Lecture 10- Drugs Affecting The Respiratory System; Asthma, COPD, Cough Flashcards
Asthma
Chronic inflammatory disorder of airways= results in airway obstruction in response to external stimuli
Symptoms;
-acute bronchoconstriction (immediate)
-shortness of breath
-chest tightness
-wheezing
-rapid respiration
-cough
^can happen each time airways are irritated
Features of asthma
*airway inflammation;
-swelling & thick mucus production
*bronchospasm;
-constriction of the muscles around the airways= airways become narrow
*airway hyper-reactivity; abnormal sensitivity of the airways to wide range of external stimuli; pollen, cold air + tobacco smoke
Pathogenesis of asthma
*Important mediators involved;
-leukotriene B4, cysteinyl leukotrienes (C4 + D4), interleukins (IL4,5+13) & tissue damaging eosinophil proteins
*Immediate phase of the asthmatic attack;
-occurs abruptly, caused by a spasm of the bronchial smooth tissue + allergen reaction with mast cell-fixed IgE= release of spasmogens; histamine + leukotriene
*Late phase of the asthmatic attack;
-progressing inflammatory reaction; occurred during the immediate phase
-inflammatory cells= activated eosinophils = release cysteinyl leukotrienes
Drugs used to treat asthma
*bronchodilators;
-B2- adrenoceptor agonists;
= salbutamol, salmeterol + formoterol = inhalation
*Xanthines;
= theophylline (formulated as aminophylline)
*Cysteinyl leukotriene receptor antagonists;
= montelukast + zafirlukast
*Muscarinic receptor antagonists;
= ipratropium
*Anti-inflammatory steroids (corticosteroids)
= beclomethasone, budesonide + fluticasone
B2-adrenoceptor agonists
-inhaled agonists with B2 activity= choice for mild asthma
^dilate the bronchi by a direct action of the B2 adrenoceptors on the smooth muscle
-relax bronchial muscle regardless of which spasmogens are involved
-given by inhalation of aerosol powder/ nebulised solution
-metered dose inhaler= used for aerosol preps
B2-adrenoceptor agonists
*short-acting agents= salbutamol + terbutaline
-given by inhalation, max effect occurs within 30 mins + duration of action is 3-5 hours, prn to control symptoms
*longer-acting agents= salmeterol + formoterol
-given by inhalation, duration of action is 8-12 hours, given regularly; twice daily
-slow onsets of action + should not be used for quick relief
B2-adrenoceptor agonists
Unwanted effects;
-results from systemic absorption, tremor + tachycardia
Clinical use as bronchodilators;
-short-acting drugs= prevent/treat wheeze in patients with reversible obstructive airways disease
-long-acting drugs= prevent bronchospasm in patients that require long-term bronchodilator therapy
Xanthines-theophylline
-used as theophylline ethylenediamine (aminophylline)
-bronchodilator= cause side effects like; tachycardia, agitation, seizures than the B2-adrenoceptor agonists
-less favourable risk- been replaced with B2-AA
-relaxant effect on smooth muscle= attributed to inhibition of the phosphodiesterase isoenzymes with resultant increase in cAMP
Cysteinyl leukotriene receptor antagonists
LT, B4, LTC4, LTD4 + LTE4= products of the arachidonic acid metabolism (slide 15)
-constrict bronchiolar smooth muscle
-lukasts- montelukast + zafirlukast= selective, reversible inhibitors of cysteinyl leukotriene-1 receptor
^relax the airways in mild asthma but are less effective than salbutamol
-action is additive with B2-adrenoceptor agonists
Muscarinic receptor antagonists
-anticholinergic agents= less effective than B2-AA
^block the vagally mediated contraction of airway smooth muscle + mucus secretion
*ipratropium = useful in patients who are unable to tolerate B2-AA
^has a slow onset of action + nearly free of side effects
^given by aerosol inhalation; nitrogen compound, highly polar + not well absorbed into the circulation & does not have much action at Muscarinic receptors
Anti-inflammatory steroids (corticosteroids)
*beclomethasone
*budesonide
*fluticasone
Anti-inflammatory steroids (corticosteroids)
-first choice drugs for persistent asthma (mild, moderate or severe)
-prevent the progression of chronic asthma + are effective in acute severe asthma
-directly target underlying airway inflammation by decreasing inflammatory cascade, reversing mucosal oedema, decreasing the permeability of capillaries + inhibiting the release of leukotrienes
-after several months of use= reduce the hyperresponsiveness of the airway smooth muscle to a variety of stimuli
Corticosteroids
-adverse effects of inhaled steroids;
*oropharyngeal candidiasis can occur
*sore throat and croaky voice
*regular high doses= can produce some adrenal suppression
Chronic obstructive pulmonary disease (COPD)
-chronic, irreversible obstruction of airflow
*smoking= major risk factor
-linked to the progressive decline of lung function
Short-acting drugs;
= ipratropium + salbutamol
Long acting drugs;
= tiotropium, salmeterol + formoterol
-theophylline= can be given by mouth
-long term oxygen therapy= at home prolongs life in patient with severe disease
Cough
-defence mechanism of the respiratory system in response to irritants
*productive cough= clear the respiratory airways of the irritant + excess secretions
-defence reflex against an underlying bacterial infection = should not be suppressed
*non-productive (dry) cough= should be suppressed
-mucus settles lower in airways of lungs= result of an infection/respiratory disease
