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