Therapy of bronchial asthma

Management

A. Non drug treatment :• Avoid exposure to antigen .• Avoid humidity.• Avoid drugs which precipitate asthma as

(parasymathomimetics- morphine , penicillins, and NSAIDS).

B. Drug treatment:1. Bronchodilators.

A. Beta agonists B. Muscarinic antagonist C. Methylxanthens

2. Anti-inflammatory A. CorticosteroidsB. Leukotriene antagonists

3. Prophylactic treatment: A. Cromlyn

1. Bronchodilators

There are three groups of bronchodilator drugs;A. B-adrenergic agonists.B. Muscarinic receptor anatgonists.C. Methyl xanthines: theophylline derivatives.

A. -Adrenergic agonists

• They are classified into:I. Non-selective -stimulants: i.e. stimulate β

receptors and other receptors: (Epinephrine, Ephedrine, Isoprenaline)

II. Beta 2 agonist: Salbutamol, Terbutaline and Bambuterol.

Mechanism of action role of β receptors in the bronchi

• Binding of adrenergic -agonist with receptors activate adenyl cyclase cAMP which will lead to:– Relax the airway muscles.– Inhibit release of mediators from mast cells– Enhances mucociliary function.– Decreases vascular permeability.

I. Non selective β agonists

Epinephrine (Adrenaline)Mechanism of action• It directly stimulate alpha and beta adrenoceptors.Pharmacological Effects• Bronchodilatation (2) • Decongestion (vasoconstriction of blood vessels)(1).• Anti-allergic effect: It is the physiological antidote to

histamine

Therapeutic Uses• Acute attack of bronchial asthma • Treatment of allergic reaction e.g. urticaria,

angioedema, anaphylactic shock.Side Effects (due to non selectivity)• Tachycardia, palpitation, anxiety, headache, tremors,

hypertension.Contraindications• Heart diseases.• Hypertension.• Pulmonary embolism.

II. Selective 2 agonists

• Short acting: Albuterol, terbutaline, metaproterenol (duration of action less than 6hrs ) used in emergency

• Long acting: salmetrol, formoterol (duration of action more than 12hrs) used for prophylaxis

• Given by inhalation Adverse effects:• Tremors of skeletal muscle.• Tachycardia.• Hypokalemia • Tolerance may occur with prolonged use.

B. Muscarinic receptor antagonists

Mechanism of action:• They competitively block muscarinic receptors in the

airways and effectively prevent the braonchoconstriction caused by vagal discharge.

Classified into: 1. Non selective (e.g. atropine): has a lot of

antimuscarinic side effects???

2. Selective (e.g. Ipratropium, Tiotropium)• Ipratropium given by inhalation • It has very few systemic antimuscarinic effects

because it is a quaternary amine i.e. poorly absorbed

• Ipratropium is less effective than 2 agonists so it is not administered alone.

C. MethylxanthinesClassified into:1. Natural: Three major methylxanthines are found in the

plants, caffeine (in coffee) theophylline (in tea) and theobromine (in cocoa).

2. Synthetic: aminophylline Mechanism of action:• Block adenosine receptors. • They inhibit the enzyme phosphodiestrase (PDE) leading

to an increase in the intracellular cAMP level.• They stimulate the release of epinephrine from adrenal

medulla and inhibit COMT (it metabolizes epinephrine)

Pharmacological effects:• Respiratory effects: – Bronchodilators .

• CNS effects: – Reduced fatigue, improved mental performance,

increased alertness and power of concentration. – Large doses may produce restlessness, insomnia,

headache and convulsions.

• CVS effects:– Xanthines cause constriction of the cerebral

vessels– Peripheral vasodilatation, increase the heart rate – Mild elevation in BP

• Diuretic action: xanthines cause weak diuresis.• GIT: Stimulation of GI motility.

Therapeutic Uses:1. Asthma and COPD2. Other uses: Headache (caffeine + aspirin), Migraine

(Caffeine + ergotamine)Adverse effects:• GIT: nausea, vomiting, anorexia, reactivation of

peptic ulcer.• CVS: tachycardia and arrhythmias. Rapid I.V. injection

can cause hypotension, syncope and cardiac arrest.• CNS: irritability, insomnia, nervousness &

convulsions.

2. Anti-inflammatory drugsA. Corticosteroids• Cornerstone in the therapy of asthma. • They reduce bronchial hyperactivity and inflammation

that accompanies asthmaMechanism of action: • Reduce the synthesis of arachidonic acid by

phospholipase A2 and inhibit the expression of COX2 which lead to reduction of inflammatory mediators (especially leukotrienes which play an important role in asthma)

• It is suggested that it increases the responsiveness of beta receptors in the airways

Indications • Asthma: may be used systemically (hydrocortisone,

prednisolone) or by inhalation (beclomethazone, fluticasone and triamcinolone)

Adverse effects:• Systemic corticosteroids (if used in high doses for long

time): hypertension , diabetes mellitus, weight gain, salt and water retention, immunosuppression with flare of infection, depression, psychosis, growth retardation in children, peptic ulcer and cataract.

• Inhaled steroids: oropharyngeal candidiasis which can be avoided by use of mouth wash and gargle after each inhalation.

B. Leukotriene inhibitors1. Zafirlukast and montelukast, are now available

leukotriene receptor antagonists.– They are not recommended acute episodes – Toxicity is generally low – Rarely Churg-Strauss syndrome have been reported

2. Zileuton, a leukotriene synthesis inhibitor. – Selectively inhibit 5-lipoxygenase, a key enzyme in

the conversion of arachidonic acid to leukotrienes– The drug is effective in preventing exercise-induced

and antigen-induced and aspirin-induced asthma – Toxicity: elevation of liver enzymes

C. Anti IgE antibody • Omalizumab is murine monoclonal antibody to

human IgE • It binds to IgE on sensitized mast cells and prevent

activation by antigens and subsequent release of inflammatory mediators

• Approved for prophylactic management of asthma • It is very expensive and must be administered

parentally

3. Prophylactic treatment

• Mast cell stabilizers: Disodium Cromoglycate and Ketotifen

• They inhibits or prevents bronchospasm induced by various stimuli including antigens, exercise, cold or dry air.

• Used in prevention of asthma (not treatment)Mechanism of action: • Inhibit Ca++ influx across mast cell membrane. • Stabilizes mast cells so preventing release of

mediators induced by antigens & nonspecific stimuli.

PHARMACOLOGY OF OXYGEN

Oxygen Adminstrations 1- Mixtures of oxygen: Oxygen can be given in mixture with CO2 or helium 2- Humidified oxygen: Oxygen can be given under water sealing to prevent irritation of nose, pharynx and trachea 3- Hyperbaric oxygen.Therapeutic uses of oxygen : Correction of hypoxiaMethods of administration- O2 is administrated by inhalation. Devices for inhalation include nasal cannula, masks, and oxygen tents.- Hyperbaric oxygen is given in pressure chamber of O2 therapy.

Dangers, adverse effects and precautions1-Fire and explosion can occur2-In case of respiratory depression:CO2 accumulates leading to CO2 narcosis and failure of the respiratory center. If pure O2 was administered, the hypoxia is corrected and the patient enters into apnea. So those patients are oxygenated with artificial respiration.3-Rapid withdraw of O2 may lead to sever hypoxemia.

4-Terry syndrome (retinopathy of prematurity) :O2 should be used only when needed and its concentration must not exceed 35-40% in premature infants.5-O2 under pressure greater than 2 atmospheric can cause toxic effects on CNS

Good Luck