Objectives What is bronchial asthma?

Etiology

Pathophysiology of Asthma

Approaches to treatment

Phamacotherapy

Treatment plan

Drug delivery

Status Asthmaticus

Bronchial Asthma

300 million people

Adult 10-12 %

Children 15%

Bronchial Asthma

Definition: It is a syndrome

characterised by inflammation

and hyperresponsiveness of

tracheobronchial tree resulting

in reversible narrowing of air

tubes, mucosal oedema and

mucus plugging.

Etiology

Pathophysiology

Pathophysiology

Signs & Symptoms Dyspnoea

Wheezing

Cough

Limitation of activity

Approaches To TreatmentPrevention of Ag : Ab reaction

Neutralisation of IgE

Suppression of inflammation and hyperreactivity

Prevention of release of mediators

Antagonism of released mediators

Blockade of constrictor neurotransmittor

Mimicking dilator neurotransmittor

Directly acting bronchodilators

Drugs used in Asthma

Bronchodilators

• β2 agonists

• Methylxanthines

• Anticholinergics

Anti-inflammatory

agents

• Corticosteroids

• Chromones

• Lukasts

• 5-LOX inhibitor

• Antihistaminics

• 5-HT antagonists

Miscellaneous

• Mucolytics

• Antibiotics

• Monoclonal antibodies

• Desensitization

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Bronchodilators

β2

agonistsSABA:

• Salbutamol

• Terbutaline

LABA:

• Salmeterol

• Formeterol

Methylxanthines

Theophylline

Anticholinergics

Tiotropiumbromide

Ipratropiumbromide

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β2 sympathomimeticsACTIONS:

Bronchodilatation

Inhibits mediator release

Increase mucus clearance

β2 receptor stimulation

Increased cAMP

Relaxation of bronchial muscle

β2 Agonists

SABA

• Salbutamol, Terbutaline

• Maximum effect in 30 min

• Duration of action 4-6 hrs

• Used on ‘as needed’ basis

LABA

• Salmeterol, Formoterol

• Duration of action 12 hrs

• Used regularly

β2 agonists

ADRs

Muscle tremors

Palpitation,restlessness

Ankle edema

Throat irritation

MethylxanthinesTheophylline

Bronchodilatation

release of mediators

Narrow margin of safety

Ideal for night time symptoms

OTHER USES

COPD

Apnoea in premature infants

Mechanism of Action

adenylylcyclase

ATP

cAMP

5 AMP

Phosphodiesterase

Theophylline

Adverse effectsGastric pain, vomiting

Tremors, palpitation

Hypotension

Convulsions

Insomnia

Drug Interactions agents inducing metabolism

smoking

phenytoin

rifampicin

agents inhibiting metabolism erythromycin

OCPs

ciprofloxacin

AnticholinergicsIpratropium bromide, Tiotropium bromideACTIONS:

Relaxes bronchial smooth muscle

may increase mucociliary clearance

act in larger airways

less effective than sympathomimetics

suitable for prophylactic use

combination is useful

very few side effects - safe

Mechanism of Action

Anti-inflammatory Agents

Corticosteroids

Inhalational:

• Beclomethasone

• Flunisolide

• Budesonide

Systemic:

• Hydrocortisone

• Prednisolone

• Methyl prednisolone

Chromones

Cromolyn sodium

( MDI )

Nedocromil

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Anti-inflammatory Agents (cont..)5-HT inhibitors & Antihistaminic

Ketotifen

(Oral )

Pizotifen

Lukasts ( Oral )

Zafirlukast

Montelukast

Pranlukast

Acolade

5-LOX inhibitors

Zileuton

(oral)

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CorticosteroidsPrednisolone, BeclomethasoneADVANTAGES

more complete and sustained relief

improve airflow

Influence airway remodeling

retard progression of disease

Mechanism of Action

Inhaled v/s Systemic corticosteroidsINHALED SYSTEMIC

Beclomethasone, BudesonideTargeted drug delivery

Systemic side effects are less

Used as a prophylactic drug

Cannot be withdrawn abruptly – bronchial hyperreactivity

Prednisolone, HydrocortisoneSystemic side effects are marked

Used in chronic severe asthma

Can be tapered rapidly

Inhibits degranulation of mast cells

Restricted release of mediators

Inhibition of chemotaxis

CHROMONESSod cromoglycate, Nedocromil

Chromones contd…

Long term treatment - cellular inflammatory response

Ineffective during an attack

USES

prophylaxis in asthma

allergic rhinitis

allergic conjunctivitis

CHROMONES

Bronchospasm

Cough

Nasal congestion

Arthralgia

Rashes

ADRs

Leukotriene AntagonistsMontelukast and Zafirlukast

Prophylaxis of mild to moderate asthma

Alternatives to inhaled Glucocorticoids

Acceptable in children

Effective in aspirin induced asthma

Safe drugs

Mode of action

AntagoniseLTs

Inhibit receptors

Mechanism of Action

Anti IgE AntibodyOmalizumab

• Inhalational• Oral• Parenteral

Drug Delivery

Inhalational Drug Delivery SystemsMDI Dischalers Spacer

Rotahalers Nebulizer

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Green[Salmeterol]

Orange[Fluticasone]

Blue[SABA]

Brown [budesonide]

Status AsthmaticusAcute severe life threatening form of asthma.

TREATMENT:

Hydrocortisone 100mg iv stat

Nebulized Salbutamol 2.5-5mg +Ipratropium bromide 0.5 mg

High flow O2 inhalation

Salbutamol/ Terbutaline 0.4mg im/sc

Intubation and mechanical ventilation

Antibiotics

Saline + sod. bicarbonate