OIA2004 PHARMACOLOGY OF ASTHMA

Asthma pathophysiology

Airway obstruction from bronchoconstriction, inflammation, and mucus hypersecretion.

Therapeutic goals in asthma

Reduce intensity/frequency of symptoms and minimize activity limitation.

β2 agonists mechanism

Relax bronchial smooth muscle via β2-receptor activation → bronchodilation.

Short-acting β2 agonists (SABAs)

Rapid onset (5–30 min), relief lasts 4–6 hrs; used for acute symptom relief.

Examples of SABAs

Salbutamol (albuterol), levalbuterol, terbutaline (SC).

SABAs key points

No anti-inflammatory action; not for persistent asthma monotherapy.

SABA side effects

Tachycardia, insomnia , tremors, hyperglycemia, hypokalemia, hypomagnesemia (minimized by inhalation).

Long-acting β2 agonists (LABAs)

Salmeterol, formoterol; duration ≥12 hrs due to high lipid solubility.

LABAs caution

Not for acute attacks; must be combined with an anti-inflammatory (e.g. ICS).

LABA side effects

Same as SABAs: tremors, tachycardia, etc.

ICS role

Primary anti-inflammatory agents; cornerstone for persistent asthma control.

ICS examples

Beclomethasone, fluticasone, budesonide (not listed in doc, but relevant).

ICS + LABA combinations

Improves control in moderate/severe asthma (e.g. fluticasone + salmeterol).

Leukotrienes in asthma

Derived via 5-lipoxygenase; cause bronchoconstriction, mucus production, eosinophil recruitment.

Zileuton

5-lipoxygenase inhibitor — blocks LT synthesis.

Montelukast, zafirlukast

Cysteinyl leukotriene receptor antagonists — block LTD₄, LTE₄ effects.

Indications for LTRAs

Prevention and long-term control of asthma; not for acute relief.

Zafirlukast metabolism

Food impairs absorption; inhibits CYP enzymes

LTRAs side effects

Headache, dyspepsia, elevated liver enzymes (esp. zileuton).

LTRAs excretion

Zileuton → urine; montelukast & zafirlukast → bile.

Cromolyn mechanism

Prevents mast cell degranulation and histamine release — anti-inflammatory.

Cromolyn indications

Prophylaxis in mild persistent asthma; not for acute attacks.

Cromolyn disadvantages

Short duration, requires TDS dosing → poor adherence.

Cromolyn side effects

Cough, throat irritation, unpleasant taste.

Theophylline mechanism

Bronchodilation via PDE3 inhibition; immunomodulation via PDE4 inhibition.

Therapeutic use

Chronic asthma; rarely used due to side effect profile and need for monitoring.

Theophylline adverse effects

Nausea, vomiting, arrhythmias, seizures at high levels.

Clearance variations

↑ in children and smokers; ↓ in neonates, liver disease, elderly.

Therapeutic range

5–20 mg/L; toxicity >20 mg/L, seizures >40 mg/L.

TDM necessity

Essential due to narrow therapeutic window.

Metabolism site (Theophylline)

Liver; affected by drug interactions, smoking, hepatic function.

Factors affecting clearance

↑ by enzyme inducers, smoking; ↓ by hepatic disease, certain drugs.

Ipratropium mechanism

Blocks muscarinic receptors → prevents vagally-mediated bronchoconstriction and mucus secretion.

Ipratropium indications

Asthma (adjunct), COPD, intolerant to SABAs, used in ED settings with SABA.

Onset of ipratropium

Slower than SABAs — not suitable as sole rescue medication.

Anticholinergic side effects (Ipratropium)

Dry mouth (xerostomia), bitter taste.

All asthma patients

Must have a rescue inhaler (usually a SABA).

Controller medications

Required for persistent asthma to prevent inflammation and remodeling.

LABA monotherapy

Contraindicated due to risk of asthma-related death — always combine with ICS.

Non-pharmacologic adjuncts

Trigger avoidance, smoking cessation, vaccination (e.g. flu, pneumococcus).