Understanding Drugs and Asthma

Drugs and Asthma

• Asthma involves the narrowing and inflammation of airways, leading to breathing difficulties.
• Different drugs target different aspects of asthma, including inflammation, bronchoconstriction, and mediator release.

Asthma

• Asthma involves airways that become narrowed and inflamed.
• The diagram shows normal airways, asthmatic airways during attack, and relaxed smooth muscles in a healthy state.
• Air becomes trapped in the alveoli and smooth muscles tighten during an attack.

Drug Treatment of Asthma

• Intermittent Reliever Therapy: Short-acting β2-adrenoceptor agonists (SABA) are used for rapid relief.
• Regular Preventer (Maintenance) Therapy: Low-dose inhaled corticosteroids are used regularly for long-term control, alongside other options.
• Initial Add-In Therapy: Leukotriene Receptor Antagonists (oral) and long-acting β2-adrenoceptor agonists (LABA) can be added to the above for particular cases.
• Additional Controller Therapy: Long-acting muscarinic antagonists (LAMA) and theophylline can be used in some scenarios.
• Continuous corticosteroid therapy: Prednisolone is an example of an oral continuous corticosteroid.

Inhalers, Spacers and Nebulisers

• MDI spacers help improve delivery of medication.
• Spacers reduce the amount of medication that's deposited in the mouth and throat.
• Spacers help improve medication delivery to the lungs.

Short-acting β2-adrenoceptor agonists (SABA)

• Examples include salbutamol and terbutaline.
• These drugs act on β2 receptors in the lungs.
• They cause smooth muscle relaxation, widening airways .

SABA – Mechanism of Action

• Salbutamol and Terbutaline bind to β2-adrenoceptors on airway smooth muscle cells.
• This triggers a cascade of intracellular events that lead to smooth muscle relaxation.
• Resulting in bronchodilation.

SABA - Metered Dose Aerosol

• The medication is delivered via inhaler, as a pressurized suspension, with propellant.
• Propellants are hydrofluoroalkanes, not CFCs.
• Mechanisms: The drug dilates bronchioles, promotes immediate relief, has a duration of 3-5 hours, and reduces mediator release from mast cells.
• In addition, these may inhibit TNF-alpha and increase mucus clearance.

Inhaler vs Spacer

• Using a spacer with an inhaler improves deposition in the lungs and reduces oropharyngeal deposition.
• The correct technique for using a metered-dose inhaler with a spacer is demonstrated.

Breath-activated Inhalers

• Different types of breath-activated inhalers are discussed, including Autohalers, Accuhalers, Turbohalers, and Diskhalers.
• These inhalers deliver medication as dry powder.

SABA - Adverse Effects

• Side effects include tachycardia, hypokalaemia, tremor, and tolerance.
• Genetic polymorphisms can influence the response to the treatment.

Regular Preventer (Maintenance) Therapy

• Treatment involves a short-acting β2 agonist as needed, and a low-dose inhaled corticosteroid as a component of the preventative therapy.
• Treatment is scaled accordingly if symptoms are more frequent.

Inhaled Corticosteroids

• Types include beclometasone dipropionate, fluticasone, and budesonide.
• These reduce inflammation in the airways.

Inhaled steroids

• Inhaled steroids have a slow onset of action (3-7 days).
• They are not bronchodilators, offering no immediate relief.
• Oral candidiasis is a potential side effect.
• The amount absorbed systemically can be reduced by using a spacer.

Step 3 Initial Add-In Therapy

• This involves adding a leukotriene receptor antagonist (oral) and a long-acting β2-adrenoceptor agonist (inhaled LABA) to the existing preventative treatment.

A. An ORAL asthma agent - montelukast

• Montelukast is an oral leukotriene receptor antagonist.
• Reduces inflammation and bronchoconstriction.

Leukotrienes

• Leukotrienes are inflammatory mediators.
• Blockade/inhibition of leukotrienes provides relief.

Montelukast – A Leukotriene Receptor Antagonist

• Montelukast is a cysLT1 receptor antagonist.
• This drug reduces inflammation, including reduced airflow obstruction, bronchoconstriction, and inflammatory cell infiltration, in the airways.
• Common side effects include gastrointestinal issues, skin reactions, and upper respiratory tract infection.
• Potential for neuropsychiatric risk should be considered

B. Long acting β2-adrenoceptor agonists (LABA)

• Include formoterol and salmeterol.
• Long-term control of asthma symptoms.

Maintenance and Reliever Therapy (MART)

• Combines inhaled corticosteroids with LABAs for combination therapy.

4. Additional Controller Therapies

• Additional controllers may include long-acting muscarinic antagonists (LAMAs) and theophylline.
• Theophylline is taken orally.

B. Long-acting muscarinic receptor antagonist (LAMA)

• This drug (Tiotropium) is a long-acting muscarinic receptor antagonist delivered via inhaler to reduce bronchoconstriction.
• Reduces inflammation and bronchoconstriction.

Theophylline

• It is a bronchodilator that relaxes airway smooth muscle and has other beneficial effects, given orally.
• It is administered twice daily.

Step 5: Continuous corticosteroid (oral)

• Specialist therapy involves oral prednisolone.
• Prednisolone is an anti-inflammatory and immunosuppressant.

Prednisolone

• Prednisolone is an oral corticosteroid that blocks the synthesis of inflammatory substances, like prostaglandins and leukotrienes in the airways (with resulting anti-inflammatory and immunosuppressant effects).
• It reduces inflammation and the immune response.
• Potential side effects include adrenal suppression, requiring careful monitoring and gradual tapering of the dose.

Adverse Effects : Glucocorticoids

• Possible side effects of glucocorticoids include euphoria in some, thin arms, legs and muscle wasting, buffalo hump, increased abdominal fat, cataracts, skin thinning and easy bruising, and more.
• Possible side effects include osteoporosis, hyperglycaemia, negative nitrogen balance, increased appetite, increased susceptibility to infection and obesity.

Adrenal Suppression

• Sudden withdrawal of prednisolone can cause adrenal suppression.
• Patients should be monitored and slowly taper off the drug.

Severe Asthma and The Eosinophil

• Severe asthma is characterized by frequent attacks and/or a need for oral steroids.
• Eosinophils are immune cells that play a role in asthma inflammation.

Interleukin IL-5 Inhibitors

• These drugs block the action of Interleukin-5 (IL-5), which is important for eosinophil activation/recruitment.
• Includes monoclonal antibodies like Nucala (mepolizumab) which is used for subcutaneous injection every 4 weeks.

Major drugs to remember for the treatment of Asthma

• Salbutamol, Beclometasone, Montelukast, Salmeterol, Tiotropium, Theophylline, Prednisolone, and Mepolizumab are major drugs to treat asthma.

Summary: Drug Treatment of Asthma

• Short-acting β2-agonists (SABA) for rapid relief.
• Regular preventers (maintenance) with inhaled corticosteroids for long-term control.
• Initial add-ins such as Leukotriene receptor antagonists or long-acting β2-agonists (LABAs) are added according to specific cases.
• Additional controller therapies such as long-acting muscarinic antagonists(LAMAs) and theophylline may be used in specific cases.
• Continuous corticosteroid therapy with Prednisolone may be considered under specialist care.