Pharmacology : Asthma & COPD Flashcards
What are the physiological changes in an asthmatic patient?
- bronchial muscular spasm
- increased mucus secretion
- inflammation of airway
- swollen mucosa
- hyper inflation of alveoli leading to loss of elasticity and alveoli collapse
What are the 3 mediators involved in an asthma episode?
- Histamine ( edema, inflammation, smooth muscle spasm)
- Acetylcholine (bronchial constriction, bronchi secretion)
- Leukotrienes ( bronchial constriction, mucus secretion)
What are the phases of an asthma attack? Compare them.
Acute/ immediate phase vs Late phase.
Immediate phase
- mast cells (mononuclear cells) release
- bronchospasm
Late phase
- chemotaxins & chemokines from immediate phase trigger subsequent asthma response,
- infiltration of Th2 cells, monocytes and eosinophils
- airway inflammation/ airway hyper-reactivity
- bronchospasm, wheezing
What are the 2 ways of management aimed in asthma patients?
- Symptoms reliever (e.g. SABA )
- to relieve bronchoconstriction
- Symptoms controller (e.g. LABA )
- to reduce inflammation and prevent lung damage
What are the THREE main drug classes used in asthma?
- Bronchodilators
- Anti-inflammatory and Prophylactic drugs
- Drugs affecting LEUKOTRIENE synthesis and actions
What are the 3 general drugs used as bronchodilators?
- B2-adrenoceptor agonists
- Methylxanthine drugs
- Antimuscarinic/ muscarinic receptor antagonists
What are the 2 types of B2-adrenoceptor agonists?
- Long- acting B2-adrenoceptor agonists (LABA)
- >12 hours
- salmeterol, eformoterol, bambuterol
- protection against nocturnal asthma
- prescribed with steroids
- NOT for relieving acute symptoms - Short- acting B2-adrenoceptor agonists (SABA)
- up to 6 hours
- salbutamol, terbutaline, fenoterol
- relief for acute attack
- NOT for regular use
What are the SIDE EFFECTS and CONTRAINDICATIONS for B2-adrenoceptor agonists?
What are the downsides?
Side effect : tachycardia ( because B2 selectivity is only relative and not absolute, hence chances of stimulating B1- adrenoceptor in heart I.e. excitatory effect is present)
Other side effect is skeletal muscle tremor
Contraindication : Hypertensive patients (recall that beta blockers are used to treat hypertensive patients, thus canceling effects is not wanted)
Downside : only treats symptoms (bronchospasm), inflammation is still present.
Give an example of Methylxanthine as a bronchodilator. What are its properties and mechanisms of action?
Example : theophylline
Properties : weak bronchodilator & anti-inflammatory properties (prominent immunomodulator)
Mechanism of actions (Inhibit X3) :
- Inhibition of PDE4 I.e. phosphodiesterase enzymes
- Inhibit adenosine cell surface receptors
- Inhibit infiltration and activation of inflammatory cells in airways
What are the problems with Theophylline ( a Methylxanthine drug used as a bronchodilator) in asthma patients?
- narrow TI (therapeutic index) range : may cause CVS and CNS problems
- GI side effects in 1/3 patients
- extensive p450 metabolism which is a source of many interactions
Muscarinic antagonists or antimuscarinic agents are also very effective bronchodilators.
Give an example of this drug.
Describe the mechanism and side effects of antimuscarinic agents.
Example : Ipratroprium bromide (atrovent) & Tiotropium (long- acting analog)
Mechanism : competitive inhibition of Ach at M3 receptors in the lungs > bronchodilation & decrease mucus secretion
Side effects : atropine-like effects at high doses I.e. dry mouth, unrinary retention, mydriasis
What are the examples of corticosteroids (anti-inflammatory drugs) used in asthma cases?
Prednisolone, Budesonide, Beclomethasone.
Describe the mechanism of action for corticosteroids.
Has anti-inflammatory and immunosuppressant effects, relaxes airway indirectly.
- Inhibits infiltration of inflammatory cells such as mast cells, eosinophils and lymphocytes.
- Inhibits arachidonic acid synthesis by phospholipase A2;
- causes COX-2 blockade, thus decreasing leukotriene production ( reducing hyper-responsiveness and inflammation).
- Increase responsiveness of B2-adrenoceptors in airways.
What are the side- effects of corticosteroids?
- Osteoporosis in children
- Oropharyngeal candidiasis (inhalation)
- Systemic effects of adrenal insufficiency (oral)
- Poor compliance due to ‘steroid-phobia’
What are Cromolyn and Nedocromil (anti-inflammatory drugs) used for?
For asthma cases (not bronchodilators) as mast- cell stabilizers.
They are found to prevent release of mediators.
Proposed mechanism : alter chloride channels function in cell membrane, thus inactivating mast cells.
Less effective than corticosteroids, used in ‘steroid phobia’ patients as prophylactic drugs, useful in exercise-induced and specific allergen induced asthma.
