours.Guaiphenesin -1 hour.
TOXICITY
Terbutaline Sulfate: Oral LD50(rat) = 8.7 g/kg; Oral LD50(mouse) = 205 mg/kg; Oral LD50(dog) = 1.5 g/kg; IP LD50(rat)= 220 mg/kg ; IP LD50(mouse) = 130 mg/kg; Oral LD50(rabbit) = >8 g/kg; IV LD50(mouse) = 36 mg/kg; IV LD50(dog) = 116 mg/kg; IV LD50(rabbit) = 110 mg/kg.Guaiphenesin -LD50 1510 mg/kg (rat, oral).
FOOD INTERACTIONS
avoid alcohol
SIDE EFFECTS
Ambroxol-Running nose, tears, gastric irritation and hypersensitivity.Terbutaline-Nervous and excitable. Headache. Upset stomach or throwing up. Many small meals, good mouth care, sucking hard, sugar-free candy, or chewing sugar-free gum may help. Dry mouth. Good mouth care, sucking hard, sugar-free candy, or chewing sugar-free gum may help. See a dentist often. Not able to sleep. – Shot: – Low blood pressure. Flushing. Wearing layers of clothes or summer clothes and staying in cool places may help. Low potassium levels. Signs include feeling tired, weak, numbness, or tingling; muscle cramps; hard stools (constipation); throwing up; or a fast heartbeat. High blood sugar may cause diabetes while on this drug. This most often goes back to normal when this drug is stopped.Guaiphenesin -Feeling dizzy. Rise slowly over a few minutes when sitting or lying down. Be careful climbing. Headache. Upset stomach or throwing up. Many small meals, good mouth care, sucking hard, sugar-free candy, or chewing sugar-free gum may help.