Asthma by jitendra bhangale

7/19/2012

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© 2010 Delmar, Cengage Learning1

By- Jitendra Bhangale

Assistant Professor & Head,

Department of Pharmacology,

Smt N. M. Padalia Pharmacy College,

Ahmedabad


Introduction

Etiology

Pathophysiology

Symptoms

Diagnosis

Management

References

By Jitendra BhangaleAsst. Prof. Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, Ahmedabad

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Asthma is a chronic inflammatory disorder of the airways in

which many cells and cellular elements play a role, in particular,

mast cells, eosinophils, T lymphocytes, macrophages, neutrophils,

and epithelial cells.

In susceptible individuals, this inflammation causes recurrent

episodes of wheezing, breathlessness, chest tightness, and

coughing, particularly at night or in the early morning.

The inflammation also causes an associated increase in the

existing bronchial hyperresponsiveness to a variety of stimuli.




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Mast cells,Mononuclear cells

Chemotaxins,chemokines

SpasmogenscysLTs,H, PGD2

Bronchospasm

Eliciting agent:Allergen or

Non-specific stimulus

Epithelial damageAirway

inflammation

Mediatorse.g. cysLTs,

NO

Infiltration of cytokine-Releasing Th2 cells,

& monocytes, & activation ofinflammatory cells, particularly

eosinophils

Airway hyper-reactivity

Bronchospasm,Wheezing,coughing

Immediate phase Late phase



Mediators potentiate inflammation & damage epithelium

Allergens

T lymphocytes activated& secrete lymphokines

Lymphokines activates eosinophils& secrete mediators & damaging proteins

Enhancing BHR


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Hypoxemia Airway Inflammation

Acute Chronic Bronchospasm

Hypersecretion production Cough Wheezing Dyspnoea




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Acute severe asthma:

Upright position,

Can’t complete sentences in one breath,

Tachypnea > 25/min,

Tachycardia > 110/min, PEF < 50% of pred or best,

Prolonged expiration, Breath sounds decreased,

Inspiratory and expiratory rhonchi, Cough

Chronic asthma: Dyspnoea on exertion,

wheeze,

chest tightness and cough on daily basis, usually at night and early morning;

productive cough (mucoidsputum),

recurrent respiratory infection,

expiratory rhonchi throughout and accentuated on forced expiration.



1) SpirometerIn asthma, the following results may be obtained on spirometry:

Sr.no Interpretation

1 Normal spirometryAsthma in remission or asthma under control

2 FEV1 <80% FVC

Airflow obstruction present (can be graded based on amount of reduction)

3FEV1 increase by 15% or more

than 200 mL after bronchodilator Significantly reversible airflow obstruction


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2) Peak Expiratory Flow Rate:

Mini Wright's peak flow meter



Chest X-Ray

Allergy Tests


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Clinical features before treatment

Symptoms Night time symptoms PEF Daily

medications

STEP 4Severe

Persistent

Continuous,Limited physical

activityFrequent

≤60% predictedVariability >30%

High dose inhaledCS & LAβA

STEP 3ModeratePersistent

Daily >time/weak>60%-<80% predicted

Variability >30%

Low to medium dose CS & LAβAAlternative:-LA or

theophylline

STEP 2Mild

Persistent

≥1 time a weekBut <1 time a day

>2 times a months

≥80% predictedVariability 20-30 %

Low dose CS

STEP 1Mild Intermitte

nt

< 1 time a weekAsymptomatic &Normal PEF betw

attacks

≤2 times a months

≥80% predictedVariability <20%

No daily medication

needed.

Quick relief all patients

Short acting bronchodilatorUse of short acting β2 agonists

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Initial assessmentHistory, physical examination, PEFR

Good response

Add systemic corticosteroids

Discharge

Incomplete/ poor response

Poor response

Initial therapyInhaled β2 agonist.o2 if needed

Admit to hospital

Good response Respiratory failure

If stable Discharge to

home

Admit to ICU

Observe for at least 1 hr




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SR.NO. DEVICE DRUGS

I Metered dose Inhaler (MDI)

a CFC MDI All classes

b HFA MDI Albuterol

c Autohaler MDI Beclomethasone Pirbuterol

II Dry powder Inhaler (DPI)

a Rotahaler Albuterol

b Terbuhaler Budesonide

c DiskusFluticasoneSalmeterol

Fluticasone/salmeterol

d Aerolizer Formoterol

e Twisthaler mometasone

III Nebulizer

a Jet NebulizerAll classes except long acting β2-

agonists

b Ultrasonic NebulizerCromolyn solution

Short acting β2-agonist solution

IV Spacer Devices



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I) Bronchodilatorsa. Sympathomimetics

AdrenalineEphedrineSalbutamolTerbutalineBambuterolSalmeterolFormoterol

b) MethylxanthinesTheophylineAminophyllineCholine theophylineHydroxyethyl theophylline

c) AnticholinergicsAtropine methnitrateIpratropium bromideTiotropium bromide

II) Leukotriene antagonistsMontelukastZafirlukastZileuton

III) Mast cell stabilizersSodium cromoglycateNedocromilKetotifen

IV) CorticosteroidsSystemic

HydrocortisonePrednisolone…etc

• InhalationalBeclomethasone

dipropionateBudesonideFluticasone propionateflunisolide


Therapeutic action of β2 agonists:- Relax contracted bronchial smooth muscle Prevent bronchial smooth muscle contraction by various stimuli Increase mucous clearance Prevent mast cell mediator release Prevent edema induced by histamine, etc. by preventing increase

in endothelial permeability Delivery By Aerosol: mild to moderately severe asthma only often used in conjunction with other drugs; e.g. to promote better

delivery of cromolyn or corticosteroids to the distal airways. Systemically: available orally and for injection


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Adverse effect Muscle tremor due to skeletal muscle β-receptors

Tachycardia and palpitations due to reflex cardiac stimulation secondary to peripheral vasodilation, stimulation of myocardial β1 receptors

Metabolic effects: increased FFA, glucose, lactate after large systemic doses

Hypokalemia (due to stimulation of K+ entry into skeletal muscle



Major therapeutic actionsRelaxes bronchial smooth muscleDecreases mast cell mediator releaseIncreases mucocilliary clearance

Mechanisms of actionInhibition of phosphodiesterasesIncrease intracellular cAMP

Adenosine receptor antagonismAdenosine causes bronchoconstriction in asthmaticsBronchoconstriction prevented by theophylline at therapeutic concentrations

OtherIncreased epinephrine secretion form adrenal medulla; increase small and cannot account for the bronchodilationAntagonizes some prostaglandins in smooth muscle


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DeliveryIneffective by inhalation; requires build-up of effective plasma concentrationIntravenous; for severe acute asthma only

Side effects of MethylxanthineNauseaVommitingHeadacheRestlessnessIncreased acid secretionDiuresisConvulsionsCardiac arrhythmiasCNS stimulation



Mechanism of Action

Mast cell stabilization

Inhibition of degranulation by a variety of stimuli, including cell-bound IgE

allergen Interactions

Inhibition of leukotriene production

Above actions due to blockage of calcium influx into mast cells

No bronchodilator or antihistamine activity


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DeliveryLess than 1% of an oral dose of cromolyn is absorbed, so

therapeutic effects are achieved through local administration via inhalation:In 4% solution - By aerosol spray or nebulizerPowdered drug - as capsules to use in powered turbo-inhaler or as a metered dose InhalerAdverse reactions:Bronchospasm, Cough, Laryngeal edema, Joint swelling or painHeadacheRash,Nausea



Mechanisms of action due to anti-inflammatory properties

Reduces number and activity of inflammatory cells in airways

Inhibits release of arachidonic acid metabolites

Prevents increased vascular permeability

Suppresses IgE binding

Increases β-adrenergic responsiveness

DeliveryAerosolOral or IV

for severe episodes: prednisone


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Side Effects of Inhaled Preparations

Dysphonia

Oropharyngeal candidiasis

Both can be reduced by mouth rinsing with water after

administration and through use of appropriate spacers with the inhaler

to avoid oral deposition



PDE4 inhibitors

Inhaled ciclosporin A

Monoclonal antibodies against IgE, CD4 cells, and Th2 cytokines (e.g.,

interleukin 4 and 5)

More specific immunotherapy

Antagonists to chemokines, adhesion molecules, proinflammatory cytokines,

tumour necrosis factor , interleukin 1

Antisense oligonucleotides and gene therapy

Inhibitory cytokines interleukin 10


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Action of PDE4 inhibitorsRelax airway smooth muscleReduce bronchoconstrictionDecrease oedemaReduce secretion of inflammatory mediators, such as histamine, leukotrineand chemokines (IL-4, IL5)Block leukocyte adhesion to vascular endothelial cellsBlock generation of oxygen derived free radicals

E.g..Roflumilast (Altana pharma)Cilomilast (GSK)S-5751 (Shionogi)



Mechanism of action:-Monoclonal antibodies blocks the attachment of the IgE to

the Fc receptors on mast cells and basophils and the subsequent release of histamine by those cells upon exposure to allergen.


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Asthma by jitendra bhangale

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