Drugs Used to Treat Asthma

Drugs Used to Treat Asthma

 Asthma is an inflammatory disease of the airways characterized by episodes of acute bronchoconstriction causing shortness of breath, cough, chest tightness, wheezing, and rapid respiration.
Airflow obstruction in asthma is due to bronchoconstriction that results from:
 contraction of bronchial smooth muscle
 inflammation of the bronchial wall
 increased mucous secretion

TYPES OF ASTHMA

 Asthma associated with specific allergic reactions
 Asthma not associated with known allergy
Exercise-induced asthma
Asthma associated with chronic pulmonary disease

APPROACHES TO TREATMENT

Prevention of exposure to allergen(s)
Reduction of the bronchial inflammation and hyperreactivity
Dilatation of narrowed bronchi
Reduction of the bronchial inflammation and hyperreactivity.
1.Glucocorticoids
2.Mast Cell Stabilizers: Sodium cromoglicate (cromolyn, Intal) Nedocromil sodium
3.Other drugs. Ketotifen


1. ( Glucocorticoids)
 prednisolone (orally)
 beclomethasone, fluticasone and budesonide (by inhalation)

( Glucocorticoids)

MOA:
 Inhibition of the influx of inflammatory cells into the lung after allergen exposure
 inhibition of the release of mediators from macrophages and eosinophils, and T lymphocytes)
 reversing mucosal edema
 decreasing the permeability of capillaries
 inhibiting the release of leukotrienes.
 After several months of regular use reduce the hyperresponsiveness of the airway smooth muscle to stimuli, such as allergens, irritants, cold air, and exercise.
 Increase the number of B2 receptors so promote bronchodilatation mediated by B2 receptors
 Oral/systemic: Patients with severe exacerbation of asthma (status asthmaticus) may require intravenous administration of methylprednisolone or oral prednisone.
Inhaled Corticosteroids Side Effects:
 Pharyngeal irritation
 Coughing
 Dry mouth
 Oral fungal infections (so gargle and rinse the mouth with water afterward to prevent the development of oral fungal infection)
 Dysphonia (horseness)
 Oral or parenteral glucocorticoids have a variety of adverse effects and potentially serious side effects
2.Sodium cromoglicate (cromolyn, Intal)
MOA:
 Stabilize the cell membranes of inflammatory cells (mast cells, monocytes, macrophages
 preventing release of harmful cellular contents(Indirect-acting agents that prevent bronchospasm)


pk:
■ poorly absorbed from the gastrointestinal tract eell absorbed from the lung given by inhalation (as powder, aerosol or nebulizer)
■ eliminated unchanged in the urine and bile.
Uses:
 chronic asthma
 Children asthma
 Pregnant wemon
 Exercise induced asthma
 Allergic rhinitis

3.Other drugs. Ketotifen is a histamine H1-receptor blocker which may also have some antiasthma effects .
In common with other antihistamines it causes drowsiness.

bronchodilators

1. Adrenergic agonists
2. Xanthine Derivatives
3. Antimuscarinic bronchodilator

1.Adrenergic agonists

 Nonselective adrenergics stimulate alpha1, beta1 (cardiac), and beta2 (respiratory) receptors.
Example: epinephrine are less safe, being more likely to cause cardiac arrhythmias
 Nonselective beta-adrenergics stimulate both beta1 and beta2 receptors.
Example: isoproterenol
 Selective beta2 drugs stimulate only beta2 receptors.
Example: albuterol


BETA-ADRENOCEPTOR AGONISTS
MOA
 Activation of beta2 receptors activate cAMP, which relaxes smooth muscles of the airway and results in bronchial dilation and increased airflow.
 B2- adrenoceptor activation also stabilises mast cells
BETA-ADRENOCEPTOR AGONISTS
 Albuterol, terbutaline, salbutamol
 Short-acting
 Rapid onset of action 15-30min and provide relief for 4-6 hours
 Drug of choice for acute asthma
BETA-ADRENOCEPTOR AGONISTS
Salmeterol and formoterol
 Slow onset of action
 Long-acting
 12 h or more
 Used for prophylaxis

Side effect:

 Cardiac arrythmia(dose depended)
 Oral and parenteral B2 agonist cause vasodilatation in the skeletal muscle vessels and this may lead to hypotension and tremor.

2- Xanthine Derivatives

Theophylline, a methylxanthine
 Inhibition of phosphodiesterase (PDE),since this enzyme hydrolyzes cyclic nucleotides and this lead to increase cAMP
 cause bronchodilation by relaxing smooth muscles of the airways.
 relief of bronchospasm and greater airflow into and out of the lungs.
 causes CNS stimulation.
 causes cardiovascular stimulation: increased force of contraction and increased HR, resulting in increased cardiac output
 increased blood flow to the kidneys (diuretic effect).
Pk:
 rapid and complete Absorption from GIT
 90% is metabolised by the liver
 The tl/2 is 8 h
 tobacco smoking enhances theophylline clearance by inducing hepatic P450 enzymes.
 low therapeutic index,
 use of theophylline in status asthmaticus.
Side effect of theophyllin
 nausea and diarrhoea, Vomiting ,Gastroesophageal reflux during sleep
 the chief dangers are cardiac arrhythmia, hypotension, hypokalaemia and seizures.


DRUG INTERACTION of theophyllin
 Enzyme inhibition by erythromycin, allopurinol or oral contraceptives increases the plasma concentration of theophylline;
 enzyme inducers such as carbamazepine, phenytoin and
rifampicin reduce the concentration.

3.Antimuscarinic bronchodilators

 Blockade of muscarinic (M3) receptors and causes bronchodilation, the preferred antimuscarinics
 ipratropium
 oxitropium.
These synthetic compounds permanently charged molecules ,prevents absorption after inhalation And minimises antimuscarinic effects outside of the lung.

Uses:

acute severe asthma when combined with (B2- adrenoceptor agonists.
Leukotriene receptor antagonists
 montelukast
 zafirlukast
 zileuton

MOA:

montelukast Zafirlukast are competitively prevent the bronchoconstrictor effects of leukotrienes
 (by blocking their receptor)
 prevent leukotrienes from attaching to receptors on cells in the lungs and in circulation.
 Blocking the Inflammation in the lungs
Montelukast (once per day)
Zafirlukast ( twice per day)


Leukotriene receptor antagonists USES:
 Prophylaxis and chronic treatment of asthma

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