ANTI - ASTHMATIC AGENTS AND COUGH SUPPRESSANTS

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ANTI – INFLAMMATIRY AGENTS USED IN ASTHMA AND COUGH SUPPRESSANTS :

ANTI – INFLAMMATIRY AGENTS USED IN ASTHMA AND COUGH SUPPRESSANTS A PRESENTATION BY: ANURADHA PANDEY DEPT.OF PHARMACOLOGY NIPER1113PC05

ASTHMA:

ASTHMA Asthma is an inflammatory condition in which there is recurrent reversible airway obstruction in response to irritant stimuli CHARACTERISTICS: Wheezing Breathlessness Coughing Reversibility of airway obstructions Bronchial hyper-reactivity Airway inflammation

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TYPES : EXTRINSIC ASTHMA: mostly episodic less prone to status asthmaticus INTRINSIC ASTHMA: perennial status asthmaticus is common

DIAGNOSIS OF ASTHMA:

DIAGNOSIS OF ASTHMA Detailed medical history Cough Recurrent wheeze Recurrent dyspnea Recurrent chest tightness Spirometry demonstrating reversibility Methacholine challenge if unable to document airway reversibility with spirometry

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ASTHMA TRIGGERS Inhalant allergens Animal dander, house dust mites, cockroach allergen, indoor molds outdoor allergens- pollens Exercise/cold air Irritants tobacco smoke Indoor and outdoor pollutants

PATHOGENESIS:

PATHOGENESIS

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Reversible airway obstruction Airway remodeling

APPROACH FOR TREATMENT OF ASTHMA:

APPROACH FOR TREATMENT OF ASTHMA Prevention of ag:ab reaction Suppression of inflammation and bronchial hyper reactivity Prevention of release of mediators Antagonism of released mediators Blockade of constrictor neurotransmitters Mimicking dilator neurotransmitter Directly acting bronchodilators

BRONCHIAL ASTHMA:

BRONCHIAL ASTHMA Relaxation Bronchial Tone Constriction Leukotrienes Adenosine Acetylcholine CAMP ATP PDE AMP

DRUGS USED::

DRUGS USED: BRONCHODILATOR SYMPATHOMIMETICS : adrenaline , salbutamol METHYLXANTHINES: theophyllines , aminophylline ANTICHOLINERGICS: atropine, ipratropium LEUKOTRIENE ANTAGONIST: Motelukast , zafirlukast MAST CELL STABILISER Cromoglycate , nedocromil , ketotifen CORTICOSTEROIDS SYSTEMIC:hydrocortisone,prednisolone INHALATIONAL:beclomethasone,fluticasone

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ANTI-INFLAMMATORY AGENTS

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MAST CELL STABILISERS Cromolyn sodium & nedocromil MECHANISM : Stabilize antigen-sensitized mast cells by reducing calcium influx and subsequent release of inflammatory mediators( histamine,LTs,PAF,IL ) ACT ON: mast cells, for inhibition of the early response to antigen challenge eosinophils , for inhibition of the inflammatory response to inhalation of allergens ROUTE OF ADMINISTRATION : metered dose inhaler of cromolyn sodium

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INDICATIONS : bronchial asthma allergic rhinitis allergic conjunctivitis ADVERSE EFFECTS : bronchospasm throat irritation cough arthalgia

ANTI HISTAMINICS:

ANTI HISTAMINICS ketotifen Inhibits stimulation of immunogenic &inflammatory cells (mast cells,macrophages,neutrophils ) Other uses: Atopic dermatitis Perennial rhinitis Conjunctivitis Pharmacokinetics: orally absorbed, 50%bioavailability, half life=22 hrs Adverse effects:sedation,dry mouth,nausea,weight gain

ANTAGONISM OF RELEASED MEDIATORS :

ANTAGONISM OF RELEASED MEDIATORS LEUKOTRIENE ANTAGONISTS : Montelukast & zafirlukast MECHANISM: Competitively inhibit cysLT1 & LTD 4 receptor mediated bronchoconstriction,increased vascular permeability & recruitment of eosinophils ADVERSE EFFECTS: Headache Rashes Eosinophilia Neuropathy Chrug strauss syndrome

5-LOX INHIBITOR:

5-LOX INHIBITOR Zileuton MECHANISM: Blocks LTC4/D4 &B4 synthesis Prevents LT induced responses including those exerted by cysLT1 receptor LIMITATIONS: Short duration of action Hepatotoxicity USES : Exercise and antigen-induced bronchospasm Aspirin allergy

ANTI-IgE ANTIBODY:

ANTI- IgE ANTIBODY Omalizumab Humanized murine monoclonal antibody to human IgE Neutralises free IgE in circulation without activating mast cells &other inflammatory cells Reduces exacerbations &steroid requirement Used for patients with positive skin test or raised IgE levels Given parenterally ( i.v or s.c .)

CORTICOSTEROIDS:

CORTICOSTEROIDS Beclomethasone & budesonide Reduce bronchial hyperreactivity,mucosal edema & suppressing inflammatory response to ag-ab reaction or other trigger stimuli Provides sustained symptomatic relief influences airway remodelling,disease progression

Systemic steroid therapy:

Systemic steroid therapy Short “bursts” (3- 10 days) hasten the recovery from an asthma exacerbation Reduce hospitalizations Reduce the rate of relapse Optimal dosage not established USED IN: Severe chronic asthma Status asthmaticus /acute asthma exacerbation

Inhaled Corticosteroids:

Inhaled Corticosteroids High topical & low systemic activity with the most effective long-term control Inhibit formation of cytokines that cause chronic inflammation (IL-1, IL-2, IL-3, IL-5, GM-CSF) Reduce eosinophils and T H 2 lymphocytes count Decrease arachidonic acid metabolism by inhibiting PLA-2 ADVERSE EFFECTS: Hoarseness of voice Dysphonia Sore throat Oropharyngeal candidiasis Osteoporosis

COUGH:

COUGH Coughing is a protective mechanism for expulsion of respiratory secretions or foreign particles from air passage It occurs due to stimulation of mechano / chemoreceptors in respiratory passage or stretch receptors in lungs that cause stimulation of cough center in medulla Cough suppressants are used in dry unproductive cough or if cough is unduely tiring,disturbs sleep or is hazardous( hernia,piles,ocular surgery)

COUGH SUPPRESSANTS:

COUGH SUPPRESSANTS CLASSIFICATION: OPIOIDS:codeine,pholcodeine,morphine NON OPIOIDS: noscapine , dextromethorphan,oxeladin ANTIHISTAMINICS:chlorpheniramine,diphenhydramine,promethazine MECHANISM: Raises threshold of cough centre or reduces tussal impulses or both

OPIOIDS::

OPIOIDS : CODEINE: More selective anti tussive through opioid receptors located in brain Low abuse liability Drawbacks: constipation,respiratory depression & drowsiness Contraindications:asthma &diminished respiratory reserve PHOLCODEINE No analgesic or addictive property Longer acting(12hrs or more) Dose=10-15mg

NON OPIOIDS:

NON OPIOIDS DEXTROMETHORPHAN Equally effective as codeine,no mucociliary depression No constipation or addictive effect Mild side effects

ANTIHISTAMINES:

ANTIHISTAMINES Give relief in cough due to their sedative and anti cholinergic actions (reduce secretions) Chlorpheniramine : 2-5mg Diphenhydramine : 15-25mg promethazine: 15-25mg

REFERENCES:

REFERENCES Essentials of medical pharmacology;KD Trpathi;sixth edition;2008;published by Jaypee brothers;page no:213-227 Rang and Dale’s pharmacology;H.P.Rang , M.M.Dale ; sixth edition;2008;published by Churchill Livingstone; page no:356-366.

THANK YOU…..:

THANK YOU…..

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