respiratory drugs -surag khadka. learning outcomes classes of drugs moa of the following beta-2...
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Respiratory drugs-Surag Khadka
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Learning outcomes
• Classes of drugs
• MoA of the following• Beta-2 agonists
• Anti-cholinergics
• Leukotriene antagonists
• Methylxanthines
• Steroids
• Corelate MoA with pathophysiology
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Asthma drugs
• Smooth muscle dysfunction Rx:• Beta-2 agonists
• Anti-cholinergics
• Methylxanthines
• Leukotriene antagonists
• Airway inflammation Rx:• Glucocorticoids
• Mast cell stabilisers
• Airway remodelling Rx: ?????
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Drugs to treat asthma
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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
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Acute asthma management
• Oxygen
• Beta-2 bronchodilators
• Glucocorticoids
• Ipratropium
• Magnesium Sulphate
• IV aminophylline
• ABx
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COPD management
• Stop smoking!
• Bronchodilator therapy (SABA/SAAC)
• Combination therapy (LABA + inhaled steroids + LAAC)
• Oral theophylline
• Home O2
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Mechanism of Actions
• Bronchodilators• Beta-2-agonists
• Anti-cholinergics
• Methylxanthines
• Leukotriene receptor antagonists
• Anti-inflammatory agents• Glucocorticoids
• Mast cell stabilisers
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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
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Beta-2 agonist desensitisation
• ↑SABA/LABA
• ↑ AC
• ↑ ATPcAMP
• ↑ cAMP= ↑PDE
• ↑PDE = breakdown of cAMP
• Side effects:• Tremor, Tachycardia, Arrythmia
• Headache
• Hypokalaemia
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SABA v LABA
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Anti-cholinergics
• Blocks M3 receptor
• ↓PLC
• ↓Calcium release from ER
• ↓ Smooth muscle contraction
• Bronchodilation
• Side effects: • Dry Mouth,
• Nausea, Headache, Cough
• Bronchospasm (Paradoxical)
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Methylxanthines
• Eg: Theophylline, Aminophylline
• Full mechanism NOT clear
• Thought to inhibit PDE ↑ cAMP Bronchodilation
• Side effects: Insomnia, Vomitting, Cardiac arrhythmias, seizures
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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
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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
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Any questions?