Bronchial asthma

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BRONCHIAL ASTHMA

Transcript of Bronchial asthma

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BRONCHIAL ASTHMA

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Introducation

Asthma derived from Greek word- To stay awake in order to breath

OR

Difficulty in breathing

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Asthma is a chronic inflammatory disease in which patient suffers with reversible episodes of airway obstruction due to bronchial hyper responsiveness.

(Damage of bronchial epithelium (mucous layer) by chemical mediators. So direct expose of bronchi to irritant stimuli)

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Early phase (Acute)

-Due to bronchial smooth muscle spasm.

- Excessive secretion of mucus.

Chronic phase

Continuous Inflammation, fibrosis, oedma, necrosis of bronchial epithelial cells.

It has 2phases

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Clinical hallmarks

Recurrent episodic coughing Shortness of breathing Chest tightness Wheezing

Symptoms are worsening at night

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Asthma described as two type

Extrinsic(Atopic extrinsic asthma)

It is associated with exposure of specific allergen

Ex:- House dust, pollen

It is episodic and less prone to develop to status asthmaticus.

Intrinsic(Non atopic extrinsic asthma)

It is associated with some non specific stimulants

Ex:- chemical irritantsIt is perenial and prone

to develop to status asthmaticus.

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Pathophysiology Allergen enter (Foreign body)

Immunological reaction (AG:AB Complex formation)

Circulation in blood

Basophiles, Neutrophilis engulf

Cause neutralization contd..,

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Whenever same allergen re exposed

Activation of AG:AB complex

Reacts with lung mast cells (Degranulation of mast cells)

Spasmogens release(Like Histamine,5HT,PGs,LT4, Cytokines)

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Bronchial Tone

IgE-Antigen Complex

Basophil

Activation

Eosinophil

Activation

Chemical mediatorsHistamine, LTC4, LTD4, LTB4,Cytokines, Adenosine, PGD2, PAF,ECP and Neuropeptides

Cause inflammation, oedema, bronchospasm, muscus secretion, epithelial damage

Mast CellDegranulation

In early phase these mediators leads to bronchoconstriction

In late phase inflammation, pulmonary oedema, mucous secretion bronchial hypersensivity and epithelial damage

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It divided into two categories

1. Short term relievers.( Bronchodilators)

2. Long term controllers.

Asthma therapy

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Bronchial Tone

Bronchoconstriction

Bronchodilitation

Bronchial Smooth Muscle

IgE-Antigen Complex

Basophil

Activation

Eosinophil

Activation

Chemical mediatorsHistamine, LTC4, LTD4, LTB4,Cytokines, Adenosine, PGD2, PAF,ECP and Neuropeptides

Cause inflammation, oedema, bronchospasm, muscus secretion, epithelial damage

β2 AGONISTS Inhibit release

β2

SALBUTAMOLβ2 AGONISTS

5AMP

AC

CARTICOSTEROIDS

ATP

THEOPHYLLINE

M3

GTP

GC

cGMP

IPRAT

ROPI

UM

M3 A

GONIS

TS

Adenosine

Mast CellDegranulation

cAMPPDE

THEOPHYLLINE

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Bronchial Tone

Bronchoconstriction

Bronchodilitation

Bronchial Smooth Muscle

IgE-Antigen Complex

Basophil

Activation

Eosinophil

Activation

Chemical mediatorsHistamine, LTC4, LTD4, LTB4,Cytokines, Adenosine, PGD2, PAF,ECP and Neuropeptides

Cause inflammation, oedema, bronchospasm, muscus secretion, epithelial damage

CARTICOSTEROIDS

LT-ANTAGONIST

Leukotrienes

SOD. CROMOGLYCATEStabilises Mast Cells

Mast CellDegranulation

INFECTION

NITRIC OXIDE

DONORS

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Drugs Used in Bronchial Asthma

1. Selective β2– Agonists

Short acting Salbutamol, Terbutaline, Remiterol, Fenoterol, Bitolterol

Long-acting Salmeterol, Formoterol, Bambuterol

2. Non-Selective Sympathomimetics

Adrenaline, Ephedrine, Isoprenaline, Orciprenaline

(Metaproterenol), Isoetharine

BRONCHODILATORS

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3. AnticholinergicsIpatropium, Tiotropium, Oxitropium

4. Methyl XanthinesTheophylline, Aminophylline, Diprophylline, Choline theophyllinate

Anti inflammatory Drugs (Controllers)

Corticosteroids1. Oral : Prednisolone, Methylprednisolone2. Parenteral : Methyl prednisolone, Hydrocortisone3. Inhalational : Beclomethasome, Fluticasone, Triamcinolone, Budesonide, Flunisolide

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Mast Cell StabilisersSodium Cromoglycate, Nedocromil, Ketotifen

Leukotriene Modulators:1. 5-Lipoxygenase Inhibitor : Zileuton

2. LT – Receptor Antagonists : Zafirlukast, Montelukast, Iralukast, Pranlukast

Monoclonal Anti-IgE AntibodyOmalizumab

Miscellaneous:

NO, Calcium channel blockers

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Sympathomimetic agents ß2 receptors are present in the airway

smooth muscle. These agents acts on ß2 receptors cause

bronchodilatation These are only provide relief M.O.A:

cAMPBonchodilatation Release of bronchoconstricting mediators

from mast cells Inhibit macrovascular leakage Mucociliary clearence

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Epinephrine:

Rapid bronchodilator when inj/SC/inhaled(320µg/puff) Onset of action 15min after inhalation Duration of action:60-90min.

ADR:- Acts on β1 receptor cause Tachycardia Arrhythmias Worsening angi So rarely prescribed.

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Ephedrine: α,β1, β2

Ephedrine has a longer action

Oral activity

Lower potency

Pronounced central effects.

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β2 Selective

Short acting : Terbutaline, Salnutamol On inhalation they have rapid onset(1-5Min) Short duration of action preferred for acute attack Route: Inhalation 100-200µg/6hourly Other MDI, Oral, IM, IV

Terbutaline is the only one drug safely used during the pregnancy.

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Long acting: Salmeterol, bambutarol

Long acting but slow onset of action Preferred for maintenance therapy Not useful in acute attack due to slow onset of

actionRoute: Inhalation 50µg twice daily.

Formoterol: Long acting Rapid onset Preferred for prophylaxis due to long actingRoute: Inhalation 12-24µg twice daily

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ADR of Sympathomimetics

By oral route stimulate β2 receptors in skeletal muscle cause tremors, Orthostatic hypotension.

Tachycardia (High dos also stimulate β1 receptors in heart)

Restlessness

Tolarance occurs.

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Antimuscurnic agent Less effective then β agonists

MOA: By blocking M3 receptors on air way smooth muscle and prevents Ach action.

-They acts by cGMP levels in bronchial smooth muscle.

Ipatropium:- -Poor absorption from bronchi into systemic

circulation -Do not cross BBB.-Also mucus secretion

Ipatropium + β2 (Salbutamol) work better in serve asthma and long duration of action

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Methyl Xanthenes MOA:

i) Inhibition of PDE 3,4. These enzyme are responsible for metabolism of cAMP.

ii) Blockade of Adenosine receptors.

Actions: Theophyline exhibits bronchodilatory action Anti Inflammatory Immunomodulator Respiratory stimulation Diaphragmatic contractility Mucociliary clearance

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Pharmaco Kinetics:

Oral/ParentalFood delay the rate of absorptionWell distributedCross placental & BBBMetabolized in LiverExcreted in urine

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ADR: Low therapeutic window, CNS stimulant drugs Plasma levels 10-20µg/ml, Narrow safety

Restlessness, insomnia, headache, tremors

Nausea,VomitingPeptic ulcer

Tachycardia, palpitation, hypotension, arrythimiasTheophyline: potent vasodilator, reflex tachcardia, oral route Aminophyline: Slow IV infusion

XanthenesGIT Diuresis

Heart

CNS

20µg/ml

40µg/ml

20µg/ml

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Corticosteroids (Controllers) Glucocorticosteriods induce synthesis of lipocotrin

which inhibits pholipaseA2 there by preventing

formation of mediators such as PGs,TAX2, LTand

other mediators.

Actions: Anti allergic, anti inflammatory,

immunosuppressant ( AG:AB reactions ), Mucosal

oedema, bronchial hyperactivity, Enhance β

adrenergic action by up regulation of β2 receptors in

lung.

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Inhalator glucocorticosteriods such as beclomethasone, budesonide and fluticasone are used as prophylactic agents in asthma.

PK: Well tolerated less systemic side effects.

Common side effects: Dryness of mouth Voice change Oropharangeal candidiats.Systemic are used in acute severe and chronic severe

asthma.

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Mast cell stabilizers Non bronchodilating, Non steroid drugs, used for prophylactic

treat.MOA: Prevent degranulation and release of chemical mediators from

the mast cells. They stabilize the mast cells by preventing transmembarane

influx of Ca ions.PK: Highly ionized Least systemic absorption well tolerated.Uses: Allergic asthma, allergic conjunctivitis, allergic rhinitis,

allergic dermatitis.Ketotifen (Mast stab.+ Antihistamincs)

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LT Modulators LT are powerful bronchoconstrictors. Action by preventing their synthesis or blocking

effect on cys LT receptors

Synthesis inhibitors (Lipooxygenase) Zafirlukast,Montelukast

PK: Well absorbed after oral administration Highly bound to plasma protein Metabolized by liver Effective for prophylactic treat of mild asthma.

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ADR: Head ache skin rashes rarely eosinophilia Zileuton cause hepatic toxicity.

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Monoclonal anti IgE antibody MOA:- AG:Ab complex formation by AB action Omalizumab: Recombinant humanized

monoclonal antibody. Inhibit the binding site of IgE to mast cells and

basophils PK: administered parentarally Uses: Moderate to severe asthma and allergic

disorders. Indicated for asthmatic patients who are not

adequately controlled by inhalational corticosteroids.

ADR: Inj site redness, itching, stinging.

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Miscellaneous

NO: It dilate pulmonary blood vessels and relax airway smooth muscle.

Uses: For acute severe asthma and management of pulmonary hypertension.

Ca channel blockers: Broncho constriction ultimately involves

some degree of ca into cells Nefedpine / Verapamil should provide relief in asthma.

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RX Status asthmatics (Acute severe asthma)

Status asthmatics a severe acute asthma, which is a life threatening condition involving exhaustion, cyanosis, bradicardia,hypotension, dehydration and metabolic acidosis.

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Humidified O2 inhalation

Inj. Aminophyline 500mg in 10ml of 5% Glucose IV Slow

Neubulized β2 adrenergic agonist + anti cholinergic agent

Systemic glucocorticosteroids IV (Hydrocortisone 200mgIV)

immediately

IV fluids to correct dehydration.

K supplements: To correct hypokalemia produced by repeated

administration of salbutamol.

NaHCo3 (Sodium bicarbonate) to treat acidosis.

Antibiotics to treat infection (Cap. Ampicillin 250mg 1tab tds-

7days

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DRUGS TO BE AVOIDED IN ASTHMA

β adrenergic blockers

Cholinergic agents

NSAIDS ( cause hyperapoenia) except paraceatamol.

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