PPT Flashcards
Describe the Strategies for Pharmacology of Asthma
- Promote Bronchodilation directly - beta2-adrenoreceptor agonists, Anti-muscarinics, Methylxanthines
- Reduce Tissue Inflammation and Allergy Triggers - Corticosteroids, Leukotriene Receptor Antagonists
O SHIT (acronym)
- Useful acronym for Severe Acute Asthma Treatment
- O - Oxygen
- S - Salbutamol (beta-2 Agonist Class)
- H - Hydrocortisone (Corticosteroid)
- I - Ipratropium (Anti-muscarinic)
- T - Theophylline (Metyhlxanthine)
Describe Normal Nervous System Involvement in Airway Regulation
- Sympathetic NS - Mostly via adrenergic nerve fibres and noradrenaline - Drives BronchoDILATION
- Parasympathetic NS - Mostly via cholinergic nerve fibres and acetylcholine - Drives BronchoCONSTRICTION
Define Bronchospasm
Tightening of muscles that line the bronchi in the lungs
Describe the Mechanism of Action Of Salbutamol
- Beta-2 agonist
- Binds to Beta-2 Adrenergic Receptor (normal ligand adrenaline&noradrenaline)
- Results in activation of cAMP and Increased Concentration within the smooth muscle cell. A small, diffusible intracellular mediator
- Activates PKA - Protein Kinase A enzyme, phosphorylates target molecules
- Result: Reduced activity of myosin light chain kinase; Promotes Dephosphorylation of Myosin Light Chain. + Reduced Cytoplasmic calcium (drives into storage vesicles) reduces smooth muscle contraction
- Overall: Reduces smooth muscle contraction
- Dilation of the airway
- More air enters the lung and reduces bronchospasm symptoms
What are the Cellular and Molecular Targets of Beta-2 Adrenoreceptor agonists
- Cellular Target - Bronchiolar Smooth Muscle Cells
- Molecular Target - Stimulation of Beta-2 Adrenergic Receptors
What are the side effects of Beta-2 Adrenoreceptor use?
- Tremor
- Tachycardia
- Cardiac Arrythmia
- Less profound when an inhaler is used
- As introducing cardiovascular stimulant
What Class of drug does Salbutamol belong to? What is it’s Mechanism of Action
- Short-acting
- Beta-2 Adrenoreceptor Agonist
- Stimulation of Beta-2 Adrenergic Receptors on Bronchiolar Smooth Muscle cells
What Class of drug does Terbutaline belong to? What is it’s Mechanism of Action
- Short-acting
- Beta-2 Adrenoreceptor Agonist
- Stimulation of Beta-2 Adrenergic Receptors on Bronchiolar Smooth Muscle cells
What Class of drug does Salmeterol belong to? What is it’s Mechanism of Action
- Long-acting
- Beta-2 Adrenoreceptor Agonist
- Stimulation of Beta-2 Adrenergic Receptors on Bronchiolar Smooth Muscle cells
What Class of drug does Formoterol belong to? What is it’s Mechanism of Action
- Long-acting
- Beta-2 Adrenoreceptor Agonist
- Stimulation of Beta-2 Adrenergic Receptors on Bronchiolar Smooth Muscle cells
Compare the Difference between Short-acting and Long-acting Beta-2 agonists
- Salbutamol (short-acting) binds directly to Beta2 adrenergic receptor
- Salmeterol (long-acting) enters plasma membrane and interacts with receptor active site via Membrane Translocation - Takes longer
- Formoterol (long-acting) - Diffuses into membrane proximal to receptor and interacts with active site as a depot
- Different in timescale and kinetics, precipitates longer or shorter stimulation responses
State the Methylxanthines
- Theophylline
- Aminophylline
What Class of drug does Theophylline belong to? What is it’s Mechanism of Action
- Methylxanthines
- Blockade of Phosphodiesterase (PDE enzymes) on Bronchiolar Smooth Muscle cells
What Class of drug does Aminophylline belong to? What is it’s Mechanism of Action
- Methylxanthines
- Blockade of Phosphodiesterase (PDE enzymes) on Bronchiolar Smooth Muscle cells
Explain the Mechanism of Action of Theophylline
- Methylxanthine
- Blockade of Phosphodiesterase (PDE) enzymes
- Subsequently sustains cAMP levels and promoting muscle relaxation (bronchodilation)
- Oral tablet/IV in Acute Asthma
Explain the Mechanism of Action of Aminophylline
- Methylxanthine
- Blockade of Phosphodiesterase (PDE) enzymes
- Subsequently sustains cAMP levels and promoting muscle relaxation (bronchodilation)
- Oral tablet/IV in Acute Asthma
Explain the Mechanism of Action of Methylxanthines
- Blockade of Phosphodiesterase (PDE) enzymes (usually breaks down cAMP)
- Subsequently sustains cAMP levels and promoting muscle relaxation (bronchodilation)
What are the side effects of Methylxanthines
- Very toxic cardiac & neurological side effects, monitoring of serum levels required
- Possible cardiac arrhythmias + seizures
- Usually used in emergencies
Explain the Mechanism of Action of Anti-Muscarinics
- Ipratropium (short-acting), Tiotropium (long-acting), Glycopyrronium (Long-acting)
- M3 Muscarinic Acetylcholine Receptor Antagonist on Bronchiolar Smooth Muscle Cells
- Inhibition of Phospholipase C enzymes (PLC), reducing IP3 Generation, reducing calcium release from intracellular stores into cytoplasm
- Reduced cytoplasmic calcium reduces smooth muscle contraction I/e promotes bronchodilation by suppressing bronchoconstriction
What are possible side effects of Anti-Muscarinics for Airway Diseases?
- Dry Mouth
- Constipation
- Urinary Retention
What are the Cellular and Molecular Targets of Methylxanthines
- Cellular - Bronchiolar Smooth Muscle cells
- Molecular - Phosphodiesterase Enzyme (PDE) Blockade
What are the Cellular and Molecular Targets of Anti-Muscarinics for Airway Diseases
- Cellular - Bronchiolar Smooth Muscle cells
- Molecular - Blockade of M3 Muscarinic Acetylcholine Receptors
What Class of drug does Ipratropium belong to? What is it’s Mechanism of Action
- Short-acting
- Anti-Muscarinic
- Blockade of M3 Muscarinic ACh Receptors on Bronchiolar Smooth Muscle Cells