Anti asthmatic drugs

Asthma • Asthma is a disease associated with inflammation of the airway

wall. It is characterised by hyper responsiveness of tracheo-bronchial smooth muscle to a variety of stimuli , resulting in narrowing of air tubes and accompanied by increased secretion , mucosal edema and mucus plugging.

• Characters :– Clinical : (recurrent bouts of coughing, shortness of breath, chest

tightness, and wheezing)– Physiological : (widespread, reversible narrowing of the bronchial

airways and a marked increase in bronchial responsiveness to inhaled stimuli)

– Pathological : (lymphocytic, eosinophilic inflammation of the bronchial mucosa, remodeling of the bronchial mucosa, with deposition of collagen , hyperplasia of the cells of all structural elements )

• Sub types of asthma – Allergenic – Non allergenic – Extrinsic asthma : mostly episodic , less prone to status

asthmaticus – Intrinsic asthma : perennial , status asthmaticus common

• Trigger factors : infection, irritants , pollution , exercise , exposure to cold air , psychogenic)

• COPD- progressive disease with emphysema and bronchial fibrosis in variable proprtions – mostly caused due to smoking but may be aggravated by the trigger factors .

Classification of drugs used in asthma

1) BRONCHODILATORS : i) sympathomimetics :a) selective β2 agonists : ( salbutamol , terbutaline )

b) non selective β agonists : isoprenaline c) non selective adrenergic agonists :( adrenaline , ephedrine )Short acting : albuterol , levalbuterol, metaproterenol, terbutaline , and pirbuterollong acting : salmeterol, formoterol ii) methyl – xanthine derivatives : ( aminophylline , theophylline iii) anti cholinergics : atropine , ipratropium

2) Leukotriene antagonists : zafirleukast, monteleukast, zileuton

3) Mast cell stabilizers : sodium cromoglycate , nedocromil , ketotifen

4) Corticosteroids : i) systemic : hydrocortisone , prednisolone ii) inhalational : beclomethasone , budesonide , fluticasone , flunisolide

5) Anti Ig-E monoclonal antibodies : omalizumab

Sympathomimetics : salbutamol

• Used for acute management , best reliever • Stimulates adenylyl cyclase and increase the

formation of intracellular cAMP• relaxes airway smooth muscle and inhibits release of

bronchoconstricting mediators from mast cells. They may also inhibit microvascular leakage and increase mucociliary transport by increasing ciliary activity.

• Available as metered dose inhalers , • Bronchodilation maximal within 15–30 minutes and

persists for 3–4 hours

• Indications :– Bronchospasm and bronchial asthma – Chronic bronchitis– Emphysema – Threatened abortion ( relaxes uterus )

Adverse effects :– Nervousness – Drowsiness – Weakness – Tachycardia – Headache – Tremor – Dizziness

• Contraindications :– Hyperthyroidism– Cardiac arrhythmia – Diabetes mellitus – Hypertension– Ischaemic heart disease, – Antepartum haemorrhage– Toxaemia of pregnancy – Hypersensitivity

Dose :oral :2-4 mg

Im/sc: 0.25-0.5 mg Inhalation :- 100-200 mcg in puffs

ADRENALINE(EPINEPHRINE)

Adrenaline is produced in the body by the cells of adrenal medulla and chromaffin tissue.

Epinephrine is destroyed by the stomach acid and is therefore not effective if taken orally.It is usually given by subcutaneous or IM injection.

USES• Bronchial asthma• To provide rapid relief of acute allergic reactions to drugs and other

allergens,anaphylactic reactions• Adrenaline is given along with local anaesthetics to prolong the actions

of anaesthetics• Topical haemostatic to stop haemorrhage• Wide angle glaucoma• Cardiac resustication

ADVERSE EFFECTS• Fear• Anxiety• Restlessness• Headache• Tremors• Palpitation• Tissue necrosis• Large doses cause sharp rise in BP leading to cerebral

haemorrhage.

PRECAUTIONSAdrenaline can cause sudden death in hypoxic subjectsCause serious toxicity in patients receiving tricyclic antidepressants like imipramine CONTRAINDICATIONSHypertensionHyperthyroidismIschemic heart disease DOSES0.5ml of a 1:1000 solution IM(this dose of drug should not be injected in vein by mistake as a sudden IV injection can

precipitate a fatal cardiac arrhythmia.IV bolus in a dose of 1mg (10ml of a 1:10000 solution) as a stimulant to the heart in

cardiac arrest.

Methyl xanthines

• Aminophylline is a soluble physical complex of theophylline and ethylenediamine.

• Mechanism : – Blocks bronchoconstrictor action of adenosine by

competitive inhibition of purinergic receptors in bronchus – Inhibits enzyme phosphodiesterase ( PDE ) and prevents

degradation of cAMP and cGMP– Translocates Ca ++ and makes it unavailable for

degradation of mast cells

• Pharmacological actions :1) Lungs : bronchodilation 2) CNS : CNS stimulation , nervousness, anxiety ,

tremor , anxiety , insomnia , stimulates respiratory centres

3) CVS : cardiac acceleration . Positive inotropic and chronotropic action , vasodilation

4) Kidney : weak diuresis

• Indications : – Severe bronchial asthma – COPD– Apnoea in pre term baby – Ordinary headache ( caffeine + aspirin)– Migraine

• Contraindications – Cardiac or liver failure – Peptic ulcer – Pregnancy

• Adverse effects – Tachycardia – Palpitations – Nausea – Cardiac arrhythmia – Nervousness – Convulsions ( rapid iv )

• Overdosage causes :– Cardiac arrhythmia– Hypotension – Hypokalemia – Seizures – Severe vomiting

Treatment :– Gastric lavage – Activated charcoal – K replacement – Diazepam

Anti cholinergic drug : atropine

• Cause bronchodilation by blocking cholinergic constrictor tone

• Act primarily in larger air ways

Leukotriene antagonists leukotriene are substances produced by inflammatory white cells ,which cause spasm of

the bronchial muscle . Drugs are becoming available which prevent spasm either by blocking the action of

leukotrines or by preventing inflammation .They also diminish hyperactivity of the bronchial mucosa and reduce inflammation.

MONTELUKAST AND ZAFIRLUKAST

These drugs antagonize cystenyl LT1 receptor mediated bronchoconstriction ,increased vascular permeability and eosinophil recruitment.

Well absorbed orally , highly plasma protein bound and metabolized by Cytochrome P450 group of enzymes

ZILEUTON: 5-LOX inhibitor

INDICATIONS Mild to moderate asthmaPreventing exercised induced asthmaAspirin induced asthma ADVERSE EFFECTS HeadacheEosinophiliaRashesNeuropathyChurg – strauss syndrome ( vasculitis with eosinophilia)

Corticosteroids Exact mechanism of action of corticosteroids is not fully understood .these drugs do

not relax airway smooth muscle directly.However they produce marked increase in airway caliber through following mechanism

1.Corticosteroids probably have a nonspecific anti-inflammatory activity which reduces mucosal oedema and the viscous sputum.

2.corticosteroids modify immune response and stabilize mast cells3.corticosteroids restore responsiveness of β2 adrenergic receptors to agonists which may

be impaired in some asthmatics.

USES• Used to treat mild to moderate asthma• Used to treat asthma that do not improve adequately with bronchodilators or

that worsens despite maintenance of bronchodilator therapy• Used in status asthmatic patients when he becomes refractory or asthma stand

in way of his life

ADVERSE EFFECTS• Fluid retension• Increased red cell mass• Wt.gain• Peptic ulcer • Oropharyngeal thrush• Hoarseness and weakness of voice DOSE• Hydrocortisone—inj IV:200mg repeated 4hrly• Prednisolone—tab(5mg):30-60mg/day• Beclomethasone---inhalation:100microgram,3-4times daily,2puffs 4 times per

day• Betamethasone---inhalation 200microgram 3-4 times daily

Mast cell stabilisers SODIUM CROMOGLYCATE

It is an effective drug against both early and late phase of bronchial asthma ,when given prophylactically.children seems to respond to it better than adults.however it should be tried in all patients whose asthma is poorly controlled with bronchodilators.

MECHANISM OF ACTION

1.It acts by inhibiting degranulation of sensitized mast cells .

chromoglycin sodium

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reduce accumulation of intracellular Ca ion induced by antigen in sensitized mast cells

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inhibit degranulation of mast cells

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no release of histamines,5HT

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prevents bronchoconstriction(prophylaxis)

USES• Prophylaxis of• -exercise:induced bronchoconstriction• -aspirin:induced bronchoconstriction• -bronchospasm:induced by industrial agents for eg wood dust• Extrinsic (allergic) asthma in young patients• Intrinsic asthma in old patients• Allergic rhinitis• To prevent seasonal increase in bronchial reactivity in patients with alleric asthma ADVERSE EFFECTS• It is a very safe drug .Its adverse effects are rare .However dry powder inhaler may

cause • -throat irritation• -coughing• -occassionally wheezing DOSE20mg 4 times daily(4 inhalation daily)

Choice of treatment1) Mild episodic asthma ( symptoms less than once daily): inhaled short acting

beta-2 agonist2) Seasonal asthma : sod cromoglycate or low dose inhaled steroid ( 200-

400mcg/day) 3-4 weeks before anticipated attack 3) Mild chronic asthma with occasional exacerbations : symptoms once daily –

regular inhaled low dose steroid or inhaled cromoglycate 4) Moderate asthma with frequent exacerbations ( attacks affecting activity and

occuring more than once daily) : increased dose of inhaled steroid ( upto 1600 mcg/day)

5) Severe asthma : ( continuous symptoms / frequent exacerbations / need hospitalisation) : regular inhaled steroid ( 800-2000 mcg/day + inhaled long acting beta-2 agonist twice daily)

6) Status asthmaticus /refractory asthma : i) Hydrocortisone 100 mg iv stat followed by 100mg/8hr infusionii) Nebulised salbutamol + ipratropium intermittent inhalations iii) Intermittent humidified oxygen inhalationiv) Salbutamol/ terbutaline 0.4 mg im/sc may be added v) Chest infection to be treated with antibiotics vi) Dehydration and acidosis to be treated