EXPECTORANT.pdf

cough

1. ANTITUSSIVE
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2. Contents
Introduction
Definition
Mechanism of cough production
Types of cough
Classification
AntitussivesMOA
Drugs
Screening methods
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3. Introduction
Symptom of respiratory system:
no sputum---antitussives
Cough
sputum---expectorants
Asthma-----antiasthmaticdrugs
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4. DEFINITION
ANTITUSSIVE:-
Adrugthatsuppressescoughingpossiblyby
reducingtheactivityofthecoughcenterinthebrain.
EXPECTORANT:-
Adrugthatenhancesthesecretionofsputum.
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5. Cough receptors (chemo-and-mechanoreceptors )
lie in mucosa of the bronchial tree from the nose
to the distal bronchi.
The impulses from these receptors are
transmitted through the vagusand
glossopharyngealnervesto the cough center in
the medulla.
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6. 6

7. Mechanismofcoughproduction
The cough receptors lie in the mucosa of the bronchial tree.
Afferent impulses passes to the medulla.
Then an autonomic sequence of events is triggered by
medulla
causing certain effects.
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8. Two Basic Types of Cough
Productive cough
Congested, removes excessive secretions
Nonproductive cough
Dry cough
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9. Classification of cough
Acute:-less than 3 weeks.
Sub-Acute:-between 3-8 weeks.
Chronic:-longer than 8 weeks.
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10. COUGH PHYSIOLOGY
CoughReflex:-
-Initiatedbyirritationofsensoryreceptorsinthe
respiratorytract.
-Toremovesecretionofforeignobjects.
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11. Coughing
Mostofthetime,coughingisbeneficial
Removesexcessivesecretions
Removespotentiallyharmfulforeign
substances
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12. CLASSIFICATION
1)CENTRALLY ACTING ANTITUSSIVE:-
Narcotic antitussive:-
Codeine
Hydrocodone
Oxycodone
Non-narcotic antitussive:-
Dextromethorphan
Noscapine
Propoxyphene
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13. CLASSIFICATION
2)PERIPHERALLYACTINGANTITUSSIVE:-
Mucosalanaesthetics:-
Benzonatate
Chlophedianol
Hydratingagents:-
Steam
Aerosols
Miscellaneous:-
Bromhexine
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14. ANTITUSSIVE MOA
OPIOIDS:-
Suppressthecoughreflexbyactingonthe
coughcenterinthemedulla.
NON-OPIODS:-
Suppressthecoughreflexbynumbingthe
stretchreceptorsintherespiratorytractandpreventing
thecoughreflexfrombeingstimulated
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15. ANTITUSSIVE INDICATION
Usedtostopthecoughreflexwhenthecoughis
non-productivei.edrycough.
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16. ANTITUSSIVE CONTRAINDICATIONS
Asthma
COPD
Hypersensitivity
Head injury
Pregnancy
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17. Codeine
Selectivelysuppresscoughcenterinmedullaoblongata.
Pharmacokinetics:
Wellabsorbedfromoralandinjection.
10%convertedtomorphinethroughdemethylation.
ClinicalUses:
Drycough
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18. Codeine: Brand Names
Codifos
Corex
Codokuff
Cufex
Tossex
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19. Codeine: Possible Side Effects
Shortnessofbreath
Sedation
Euphoria
allergicreactions
constipation
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20. Hydrocodone
Antitussiveagent
Analgesicagent
morepotentthancodeine
5mgofhydrocodoneisequivalentto30mgof
codeinewhenadministeredorally
Iscombinedwithananticholinergicdrug
(homatropine)
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21. Hydrocodone:
Possible Side Effects
Light-headedness
Sedation
Constipation
allergic reactions
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22. Dextromethorphan
Dextrorotatorystereoisomersofamethylated
derivativeoflevorphanol.
ClinicalUse:
Drycough.
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23. Dextromethorphan: Brand Names
Suppressa
Corex-DX
Cotuss
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24. Dextromethorphan:Possible Side Effects
Slowbreathing
Confusion,hallucinations
Anxiety
Restlessfeeling
Nervousness
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25. Benzonatate
Isanon-narcoticcoughmedicine
Itworksbynumbingthethroatandlungs,making
thecoughreflexlessactive
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26. Benzonatate: Possible Side Effects
Headache
Drowsiness
Upset stomach
Constipation
Mild itching or skin rash
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27. ANIMAL MODELS
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28. ANIMAL MODELS
1.Antitussiveactivityafterirritantinhalationinguineapig.
2.Coughinducedbymechanicalstimulation.
3.Coughinducedbystimulationofthenervuslaryngicus
superior.
4.Coughinducedbyammoniainthecat
5.Coughinducedbysulfuricacidinthedog
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29. Antitussiveactivity after irritant inhalation in
guinea pig
Purposeandrationale:-
Thesensitivereceptarsarelocatedinbronchialtreeand
stimulatedmechanicallyandchemically.
Requirements:
Guinea pigs (300-400g),
7.5% Citric acid in water,
Test & standard substance,
Cylindrical glass vessel.
Cylindrical glass vessel
with 2 tubes at either ends.29

30. Procedure:-
Guinea pig of either sex 300-400gm
Animal placed in cylindrical glass vessel
Guinea pig exposed to aerosol of 7.5% citric acid in water 10 min
No of tussiveresponse is registered
One hour later test substance is applied s.cor orally
After 30 min guinea pig is subjected to aerosol again
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31. Evaluation:-
Thenumberofcoughsaftertreatmentis
expressedaspercentageofthecontrolperiod.Using
variousdosesED50valuescanbecalculated.
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32. Cough induce by mechanical stimulation
Purpose and rationale :
Coughcanbeinducedbymechanicalstimulationof
thetracheainanesthetizedguineapigs.
Requirements :
Maleguineapigs(350-400g),Testdrug,Standarddrug-
codeine(15,30,&60mg/kg),Thinsteelwire.
Thin steel wire inserted
into trachea
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33. Procedure :
Maleguineapigsarelightlyanesthetized.
Maintainconstantbodytemperatureof37
0
Cbymeansofheatedplate.
Thinsteelwireisgentlyinsertedintothetracheathroughasmall
incisionnearcricoidcartilage.
Coughsareevokedbypushingthesteelwiretoreachbifurcationof
trachea
Animalsarerandomlyassignedtoreceivethetestdrugatvariousdoses
orthestandard(codeine15,30,60mg/kg).Tenanimalsperdoseare
used.
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34. Evaluation:
•Evaluationofstatisticalsignificanceoftheresultisperformed
withstudent’st-test.
•ED
50valuesdeterminedbylogittransformation.
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35. Cough induced by stimulation of the nervus
laryngicussuperior :
Purposeandrationale:
StimulationofNervouslaryngicussuperiorinduces
coughing.Antitussiveagentswithpredominatelycentral
actionsuppressthecoughingreflex.
Requirements:
Catsofeithersex(2-3kg),
Pentobarbital(40mg/kg),
Testcompound,
Standard–Codeinephosphate
Fleischtubepneumotachograph.
Fleischtube pneumotachograph
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36. Procedure:
Catsofeithersexareanesthetized.
Thefurisshavedventrallyattheneck&smallincisionsaremadeatbothsides
oflarynx.
Thetracheaiscannulated.ThecannulaisconnectedwithFleischtube
Onefemoralarteryandonefemoralveiniscannulated
SmallhookelectrodesareattachedtoeachlaryngealnerveandWave
impulsesareappliedevery5min(control)
IntensityofforcedexpirationismeasuredbyFleischpneumotachograph&
recordedwithbloodpressureonapolygraph.Thestimuliarerepeated
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37. Evaluation:
Totalorpartialsuppressionofforced
expirationarerecordedovertime&expressedas
percentageofcontrol.
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38. Coughinducedbyammoniainthecat
Purpose and rationale :
Coughisinducewiththehelpofammonia.
Requirements :
Cats,6%pentobarbitonesodium,smokedpaper
kymograph,Trachealcannula,ammoniavapour,polythene
tube.
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39. Procedure :
Cats are lightly anaesthetized.
The trachea is then cannulated; The carotid artery is connected
to a mercury nanometer.
Injections are made intravenously in the femoral vein.
Coughsarerecordedonasmokedkymographbyalightlysprung
lever
Ammoniaisleadintorespiratorysystembymeansofathreeway
tap.
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40. Thecatisallowedtoinhaleammoniavapourforoneinspiration.
Thecoughstimuliareappliedeverythreeminutesuntil3or4
control
coughresponsesofsimilarintensityanddurationareobtained.
Thetestdrugisthenadministeredintravenouslyandcough
stimuliare
repeatedatsimilarintervalsuntilthecoughresponsereturnsto
normal.
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41. Evaluation:
codeineisusedastheantitussivestandard,sinceit
supressescoughingcompletelyatadoseof2mg/kgorless.
Pholcodeineandihydrocodeineareapproximatelyaspotentas
codeine.Thetestdrugsarescoredaccordingly.
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42. Coughinducedbysulfuricacidinthedog
Rationale:
Coughisinducewiththehelpofsulfuricacid
Requirments:
Dogs,DeVilbissnebulizers,0.5MSulfuricacid,Codeine,
dihydrocodeine,testantitussivedrugs.
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43. Procedure:
Dogsareplacedinaspecialwoodenbox.
Throughtwoholesafinevapourof0.5Msulfuricacidis
sprayed.
Acountofthenumberofcoughsisobtainedbylistening
throughearphonestoamicrophoneattachedtothedog`s
throat.
After two test periods 1 hour apart, a drug is given before the
next test period.
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44. Evaluation:
Thepercentinhibitionisobtainedbydividingthe
numberofcoughsbythenumberofcoughsduringthecontrol
period.
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45. Referensces
Vogel,W.H.,Scholkens,B.A.,Sandow,J.,Muller,G.andVogel
W.F.,:DrugDiscoveryandEvaluationPharmacologicalAssays.
2
nd
ed.Spinger-VerlagBerlinHeidelberg,NewYork,Germany,
pp.352-376(2002).
Turner,R.A.,Hebborn,P.,:ScreeningMethodsof
Pharmacology,Vol.-1.AcademicPress,London,pp.238
(1971).
www.wikipedia.com.
Tripathi,K.D.,:EssentialsofMedicalPharmacology.5
th
ed.
JaypeeBrothersMedicalPublishers(P)Ltd.,NewDelhi,India,
pp.195,209(2004).
www.googleimages.com
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