Bronchodilators Flashcards
Describe allergic asthma.
- Commonly seen in children
- Triggered by allergens which cause IgE production
- Exposure to antigen causes IgE binding
- Stimulation of mast cells to release chemical mediators e.g leukotrienes and histamines
Describe non-atopic asthma. PART 1
- Likely to occur in adults
- Usually caused by irritants - causative agent generally unknown
- Can be due to viral infection/aspirin sensitivity/sensitisation to specific chemicals
Describe non-atopic asthma. PART 2
- Stimulate sensory receptors and nerves in airways
- Increased eosinophil count/other inflammatory mediators normal
What are the main inflammatory changes in the airways?
- HYPER-RESPONSIVENESS - exaggerated bronchoconstriction at low doses of stimulus
- CHARACTERISED BY HYPERSENSITIVITY - normal response at low doses of stimulus
- CHARACTERISED BY HYPER-REACTIVITY - exaggerated response at normal doses
Describe the immediate and delayed phase of asthma.
- BRONCHOSPASM - caused by spasmogens and chemokines released from mast cells e.g leukotrienes
- DELAYED - influx and actication of inflammatory cells e.g PAF and leukotrienes causing mucus production and airway inflammation
- Can be reversed by salbutamol
Describe the arachadonic acid pathway.
- Phospholipase A2 released from plasma membrane and activates arachadonic acid.
- Cyclooxygenase produces prostaglandins causing bronchoconstriction
- 5-lipoxygenase produces leukotrienes - causing bronchoconstriction and mucus secretion
Describe the innervation of bronchial smooth muscle.
- Irritant receptors and C-fibres respond to extrinsic and intrinsic agents. Cause bronchoconstriction.
- PARASYMPATHETIC - M3 receptors - cause constriction
- NO SYMPATHETIC INNERVATION - circulating adrenaline acts on B2 receptors causing relaxation
Describe the mechanism of action of beta agonists with examples.
- Activates the Gs pathway
- Reduced release of bronchoconstricting agents from mast cells
- EXAMPLES - salbutamol, salmeterol and formoterol
Describe SABAs
- EXAMPLE - salbutamol
- Acute effect - onset of 5-30 min with relief for 4-6h
- Protects against various stimuli e.g exercise
- Used for acute exacerbations
- Preferred delivery - inhalation rather than systemic
Describe LABAs. PART 1
- EXAMPLES - salmeterol and formoterol
- Chemical analogue of salbutamol
- Long lipophilic side chain - anchors drug in lipid membrane
- Allows active portion of molecule to remain at receptor site
- Used in combination e.g with corticosteroids.
Describe LABAs. PART 2
- Provides bronchodilation for at least 12hrs
- Slow onset - not used in acute asthma attacks
What are the side effects of beta-2 agonists?
- Uncommon at normal doses
- At high doses - tachycardia, hyperglycaemia and skeletal muscle tremors
Describe muscarinic antagonists. PART 1
- EXAMPLE - ipratropium and tiotropium
- Second line drugs - used as an alternative
- Competitive antagonists for ACh at M3 receptors
- Relaxes bronchial smooth muscle
- Reduced mucus secretion
Describe muscarinic antagonists. PART 2
- No effect on delayed phase
- Not effective in asthma unless COPD also present
- Useful in patients not able to tolerate adrenergic agonists (eg patients with ischaemic heart disease/tachycardia)
Describe the mechanism of action of respiratory muscarinic receptor antagonists.
- Blocks the Gq pathway
Describes the pharmacokinetics of muscarinic receptor antagonists e.g ipratropium.
- Administered by inhalation
- Highly absorbed across respiratory epithelium
- 8% bioavailability (2% when orally) so high potency - less drug required to elicit response
- Onset following 30-60 minutes, relief for 4-6hrs
What are the side effects of muscarinic antagonists?
- Systemic anticholinergic side effects
- EXAMPLE: Tachycardia, nausea, blurred vision, dried mucuous membranes
Describe aminophylline.
- Second line drug
- 2:1 complex of theophylline and ethylenediamine
- Causes acute bronchodilation - may inhibit delayed phase
- Administered orally
- Narrow therapeutic window - CONSTANT MONITORING by titrate to desired dose
What is the mechanism of action of aminophylline?
- Inhibits PDE2
- Reduced breakdown of cAMP to AMP
- Smooth muscle relaxation
Describe the pharmacokinetics of aminophylline. PART 1
- Effects unpredictable. Not predicted by age, sex, body weight etc.
- Administered orally and IV
- 100% bioavailability orally - no first pass effect
- 3-5 half lives to reach steady state concentration
- Usually either a very large or very small dose given
Describe the pharmacokinetics of aminophylline. PART 2
- 40% bound to albumin
- Low Vd - 0.5litres per kg
- Half life is variable
- Usually loading dose of 10-20 mcg/ml used
- > 20mcg/ml - will cause high severity and frequency of adverse drug reactions
Describe the pharmacokinetics of aminophylline. PART 3
- Theopylline primarily eliminated by hepatic metabolism
- Hepatic impairment effects clearance by 50% - not used in hepatic failure
- 90% released as range of acids. 15-20% as 3-methylxanthine - active metabolite
- 10% of theophylline recovered as unchanged drug.
Describe the pharmacokinetics of aminophylline. PART 4
- No change in renal impairment in adults
- 50% reduction in clearance in neonates
What is the mechanism of action of montelukast?
- Leukotriene receptor antagonist
What are the side effects of aspirin?
- Ringing in ears
- Nausea, stomach pain, heartburn, vomiting
- Bloody vomit
- Rash
- Fast heartbeat
- Labored breathing, wheezing
What are the side effects of beta-blockers?
- Beta 1 blockers affect heart
- Beta 2 blockers affect lungs
