1 DRUGS AFFECTING RESPIRATORY SYSTEM. 2 ASTHMA chronic inflammatory airway disease excessive tracheobronchial reactivity SYMPTOMS wheezing, chest tightness,

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DRUGS AFFECTING RESPIRATORY

SYSTEM

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ASTHMAASTHMAchronic inflammatory airway disease excessive tracheobronchial reactivity

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

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ASTHMA ASTHMA –– 5% POPULATION 5% POPULATION

ALLERGIC FAMILY HISTORY HYPERSENSITIVITY Ig E MEDIATED RESP INFECTIONS DRUGS CHEMICAL

IRRITANTS

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TRIGGERING FACTORSTRIGGERING FACTORS RESPIRATORY INFECTIONS Cold Air Fog Wood smoke; tobacco smoke Emotions Stress Laughter Anxiety Exercise (dry, cold weather especially ) OCCUPATION

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DRUGSDRUGSASPIRIN

NSAIDS

BETA – BLOCKERS

PRESERVATIVES – Sulfites– Benzalkonium chloride

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CONCEPTCONCEPT

CONTINUAL AIRWAY INFLAMMATION

EXACERBATED BY TRIGGERING FACTORS

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INTERACTIONSINTERACTIONS

Airway inflammatory cells,

Inflammatory mediators,

Cytokines,

Surface epithelium.

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CELLS INVOLVEDCELLS INVOLVED Mast cells, Eosinophils,

T-lymphocytes,

Macrophages,

Neutrophils,

Epithelial cells

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CHEMICAL MEDIATORSCHEMICAL MEDIATORS

HISTAMINE

LEUKOTRIENE

BRADYKININ

PLATELET ACTIVATING FACTOR

PROSTAGLANDIN E2, F2, D2

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Rationale for Pharmacological Rationale for Pharmacological Intervention Intervention

Reduction of mast cell degranulation

– Sympathomimetic agents

– Cromolyn / Nedocromil

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Rationale for Pharmacological Rationale for Pharmacological Intervention Intervention

Reduction of cholinergic influence from vagal motor nerves – Antimuscarinic agents

Direct relaxation of airway smooth muscle – Sympathomimetic drugs – Theophylline

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Agents acting on Beta Adrenergic Agents acting on Beta Adrenergic ReceptorsReceptors

Albuterol Bitolterol Pirbuterol Salmeterol Terbutaline Ephedrine Epinephrine Ethylnorepinephrine Isoetherine Isoproterenol Metaproterenol

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Sympathomimetic DrugsSympathomimetic Drugs ACTIONS ACTIONS

Relax airway smooth muscle

May Inhibit release of some mast cell bronchoconstrictive mediators

May inhibit microvascular leakage

May increase mucociliary transport

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ßß2 receptor activation2 receptor activation

Relaxation of airway smooth muscle

Skeletal muscle tremor (toxicity)

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Beta 2 agonistsBeta 2 agonists

Short acting Albuterol, Pirbuterol, Epinephrine,

Terbutaline. Route : Inhalational Uses : Acute conditions & Symptomatic

treatment of asthma No anti inflammatory action Never used as sole agent Side effects : Tachycardia, Hyperglycemia,

tremors.

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Beta 2 agonistsBeta 2 agonists

Long acting : SALMETEROL

SLOW ONSET OF ACTIONLONG DURATION OF ACTION : 12 hrs

NOT FOR ACUTE ASTHMATIC ATTACKUSED for Maintainance

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Anticholinergic Agent

– Ipratropium bromide– Competitive blocker of muscarinic receptors –

prevents bronchoconstriction.

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IpratropiumIpratropium

DOC for beta-blocker-induced bronchospasm

USEFUL FOR Pt. INTOLERANT TO BETA 2 AGONISTS

MORE USEFUL IN ELDERLY

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MAST CELL STABILIZERSMAST CELL STABILIZERS

CROMOLYN , NEDOCROMIL

Chloride-mediated channel effects:  Inhibition of cough  Inhibition of early response to antigens

(mast cells)  Inhibition of late response to antigens

(eosinophils)

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CROMOLYN, NEDOCROMILCROMOLYN, NEDOCROMIL

PROPHYLACTIC ANTI INFLAMMATORY

NO DIRECT ACTION ON AIRWAYS

NOT USEFUL IN ACUTE. ASTHMATIC ATTACK

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USES : PROPHYLACTIC AGENT FOR– EXERCISE INDUCED ASTHMA– ALLERGEN INDUCED ASTHMA

SIDE EFFECTS : THROAT IRRITATION , COUGH

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METHYLXANTHINESMETHYLXANTHINES

THEOPHYLLINE ( AMINOPHYLLINE )

ACTION : DIRECT BROCHODILATORMech :??

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Central Nervous System Central Nervous System EffectsEffects

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

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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

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THEOPHYLLINE - USETHEOPHYLLINE - USE

Relieves airway obstruction:

– In acute asthma

– Reduces symptoms severity

– In chronic asthma

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THEOPHYLLINE THEOPHYLLINE –– SIDE SIDE EFFECTSEFFECTS

Nausea, Headache, Insomnia, Nervousness

Seizures, Neuromuscular irritability, Tremor,

Arrhythmias, hypokalemia, hyperglycemia, vomiting

IV push - seizures/cardiac arrhythmias

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Corticosteroids Corticosteroids NO DIRECT ACTION OVER AIRWAYS

INHIBIT INFLAMMATIONDECREASE ACTIVITY OF CELLSDECREASES RELEASE OF

MEDIATORSDECREASE HYPERRESPONSIVENESS

OF AIR WAYSDECREASES MUCOSAL EDEMA

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BeclomethasonePrednisoneFluticasoneFlunisolideTriamcinolone

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CORTICOSTEROIDS - USESCORTICOSTEROIDS - 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

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ROUTESROUTES

ORAL

PARENTERAL

INHALATIONAL

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ADVERSE EFFECTSADVERSE 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

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Other drugsOther drugsInterruption of leukotriene Interruption of leukotriene

pathwayspathways

Inhibition of 5-lipoxygenase-- Zileuton  

Rationale: Prevents leukotriene synthesis Effective for maintenance treatment of

asthma Requires monitoring for hepatic toxicity

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Inhibition of leukotriene D4 Inhibition of leukotriene D4 receptor bindingreceptor binding

Zafirlukast Montelukast

Less effective than steroids

SIDE EFFECT : BLEEDING COMPLICATIONS

Monitor hepatic function

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Drugs to Treat CoughDrugs to Treat Cough What causes a cough?

– Irritation of mucosal surfaceInflammation, hypersecretion

Solutions:– Decrease sensitivity of CNS cough center,

decrease secretionsCodeine, Hydrocodone, HydromorphoneDextromethorphan

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Drugs for Allergic RhinitisDrugs for Allergic Rhinitis The Problem:– Inflammation of mucous membranes– IgE-mediated– Mast cell degranulation

The solution:– Antihistamines (eg:

Diphenhydramine)– α-adrenergic agents (eg:

Phenylephrine)– Steroids (eg: Beclomethasone)– Cromolyn

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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.

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ANTIHISTAMINESANTIHISTAMINES

H1 receptor blockerDiphenhydramineClorpheniramineLoratidineTerfenadineAstemizoleCetirizine

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Alpha adrenergic agonistsAlpha adrenergic agonists

PhenylephrineOxymetazolineEphedrinePhenylpropanolamineTetrahydrozolineNaphazolineXylometazoline

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Drugs to Treat COPD Drugs to Treat COPD The Problem:

– Chronic, irreversible airflow obstruction

– Variety of causes The Solutions:

– β2 agonists

– Theophylline– Glucocorticoids– Ipratropium

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Treatment mainly based on assessing any reversible component of the disease.

To prevent the acute exacerbations.

Symptomatic