drugs used in asthma by s.bohlooli, phd. asthma therapy short term relievers bronchodilators long...
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Drugs used in asthma
ByS.Bohlooli, PhD
Asthma therapy Short term
relievers Bronchodilators
Long term controllers Anti-inflammatory
agent Leukorienes
antagonist
Pathogenesis of asthma
Pharmacologic significance of lung innervation
Reach in Vagal innervation Post-synaptic M3 receptors Pre-synaptic M2 receptors
Spare noradrenergic innervation Role of Peptidergic neurons?
Basic pharmacology Sympathomimetic
agents Methylxanthine drugs Antimuscarinic drugs Corticosteroids Cromolyn &
Nedocromil Leukotriene pathway
inhibitors Anti-IgE monoclonal
antibodies
Calcium channel blockers
Nitric oxide donors Possible future
therapies
Sympathomimetic agents
Relaxation of airway smooth muscle
Inhibition of release of bronchoconstricting substances from mast cells
Increasing mucociliary transport Inhibition of microvascular leakage
Some sympathomimetic agents
Albuterol Terbutaline Metaproterenol Pirbuterol Salmeterol Formoterol
the disposition of inhaled drugs
Methylxanthine drugs: chemistry
Methylxanthine drugs: mechanism of action
Inhibition of several family of phophodiesterases Increased intracellular level of cAMP
and cGMP Bronchodilation Decreased release of mediators from
mast cells
Inhibition of adenosine receptors
Methylxanthine drugs: Organ effects
CNS: alertness, deferral of fatigue, nervousness, insomnia, convulsions
Cardiovascular: cardiac stimulation Gastrointestinal tract: secretion of acid
and enzymes increases Kidney: weak diuretic Smooth muscle: Skeletal muscle: improving contractility
Methylxanthine drugs: clinical use
Theophylline Slightly soluble in water Narrow therapeutic window Effects related to plasma
concentration
Antimuscarinic agents
Degree of parasympathetic involvement varies in subjects
Ipratropium bromide Tiotropium
Corticosteroids
Effective on all indices of asthma Lipid soluble corticosteroids:
Beclomethasone, butenoside, flunisolide, fluticasone, triamcinolone
Potential Adverse Effects Associated with Inhaled Glucocorticoid
ADVERSE EFFECT RISK
Hypothalamic-pituitary-adrenal axis suppression
No significant risk until dosages of budesonide or beclomethasone increased to >1500 ug/day in adults or >400 ug/day in children
Bone resorption Modest but significant effects at doses possibly as low as 500 ug/day
Carbohydrate and lipid metabolism
Minor, clinically insignificant changes occur with dosages of beclomethasone >1000 ug/day
Cataracts Anecdotal reports, risk unproven
Skin thinning Dosage-related effect with beclomethasone dipropionate over a range of 400 to 2000 ug/day
Purpura Dosage-related increase in occurrence with beclomethasone over a range of 400 to 2000 ug/day
Dysphonia Usually of little consequence
Candidiasis Incidence <5%, reduced by use of spacer device
Growth retardation Difficult to separate effect of disease from effect of treatment, but no discernible effects on growth when all studies are considered
SOURCE: Modified from Pavord and Knox (1993) and Barnes (1995).
Cromolyn & nedocromil
Cromolyn & nedocromil
Effective only when taken prophylactically Extremely insoluble salts Alteration in function of delayed chloride
channel On nerve: cough On mast cells: inhibition of antigen challenge On eosinophils: inhibition of inflammatory response
to inhaled allergens
Cromolyn & nedocromil: clinical use
Effectiveness should test on 4 weeks trial
Blocks bronchoconstriction: Antigen inhalation Exercise Aspirin Occupational asthma
Allergic rhinoconjunctivitis Because of lack of serious toxicity have
widespread use in children
Leukotriene pathway inhibitors
Anti-IgE monoclonal antibodies
Other possible treatment
Calcium channel blockers Nitric oxide donors Antimicrobial therapy of chronic
airway infection with chlamydia & mycoplasma pneumeniae