Respiratory drugs-Surag Khadka

Learning outcomes

• Classes of drugs

• MoA of the following• Beta-2 agonists

• Anti-cholinergics

• Leukotriene antagonists

• Methylxanthines

• Steroids

• Corelate MoA with pathophysiology

Asthma drugs

• Smooth muscle dysfunction Rx:• Beta-2 agonists

• Anti-cholinergics

• Methylxanthines

• Leukotriene antagonists

• Airway inflammation Rx:• Glucocorticoids

• Mast cell stabilisers

• Airway remodelling Rx: ?????

Drugs to treat asthma

Chronic Asthma (BTS guidelines)

• SABA

• + Inhaled steroid

• + LABA (Consider increasing inhaled steroid if that doesn’t work)

• + Leukotrine antagonist (Consider further increasing inhaled steroid dose)

• + Daily steroid TABLET

Acute asthma management

• Oxygen

• Beta-2 bronchodilators

• Glucocorticoids

• Ipratropium

• Magnesium Sulphate

• IV aminophylline

• ABx

COPD management

• Stop smoking!

• Bronchodilator therapy (SABA/SAAC)

• Combination therapy (LABA + inhaled steroids + LAAC)

• Oral theophylline

• Home O2

Mechanism of Actions

• Bronchodilators• Beta-2-agonists

• Anti-cholinergics

• Methylxanthines

• Leukotriene receptor antagonists

• Anti-inflammatory agents• Glucocorticoids

• Mast cell stabilisers

Beta-2 agonist

• Binds with Adenyl Cyclase (AC) via GPCR

• AC leads to ATP cAMP

• cAMP activates PKA

• PKA phosphorylates MCLK leading to its deactivation

• This leads to ↓smooth muscle contraction

Beta-2 agonist desensitisation

• ↑SABA/LABA

• ↑ AC

• ↑ ATPcAMP

• ↑ cAMP= ↑PDE

• ↑PDE = breakdown of cAMP

• Side effects:• Tremor, Tachycardia, Arrythmia

• Headache

• Hypokalaemia

SABA v LABA

Anti-cholinergics

• Blocks M3 receptor

• ↓PLC

• ↓Calcium release from ER

• ↓ Smooth muscle contraction

• Bronchodilation

• Side effects: • Dry Mouth,

• Nausea, Headache, Cough

• Bronchospasm (Paradoxical)

Methylxanthines

• Eg: Theophylline, Aminophylline

• Full mechanism NOT clear

• Thought to inhibit PDE ↑ cAMP Bronchodilation

• Side effects: Insomnia, Vomitting, Cardiac arrhythmias, seizures

Leukotriene receptor antagonists

• Leukotriene Airway inflammation and bronchospasm

• Leukotreine receptor antagonists Prevents this

• Used as a preventer

• Side effects:• Abdominal Pain

• Headache, Thirst and restlessness

Glucocorticoids

• Activates GR interaction with nuclear DNA Influences gene expression

• Inhibition of pro-inflammatory products

• Expression of anti-inflammatory products

• Side effects:• Think of Cushings

Any questions?