AEROVENT INHALER

Indications

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Exercise-induced bronchospasm
• Other conditions associated with reversible airways obstruction

Dosage

Children: Child 5–11 years: 2.5 mg via nebulisation or 50 micrograms by inhalation; Child 12–17 years: 5 mg via nebulisation or

Adults: 500 micrograms every 4 hours if required, or 50 micrograms by inhalation twice daily, with possible increase to 100 micrograms twice daily in more severe cases.

Mechanism of action

Salbutamol preferentially binds to beta-2 adrenergic receptors, stimulating adenyl cyclase and increasing intracellular cyclic AMP. This results in protein kinase A activation, which inhibits myosin phosphorylation and reduces intracellular calcium concentrations, leading to smooth muscle relaxation in the airways. Additionally, increased cyclic AMP inhibits the release of inflammatory mediators from mast cells.

Pharmacodynamics

Salbutamol is known for its bronchodilatory effects, particularly in asthma and chronic obstructive pulmonary disease (COPD). It selectively stimulates beta-2 receptors, which are predominantly located in bronchial smooth muscle. The drug is effective in providing rapid relief from bronchospasm and has been shown to prevent exercise-induced bronchospasm. The R-isomer of salbutamol is primarily responsible for its therapeutic effects, while the S-isomer may contribute to side effects. Salbutamol may also induce metabolic effects, such as hyperglycemia.

Pharmacokinetics

Salbutamol is administered via inhalation, with onset of action typically occurring within minutes. Its duration of action is around 4 to 6 hours for the immediate-release formulation. The drug undergoes hepatic metabolism and is excreted primarily in urine. Its pharmacokinetic profile can vary based on the route of administration, with inhalation providing faster and more localized effects compared to oral or parenteral routes.

Adverse effects

• Tremors
• Nervousness
• Palpitations
• Tachycardia
• Headache
• Dizziness
• Nausea
• Hypokalemia
• Increased blood glucose levels

Interactions

• Other beta-agonists
• Beta-blockers
• Diuretics
• Monoamine oxidase inhibitors (MAOIs)
• Thyroid hormones
• Caffeine

Precautions

• Use with caution in patients with cardiovascular disorders
• Hypertension
• Hyperthyroidism
• Diabetes mellitus
• Seizure disorders
• Pregnancy and breastfeeding

Pregnancy

Inhaled drugs for asthma can be taken as normal during pregnancy.

Breast-feeding

Inhaled drugs for asthma can be taken as normal during breastfeeding.

Storage

Store below 25 degrees Celsius. Protect from light and moisture.

Formulations

• Inhalation aerosol
• Inhalation solution
• Inhalation powder

Indications

• Prophylaxis of asthma
• Management of allergic rhinitis
• Treatment of nasal polyps

Dosage

Children: For children aged 2–11 years, the dose is 100–200 micrograms twice daily; for children aged 12–17 years, 200–400 micrograms twice daily, adjusted according to response.

Adults: For adults and children over 12 years with chronic asthma, the usual starting dose is 200-400 micrograms twice daily, which may be increased if necessary.

Mechanism of action

Beclometasone dipropionate acts by binding to glucocorticoid receptors in target cells, leading to the modulation of gene expression and the inhibition of pro-inflammatory cytokines, thereby reducing inflammation and hyperresponsiveness in the airways.

Pharmacodynamics

As a potent anti-inflammatory agent, beclometasone dipropionate decreases the infiltration of inflammatory cells into the airways, reduces mucus production, and enhances beta-adrenergic responsiveness. This results in improved airflow and reduced asthma symptoms.

Pharmacokinetics

Beclometasone dipropionate is administered via inhalation, where it undergoes extensive first-pass metabolism in the liver. Its systemic bioavailability is low due to significant hepatic metabolism. The drug has a long duration of action, with effects lasting for 12-24 hours, allowing for once or twice-daily dosing.

Contra-indications

• Hypersensitivity to beclometasone dipropionate or any of its excipients
• Hypersensitivity to atropine or its derivatives

Adverse effects

• Throat irritation
• Wheezing
• Nasal complaints
• Headache
• Nausea
• Stomatitis
• Gastrointestinal absorption may occur
• Corneal oedema
• Eye disorders
• Eye pain
• Palpitations

Precautions

• Monitor growth in children receiving prolonged treatment
• Consider systemic corticosteroid side effects with high doses or prolonged use

Pregnancy

Manufacturer advises only use if potential benefit outweighs the risk.

Breast-feeding

No information available-manufacturer advises only use if potential benefit outweighs risk.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Inhalation aerosol (Clenil Modulite®)
• Inhalation powder (Qvar®)

Indications

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Allergic rhinitis
• Topical treatment of inflammatory skin conditions

Dosage

Children: Dosing in children should be determined based on the BNF for Children. Refer to the BNF for specific paediatric dosing information.

Adults: The dosage for adults varies depending on the condition being treated. Refer to the BNF for specific dosing guidelines.

Mechanism of action

Beclometasone acts by binding to glucocorticoid receptors, leading to the modulation of gene expression. This results in the inhibition of pro-inflammatory cytokines and the promotion of anti-inflammatory proteins, thereby reducing inflammation and immune response.

Pharmacodynamics

As a corticosteroid, beclometasone exerts its effects by modulating various cellular functions. It decreases the migration of leukocytes to sites of inflammation, reduces capillary permeability, and inhibits the release of enzymes that contribute to the inflammatory response. The therapeutic effects are evident in conditions characterized by excessive inflammation.

Pharmacokinetics

Beclometasone is well-absorbed when administered by inhalation, and its bioavailability is significantly enhanced when delivered directly to the lungs. It undergoes extensive first-pass metabolism in the liver, which reduces systemic exposure. The half-life of beclometasone is approximately 15 hours, and it is primarily excreted via the urine as metabolites.

Contra-indications

• Hypersensitivity to beclometasone or any of its components
• Systemic fungal infections
• Active or latent tuberculosis

Adverse effects

• Local irritation
• Dryness of the throat
• Cough
• Dysphonia
• Oral candidiasis
• Adrenal suppression (with prolonged use)

Interactions

• cobicistat+beclometasone: Unknown (increases exposure)
• idelalisib+beclometasone: Unknown (increases exposure)
• clarithromycin+beclometasone: Unknown (increases exposure)

Precautions

• Use with caution in patients with active infections
• Monitor for signs of adrenal insufficiency in long-term therapy
• Consider alternate therapy in patients with a history of severe allergic reactions

Pregnancy

Beclometasone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult a healthcare provider.

Breast-feeding

Beclometasone is excreted in breast milk. Caution should be exercised when administering to nursing mothers.

Storage

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

Formulations

• Inhaler
• Nasal spray
• Topical cream
• Topical ointment

Mechanism of action

In vitro studies and in vivo pharmacologic studies have shown that salbutamol has a preferential effect on beta2-adrenergic receptors compared with isoproterenol. Although beta2­ adrenoceptors are the predominant adrenergic receptors in bronchial smooth muscle and beta1 adrenoceptors are the predominant receptors in the heart, there are also beta2-adrenoceptors in the human heart comprising 10% to 50% of the total beta-adrenoceptors. The precise function of these receptors has not been established, but their presence raises the possibility that even selective beta2-agonists may have cardiac effects. Activation of beta2-adrenergic receptors on airway smooth muscle leads to the activation of adenyl cyclase and to an increase in the intracellular concentration of cyclic-3′,5′-adenosine monophosphate (cyclic AMP). This increase of cyclic AMP leads to the activation of protein kinase A, which inhibits the phosphorylation of myosin and lowers intracellular ionic calcium concentrations, resulting in relaxation. Salbutamol relaxes the smooth muscles of all airways, from the trachea to the terminal bronchioles. Salbutamol acts as a functional antagonist to relax the airway irrespective of the spasmogen involved, thus protecting against all bronchoconstrictor challenges. Increased cyclic AMP concentrations are also associated with the inhibition of release of mediators from mast cells in the airway. Salbutamol 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 electrocardiographic changes. A measurable decrease in airway resistance is typically observed within 5 to 15 minutes after inhalation of salbutamol. The maximum improvement in pulmonary function usually occurs 60 to 90 minutes after salbutamol treatment, and significant bronchodilator activity has been observed to persist for 3 to 6 hours. Adrenergic bronchodilators act by stimulating beta2-adrenergic receptors in the lungs to relax bronchial smooth muscle, thereby relieving bronchospasm. /Adrenergic bronchodilators/ Primarily stimulates beta2-adrenergic receptors, with some minor beta1-adrenergic activity. 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 the predominant receptors in bronchial smooth muscle, date indicate that there is a population of beta2-receptors in the human heart existing in a concentration between 10% and 50% of cardiac beta-adrenergic receptors. The precise function of these receptors has not been established. Activation of beta2-adrenergic receptors on airway smooth muscle leads to the activation of adenylcyclase and to an increase in the intracellular concentration of cyclic-3',5'-adenosine monophosphate (cyclic AMP). This increase of cyclic AMP leads to the activation of protein kinase A, which inhibits the phosphorylation of myosin and lowers intracellular ionic calcium concentrations, resulting in relaxation. Albuterol relaxes the smooth muscles of all airways, from the trachea to the terminal bronchioles. Albuterol acts as a functional antagonist to relax the airway irrespective of the spasmogen involved, this protecting against all bronchoconstrictor challenges. Increased cyclic AMP concentrations are also associated with the inhibition of release of mediators from most cells in the airway.

Pharmacodynamics

Salbutamol (INN) or albuterol (USAN), a moderately selective beta(2)-receptor agonist similar in structure to terbutaline, is widely used as a bronchodilator to manage asthma and other chronic obstructive airway diseases. The R-isomer, levalbuterol, is responsible for bronchodilation while the S-isomer increases bronchial reactivity. The R-enantiomer is available and sold in its pure form as levalbuterol and subsequently may produce fewer side-effects with only the R-enantiomer present - although this has not been formally demonstrated. After oral and parenteral administration, stimulation of the beta receptors in the body, both beta-1 and beta-2, occurs because (a) beta-2 selectivity is not absolute, and (b) higher concentrations of salbutamol occur in the regions of these receptors with these modes of administration. This results in the beta-1 effect of cardiac stimulation, though not so much as with isoprenaline, and beta-2 effects of peripheral vasodilatation and hypotension, skeletal muscle tremor, and uterine muscle relaxation. Metabolic effects such as hyperinsulinemia and hyperglycemia also may occur, although it is not known whether these effects are mediated by beta-1 or beta-2 receptors. The serum potassium levels have a tendency to fall.