12 Respiratory system Flashcards
(40 cards)
12.01 β2-RECEPTOR AGONISTS
Long-acting: salmeterol, formoterol, etc. - actions
selective β2 agonists
bronchodilatation - a physiological antagonist of spasmogenic mediators
minimal action on heart: ↑rate and force
12.01 β2-RECEPTOR AGONISTS
Long-acting: salmeterol, formoterol, etc. - MOA
↓calcium-mediated contraction in bronchioles
↑cAMP which activates protein kinase A (PKA)
PKA inhibits myosin light chain kinase - the mediator of contraction
12.01 β2-RECEPTOR AGONISTS
Long-acting: salmeterol, formoterol, etc. - abs/distrib/elim
by regular inhalation for chronic asthma
salmeterol: slower onset and long-acting (8-12h) when compared to salbutamol (3-5h)
12.01 β2-RECEPTOR AGONISTS
Long-acting: salmeterol, formoterol, etc. - clinical use
asthma and obstructive airways disease (main use)
long-acting compounds are typically used together with inhaled corticosteroids for nocturnal asthma, exercise-induced asthma and long-term control
12.01 β2-RECEPTOR AGONISTS
Long-acting: salmeterol, formoterol, etc. - adverse effects
tremors
tachycardia, sometimes dysrhythmias
nervousness
some peripheral dilatation
12.02 XANTHINES
Theophylline (similar: roflumilast, aminophylline = theophylline ethylenediamine) - actions
bronchodilatation
also stimulates CNS and CVS
12.02 XANTHINES
Theophylline (similar: roflumilast, aminophylline = theophylline ethylenediamine) - MOA
inhibits phosphodiesterase (PDE4) thus ↑cAMP (and ?cGMP), thus relaxing smooth muscle
inhibition of PDE4 in inflammatory cells can ↓mediator release
12.02 XANTHINES
Theophylline (similar: roflumilast, aminophylline = theophylline ethylenediamine) - abs/distrib/elim
theophylline and roflumilast are given orally
aminophylline can be given IV
metabolised mainly by cytochrome P450
plasma concentrations: ↑by liver disease, cardiac failure and viral infection; ↓by heavy drinking and smoking
plasma concentrations are affected by drug interaction: ↓by rifampicin, phenytoin and carbamazepine; ↑by erythromycin, diltiazem, fluconazole and caffeine
12.02 XANTHINES
Theophylline (similar: roflumilast, aminophylline = theophylline ethylenediamine) - clinical use
theophylline is a fourth-line drug for chronic asthma not adequately controlled by other agents
aminophylline IV is used for severe acute asthma
roflumilast is used as an add-on to bronchodilators for severe COPD
12.02 XANTHINES
Theophylline (similar: roflumilast, aminophylline = theophylline ethylenediamine) - adverse effects
GIT disturbances, tachycardia, anxiety, insomnia
high plasma concentrations of theophylline can cause serious dysrhythmias or seizures, and should be monitored
12.03 LEUKOTRIENE ANTAGONISTS
Montelukast (similar: zafirlukast) - actions
reverse bronchoconstriction
relax airway smooth muscle in mild asthma
12.03 LEUKOTRIENE ANTAGONISTS
Montelukast (similar: zafirlukast) - MOA
the drug is an antagonist at the cysteinyl leukotriene receptor (CysLT1) on which the bronchospasmic mediators LTC4, LTD4 and LTE4 act
it can ↓both the early- and late-phase responses to the inhaled allergen
12.03 LEUKOTRIENE ANTAGONISTS
Montelukast (similar: zafirlukast) - abs/distrib/elim
given orally
metabolised in the liver through cytochrome P450 2C8 and excreted mainly in bile
half-life 3-5h
12.03 LEUKOTRIENE ANTAGONISTS
Montelukast (similar: zafirlukast) - clinical use
a third-line drug for asthma
used as an adjunct to inhaled corticosteroids and long-acting β2 agonists
effective in aspirin-induced asthma and exercise-induced asthma
12.03 LEUKOTRIENE ANTAGONISTS
Montelukast (similar: zafirlukast) - adverse effects
headache
abdominal pain
12.04 INHALED MUSCARINIC ANTAGONISTS
Short-acting: ipratropium; long-acting: tiotropium, aclidinium, umeclidinium, glycopyrronium - actions
bronchodilatation by inhibiting acetylcholine-mediated bronchoconstriction and mucus secretion
no effect on the late phase
12.04 INHALED MUSCARINIC ANTAGONISTS
Short-acting: ipratropium; long-acting: tiotropium, aclidinium, umeclidinium, glycopyrronium - MOA
competitively antagonises acetylcholine action on muscarinic receptors
12.04 INHALED MUSCARINIC ANTAGONISTS
Short-acting: ipratropium; long-acting: tiotropium, aclidinium, umeclidinium, glycopyrronium - abs/distrib/elim
given by inhalation
ipratropium lasts 3-5h
long-acting agents last 12-24h
12.04 INHALED MUSCARINIC ANTAGONISTS
Short-acting: ipratropium; long-acting: tiotropium, aclidinium, umeclidinium, glycopyrronium - clinical use
for chronic asthma as an adjunct to long-acting β2 agonists and corticosteroids
for COPD
nebulised ipratropium is used in the emergency management of asthma
12.04 INHALED MUSCARINIC ANTAGONISTS
Short-acting: ipratropium; long-acting: tiotropium, aclidinium, umeclidinium, glycopyrronium - adverse effects
urinary retention, dry mouth, constipation, pharyngitis
12.05 INHALED GLUCOCORTICOIDS
Beclometasone, budesonide, fluticasone, etc. - actions
reduce hyper-reactivity and decrease the inflammatory delayed phase
no effect on the immediate phase
12.05 INHALED GLUCOCORTICOIDS
Beclometasone, budesonide, fluticasone, etc. - MOA
reduce the activation of inflammatory cells and the release of mediators, especially cytokines
12.05 INHALED GLUCOCORTICOIDS
Beclometasone, budesonide, fluticasone, etc. - abs/distrib/elim
given by inhalation with metered dose inhaler
the full action takes days to occur
often formulated together with long-acting β2 agonists in combined inhalers
12.05 INHALED GLUCOCORTICOIDS
Beclometasone, budesonide, fluticasone, etc. - clinical use
added to bronchodilator therapy if this is inadequate alone
an IV glucocorticoid (e.g. hydrocortisone) is life-saving in acute severe asthma (status asthmaticus)
