Bronchial asthma

Reference:
K. D. Tripathi. Essentials of Medical Pharmacology, 6th edition. Jaypee Publication Pg. No. 213-230.
This slide deck give detail presentation on causes, pathophysiology and pharmacotherapy of bronchial asthma.
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1. Prof. Shaikh Abusufiyan
Part-I Bronchial Asthma and
its treatment

2. 2
At the end of this e-learning session you are able to…
qDiscusscharacteristics, manifestation and
pathophysiology of asthma.
qClassify anti-asthmatic drugs.

3. Characteristics
qBronchialasthmaischaracterized
by:
"hyper-responsivenessofbronchial
smoothmuscle
"resultinginnarrowingofairtubes
"oftenaccompaniedbyincreased
secretion
"mucosaledemaandmucusplugging.

4. Causes of Bronchial Asthma

5. Allergens responsible for asthma
Mites
Hair and fur animals
Plant pollen
FoodDrugs, Enzymes, Antiobiotics
Dust

6. Genetic factor:
•Excessive production of antibodies
specific to allergyi.eIgE
atopy
(significant factor responsible for asthma).

7. Pathophysiology
qDifficulttopredict.
qThediseaseismostlyrelatedto-->type1hypersensitivity
reaction.
qAnyallergicreactionconsistof3phase:
1.Immunephase
2.Patho-chemicalphase
3.Pathophysiologicphase

8. Q&A
1.Enlist characteristics of asthma.
2.Give its few symptoms.
3.Whatarethe3phaseofallergicreactions?
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9. 1. Immune (Ag-Ab phase)
Allergens
Activation of T-cell & B cells
Formation of antibodies

10. In bronchi antibodies
bind to the
Basophils
mastcells
eosinophils

11. 2. Patho-chemical phase
Asaresultofantigen-antibodyreaction:
Basophils,mastcellsandeosinophilsmembraneof
bronchialsmoothmusclesproduces
biologicallyactivesubstances
(histamine,5-HT,prostaglandins,leukotrienes,
thromboxaneect)

12. induces:
ØInflammation
Ømucous edema
Øhypersecretion of mucous
Øcumulation of exudate in bronchial lumen.
•Patho-chemical phase
3. Patho-physiological phase
Leads to asthmatic attack

13. ManagementIncludes:
1.Preventivemeasures
Avoidthecontactwithallergen.
2.Ifitisimpossible
Hypo-sensitizationwithstandardallergens

14. 3. Drug therapy
q2 drug categories are used:
A.Anti-inflammatory
B.Bronchodilators

15. 3. Drug therapy
A.Anti-inflammatory
I.Hormone containing Ex. Corticosteroids.
—Systemic: Hydrocortisone, Prednisolone.
—Inhalational: Beclomethasone dipropionate,
Budesonide
II. Non-hormone containing
I.Mast cell stabilizersEx. Sodium
cromoglycate
II.Leukotriene antagonists Ex.Montelukast,
Zahrlukast

16. 3. Drug therapy
B. Bronchodilators
I.Anti-cholinergics: Ex.Ipratropium bromide,
Tiotropium bromide.
II.Beta-2-Agonists: Ex. Salbutamol, Terbutaline,
Formoterol, Ephedrine.
III.Methyl xanthines: Ex. Theophylline
(anhydrous), aminophylline

17. Q&A
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19. Prof. Shaikh Abusufiyan
Part-II Bronchial Asthma and
its treatment

20. 20
At the end of this e-learning session you are able to…
qDiscussmechanism of action and
pharmacology of corticosteroids.
qExplain pharmacotherapy of Status
asthmaticus and COPD.

21. Corticosteroids
Mechanism:
—They act by 3 imp mechanisms:
1. cell membrane stabilization
2. inhibition of inflammatory mediators
3. restoring the sensitivity of beta adrenergic receptors.
Improve air flow, influence air way remodeling and retard
disease progress

22. Systemic corticosteroids:
•Usedmainlyincaseof:
Severechronicasthma
Notcontrolledbybronchodilatorsand
inhaledsteroids

23. —TreatmentProtocol:
—startwithprednisolone20to60mgdaily
attemptdosereductionafter1to-2weeksofgoodcontrol
andfinallytrytoshiftthepatientontoaninhaledsteroid.
—onlyinfewcasespatientsrequirelongtermoralsteroids
—thendoseshouldbekeptatminimum.

24. `
Status asthmaticus/acute asthma attack:
—Asthmanotrespondingto-->bronchodilatortherapy
—TreatmentProtocol:
1.startwithhighdoseor;2.userapidlyactingi.v.glucocorticoid
generallyactsin6to24hours
shifttooraltherapyfor5to7daysandthendiscontinueabruptly.

25. `
Chronic obstructive pulmonary disease (COPD)
—COPD
A short course(1-to 3 weeks) of glucocorticoid

26. Inhaledcorticosteroids:
ØTheseareglucocorticoidswith-->
hightopical&lowsystemicactivity
dueto:
Øpoorabsorption
ØMarkedfirstpasseffect
ØEg.beclamethazone,budesonide,
fluticazone

27. Advantage:
ØMosteffectiveandsafe
ØConsideredtobethefirstlinedrugs-->forasthmatreatment.
Indicationsofinhaledcorticosteroids:
ØItisusedwhen;
1.inhaledB2agonistareneededondailybasis
2.diseaseisnotjustepisodic.

28. Treatment strategy for Inhaled corticosteroids
ØStartwith100to200microgBD
ØTitratedoseupwardevery3to5
days
ØMaximum400microg.

29. Treatment strategy for Inhaled corticosteroids
ØNorole-->duringanstatusasthmaticusor
incaseofacuteattack
—Short courses oforal steroid may be
initiated --> if asthma isexacerbation.
—If patients asthma well controlledfor long
period ---> can even stop inhaled steroid
—Safe during pregnancy

30. —COPD:
—Highdoseinhaledsteroids-->is
neededinadvancedCOPD
—Precaution:
—Shouldnotbeusedinearly/mild
cases

31. Q&A
1.Enlist characteristics of asthma.
2.Give its few symptoms.
3.Whatarethe3phaseofallergicreactions?
3
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32. Prof. Shaikh Abusufiyan
Part-III Bronchial Asthma and
its treatment

33. 33
At the end of this e-learning session you are able to…
qDiscusspharmacology of cromonsand
leukotriene receptor antagonists.
qExplain pharmacology of Beta2agonist.

34. Cromones
Ex. cromolyn sodium and nedocromil
—MoA: Stabilize mast cell membranes
Use: in case of:
—Aasthma of pediatric practice
—intermittent or mild type of
persistent asthma.
Leukotriene R antagonists
Ex. montelukast, zafirlukast
—Moderate Anti-inflammatory activity
Use:in case of:
—Asthma induced by aspirin
—Physical exertion induced asthma

35. LEUKOTRINE RECEPTORS ANTAGONISTS
—Montelukast and Zafirlukast:
—Both have almost similar action i.e it
produces
1.Bronchodilatation
2.Reducedsputumeosinophilcount
3.Suppressionofbronchialinflammation
andHyperactivity

36. LEUKOTRINE RECEPTORS ANTAGONISTS
–MoA: Competitive antagonism of cys LT1 R mediated
—Bronchoconstriction
—Eosinophil recruitment
—Increase vascular permeability

37. Clinical effectiveness of LTR antagonist:
•Somepatientsare:
—Responders
—AndsomeareNon-responderto
theanti-LTtherapy.

38. Clinical effectiveness of LTR antagonist:
Theyareindicatedfor:
—mildtomoderateasthmaasalternativeto
inhaledglucocorticoids.
—Moreacceptabletochildren’s
—Severeasthma
—theypermitreductioninsteroiddose
—andneedforrescueB2agonistinhalations.

39. Pharmacokinetics
—Plasma half life:
—Montelukast is 3 to 6 hrs
—While that of zafirlukastis 8 to 12 hrs.

40. Side effects
—Are Very few like:
—Eosinophilia
—Rashes
—Headache
—Neuropathy –but infrequent

41. Q&A
1.What is MOA of cromones?
2.Blocking of ______ receptors by Montelukastand
Zafirlukastresponsible for anti-asthmatic action.
3.Namecategoryofanti-asthmaticdrugswhicharemore
acceptableinpediatricspatients.
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42. Bronchodilators
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43. —InhalationBeta2-agonists
Oneofthebasicdrugamongbronchodilators.
•2types:
—Short-acting(durationofaction5to6h)
Beta2-agonistsEx.Fenoterol,salbutamol.
-Use:forquickreliefofasthma.

44. oLong-acting(t1/2:12h)Beta2-
agonists:
-Ex.Farmoterol,salmoterol
-Use:forpreventionofasthma
symptoms

45. 1. Beat2R stimulation
Increase cAMP formation in bronchial muscles
Relaxation of bronchi (Bronchodilatation)
2. In addition, increase cAMP in mast cell and other inflammatory cells
Decrease release ofmediators
Mechanism of Action

46. —Adrenalineandisoprenalineareeffective
bronchodilators
Nonselective(ProducescardiacSE)
—Theselectiveagonistsareusedinasthma-
->tominimizecardiacSE.

47. —Salbutamol(Albuterol)-->AhighlyselectiveBagonist
cardiacsideeffectsarelessprominent.
—Selectivityisfurtherincreasedby--->inhalingthedrug.

48. —InhaledSalbutamol
bronchodilatationwithin5minandtheaction
lastsfor2to4hours.
—Itis,therefore,usedtoterminateattacks
ofasthma

49. —Becauseofitss.E-->notsuitableforroundtheclockprophylaxis
—SE:
—Muscletremors.
—Palpitation
—restlessness
—nervousness
—throatirritation
—andankleoedema.

50. ORAL DOSE
—Salbutamolundergoes-->pre-systemicmetabolisminthegutwall
—oralbioavailability-->is50%.
—OralSalbutamolactsfor-->4to6hours
—Becauseofmorefrequentsideeffects,oralBeat2agonisttherapy
isreservedforpatientswho
—cannotcorrectlyuseinhalers
—orasalternative/adjuvantdrugsinsevereasthma.

51. Q&A
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53. Prof. Shaikh Abusufiyan
Part-IV Bronchial Asthma and
its treatment

54. 54
At the end of this e-learning session you are able to…
qExplainpharmacology of anti-cholinergic
and Methylxanthines.
qDiscuss management of Sever asthmatic
status.

55. —Anti-cholinergicdrugs
—Ex.atrovent,ipratropiumbromide
—usedpredominantlyinNocturnalasthma.
—andingeriatricpatients-->duetoits
minimumcardio-toxiceffect.

56. •Methylxanthine
ascomparedtootherbronchodilators
lessBroncho-dilatingpotential.
•2types:
—long-acting(t1/2-12h)-->Ex.Theodur,theopec,
theolong
—short-acting-->Ex.Aminophylline,Caffeine,theophylline

57. Pharmacological actions
CNS:
—Caffeine, theophylline:
CNS stimulants
Primarily affect the higher centers.

58. Pharmacological actions
•Caffeine: 110 to 250 mg produces
—a sense of well-being
—alertness
—Clear thinking
—allays fatigue
—Tends to improve performance
and motor activity.

59. CVS:
—Directly stimulate the heart and increases--> force of
myocardial contractions & HR.
—Theophylline--> Tachycardiacommon with theophylline
—Caffeine--> Unpredictable effect
-CO& cardiac work ---> increased.
-HR--> decreases
-Cardiac arrhythmias --> At high doses .

60. Effect on BP is variable and unpredictable:-
-Vasomotor centre & direct cardiac
stimulation--> tends to raise BP.
-Vagal stimulation& direct vasodilatation
--> tends to lower BP.
-Usually a rise in systolicand fall in diastolic
BP is observed.

61. —Smooth muscles:
—Relaxation
—Most prominent effect exerted on -->
bronchi of asthmatics
—Theophyllineis more potentthan caffeine
—But the effectis much less markedcompared
to inhaled beta R agonists
—Kidney:
-Mild diuretics

62. Q&A
1.Give action of methylxanthines on CNS.
2.What is action of Methylxanthineson bronchial smooth
muscles?
3.Namecategoryofanti-asthmaticdrugswhicharemore
acceptableingeriatricpatients.
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63. —Skeletalmuscles:3Typesofactions
—Caffeineenhances-->contractilepowerofskeletalmuscles.
—Increases-->releaseofCa2*fromsarcoplasmicreticulum
—facilitatesneuromusculartransmission-->byincreasingreleaseofAch

64. •Stomach:
Enhancessecretionofacid&pepsin
Gastricirritant

65. •Mastcellsandinflammatorycells:
Decreasesthereleaseofhistamine
contributetoanti-Inflammatoryactioninbronchialasthma.

66. Mechanism of action:
—3 distinct actions:-
(a) Release of Ca2+-->from sarcoplasmic reticulum
(b) Inhibition of phosphodiesterase (PDE)
Inhibit conversion of cAMP & cGMP--> 5-AMP & 5-GMP
Increase in level of cAMP& cGMP
Bronchodilatation, cardiac stimulation & vasodilatation

67. c)Blockadeofadenosinereceptors:
—Adenosineactsasalocalmediator-->inCNS,CVSandotherorgans.
Thefollowingeffectofadenosineareinhibited
•Contractssmoothmusclesespeciallybronchial
•Depressescardiacpacemaker
•Inhibitsgastricsecretion.
•Dilatescerebralbloodvessels

68. Management of asthmatic status (Severe asthma)
—Systemiccorticosteroids:(Methylprednisolone125mgevery6hIVor
Prednisolone50mg/dayperosorHydrocortisone200mg)
—Oxygen
—Inhalationsofshort-actingBeta-2-agonists-->Salbutamol5mgorFenoterol2
mggiventhroughnebulizer
-3timesat1sthour
-thenonceanhourtilldistinctimprovementisachieved
-then3to4timesaday.
—Inhaledanti-cholinergicdrugsorIVAminophylline.
—Ifnoniseffective-->artificiallungventilationisneeded.

69. Q&A
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