Ascoril-LS Solution

Indications

• Chronic obstructive pulmonary disease (COPD)
• Asthma
• Bronchitis
• Respiratory infections with excessive mucus production

Dosage

Children: For children aged 2 to 5 years, the recommended dose is 15 mg to 30 mg daily, divided into two or three doses. For children aged 6 to 12 years, the recommended dose is 30 mg to 60 mg daily, divided into two or three doses.

Adults: The usual adult dose is 30 mg to 120 mg daily, divided into two or three doses.

Mechanism of action

Ambroxol acts by stimulating the secretion of serous mucus in the respiratory tract, which helps to reduce the viscosity of sputum. This mucolytic action enhances the clearance of mucus, facilitating expectoration. It may also influence the production of surfactant in the lungs, contributing to improved lung function.

Pharmacodynamics

Ambroxol exhibits a dose-dependent effect on mucus viscosity and secretion. By enhancing mucociliary clearance, it aids in reducing airway obstruction and improving respiratory function. The onset of action typically occurs within a few hours after administration, with peak effects observed within 1 to 2 days of treatment.

Pharmacokinetics

Ambroxol is well absorbed after oral administration, with a bioavailability of approximately 70%. It is metabolized primarily in the liver through conjugation and oxidation, resulting in active metabolites. The elimination half-life is about 10 hours, and the drug is excreted predominantly via urine, both as unchanged drug and metabolites.

Contra-indications

• Hypersensitivity to ambroxol or any of the excipients
• Severe hepatic impairment
• Severe renal impairment

Adverse effects

• Gastrointestinal disturbances (nausea, vomiting, diarrhea)
• Skin reactions (rash, urticaria)
• Headache
• Dizziness
• Dry mouth
• Anaphylactic reactions (rare)

Interactions

• Ambroxol may enhance the absorption of other drugs due to its mucolytic properties
• Caution should be exercised when used with other cough suppressants

Precautions

• Use with caution in patients with a history of peptic ulcer disease
• Avoid use in patients with asthma unless prescribed by a healthcare professional
• Monitor renal and hepatic function in patients with pre-existing conditions

Pregnancy

Ambroxol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Data on human pregnancy are limited.

Breast-feeding

Ambroxol is excreted in breast milk. Caution is advised when administering to nursing mothers.

Storage

Store in a cool, dry place, away from light. Keep out of reach of children.

Formulations

• Oral solution
• Syrup
• Tablets
• Effervescent tablets

Indications

• Productive cough due to respiratory tract infections
• Bronchitis
• Common cold with mucus production

Dosage

Children: For children aged 6-12 years, the usual dose is 100-200 mg every 4 hours, not exceeding 1200 mg per day. For children aged 2-6 years, consult the BNF for Children for appropriate dosing.

Adults: The usual dose for adults is 200-400 mg every 4 hours, as needed, not exceeding 2400 mg per day.

Mechanism of action

Guaifenesin is believed to function by increasing mucus secretion through stimulation of gastric vagal receptors, which may result in glandular exocytosis of less viscous mucus. This action is thought to provoke coughing, assisting in the clearance of thick mucus from the airways. Additionally, it may act as an NMDA receptor antagonist, contributing to mild muscle relaxant and anticonvulsant effects.

Pharmacodynamics

Guaifenesin enhances the output of phlegm and bronchial secretions by decreasing their viscosity and surface tension. This results in increased ciliary action and promotes the removal of accumulated secretions, thus turning unproductive coughs into more productive ones. Its effects are aimed at improving mucociliary clearance in the respiratory tract.

Pharmacokinetics

Guaifenesin is absorbed from the gastrointestinal tract, with peak plasma concentrations typically occurring within 1 to 2 hours after oral administration. It is metabolized in the liver and has a relatively short half-life, necessitating frequent dosing for sustained effect. The elimination is primarily via renal pathways.

Adverse effects

• Nausea
• Vomiting
• Dizziness
• Headache
• Rash

Precautions

• Use with caution in patients with chronic cough due to asthma or emphysema.
• Consider potential allergic reactions in patients with a history of hypersensitivity.

Pregnancy

There is limited data on the safety of guaifenesin in pregnancy. It should only be used if clearly needed and prescribed by a healthcare provider.

Breast-feeding

Guaifenesin is excreted in breast milk; caution is advised when administering to nursing mothers.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Oral tablets
• Syrup
• Extended-release capsules

Indications

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Bronchospasm

Dosage

Children: Refer to the BNF for Children for specific dosing information.

Adults: Refer to the BNF for specific dosing information.

Mechanism of action

Levosalbutamol activates β2 adrenergic receptors on airway smooth muscle, which are coupled to the Gs protein. This activation stimulates adenylate cyclase, resulting in increased levels of intracellular cyclic adenosine monophosphate (cAMP). Elevated cAMP activates protein kinase A, which inhibits myosin phosphorylation and decreases intracellular calcium concentrations, leading to muscle relaxation. Additionally, increased cAMP levels can inhibit the release of inflammatory mediators from mast cells in the airways, aiding in the management of asthma.

Pharmacodynamics

Levosalbutamol works by relaxing bronchial smooth muscle, thereby increasing airflow and alleviating symptoms of acute shortness of breath. It is effective in providing rapid relief from bronchospasm associated with conditions such as asthma and chronic obstructive pulmonary disease (COPD).

Pharmacokinetics

The pharmacokinetics of levosalbutamol include a rapid onset of action, typically within 15 minutes of administration, with a duration of effect lasting up to 6 hours. It is absorbed well following inhalation, with peak plasma concentrations reached quickly. The drug undergoes hepatic metabolism, primarily through conjugation, and is excreted mainly via the urine.

Adverse effects

• Tremor
• Headache
• Palpitations
• Tachycardia
• Hypokalaemia
• Nausea

Precautions

• Use with caution in patients with cardiovascular disorders
• Monitor potassium levels in patients receiving high doses or those with risk of hypokalaemia

Pregnancy

Use in pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Levosalbutamol is excreted in breast milk, caution should be exercised when administered to a nursing mother.

Storage

Store below 25°C, protect from light and moisture.

Formulations

• Inhalation solution
• Inhaler

Mechanism of action

Although the exact mechanism of action of guaifenesin may not yet be formally or totally elucidated, it is believed that expectorants like guaifenesin function by increasing mucus secretion. Moreover, it is also further proposed that such expectorants may also act as an irritant to gastric vagal receptors, and recruit efferent parasympathetic reflexes that can elicit glandular exocytosis that is comprised of a less viscous mucus mixture. Subsequently, these actions may provoke coughing that can ultimately flush difficult to access, congealed mucopurulent material from obstructed small airways to facilitate a temporary improvement for the individual. Consequently, while it is generally proposed that guaifenesin functions as an expectorant by helping to loosen phlegm (mucus) and thin bronchial secretions to rid the bronchial passageways of bothersome mucus and make coughs more productive, there has also been research to suggest that guaifenesin possesses and is capable of demonstrating anticonvulsant and muscle relaxant effects to some degree possibly by acting as an NMDA receptor antagonist. Guaifenesin is thought to act as an expectorant by increasing the volume and reducing the viscosity of secretions in the trachea and bronchi. Thus it may increase the efficiency of the cough reflex and facilitate removal of the secretions; however, objective evidence for this is limited and conflicting. By increasing respiratory tract fluid, guaifenesin reduces the viscosity of tenacious secretions and acts as an expectorant. Guaifenesin, a commonly used agent for the treatment of cough, is termed an expectorant since it is believed to alleviate cough discomfort by increasing sputum volume and decreasing its viscosity, thereby promoting effective cough. Despite its common usage, relatively few studies, yielding contrasting results, have been performed to investigate the action and efficacy of guaifenesin. To evaluate the effect of guaifenesin on cough reflex sensitivity. Randomized, double-blind, placebo-controlled trial. Fourteen subjects with acute viral upper respiratory tract infection (URI) and 14 healthy volunteers. On 2 separate days, subjects underwent capsaicin cough challenge 1 to 2 hr after receiving a single, 400-mg dose (capsules) of guaifenesin or matched placebo. Measurements and results: The concentration of capsaicin inducing five or more coughs (C(5)) was determined. Among subjects with URI, mean (+/- SEM) log C(5) after guaifenesin and placebo were 0.92 +/- 0.17 and 0.66 +/- 0.14, respectively (p = 0.028). No effect on cough sensitivity was observed in healthy volunteers. /The/ results demonstrate that guaifenesin inhibits cough reflex sensitivity in subjects with URI, whose cough receptors are transiently hypersensitive, but not in healthy volunteers. Possible mechanisms include a central antitussive effect, or a peripheral effect by increased sputum volume serving as a barrier shielding cough receptors within the respiratory epithelium from the tussive stimulus.

Pharmacodynamics

Guaifenesin is categorized as an expectorant that acts by enhancing the output of phlegm (sputum) and bronchial secretions via decreasing the adhesiveness and surface tension of such material. Furthermore, guaifenesin elicits an increased flow of less viscous gastric secretions that subsequently promote ciliary action - all actions that ultimately change dry, unproductive coughing to coughs that are more productive and less frequent. Essentially, by decreasing the viscosity and adhesiveness of such secretions, guaifenesin enhances the efficacy of mucociliary activity in removing accumulated secretions from the upper and lower airway.

Mechanism of action

β2 adrenergic receptors on airway smooth muscle are Gs coupled and their activation by levosalbutamol leads to activation of adenylate cyclase and to an increase in the intracellular concentration of 3',5'-cyclic adenosine monophosphate (cyclic AMP). Increased cyclic AMP activates protein kinase A which itself inhibits the phosphorylation of myosin produces lower intracellular ionic calcium concentrations, inducing muscle relaxation. Increased cyclic AMP concentrations are also associated with the inhibition of the release of mediators from mast cells in the airways, potentially contributing to its benefit in asthma attacks.

Pharmacodynamics

It acts by relaxing smooth muscle in the bronchial tubes to increase air flow and relieve acute shortness of breath.