LIBITUS-PLUS 1.25MG/4MG/50MG SYRUP

Indications

• Asthma
• Chronic Obstructive Pulmonary Disease (COPD)
• Exacerbation of reversible airways obstruction
• Prevention of exercise-induced bronchospasm
• Uncomplicated premature labor (under specialist supervision)

Dosage

Adults: Initially 2.5 mg 3 times a day for 1–2 weeks, then increased to

Mechanism of action

Terbutaline exerts its effects by selectively stimulating beta-2 adrenergic receptors located in the smooth muscle of the airways. This activation leads to the activation of adenylate cyclase, resulting in increased levels of cyclic AMP (cAMP). Elevated cAMP levels promote relaxation of the bronchial smooth muscle, leading to bronchodilation. Additionally, terbutaline may inhibit the release of mediators from mast cells, reducing bronchoconstriction and inflammation.

Pharmacodynamics

The pharmacodynamic profile of terbutaline includes rapid onset of action, typically within 5 to 15 minutes when inhaled, and a duration of action of approximately 3 to 6 hours. It provides symptomatic relief from bronchospasm associated with asthma and chronic obstructive pulmonary disease (COPD). The drug is also noted for its tocolytic effects, as it can inhibit uterine contractions, making it useful in managing premature labor.

Pharmacokinetics

Terbutaline is well absorbed following inhalation and oral administration, with peak plasma concentrations occurring within 1 to 3 hours. It exhibits a volume of distribution of approximately 3 L/kg, indicating extensive tissue distribution. The drug is metabolized primarily in the liver and has a half-life of about 3 to 5 hours. Terbutaline is excreted mainly in urine, both as unchanged drug and metabolites. Its pharmacokinetic profile may be affected by factors such as age, liver function, and concomitant medications.

Adverse effects

• Tachycardia
• Palpitations
• Tremors
• Headache
• Nausea
• Dizziness
• Hypokalemia
• Hyperglycemia

Interactions

• Beta-blockers may reduce the effectiveness of terbutaline
• Corticosteroids may enhance the effect of terbutaline
• Concomitant use with other sympathomimetics may increase cardiovascular side effects

Precautions

• Use with caution in patients with cardiovascular disorders
• Caution in patients with diabetes due to potential hyperglycemia
• Monitor potassium levels in patients at risk of hypokalemia
• Monitor for paradoxical bronchospasm

Pregnancy

Terbutaline should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Terbutaline is excreted in breast milk; caution should be exercised when administering to nursing mothers.

Storage

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

Formulations

• Tablets: 2.5 mg and 5 mg
• Nebuliser solution: 0.5 mg/ml
• Injection: 0.5 mg/1 ml

Indications

• Chronic bronchitis
• Asthma
• Bronchiectasis
• Pneumonia
• Respiratory tract infections with productive cough

Dosage

Children: Refer to the BNF for Children for specific paediatric dosing recommendations.

Adults: Refer to the BNF for specific dosing information.

Mechanism of action

Bromhexine aids in mucus clearance by reducing the viscosity of mucus and activating the ciliary epithelium, allowing secretions to be expelled from the respiratory tract. Additionally, bromhexine has been shown to inhibit the transmembrane serine protease 2 receptor (TMPRSS2), which plays a crucial role in viral respiratory diseases. This inhibition may help in preventing or treating various respiratory illnesses, including COVID-19, by blocking viral entry into cells.

Pharmacodynamics

Bromhexine thins airway secretions, thus improving breathing and alleviating discomfort associated with thick mucus in the airways. Its action is particularly beneficial in respiratory disorders where mucus obstruction is a significant issue.

Pharmacokinetics

Bromhexine is well absorbed after oral administration, with peak plasma concentrations typically reached within 1 to 2 hours. It is metabolized in the liver, primarily to ambroxol, which is its active metabolite. The elimination half-life of bromhexine is approximately 8 to 12 hours, and it is excreted mainly through urine. The pharmacokinetics can be influenced by factors such as liver function and concurrent medications.

Adverse effects

• Gastrointestinal disturbances
• Nausea
• Vomiting
• Diarrhea
• Allergic reactions

Precautions

• Use with caution in patients with peptic ulcer disease
• Monitor patients with asthma or bronchospastic conditions

Pregnancy

Bromhexine should be used during pregnancy only if clearly needed and after careful consideration of the potential benefits and risks.

Breast-feeding

Bromhexine is excreted in breast milk; caution should be exercised when administering to nursing mothers.

Storage

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

Formulations

• Tablets
• Syrup
• Solution for inhalation

Indications

• Cough associated with colds
• Bronchitis
• Respiratory tract infections
• Other conditions with excessive mucus production

Dosage

Children: Refer to the BNF for Children for specific dosing guidelines based on age and

Adults: The typical adult dose is 200-400 mg orally every 4 hours as needed, not exceeding 2.4 g per day.

Mechanism of action

Guaifenesin is believed to function by increasing mucus secretion and acting as an irritant to gastric vagal receptors. This action recruits efferent parasympathetic reflexes that stimulate glandular exocytosis, resulting in a less viscous mucus mixture. Consequently, this may provoke coughing, facilitating the clearance of congealed mucopurulent material from obstructed airways, thereby improving respiratory function. Additionally, it is thought to enhance the output of phlegm and bronchial secretions by reducing their viscosity and adhesiveness, thus promoting ciliary action and improving the efficiency of the cough reflex.

Pharmacodynamics

Guaifenesin acts as an expectorant that enhances the output of phlegm and bronchial secretions by decreasing their adhesiveness and surface tension. By increasing the flow of less viscous gastric secretions, it promotes ciliary action, leading to more productive coughs. This mechanism ultimately aids in the removal of accumulated secretions from the upper and lower airways, making coughs less frequent and more effective.

Pharmacokinetics

Guaifenesin is rapidly absorbed from the gastrointestinal tract and is metabolized in the liver. It has a relatively short half-life, with peak plasma concentrations typically occurring within one hour of administration. The drug is eliminated primarily through renal excretion, with both unchanged drug and metabolites being excreted in the urine.

Adverse effects

• Nausea
• Vomiting
• Dizziness
• Headache
• Rash
• Gastrointestinal discomfort

Precautions

• Caution in patients with chronic cough associated with smoking, asthma, or emphysema
• Use with caution in patients with a history of gastrointestinal disorders

Pregnancy

Guaifenesin is categorized under FDA pregnancy category C. Risk cannot be ruled out; consult a healthcare provider.

Breast-feeding

Limited data available; exercise caution and consult a healthcare provider before use.

Storage

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

Formulations

• Oral solution
• Tablet
• Extended-release tablet
• Syrup

Indications

• Bronchospasm
• Asthma
• Chronic bronchitis
• Emphysema

Dosage

Children: Refer to the BNF for Children for specific paediatric dosing recommendations.

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

Terbutaline exerts its effects through selective agonism of beta-2 adrenergic receptors located in the bronchioles. This activation leads to the stimulation of adenylyl cyclase, which increases the levels of intracellular cyclic adenosine monophosphate (cAMP). The rise in cAMP reduces intracellular calcium concentrations, leading to the activation of protein kinase A. This enzyme inactivates myosin light-chain kinase and activates myosin light-chain phosphatase, ultimately resulting in the relaxation of smooth muscle within the bronchioles.

Pharmacodynamics

As a beta-2 adrenergic receptor agonist, terbutaline is indicated for the relief of bronchospasm in conditions such as asthma, chronic bronchitis, and emphysema. It has a rapid onset of action and a relatively short duration of effect, typically requiring administration up to three times daily in its inhaled form. The therapeutic window for terbutaline is wide, making it generally safe within prescribed doses.

Pharmacokinetics

Terbutaline is rapidly absorbed when administered via inhalation, allowing for quick therapeutic action. The drug undergoes extensive first-pass metabolism when taken orally, which may affect its bioavailability. It is primarily metabolized in the liver and has a half-life that supports frequent dosing. Excretion occurs mainly via the kidneys, with metabolites detectable in urine.

Contra-indications

• Hypersensitivity to terbutaline or any of its components
• Severe hypersensitivity to sympathomimetic amines
• Tachyarrhythmias
• Cardiac arrhythmias

Adverse effects

• Tremor
• Tachycardia
• Palpitations
• Headache
• Nausea
• Dizziness
• Muscle cramps
• Hypokalemia

Interactions

• Beta-blockers may reduce the effectiveness of terbutaline
• Concomitant use with other sympathomimetics may increase the risk of cardiovascular side effects
• Monoamine oxidase inhibitors (MAOIs) can potentiate the effects of terbutaline

Precautions

• Use with caution in patients with cardiovascular disorders
• Monitor potassium levels in patients with significant hypokalemia
• Caution in patients with diabetes mellitus as beta agonists may induce hyperglycemia

Pregnancy

Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. Category C.

Breast-feeding

Terbutaline is excreted in human milk, and caution should be exercised when administered to a nursing woman.

Storage

Store below 25 degrees Celsius. Protect from light and moisture. Keep out of reach of children.

Formulations

• Inhalation aerosol
• Oral tablets
• Injection

Mechanism of action

Inflammation of the airways, increased mucus secretion, and altered mucociliary clearance are the hallmarks of various diseases of the respiratory tract. Mucus clearance is necessary for lung health; bromhexine aids in mucus clearance by reducing the viscosity of mucus and activating the ciliary epithelium, allowing secretions to be expelled from the respiratory tract. Recent have studies have demonstrated that bromhexine inhibits the transmembrane serine protease 2 receptor (TMPRSS2) in humans. Activation of TMPRSS2 plays an important role in viral respiratory diseases such as influenza A and Middle East Respiratory Syndrome (MERS). Inhibition of receptor activation and viral entry by bromhexine may be effective in preventing or treating various respiratory illnesses, including COVID-19. In vitro studies have suggested the action of ambroxol (a metabolite of bromhexine) on the angiogensin-converting enzyme receptor 2 (ACE2), prevents entry of the viral envelope-anchored spike glycoprotein of SARS-Cov-2 into alveolar cells or increases the secretion of surfactant, preventing viral entry.

Pharmacodynamics

Bromhexine thins airway secretions, improving breathing and discomfort associated with thick mucus in airways associated with a variety of respiratory conditions.

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

Terbutaline is a selective beta-2 adrenergic receptor agonist. Agonism of these receptors in bronchioles activates adenylyl cyclase, increasing intracellular cyclic adenosine monophosphate (cAMP). Increased cAMP decreases intracellular calcium, activating protein kinase A, inactivating myosin light-chain kinase, activating myosin light-chain phosphatase, and finally relaxing smooth muscle in the bronchiole.

Pharmacodynamics

Terbutaline is a beta-2 adrenergic receptor agonist indicated to treat reversibly bronchospasm in asthmatic patients with bronchitis and emphysema. It has a short duration as the inhaled form is taken up to three times daily, and the therapeutic window is wide.