DRUGS AFFECTING THE RESPIRATORY ORGANS FUNCTION

DRUGS AFFECTING DRUGS AFFECTING

THE RESPIRATORY THE RESPIRATORY ORGANS ORGANS

FUNCTIONFUNCTION

Drugs affecting the respiratory Drugs affecting the respiratory organsorgans function function

anticough drugsanticough drugs;; expectorantsexpectorants;; breathing stimulantsbreathing stimulants;; drugs used for bronchial asthmadrugs used for bronchial asthma;; drugs used for lungs edemadrugs used for lungs edema

COUGHCOUGH

with presence of secretion inwith presence of secretion in bronchibronchi drydry

PRODUCTIVEPRODUCTIVESputum with significant viscous-elastic properties: - muco- and proteolytic drugsmuco- and proteolytic drugsSputum with significant adhesive properties: - drugs which stimulate production of surfactantdrugs which stimulate production of surfactantDecreasing of speed of mucociliar transport with unchanged properties of sputum: - drugs which stimulate ciliar functiondrugs which stimulate ciliar functionSignificant disorders of bronchial permeability, morphological changes of bronchi (atrophy of mucous membrane, bronchial stenosis), excessive production of mucus: - alkali inhalationsalkali inhalationsSigns of allergic reaction with increased histamine activity:- antihistamine drugsantihistamine drugs

NONPRODUCTIVENONPRODUCTIVECataral inflammation (usually viral), reflector and central cough: - anticough drugsanticough drugsSigns of allergic reaction: - antihistamine drugsantihistamine drugsBronchospasm: - broncholyticsbroncholytics

REHYDRANTS IN ALL CASESREHYDRANTS IN ALL CASES

Anticough drugsAnticough drugsDrugs of central actionDrugs of central action ( (depress depress central links of cough reflexcentral links of cough reflex):):а)а) narcoticnarcotic:: codeincodein, , dextromethorphandextromethorphanб) б) nonnarcoticnonnarcotic:: glaucin hydrochlorideglaucin hydrochloride ((glauventglauvent), ), oxeladin citrate (tussuprex)oxeladin citrate (tussuprex)Drugs of peripheral actionDrugs of peripheral action ( (block block sensitivesensitive receptors of cough receptors of cough reflexogenic zonesreflexogenic zones): ): libexinlibexin

Oxeladin citrateOxeladin citrate, Tussuprex, Tussuprex

Glaucin hydrochlorideGlaucin hydrochloride ( (glauventglauvent) + ) + ephedrineephedrine + + Sage oilSage oil

LibexinLibexin

ExpectorantsExpectorantsSecrete-motor drugsSecrete-motor drugs ( (stimulate stimulate expectorationexpectoration):):а) а) drugs of reflex actiondrugs of reflex action: : drugs of medical drugs of medical plantsplants, , sodium benzoatesodium benzoate, , bronchicum elixirbronchicum elixir, , mucaltinmucaltinб) б) drugs of resorbtive and local actiondrugs of resorbtive and local action: : bromide -sodium and potassiumbromide -sodium and potassium, , ammonium ammonium chloridechloride, , sodium hydrocarbonatesodium hydrocarbonate, , ether oilsether oilsBronchosecretolytic drugs Bronchosecretolytic drugs ((mucolyticsmucolytics))::а) а) proteolytic enzymesproteolytic enzymes: : tripsintripsin, , chimopsinchimopsin, , chimotripsinchimotripsin, , desoxyribonuclease desoxyribonuclease б) б) mucolyticsmucolytics: : acetylcysteinacetylcystein, , carbocysteincarbocysteinв) в) drugs which influence surfactant drugs which influence surfactant production or surfactantsproduction or surfactants: : bromhexin, bromhexin, ambroxol, “Alveofakt”, “Ekzosurf”ambroxol, “Alveofakt”, “Ekzosurf”

Drugs of medical plantsDrugs of medical plants

Althea officinalisAlthea officinalis ThermopsisThermopsis Viola Viola

Combined remedyCombined remedy “ “BronchicumBronchicum””

MucaltinMucaltin (Mucaltinum) (Mucaltinum)

Drugs of medical plantsDrugs of medical plants

Ledum palustraeLedum palustrae Origanum vulgarisOriganum vulgaris

Crystal tripsinCrystal tripsin (Trуpsinum crystallisatum) (Trуpsinum crystallisatum) Ampoules -Ampoules - 0,005 0,005 gg andand 0,01 0,01 gg

AcetylcysteinAcetylcystein (Acetylcysteinum) (Acetylcysteinum) Forms of production:Forms of production: tablets - tablets - 0,1, 0,2 0,1, 0,2 andand 0,6, 20 % 0,6, 20 % solution for inhalation in ampoules –solution for inhalation in ampoules – 5 5 andand 10 10 mlml; 10 % ; 10 % solution for injection in ampoules -solution for injection in ampoules - 2 2 ml andml and 5 % 5 % solution in ampoules –solution in ampoules –

1010mlml. .

BromhexinBromhexin (Bromhexinum) (Bromhexinum)

АmbroxolАmbroxol (Lasolvan) (Lasolvan)Forms of productionForms of production: : tablets -tablets - 0,03 0,03 and syrupand syrup..

COUGHCOUGHDry Dry

With presence of sputum in bronchiWith presence of sputum in bronchi PRODUCTIVEPRODUCTIVE

Sputum with significant viscous-elastic properties - muco- and muco- and proteolytic drugsproteolytic drugs

Sputum with significant adhesive properties - drugs which drugs which stimulate production of surfactantstimulate production of surfactant

Decreasing of speed of mucociliar transport with unchangedproperties of sputum - drugs which stimulate cilia functiondrugs which stimulate cilia functionSignificant disorders of bronchial permeability, morphological

changes of bronchi (atrophy of mucous membrane, bronchial stenosis), excessive production of mucus - alkali inhalations

Signs of allergic reaction with increased histamine activity - antihistamine drugsantihistamine drugs

NONPRODUCTIVENONPRODUCTIVECataral inflammation (usually viral), reflector and central cough -

anticough drugsanticough drugsSigns of allergic reaction - antihistamine drugsantihistamine drugsBronchospasm - broncholyticsbroncholytics

REHYDRANTS IN ALL CASES

Stimulants of breathingStimulants of breathing ((analepticsanaleptics))

Analeptics of direct actionAnaleptics of direct action: : bemegrid, ethymisol, caffeinebemegrid, ethymisol, caffeineAnaleptics of mixed actionAnaleptics of mixed action: : cordiamin, camphorcordiamin, camphor, , carbon acidcarbon acid ((carbogen – mixture of Ocarbogen – mixture of O22 and and COCO22))Analeptics of reflex actionAnaleptics of reflex action: :

lobelin, cytitonlobelin, cytiton

AethimizolAethimizol (Aethimizolum) (Aethimizolum)Sodium caffeine-benzoateSodium caffeine-benzoate (Coffeinum- (Coffeinum-

natrii benzoas)natrii benzoas)BemegridBemegrid (Bemegridum) (Bemegridum)

CordiaminCordiamin (Cordiaminum) (Cordiaminum)Camphor Camphor (Camphora)(Camphora)

DRUGS FOR BRONCHIAL DRUGS FOR BRONCHIAL ASTHMAASTHMA

IntroductionIntroduction Chronic inflammatory disease of the Chronic inflammatory disease of the

airwaysairways Most common childhood chronic Most common childhood chronic

disease disease Affects ~4.8 million (CDC, 1995)Affects ~4.8 million (CDC, 1995) >100 million days of restricted >100 million days of restricted

activityactivity 470,000 hospitalizations/yr470,000 hospitalizations/yr

IntroductionIntroduction >5000 deaths annually >5000 deaths annually

Highest in blacks ages 15-24Highest in blacks ages 15-24 Hospitalizations highest in blacks & Hospitalizations highest in blacks &

childrenchildren

Pathogenesis and Pathogenesis and DefinitionDefinition

Key pointsKey points Chronic inflammatory disorder of the Chronic inflammatory disorder of the

airwaysairways Immunohistopathologic features Immunohistopathologic features

denudation of airway epitheliumdenudation of airway epithelium collagen deposition beneath basement collagen deposition beneath basement

membranemembrane edemaedema mast cell activationmast cell activation

Working definition of asthma (1995, Working definition of asthma (1995, NHLBI)NHLBI) Asthma is a Asthma is a chronic inflammatory chronic inflammatory

disorder of the airwaysdisorder of the airways in which in which many many cells & cellular elements play cells & cellular elements play a rolea role (mast cells, eosinophils, T (mast cells, eosinophils, T lymphocytes, macrophages, neutrophils, lymphocytes, macrophages, neutrophils, & epithelial cells). & epithelial cells).

Airflow limitation Airflow limitation Acute bronchoconstrictionAcute bronchoconstriction

stress - mechanisms ??stress - mechanisms ?? Airway edemaAirway edema mediatorsmediators

increase microvascular permeability/ leakageincrease microvascular permeability/ leakage mucosal thickening & airway swellingmucosal thickening & airway swelling

airway rigidityairway rigidity

To remove attack of bronchial To remove attack of bronchial asthma asthma

Broncholytic drugsBroncholytic drugs::AdrenomimeticsAdrenomimetics ( (αα,, ββ--adremonimeticsadremonimetics, , ββ--adrenomimeticsadrenomimetics, , ββ22--adrenomimeticsadrenomimetics))MethylxantinesMethylxantinesCholinoblockersCholinoblockers ( (MM--cholinoblockerscholinoblockers, , ganglionblockersganglionblockers))

Antiallergics and drugs that Antiallergics and drugs that reduce airway reduce airway hyperresponsivenesshyperresponsivenessExpectorants Expectorants

Beta-adrenomimeticsBeta-adrenomimeticsSalbutamolSalbutamol, , Ventolin,Ventolin, Berotek,Berotek, AsthmopentAsthmopent

Asthma Treatment/Quick Asthma Treatment/Quick ReliefRelief

Short-acting betaShort-acting beta2 2 agonists agonists Relax airway smooth muscle and increase Relax airway smooth muscle and increase

in airflow in <30 minutesin airflow in <30 minutes Drug of choice for treating symptoms and Drug of choice for treating symptoms and

exacerbations and EIBexacerbations and EIB Use of >1 canister/mo indicates Use of >1 canister/mo indicates

inadequate control and indicates need to inadequate control and indicates need to intensify anti-inflammatory txintensify anti-inflammatory tx

Regularly scheduled useRegularly scheduled use NOT NOT recommendedrecommended

Long-acting beta-Long-acting beta-22 agonists agonists Relax airway smooth muscleRelax airway smooth muscle Duration of action >12 hrsDuration of action >12 hrs Not used in acute exacerbationsNot used in acute exacerbations Adjunct to anti-inflammatory tx for long-Adjunct to anti-inflammatory tx for long-

term symptom control especially term symptom control especially nocturnal symptomsnocturnal symptoms

MethylxanthinesMethylxanthinesTheophyllinTheophyllin (of prolonged action)(of prolonged action)

MethylxanthinesMethylxanthines Provides mild-moderate bronchodilationProvides mild-moderate bronchodilation Low dose has mild anti-inflammatory Low dose has mild anti-inflammatory

actionaction Sustained release form used as alternative Sustained release form used as alternative

but not preferredbut not preferred to long-acting beta to long-acting beta22 agonists to control nocturnal symptomsagonists to control nocturnal symptoms

Use may be necessary because of cost or Use may be necessary because of cost or patient compliancepatient compliance

M-cholinoblockersM-cholinoblockersAtropine sulfateAtropine sulfate, , Solutan, Ipratropii Solutan, Ipratropii

bromidum (Atrovent)bromidum (Atrovent)

Anticholinergics Anticholinergics Cholinergic innervation important in Cholinergic innervation important in

regulation of airway smooth muscle toneregulation of airway smooth muscle tone Ipratropium bromide (quaternary Ipratropium bromide (quaternary

derivative of atropine without its’ side derivative of atropine without its’ side effects)effects)

Additive benefit with inhaled beta Additive benefit with inhaled beta 22--agonists in severe asthma exacerbationsagonists in severe asthma exacerbations

Effectiveness in long-term management not Effectiveness in long-term management not demonstrateddemonstrated

Inhibitors of mast cells Inhibitors of mast cells degranulationdegranulation

Cromolyn, KetotifenCromolyn, Ketotifen and and NNedocromiledocromil antagonize antigen-induced (IgE-mediated) antagonize antigen-induced (IgE-mediated) mast cell degranulation mast cell degranulation

they prevent the release of histamine and they prevent the release of histamine and slow-reacting substance of anaphylaxis (SRS-slow-reacting substance of anaphylaxis (SRS-A) - mediators of type I allergic reactionsA) - mediators of type I allergic reactions

their beneficial effects in the treatment of their beneficial effects in the treatment of asthma are largely asthma are largely prophylacticprophylactic

Cromolyn & nedocromil Cromolyn & nedocromil Have distinctive propertiesHave distinctive properties Similar anti-inflammatory reactionsSimilar anti-inflammatory reactions

blocks Clblocks Cl - - channels channels modulate mast cell mediator releasemodulate mast cell mediator release modulate eosinophilic recruitmentmodulate eosinophilic recruitment inhibits early and late asthmatic response to inhibits early and late asthmatic response to

antigen challengeantigen challenge

Cromolyn & nedocromilCromolyn & nedocromil Similar anti-inflammatory reactionsSimilar anti-inflammatory reactions

inhibits bronchospasm (exercise, cold dry inhibits bronchospasm (exercise, cold dry air, bradykinin aerosol)air, bradykinin aerosol)

nedocromil more potent in inhibiting nedocromil more potent in inhibiting bronchospasm in the above situationsbronchospasm in the above situations

Both reduce asthma symptoms Both reduce asthma symptoms improve PFimprove PF reduce need for short acting beta2 agonistsreduce need for short acting beta2 agonists

Cromolyn & nedocromilCromolyn & nedocromil Dosing requirementsDosing requirements

recommended for both 4 X/dayrecommended for both 4 X/day nedocromil effective at 2 X/daynedocromil effective at 2 X/day

Clinical response for both is less Clinical response for both is less predictable than steroidspredictable than steroids

Both have strong safety profileBoth have strong safety profile

KetotifenKetotifen TiladeTilade ( (sodium nedocromilsodium nedocromil))

Corticosteroid hormones in the Corticosteroid hormones in the management of asthmamanagement of asthma

In 1991- guidelines for the diagnosis and In 1991- guidelines for the diagnosis and management of asthma were published management of asthma were published by the National Asthma Education by the National Asthma Education Program (USA). This report described Program (USA). This report described the patho-physiology of asthma including the patho-physiology of asthma including airway obstruction, airway inflammation, airway obstruction, airway inflammation, and airway hyperresponsiveness. and airway hyperresponsiveness.

Since then, Since then, corticosteroids have moved corticosteroids have moved to the forefront in the treatment of to the forefront in the treatment of asthmaasthma..

CorticosteroidsCorticosteroids Dose dependent on product and Dose dependent on product and

delivery devicedelivery device 2 X/day use is common in moderate-to-2 X/day use is common in moderate-to-

severe persistent asthma severe persistent asthma 1 or 2 X/day may be used in mild 1 or 2 X/day may be used in mild

persistent asthmapersistent asthma

Inhaled corticosteroidsInhaled corticosteroids BeclomethasoneBeclomethasone

BudesonideBudesonide Dexamethasone Dexamethasone

Flunisolide Flunisolide Fluticasone Fluticasone

TriamcinoloneTriamcinolone

Administration corticosteroids by Administration corticosteroids by inhalation limits the systemic adverse inhalation limits the systemic adverse

reactions associated with oral or reactions associated with oral or parenteral therapy parenteral therapy

Administration of inhaled Administration of inhaled corticosteroidscorticosteroids

by the use of chambers or spacers by the use of chambers or spacers these devices help decrease systemic these devices help decrease systemic

absorption and subsequent adverse absorption and subsequent adverse reactions of the corticosteroids reactions of the corticosteroids

most inhaled therapy is delivered via most inhaled therapy is delivered via metered dose inhalersmetered dose inhalers

other method - the breath-actuated other method - the breath-actuated dry powder inhaler devices dry powder inhaler devices (Rotahaler, Diskhaler, Turbuhaler) (Rotahaler, Diskhaler, Turbuhaler)

PrednisolonPrednisolon, , HydrocortizoneHydrocortizone, , DexamethazoneDexamethazone..

Leukotriene modifiersLeukotriene modifiers Leukotrienes are potent biochemical Leukotrienes are potent biochemical

mediators released from mast cells, mediators released from mast cells, eosinophils, and basophils that:eosinophils, and basophils that: contract bronchial smooth musclecontract bronchial smooth muscle increase vascular permeabilityincrease vascular permeability increase mucus secretionsincrease mucus secretions attract & activate inflammatory cells in attract & activate inflammatory cells in

airwaysairways

Potential role in the treatment Potential role in the treatment of asthmaof asthma

ZileutonZileuton - a 5-lipoxygenase inhibitor - a 5-lipoxygenase inhibitor

ZafirlukastZafirlukast - a leukotriene-receptor antagonista leukotriene-receptor antagonist

Leukotrienes attract cellular infiltrates Leukotrienes attract cellular infiltrates

producing epithelial injury, abnormalities in producing epithelial injury, abnormalities in neural mechanisms, increases in airway smooth neural mechanisms, increases in airway smooth muscle responsiveness, and airway obstructionmuscle responsiveness, and airway obstruction

Leukotriene modifiersLeukotriene modifiers Zafirlukast & zileuton (oral tabs)Zafirlukast & zileuton (oral tabs)

improves lung fx and diminishes symptoms improves lung fx and diminishes symptoms & need for short-acting beta& need for short-acting beta22 agonists agonists

Studies in mild-moderate asthma Studies in mild-moderate asthma showing modest improvementsshowing modest improvements

Alternative to low-dose inhaled steroids Alternative to low-dose inhaled steroids for pts. with mild persistent asthmafor pts. with mild persistent asthma

Further study in of other groups neededFurther study in of other groups needed

Leukotriene modifiersLeukotriene modifiers Zafirlukast - leuktriene receptor antagonistZafirlukast - leuktriene receptor antagonist

attenuates late response to inhaled allergen and attenuates late response to inhaled allergen and post-allergen induced bronchospasmpost-allergen induced bronchospasm

modest improvement in FEVmodest improvement in FEV1 1 (11% > placebo)(11% > placebo) improved symptomsimproved symptoms reduced albuterol usereduced albuterol use

Warning - increases warfarin half-life and Warning - increases warfarin half-life and PT & PTT must be monitored with dose PT & PTT must be monitored with dose adjustment when indicatedadjustment when indicated