BRONCHIAL ASTHMA

LEARNING OBJECTIVES

• To know the commonly used drugs in bronchial asthma

• To understand the mechanism of action of the major classes of drugs used in bronchial asthma

• To know the adverse effects of these drugs

BRONCHIAL ASTHMA• Chronic inflammatory disease• Reversible episodes of airway obstruction• Due to hyperresponsiveness of tracheobronchial smooth muscle to various stimuli, resulting in :-Bronchospasm-Narrowing of airtubes-Mucosal edema-Increased bronchial mucus secretion and mucus plugging

Cardinal symptoms

• Breathlessness

• Wheezing

• Cough

• Chest tightness

Trigger factors for asthma

• Infection• Irritants (pollen, house dust mites, chemical etc.)• Pollutants• Exercise• Exposure to cold air• Psychogenic

Different types of asthma

• Acute asthma• Chronic asthma

• Extrinsic asthma• Intrinsic asthma

Status asthmaticus

Pathophysiology Inflammation underlying hyperactivity• Early reaction – Reversible airway obstruction• Late reaction – Worsening of disease

• Increased vagal discharge to bronchial muscle

Bronchoconstriction and increased mucus secretion

• Adenosine - bronchoconstriction

Approaches to treatment• Prevention of Ag-Ab reaction – avoidence of antigen• Suppression of inflammation and bronchial hyperactivity

– corticosteroids• Prevention of release of mediators – mast cell stabilizers• Antagonism of released mediators – LT antagonists• Blockade of constrictor neurotransmitter –

anticholinergics• Mimicking dilator neurotransmitter – sympathomimetics• Directly acting bronchodilators – methylxanthines

ClassificationA. Bronchodilatorsi. Non-selective sympathomimetics – Adrenaline,

ephedrine, isoprenalineii. Selective beta2 agonists - Salbutamol, terbutaline,

salmeterol, formoteroliii.Anticholinergics – Ipratropium bromide, atropine

methonitrateiv.Methylxanthines – Theophylline, aminophylline, choline

theophyllinate

B. Corticosteroidsi. Systemic – Oral: Prednisone Parenteral : Methylprednisolone,

hydrocortisoneii. Non- systemic – Inhalational : Beclomethasone,

fluticasone, budesonideC. Mast cell stabilizers – Nedocromil, ketotifen, sodium

cromoglycateD.Leukotrine (LT) modulatorsi. 5’- lipoxygenase inhibitors – Zileutonii. LT receptor antagonist – Zafirlukast, montelukast

Role of beta agonists in asthma

MOA 2 agonists have other beneficial effects including inhibition of mast cell-mediator release, prevention of microvascular leakage and airway edema, and enhanced mucocillary clearance. The inhibitor effects on mast cell actions suggest that 2 agonists may modify acute inflammation.

SympathomimeticsMode of administration• Inhalation – metered dose

inhaler, nebulizer, spinhaler, rotahaler, spray

• Oral• i.m. or i.v. injection

• Adrenaline – prompt but short-lasting action; rarely used because of adverse effects

• Isoprenaline – prompt and marked bronchodilatation; disadvantage – tachycardia

• Ephedrine – mild slowly developing bronchodilatation; used for mild to moderate asthma

• Salbutamol – inhaled drug – rapid onset, short duration of action; used for acute attack

A/E: tremors, tachycardia, palpitation, nervousness

• Terbutaline – can be used safely during pregnancy

• Salmeterol – slow onset of action, long acting; used for maintenance therapy and nocturnal asthma

• Formoterol – faster onset of action, long acting; used for acute attack and maintenance therapy

Limitations• Non-selective sympathomimetics – cardiac side effects

(β1 action) – not preferred in elderly or heart patients

• Long term use of salbutamol and terbutaline – downregulation of receptors – diminished responsiveness – worsening of disease

Anticholinergics• MOA• Atropine and ipratropium antagonize

the actions of Ach at parasympathetic, postganglionic, effector cell junctions by competing with Ach for M3 receptor sites.

• This antagonism of Ach results in airway smooth muscle relaxation and bronchodilation.

Anticholinergics• Mode of administration - inhalation• Slow onset of action – better suited for regular

prophylactic use • Indications –

– Asthmatic bronchitis– Psychogenic asthma

COPD Nebulized ipratropium + salbutamol – refractory asthma

Methylxanthines• MOA –i. Inhibition of phosphodiesterase – increased

cAMP and cGMP level ii. Blockade of adenosine receptors• Mode of administration - oral, i.m., i.v. , rectal

suppositories

Plasma therapeutic range – 5-20 µg/mlSide effects :• GIT: nausea, vomiting, gastritis, aggravation of

peptic ulcer• CVS: tachycardis, palpitation, arrhythmias,

hypotension• CNS: insomnia, headache, delirium,

restlessness, tremor• Diuresis, flushing• Rapid i.v. – syncope and sudden death

Methylxanthines x Sympathomimetics

potentiate the effects of sympathomimetics • Bronchodilatation – beneficial• Cardiac stimulation - harmful

CorticosteroidsMOA:• Decreases the synthesis of inflammatory mediators• Prevent recruitment, proliferation and activation of

leukocytesSystemic steroid therapy – • Severe chronic asthma• Status asthmaticus Inhaled steroids – Long term treatment of asthma

• Others Indications RhinitisNasal polyposisAdverse effects Inhaled steroids– drymouth, dysphonia, sore throat,

oropharyngeal candidiasis

Systemic steroids – mood changes, osteoporosis, hyperglycemia, hypertension, HPA axis suppression

• MOA – They block IgE-regulated calcium channels

essential for mast cell degranulation– Prevent the release of histamine and related

mediators.

Mast cell stabilizers

Mast cell stabilizers

Mode of administration - inhalation, oralIndications• Bronchial asthma• Allergic rhinitis – nasal spray• Allergic conjunctivitis – eye dropsAdverse effects - irritation, cough, dry mouth,

sedation, headache, rashes

Leukotriene modulators

IndicationsProphylactic treatment of mild to moderate

asthmaAdverse effectsHepatotoxicity, headache, GI distress, rashesZafirlukast – Churg-Strauss syndrome

Treatment of status asthmaticus• Humidified oxygen inhalation• Nebulized salbutamol+ ipratropium• Systemic steroids – hydrocortisone,prednisolone i.v.• IV fluids – correct dehydration• Potassium supplements – correct hypokalemia• Sodium bicarbonate – treat acidosis• Antibiotics – treat infection

Drugs contraindicated in bronchial asthma

• Beta blockers• Cholinergic drugs• NSAIDs ( expect paracetamol)

Recent advances

Omalizumab - anti IgE antibody