8. Management of Bronchial Asthma and Cough

Define cough and list some of its features .

• Protective reflex

• Expulsion of respiratory secretions or foreign particles from air passage

• Occurs due to stimulation of receptors in throat, respiratory passage/lungs

• Useful (productive)/useless (non-productive)

• Specific remedies (antibiotics)

• Symptom/non-specific treatment

List the drug classifications that are used to treat cough.

1. Expectorants/mucokinetics

2. Antitussives/cough center suppressants

3. Adjuvant antitussives

List the 2 categories of expectorants/mucokinetics.

1. Bronchial secretion enhancers

2. Mucolytics

List the 2 categories of antitussives/cough center suppressants.

1. Opioids

2. Antihistamines

Name the category of drugs that comes under adjuvant antitussives.

Bronchodilators

Expectorants/Mucokinetics

List bronchial secretions enhancers.

1. Vasaka

2. Guaiphenesin

3. Sodium citrate

4. Potassium citrate

5. Potassium iodide

6. Ammonium chloride

Expectorants/Mucokinetics

List mucolytics.

1. Bromhexine

2. Acetylcysteine

3. Ambroxol

Antitussives/Cough Center Suppressants

List opioids.

1. Codeine

2. Pholcodeine

3. Dextromethorphan

Antitussives/Cough Center Suppressants

List antihistamines.

1. Chlorpheniramine

2. Promethazine

3. Diphenhydramine

Adjuvant Antitussives

List bronchodilators.

1. Salbutamol

2. Terbutaline

3. Salmeterol

Expectorants/Mucokinetics

How do expectorants work?

Increase bronchial secretions or reduce its viscosity, facilitating its removal by coughing

Expectorants/Mucokinetics - Bronchial Secretion Enhancers

Where do Vasaka and Guaiphenesin come from and what do they do?

• Plants products

• Enhance bronchial secretions

Expectorants/Mucokinetics - Bronchial Secretion Enhancers

Are Vasaka and Guaiphenesin used alone or in combination?

In combination with antitussives/antihistamines

Expectorants/Mucokinetics - Mucolytics

Describe the mechanism of action of bromohexine.

• Potent mucolytic and mucokinetic

• Capable of inducing thin, copious bronchial secretions

• Breaks network of fibers in sputum

• Useful if mucus plugs are present

Expectorants/Mucokinetics - Mucolytics

When should bromohexine NOT be used?

Dry cough

Expectorants/Mucokinetics - Mucolytics

List the adverse effects of bromohexine.

1. Rhinorrhea

2. Lacrimation

3. Gastric irritation

Antitussives

Describe the mechanisms of antitussives.

• Act in CNS to raise threshold of cough center

• Act peripherally in respiratory tract to reduce tussal impulses

• Aim to control rather than eliminate cough

Antitussives

When should antitussives be used?

ONLY dry unproductive cough

Antitussives - Opioids

Describe codeine.

• Antitussive

• Opium alkaloid, like morphine

• More selective for cough center

• Suppresses cough for about 6 hours

• Abuse liability is low (but present)

• Other substitutes: pholcodeine, dihydrocodeine

Antitussives - Opioids

List the adverse effects of codeine.

1. Constipation

2. Respiratory depression (at high doses)

3. Drowsiness (at high doses)

Antitussives - Opioids

When is codeine contraindicated?

In asthmatics (worsening due to histamine release and build up of mucus)

Antitussives - Opioids

Describe dextromethorphan and its effectiveness.

Synthetic compound

As effective as codeine

Antitussives - Opioids

Describe noscapine and its mechanisms.

• Naturally occurring opium alkaloid

• Devoid of analgesic or dependence inducing properties

• Minimum constipating effects

• Popular cough suppressant

• Can release histamine, produce bronchoconstriction in asthmatics (hence, contraindicated)

Antitussives - Antihistamines

Describe the use of antihistamines.

• H₁ receptor antagonists

• Provide relief for cough due to antihistamine, sedative, and anticholinergic actions

• Added to antitussive/expectorant formulations

• Used for cough in respiratory allergic states

Adjuvant Antitussives - Bronchodilators

Describe what bronchodilators are used for.

• Relieve cough in bronchial hyper-reactive patients (bronchospasm can induce/aggravate cough)

• Improve effectiveness of cough in clearing secretions by increasing surface velocity of airflow during cough

• Used ONLY when bronchoconstriction is present

Describe asthma, its symptoms, and mechanisms.

• Hyper-responsiveness of tracheo-bronchial smooth muscles to a variety of stimuli

• Symptoms: dyspnoea, wheezing, cough

• Mast cells (lungs) and inflammatory cells release mediators like

  • histamine

  • TNF-α

  • prostaglandins

  • leukotriene

  • interleukins

• These mediators constrict bronchial smooth muscle, mucosal edema, produce viscid secretions, resulting in reversible airway obstruction

List the classifications of drugs to treat asthma.

1. Bronchodilators

2. Corticosteroids

3. Mast Cell Stabilizers

4. Leukotriene modulators

5. Anti-IgE antibody

List the categories of bronchodilators.

1. Selective β₂-agonists

2. Non-selective sympathomimetics

3. Anticholinergic

Bronchodilators

List selective β₂-agonists.

1. Salbutamol (short-acting)

2. Terbutaline

3. Salmeterol (long-acting)

Bronchodilators

List non-selective sympathomimetics.

1. Epinephrine

2. Ephedrine

3. Isoprenaline (non-selective action, use has been declined)

Bronchodilators

List anticholinergics.

1. Ipratropium

2. Tiotropium

List the categories of corticosteroids.

1. Inhalational

2. Systemic

Corticosteroids

List inhalational corticosteroids.

1. Beclomethasone

2. Fluticasone

3. Budesonide

Corticosteroids

List systemic (oral) corticosteroids.

1. Prednisolone

2. Hydrocortisone

3. Prednisone

List mast cell stabilizers.

1. Sodium cromoglycate

2. Nedocromil (reserved for prophylactic use in chronic/seasonal asthma; ineffective in acute conditions

List leukotriene modulators.

1. Montelukast

2. Zafirlukast

List the anti-IgE antibody.

Omalizumab (monoclonal antibody)

Bronchodilators

Describe salbutamol/albuterol and their mechanisms.

• Highly selective β₂ agonist; cardiac side effects less prominent

• Improves pulmonary function by relaxing bronchial smooth muscles, relieves asthmatic symptoms

• Do not control disease process

Bronchodilators

Briefly describe salbutamol and terbutaline and how they can be administered.

• Widely used

• Short-acting

• Oral/inhalational/SC/IM

• When inhaled, produce bronchodilation in 5 mins that lasts up to 2-4 hours

Bronchodilators

Describe the mechanism of action of salbutamol.

• Activates β₂ receptors present on airway smooth muscles; activates adenyl cyclase (AC), enhancing release of cAMP (relaxes smooth muscles)

• They relax airway smooth muscles, inhibit release of chemical mediators (bronchoconstricting) from mast cells

(PDE - phosphodiesterase)

Bronchodilators

List the adverse effects of salbutamol.

• Minimal when inhaled

• Oral:

  1. Tremors

  2. Tachycardia

  3. Restlessness

  4. Nervousness

  5. Ankle edema

  6. Throat irritation

• Continued use causes desensitization/down regulating of β₂ receptors (diminished responsiveness)

Bronchodilators

Describe theophylline.

• Used with β₂ agonists

• Narrow therapeutic angle = second choice in asthma

Bronchodilators

Describe the mechanism of theophylline. What is it used for?

• Inhibits phosphodiesterase (PDE); PDE III (airway smooth muscles) and IV (eosinophils and mast cells)

• Responsible for degradation of cAMP and cGMP

• cAMP/cGMP levels get elevated = bronchodilation

• Used in asthma, COPD, and dyspnea associated w/pulmonary edema that develops after congestive heart failure

Bronchodilators

List the adverse effects of theophylline.

Dose-dependent toxicity starts from upper part of therapeutic concentration range

• GI: nausea and vomiting

• CNS: agitation, tremors followed by seizure

• CVS: arrythmia

Corticosteroids

Describe corticosteroids and their mechanism of action.

• Powerful anti-inflammatory agents

• Inhaled corticosteroids with β₂ agonists are mainstay for chronic asthma

• Inhibit the release of mediators (leukotriene, prostaglandins), enhance β₂ receptor response

Leukotriene Inhibitors - Montelukast

Describe leukotriene inhibitors (LT) and their mechanisms of action.

• Powerful mediators of inflammation

• Stimulate bronchoconstriction, increase capillary permeability (leading to pulmonary edema), and stimulate mucus secretion

• Montelukast and zafirlukast competitively block the stimulatory effects of LT on LT-receptors

Leukotriene Inhibitors - Montelukast

List the uses and side effects of LT inhibitors.

• Prophylactic therapy of mild to moderate asthma as alternatives to inhaled corticosteroids

• Safe drugs, produces few side effects like headache and rashes

Leukotriene Inhibitors - Montelukast

How is montelukast administered?

• Once daily (advantage), 10mg (evening, usually)

• Safe in children