Week 14 Pharmacology - Respiratory Drugs Flashcards
What are the major categories of drugs used in the treatment of asthma? (Short term)
Sympathomimetics
Anti-muscarinics
Methylxanthine agents
What are the major categories of drugs used in the treatment of asthma? (Long term)
LABA
Corticosteroids
Leukotriene pathway inhibitors (montelukast)
What is the mechanism of action of adrenergic agonists in management of asthma?
Mediated through B2 receptors: agonist bind and cause airway smooth muscle relaxation (adenylyl cyclase, increased cAMP levels) and inhibit release of bronchoconstrictive agents from mast cells
Describe pharmokinetics of salbutamol:
A: Inhaled, 10% reaches bronchial tree (spacer > neb with adequate respiratory effort)
D: Maximal within 15 mins, duration 3-4 hours, crosses placenta
M: hepatic metabolism
E: 30% unchanged in urine, remained in faeces and metabolites in urine
What are adverse effects of salbutamol?
Hypotension (vasodilation)
Hypokalaemia (stimulation of Na+/K+ ATPase pump)
Tremor
Tachycardia
Lactic acidosis
What is the duration of action of LABA salmeterol or formoterol?
12hr duration of action
Highly lipid soluble, therefore large Vd and T/12
What is the mechanism of ipratropium?
Muscarinic antagonist –> competitively inhibits ACh at M3 muscarinic receptors on bronchial smooth muscle
**Main action is to antagonise vagal input to the bronchial smooth muscle, reducing bronchoconstriction and mucus production
Describe pharmacokinetics of ipratropium:
A: poor systemic absorption when inhaled, 5% bioavailability
D: Doesn’t cross BBB, onset 3-5 mins, duration 4-6 hours
M: inactive metabolites
E: 50/50 urine and faeces
What are LAMA and their duration of action?
Tiotropium: 24 hours, OD dosing
Aclidinium: 12 hrs, BD dosing
What are two common types of methylanthines?
Theophylline
Caffeine
What is the mechanism of action of theophylline?
PDE inhibition, therefore decreased metabolism of cAMP –> increased cAMP availability, leading to bronchodilation (main mechanism)
Also inhibits adenosine receptor, and can affect transcription of inflammatory genes to promote anti-inflammatory response
What are the pharmacokinetics of theophylline?
A: Good oral absorption
D: Vd 0.5L/kg
M: Liver: initially first order/concentration dependent, but becomes zero order when saturated
E: Metabolites excreted in urine
What are the pharmacodynamic effects of theophylline? (Think caffeine!)
Resp: bronchodilation, inhibition off antigen induced histamine release
CNS: cortical alertness, nervousness, tremor
CVS: positive chronotropic, inotropic, therefore increased CO
Renal: diuresis, increased GFR
What is the major drawback that limits theophylline usage in clinical practice?
Narrow therapeutic window, therefore serum monitoring required.
**N+V, arrhythmia, tremor, seizure, hypokalaemia, hyperglycaemia
What is sodium cromoglycate?
Mast cell degranulation inhibitor
Regular use can reduce symptom severity and regular bronchodilator medications, but no intrinsic bronchodilator activity itself
What is the mechanism of inhaled corticosteroids?
Broad anti-inflammatory effect through inhibition of pro-inflammatory cytokine production mediated by downregulation of gene transcription –> reduce bronchial hyperactivity and reduce frequency of asthma exacerbations, potentiate action of B-agonists
What are the pharmacokinetics of corticosteroids?
A: Usually PO in acute exacerbations, 70% bioavailability, first pass metabolism
D: Wide distribution
M: Liver
As per steroid use for other purposes, what are the adverse effects?
Osteoporosis
Adrenal insufficiency
Immunosuppression
Cataracts
What are the benefits, and the adverse effects of ICS?
Benefits: little systemic absorption, therefore limited chronic steroid effect
Adverse: oral candidiasis
What is the mechanism of action of leukotriene inhibitors (montelukast)?
- Inhibition of 5-lipo-oxygenase (preventing leukotriene synthesis from arachidonic acid
- Inhibition of LTD4 binding to its receptor, preventing bronchoconstriction, bronchial reactivity, mucosal oedema
What is the main clinical utility of montelukast?
Reduction of frequency of asthma exacerbations and improved symptom control in long term management, approved >1 yr old
Particularly beneficial in NSAID induced and exercise induced asthma.
(NSAIDs shunt AA pathway to leukotriene production)
What is the role of ketamine in asthma?
NMDA receptor antagonist
Causes transient hypoventilation, hypercapnia, bronchial smooth muscle relaxation
What is the theory as to the efficacy of heliox?
Combination of helium + oxygen (usually 80/20 or 70/30)
Density of gas is reduced, improving laminar flow and oxygen delivery to acinus.
Can be used in lower airway (asthma, COPD, bronchiolitis, bronchiectasis) as well as tracheal obstruction (croup, epiglottitis, FB, tumour)
