Drug Asthma

8/6/2019 Drug Asthma

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Drugs Used in AsthmaDrugs Used in Asthma


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Bronchial asthma Pathogenesis of asthma

Pharmacology of agents used in the

treatment of asthma Sympathomimetic agents Methylxanthine drugs

Antimuscarinic agents

Corticosteroids

Cromolyn & Nedocromil Leukotriene pathway inhibitors

Other drugs in the treatment of asthma


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Clinical hallmarks of asthma Recurrent, episodic bouts of

Coughing

Shortness of breath

Chest tightness

Wheezing


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Triggers of asthma

On exposure to

Allergens

Certain pollutants

On exercise

After a viral upper respiratory infection


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Pathologic features of asthma Contraction of airway smooth muscle

Mucosal thickening from edema and

cellular infiltration

Inspissation in the airway lumen of

abnormally thick, viscid plugs of mucus


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The two phases of asthma

FEV1; forced expiratory volume in 1 second


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Corticosteroids




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Corticosteroids




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Asthma therapies - 1 Contraction of airway smooth muscle

Bronchodilators

Beta-adrenoceptor stimulants

Methylxanthine drug


Short-term relievers


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Bronchodilation is promoted by

cAMP


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Asthma therapies - 2 Mucosal thickening from edema and cellular

infiltration

Inspissation in the airway lumen ofabnormally thick, viscid plugs of mucus

Anti-inflammatory agent Corticosteroid

Cromolyn or nedocromil Leukotriene antagonist

Long-term controllers


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Immunopathogenesis of asthma


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Corticosteroids




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Corticosteroids




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Sympathomimetic agents


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cAMP


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Sympathomimetic agents F2 selective agents

Relax airway smooth muscle

Inhibit release of some bronchoconstricting

substances from mast cells

Toxic effects

mediated mainly byF1 receptors Tachycardia

Skeletal muscle tremor


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Sympathomimetic agents;

Kinetics

measured by forced expiratory flow ratemeasured by forced expiratory flow rate

short acting;short acting;

albuterol, terbutalinealbuterol, terbutaline

halfhalf--life; 2life; 2--3 hours3 hours

long acting agonists;long acting agonists;

salmeterol, formoterolsalmeterol, formoterol

up to 12 hoursup to 12 hours


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Pharmacology of agents used in thetreatment of asthma Sympathomimetic agents

Methylxanthine drugs


Corticosteroids




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Corticosteroids




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Methylxanthine drugsSourceSource tea (theophylline), coffeetea (theophylline), coffee

(caffeine), cocoa (theobromine)(caffeine), cocoa (theobromine)

CNS Smooth m.

Mainly used


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cAMP


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Pharmacodynamics of

methylxanthines CNS effects; nervousness, insomnia,CNS effects; nervousness, insomnia,

convulsion, deathconvulsion, death

Cardiovascular effects; positive chronotropicCardiovascular effects; positive chronotropicand inotropic effects on the heartand inotropic effects on the heart

Effects on the GI tract; stimulate secretion ofEffects on the GI tract; stimulate secretion ofboth gastric acid and digestive enzymesboth gastric acid and digestive enzymes

Effects on kidney; weak diureticsEffects on kidney; weak diuretics

Effects on smooth muscle; bronchodilationEffects on smooth muscle; bronchodilation Effects on skeletal muscle; improveEffects on skeletal muscle; improve

contractilitycontractility


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Methylxanthine drugs;

clinical uses Narrow therapeutic window; 5Narrow therapeutic window; 5--20 mg/L20 mg/L

Should only be used where methods to measureShould only be used where methods to measure

theophylline blood levels are availabletheophylline blood levels are available Metabolized by liverMetabolized by liver

Decreased clearance in liver diseaseDecreased clearance in liver disease

Smoking induces hepatic enzymesSmoking induces hepatic enzymes

Increased clearance in cigarette smokingIncreased clearance in cigarette smoking

Children clear theophylline faster than adultsChildren clear theophylline faster than adults


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Corticosteroids




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Corticosteroids




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cAMP


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Antimuscarinic agents AtropineAtropine

Effective bronchodilatorEffective bronchodilator

too many side effects; not used today intoo many side effects; not used today intreatment of asthmatreatment of asthma

Ipratropium bromideIpratropium bromide poorly absorbedpoorly absorbed

does not readily cross blooddoes not readily cross blood--brain barrierbrain barrier

less systemic adverse effectsless systemic adverse effects

Also effective in patients with chronic obstructiveAlso effective in patients with chronic obstructivepulmonary disease (COPD)pulmonary disease (COPD)


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Response of patient with

COPD

to ipratropium or metaproterenol


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Response of patient

with asthma

to ipratropium or salbutamol


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Corticosteroids




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Corticosteroids




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Corticosteroids Inhaled corticosteroids:Inhaled corticosteroids:

lipidlipid--solublesoluble

beclomethasonebeclomethasone,, budesonidebudesonide,, flunisolideflunisolide,,

fluticasonefluticasone,, triamcinolonetriamcinolone

Oral corticosteroids for severe asthma:Oral corticosteroids for severe asthma:

prednisone,prednisone, prednisoloneprednisolone


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Corticosteroids;

Mechanism of actionMechanism of action AntiAnti--inflammatoryinflammatory

Inhibition of the lymphocytic,Inhibition of the lymphocytic,

eosinophiliceosinophilic airway mucosalairway mucosalinflammation of asthmatic airwaysinflammation of asthmatic airways

Inhibition of production of inflammatoryInhibition of production of inflammatorycytokinescytokines

PotentiationPotentiation of the effects ofof the effects ofFF--receptor agonistsreceptor agonists


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Corticosteroids;

Side effectsSide effects Systemic effectsSystemic effects

Adrenal suppression, osteoporosis,Adrenal suppression, osteoporosis,

cataractscataracts with oral corticosteroids therapywith oral corticosteroids therapy

Gradual tapering is neededGradual tapering is needed

OropharyngealOropharyngeal candidiasiscandidiasis,,hoarsenesshoarseness

with inhaled topical corticosteroidswith inhaled topical corticosteroids


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Corticosteroids




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Corticosteroids




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Cromolyn & Nedocromil


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Cromolyn & Nedocromil;

Mechanism of action Inhibit cellular activation

Alteration in the function of delayed

chloride channels in the cell membrane On mast cells; inhibition of the early

response to antigen challenge

On eosinophils; inhibition of the

inflammatory response to inhalation ofallergens

On airway nerves; Inhibition of cough


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Cromolyn & Nedocromil;

Clinical uses Prophylactic uses in acute asthma

Before exercise

Before unavoidable exposure to an allergen

Reduce symptomatic severity and the needfor bronchodilator medications in perennialasthma

Reduce symptoms of allergic

rhinoconjunctivitis Poorly absorbed

rare adverse effects


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Bronchial asthma

Pathogenesis of asthma




Corticosteroids




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Bronchial asthma





Corticosteroids




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Bronchial asthma





Corticosteroids




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Bronchial asthma





Corticosteroids




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Other drugs in the treatment of

asthma Anti-IgE monoclonal antibodies

Calcium channel blockers

Nitric oxide donors


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Mast cell mediator release


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Newly generated lipid mast cell mediators

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Drug Asthma