Pharmacology for Asthma & COPD Flashcards
1
Q
ANS regulates…
A
Bronchoconstriction/dilation
2
Q
Parasympathetic NS
A
- Bronchoconstriction and mucus secretion
- Site of action: bronchial smooth muscle and mucus glands
- MOA: ACh stimulates muscarinic receptors
3
Q
Sympathetic NS
A
- Bronchial dilation, mucus clearance, and mast cell stabilization to prevent degranulation
- Site of action: bronchial smooth muscle and mast cells
- MOA: NE stimulation of Beta-2 receptors
4
Q
Beta-2 Agonists
A
- Rapid Acting: Albuterol and levalbuterol
- Long-Acting: Salmeterol, Formoterol, Arformoterol, Indacterol, and Olodacterol
- Most B2-Selective: Salmeterol
- One a Day Dosing: Olodacterol, Indacterol
- Fastest Onset: Albuterol and Levalbuterol (2-3 minutes)
5
Q
Water/Lipid Solubility
A
- Hydrophilic: short duration, rapid onset, EX: Albuterol
- Amphilic: long duration, retained in lipid, rapid onset, EX: Formoterol
- Lipophilic: long duration, slow onset, slow diffusion, EX: Salmeterol
6
Q
B2 Receptor Cascade
A
B2 agonized ==> Activate Adenylyl cyclase (AC) ==> increases cAMP ==> bronchodilation and inhibit histamine release
7
Q
Beta 2 Agonist SE
A
- Result from B2 activation in extrapulmonary tissues, alpha/B1 stimulation, B2 desensitization
- Anxiety/restlessness - sympathetic stimulation
- Tremors - B2 activated in skeletal muscle
- Reflex tachycardia - B2 in blood vessels causing vasodilation
- Tolerance - B2 down-regulated from chronic use
8
Q
Muscarinic Antagonists
A
- Only glycopyrrolate (long acting): non-selective
- Tiotropium, aclindinium, umeclindinium (long acting)- slower dissociation from M3
- Ipratropium : short-acting
- Tiotropium and umeclindinium: one a day dosing
9
Q
M3>M2 Antagonism
A
- M2 being blocked allows for the release of ACh to go unchecked
- ACh can then activate M3 and cause bronchoconstriction (opposite of goal)
10
Q
Antagonizing M3
A
Block M3 ==> reduces release of intracellular calcium ==> reduces mucus secretion from goblet cell AND prevents bronchoconstriction
11
Q
Leukotriene Modifying Agents
A
- Inhibit leukotriene synthesis OR inhibit leukotriene receptors
- Zileuton: blocks 5-lipooxygenase which converts arachidonic acid converting to leukotriene A4
- Montelukast: blocks leukotriene D4 receptors
- Zafirlukast: blocks D4 & E4 receptors
- Leukotriene A4, C4, D4, and E4 go on to cause bronchoconstriction, mucus secretions, and eosinophil recruitment to lungs
12
Q
HPA Axis
A
- Hypothalmic-Pituatary-Adrenal
- Reacts to stress
- Hypothalamus reacts to stress and releases CRH
- CRH causes pituatary to release ACTH into blood stream
- Reacts with adrenal glands which release cortisol which then negatively feedbacks CRH
- Cortisol then helps increase glucose, breaks down fats, and decreases immune cell numbers per response (anti-inflammatory)
13
Q
Corticosteroid Therapy
A
- Mimics cortisol
- Affects inflammatory cells AND structural cells
- Decreases cell numbers and cytokine release: anti-inflammatory
- Structural cells: decrease leakage in endothelial cells, increases B2 receptors in airway smooth muscle, decreases mucus from mucus gland
- *Better for asthma since HDAC2 (beneficial target) is already reduced in COPD**
14
Q
ICS
A
- Minimal systemic SE
- Local SE: coughing, thrush, dysphonia
- Pneumonia (COPD)
15
Q
Corticosteroid Systemic SE
A
- HPA Axis Suppression (less cortisol secretion from desensitization from exogenous steroid use)
- Impaired growth and increased weight
- Decreased bone density
- Thinning skin
- Cataracts
- Glucose metabolism
- Cushing’s syndrome
Depends on amount of drug that enters circulation and bioavailability
