* DRUGS AFFECTING RESPIRATORY SYSTEM

*ASTHMAchronic inflammatory airway disease excessive tracheobronchial reactivity

SYMPTOMSwheezing, chest tightness, restlessnesscough, dyspnea Mostly in night / early morning

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*ASTHMA 5% POPULATIONALLERGICFAMILY HISTORYHYPERSENSITIVITYIg E MEDIATED RESP INFECTIONSDRUGSCHEMICAL IRRITANTS

*TRIGGERING FACTORSRESPIRATORY INFECTIONSCold Air Fog Wood smoke; tobacco smoke Emotions Stress Laughter Anxiety Exercise (dry, cold weather especially )OCCUPATION

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*DRUGSASPIRIN

NSAIDS

BETA BLOCKERS

PRESERVATIVES SulfitesBenzalkonium chloride

*CONCEPTCONTINUAL AIRWAY INFLAMMATION

EXACERBATED BY TRIGGERING FACTORS

*INTERACTIONSAirway inflammatory cells,

Inflammatory mediators,

Cytokines,

Surface epithelium.

*CELLS INVOLVEDMast cells, Eosinophils,

T-lymphocytes,

Macrophages,

Neutrophils,

Epithelial cells

*CHEMICAL MEDIATORSHISTAMINE

LEUKOTRIENE

BRADYKININ

PLATELET ACTIVATING FACTOR

PROSTAGLANDIN E2, F2, D2

*Rationale for Pharmacological Intervention Reduction of mast cell degranulation

Sympathomimetic agents

Cromolyn / Nedocromil

*Rationale for Pharmacological Intervention Reduction of cholinergic influence from vagal motor nerves Antimuscarinic agents

Direct relaxation of airway smooth muscle Sympathomimetic drugs Theophylline

*Agents acting on Beta Adrenergic ReceptorsAlbuterolBitolterol Pirbuterol Salmeterol TerbutalineEphedrine Epinephrine Ethylnorepinephrine IsoetherineIsoproterenolMetaproterenol

*Sympathomimetic Drugs ACTIONSRelax airway smooth muscle

May Inhibit release of some mast cell bronchoconstrictive mediators

May inhibit microvascular leakage

May increase mucociliary transport

*2 receptor activation Relaxation of airway smooth muscle

Skeletal muscle tremor (toxicity)

*Beta 2 agonistsShort actingAlbuterol, Pirbuterol, Epinephrine, Terbutaline.Route : InhalationalUses : Acute conditions & Symptomatic treatment of asthmaNo anti inflammatory actionNever used as sole agentSide effects : Tachycardia, Hyperglycemia, tremors.

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*Beta 2 agonistsLong acting : SALMETEROL

SLOW ONSET OF ACTIONLONG DURATION OF ACTION : 12 hrs

NOT FOR ACUTE ASTHMATIC ATTACKUSED for Maintainance

*Anticholinergic AgentIpratropium bromideCompetitive blocker of muscarinic receptors prevents bronchoconstriction.

*IpratropiumDOC for beta-blocker-induced bronchospasm

USEFUL FOR Pt. INTOLERANT TO BETA 2 AGONISTS

MORE USEFUL IN ELDERLY

*MAST CELL STABILIZERSCROMOLYN , NEDOCROMIL

Chloride-mediated channel effects: Inhibition of cough Inhibition of early response to antigens (mast cells) Inhibition of late response to antigens (eosinophils)

*CROMOLYN, NEDOCROMILPROPHYLACTIC ANTI INFLAMMATORY

NO DIRECT ACTION ON AIRWAYS

NOT USEFUL IN ACUTE. ASTHMATIC ATTACK

*USES : PROPHYLACTIC AGENT FOREXERCISE INDUCED ASTHMAALLERGEN INDUCED ASTHMA

SIDE EFFECTS : THROAT IRRITATION , COUGH

*METHYLXANTHINESTHEOPHYLLINE ( AMINOPHYLLINE )

ACTION : DIRECT BROCHODILATORMech :??

*Central Nervous System Effects

Increased alertness; reduced fatigue

In more sensitive individuals: nervousness/insomnia

Very high methylxanthine doses: medullary stimulation, convulsions

Primary side effect in patients requiring aminophylline (large doses) for control of asthma: nervousness & tremor

*Cardiovascular Effects: direct positive chronotropic direct enhanced myocardial contractility

GIT Effects: enhanced secretion of gastric acid and digestive enzymes

Renal Effects: weak diuretics-- not therapeutically important

*THEOPHYLLINE - USERelieves airway obstruction:

In acute asthma

Reduces symptoms severity

In chronic asthma

*THEOPHYLLINE SIDE EFFECTSNausea, Headache, Insomnia, Nervousness

Seizures, Neuromuscular irritability, Tremor, Arrhythmias, hypokalemia, hyperglycemia, vomiting IV push - seizures/cardiac arrhythmias

*Corticosteroids NO DIRECT ACTION OVER AIRWAYS

INHIBIT INFLAMMATIONDECREASE ACTIVITY OF CELLSDECREASES RELEASE OF MEDIATORSDECREASE HYPERRESPONSIVENESS OF AIR WAYSDECREASES MUCOSAL EDEMA

*BeclomethasonePrednisoneFluticasoneFlunisolideTriamcinolone

*CORTICOSTEROIDS - USESStatus asthmaticus (Combination with Beta 2 agonists)

For management of acutely ill patients

Patients not adequately maintained with bronchodilators

Patients whose symptoms are worsening, despite reasonable maintenance treatment

*ROUTESORAL

PARENTERAL

INHALATIONAL

*ADVERSE EFFECTSInhaled topical corticosteroids: oropharyngeal candidiasis Hoarseness: local effect -- vocal cords Suppression of hypothalamic-pituitary-adrenal axis Decreased bone density , delayed pubertyCataract formation High doses: dermal thinning glaucoma

*Other drugsInterruption of leukotriene pathways

Inhibition of 5-lipoxygenase-- Zileuton

Rationale: Prevents leukotriene synthesis Effective for maintenance treatment of asthma Requires monitoring for hepatic toxicity

*Inhibition of leukotriene D4 receptor binding Zafirlukast Montelukast

Less effective than steroids

SIDE EFFECT : BLEEDING COMPLICATIONSMonitor hepatic function

*Drugs to Treat CoughWhat causes a cough?Irritation of mucosal surfaceInflammation, hypersecretionSolutions:Decrease sensitivity of CNS cough center, decrease secretionsCodeine, Hydrocodone, HydromorphoneDextromethorphan

*Drugs for Allergic RhinitisThe Problem:Inflammation of mucous membranesIgE-mediatedMast cell degranulationThe solution:Antihistamines (eg: Diphenhydramine)-adrenergic agents (eg: Phenylephrine)Steroids (eg: Beclomethasone)Cromolyn

*Presents mainly with sneezing, nasal itching, watery rhinorrhea and congestion.

H/O allergen will be there

Rx - Oral antihistamines + decongestants.

In the form of intranasal spray.

*ANTIHISTAMINESH1 receptor blockerDiphenhydramineClorpheniramineLoratidineTerfenadineAstemizoleCetirizine

*Alpha adrenergic agonistsPhenylephrineOxymetazolineEphedrinePhenylpropanolamineTetrahydrozolineNaphazolineXylometazoline

*Drugs to Treat COPD The Problem:Chronic, irreversible airflow obstructionVariety of causesThe Solutions:2 agonistsTheophyllineGlucocorticoidsIpratropium

*Treatment mainly based on assessing any reversible component of the disease.To prevent the acute exacerbations.Symptomatic