Adverse drug reactions.pdf

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1. Shaikh Abusufiyan
Part-01: Adverse Drug
Reactions
Pharma Learning Forever
1

2. At the end of this e-learning session you are able to…
A. Define ADR, Distinguish between desiredand
undesired effect/side effects and adverse effect.
B. Discuss epidemiologyand predisposing factors
affectingADR.
2

3. 3
Whendrugisadministeredtoapatientit produce 2 type ofeffects:
1. Desiredeffect
Clinically beneficialeffect
2. Undesiredeffect
Pharmacological effect which isapart from desiredeffect.
3

4. 4 4
2. Undesired effect are further dividedas:
qInnoccus& harmfuleffect
are calledasadversedrugreactionor
untoward reaction.
qDruginduce diseases are called as
iatrogenicdisease.

5. Why ADR haveincreasedinnumber&severity?
qDueto:
1. Increase availability of potent drugs.
2.Availability of dangerous drugs without prescription.
3.Exposureofmantodrugs&chemicalsusedin
industry&agriculture&viapollutedenvironment.
4.Polypharmacyi.eirrationaluseofmanydrugs
together
5.Selfmedicationforminorailments.
5 5

6. qToavoiddrugreactions,whichmaybefetal
“Donotusemedicineneedlessly”.
6
qSir William Oslersaid:
Oneofthedutyofthephysicianis
to “educatethemassesnottotake
medicine”.
6

7. qTerms frequently used but oftenwrongly
interchanged are side effect andadverse
reactions.
Sideeffects:
qTherapeutically undesirable butunavoidable
effect ofdrugs.
qTheyrarely lead to serious problem.
7 7

8. Definition
Adversedrugreaction(ADR):
q“Itisobnoxious(Injurious)&
unintendedresponseofdrugwhich
occursatdosesusedinmanfor
prophylaxis,diagnosisor
therapyofdisease”.
8 8

9. qAdverse reactions:
9
Itincludes:
qAddiction
qAllergicreaction
qAnaphylacticshock
qCardiacarrhythmias
qComa
qCHF
qDiabetesmellitus
qHemorrhage, hypo or hypertensionetc
9

10. Q&A
Q.1 What is difference between desireand
undesiredeffects?
Q.2 Give reason. Why ADR have increased in
numberand severity?
Q.3DifferentiatebetweenSideeffectandADR?
1
0

11. qDrugscausing a highdegree of adverseeffect-->
should never be used for minor ailments.
qEx.Chloramphenicol--> a highly toxic antibacterialagent
“salmonella meningealinfection”.
11 11

12. •Epidemiology:isthestudyofthe
patterns,causesandeffectsofhealth
anddiseaseconditionsindefined
populations.
12

13. PredisposingfactorsleadingtoADR
Areatsubstantialriskofdevelopinghaemolytic
crisisafter use of antimalerial drug likeprimaquine.
–Race:
1. Certain population in Asiaand south
east Asia aredeficient in Glucose-6-
phosphatedehydrogenase.

14. qThe rate at which drugs are acetylated -->
varies considerably between ethnicgroups.
qRapidacetylator--> predominate amongEskimos
andslowacetylator--> dominateamong thejews.
qSlowacetylator--> morelikelytodevelop
peripheral neuropathy due toisoniazid.
q14

15. •Sex:
–Womenaremorelikelytosufferadverse
reaction to certain drugs thanmen.
–EX.Agranulocytosiscausedbyphenylbutazone
orchloramphenicolisthreetimemore
commoninwomenthaninmen.
15

16. •Age:
–Elderelypatientsover60yearsofage
-->aremorelikelytosufferadversedrug
reactions.
–Theyaremoresensitive-->totheeffectof
powerfulanalgesics
–andtheyareopttobecome-->confusedand
disturbedbybarbiturate.
16

17. •In the neonates, especially whenpremature
Someoftheenzymesinvolvein
drugmetabolismandeliminationare
poorlydeveloped
Increasetheriskofadversedrugreaction.
Eg.Chloramphenicol
17

18. Reference:
•Dr.H.P.TipnisandDr.AmritaBajaj.ClinicalPharmacy,3rd
edition.CareerPublicationPg.No:330-342.
18

19. 1
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20. Q&A
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21. Shaikh Abusufiyan
Part-02: Adverse Drug
Reactions
Pharma Learning Forever
21

22. At the end of this e-learning session you are able to…
A.Explain Predisposing factors affectingADR
such as allergic disorders, renal and hepatic
diseases, plasma protein binding and drug
formulation.
B.Discuss different types of ADR.
2
2

23. •Allergicdisorders:
–Patientwithahistoryofallergic
disorderandhypersensitivity
reactions
aremorelikelytodevelopadverse
drugreactions
23

24. •Renal and hepaticdisease:
qImpaired renalfunction
predispose adverse reactions tothe drugsthat
are excretedunchanged.
•ex. Aminoglycosides andcephalosporin.
qHepaticdysfunction:
–ADRto the drugs that are de-toxicatedin
the liver Ex.Paracetamol.
24

25. •Plasma proteinbinding:
–Decreaseinplasmaalbuminsdue to
age,malnutrition ordisease
Modifybothpharmacologicalactivity
andmetabolism of drugs that are highly
protein bound.
25

26. qFormulation ofdrugs:
•Whenpharmaceuticalmanufacturerchangedtheexcipientpresentin
somecapsulesofphenytoinfromcalciumsulphatedihydratetolactose.
Manypatientsdevelopedsymptomsofphenytointoxicity.
•additives,solubilizers,stabilizersandotherexcipients
maypotentiatedrugaction,leadingtoadversedrugreaction.
26

27. •ADRclinicallydividedbased onthosethatarisesfrom:
•Thenormal pharmacological action of adrug
•And those that represent a totally abnormal
response.
•ADR into 2types
-TypeA
-TypeB
Classification of ADR
27

28. Q&A
Q.1 Which drugs produces ADR due to renaland
hepaticdamage?
Q.2 Explain with example how change in drug
formulationproduces ADR?
2
8

29. 22
1.Type A(Augmented)
Result of augmented pharmacological action of a drugs.
Predictable on the basis of a drugs known pharmacology
And depend ondose
Ex. Haemorrhage withanticoagulant
29

30. 30
2. Type B(Bizarre)
•Aretotally abnormal & are not
expected on the basis of known
pharmacology of drugs.
•Unpredictable Ex.
1.Hypersensitivityreaction
2.altered
-ADMEpattern
-G.Imotility
-Plasma and tissuebinding

31. •Sudden drugwithdrawal
also lead to severeADR
•Ex. Narcotic analgesics, hypnotics, antihypertensive and
corticosteroids.
31

32. Other Types ofADR
25
I.PharmacologicalADRs
-Extension of therapeuticeffect
-Non therapeutic Adverseeffect
II.Non-PharmacologicalADRs
-Hypersensitivity (Drugallergy)
-Idiosyncrasy(Pharmacogenetics)
-Photosensitivity
III.Disease relatedADR
IV.Multiple drugreaction 32

33. V. MiscellaneousADRs
Carcinogenecity
Teratogenicity(Dysmorphogenesis)
Drugdependence
Over dosage (Relative &absolute)
Drug induced sexualdysfunction

34. I. Non-pharmacologicalADRs:
qoccur as a result of an abnormal sensitivity/
reactivity of theindividualto a chemicalsubstances.
qnotpredictable
qonset is often abruptunexpected.
qhave serious & occasionally fatalout come.

35. 28
Hypersensitivity:
-Alteredreactivityorsensitizationofthepatient
resultingfrompriorexposuretoadrugor
chemicalthatbehaveslikeanallergen.
35

36. 28
Hypersensitivity:
qSubsequentexposure
elicitsanantigen-antibodyreactions
that produces symptomslike
•Itching
•Oedema
•congestion.
36

37. 29
Allergic drug reactions areeither
-Immediate
-Delayed
37
Immediate:
-Developed within minutes ofdrug exposure.
-Involve formation of antibodiesthat belong to the IgEclass

38. Upon re-exposure
antigen combines withantibodies
and releases certain natural substanceslike histamine, 5HT, bradykinin and
prostaglandins.
These substances reacted with smooth muscle of many tissues (bronchi, git, blood
vessels)
to produce characteristic sign ofallergic reaction.
38

39. Delayed:
qReaction developed slowly followingdrug challenge.
Clinically itproduces
Diffuserashes
Fever
Angioedema
Swollen lymphnode
Stiffjoints
REFERRED AS SERUMSICKNESS.

40. Reference:
•Dr.H.P.TipnisandDr.AmritaBajaj.ClinicalPharmacy,3rd
edition.CareerPublicationPg.No:330-342.
40

41. 4
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42. Q&A
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2

43. Shaikh Abusufiyan
Part-03: Adverse Drug
Reactions
Pharma Learning Forever
43

44. At the end of this e-learning session you are able to…
A.Explain Idiosyncrasy, photosensitivity and
Phototoxicity .
B.Discuss teratogenic effect of drug.
4
4

45. IDIOSYNCRASY(Pharmacogenetics)
Refertopeculiarityofbodilyfunctionthatcauses
an individual to react in an abnormal manner to a
drug.
Notduetoantigen-antibodyreaction
Butitisproduceddueto--->geneticallydetermined
defectinthepatients.

46. Pharmacogentics: Study of altered drug
responsewhich are under hereditarycontrol.
Ex. Patient having G-6-PDdeficiency:
Usual dose of primaquienemay causehemolyticanemia.

47. Slow acetylators
are more likely to develop polyneuritis
withisoniazid
Fast acetylators
may show drug resistance & drug
failure.

48. Photosensitivity
Skinhypersensitivityreaction
followinguse ofmanydrugs
on exposure to sunlight is termed as
photosensitization.

49. 2type of Photosensitivity
reactions:
Photoallergic
Phototoxic

50. Photoallergic
Photosensitizingdrugformanantigenby absorptionofsunlight
&combinationwith skinprotein.
Resultantantibodyformationsensitizesthe patient to further sun
exposure.

51. Phototoxicity
51
Characterized by-->severesunburn
ItisprobablyresultofaphotosensitizingchemicalabsorbingUV
lighttosuchanextend
thatitbecometoxictoepidermalcell.
Ex:amitriptyline,carbamazepine,clindamycine.

52. Q&A
Q.1 What is idiosyncrasy?
Q.2 Which ADR is observed with slow acetylatoron treatment
with isoniazid?
Q.3 Give examplesof few phototoxic drugs.
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2

53. Teratogenicity
Administrationofcertaindrugstopregnant
women,speciallyduringthefirsttrimester
producesfataldeformities.
Suchdrugs are said to be teratogenic.
Ex.Thalidomide

54. Thalidomide: Deformities in newborn
83 54
Congenitalmalformationofthefeet.Effectsofmaternaldrugs-
thalidomide.SelectedbyTom.Notspecifiedatthesource.
UploadedtoflickrbyOtisHistoricalArchivesNationalMuseumof
HealthandMedicine.-NCP14053
CCBY2.0,File:NCP14053.jpgCreated:4February2008.

55. Butthalidomide is safe in adults.
TheUSA-FDAhasestablishedcertaincategories
indicatingpotentialforadrugtocausebirth
defect.

56. Riskbenefitratiomustbetracedineachcases
&thendecisionshouldbetaken.
Ex:.Phenytoin
Risktothefoetusfromageneralizedmaternal
seizureonwithdrawalofthedrug
maybefargreaterthantheriskofdevelopinga
congenitalabnormalities.

57. Drugswith Known teratogenic effect
includes:
-Anti-epileptics (Phenytoin,phenobarbitone)
-Anti-thyroid(Carbimazole)
-Sex hormones (androgen,progesterone)
-Anti-neoplastic
-Corticosteroids
-Sulphonylurease

58. No drug should be used during first trimesterofpregnancy
unlessverynecessary.
Foetaldamageusuallydoesnotoccur-->whendrugsare
administeredlateinpregnancy.
But it may produce complications like:
-neonatalbleeding
-respiratory depression in thefoetus.

59. Reference:
•Dr.H.P.TipnisandDr.AmritaBajaj.ClinicalPharmacy,3rd
edition.CareerPublicationPg.No:330-342.
59

60. 6
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61. Q&A
Quiz-Attendance/Feedback:
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6
1

62. Shaikh Abusufiyan
Part-04: Adverse Drug
Reactions
Pharma Learning Forever
62

63. At the end of this e-learning session you are able to…
A.Why ADRare difficult to detect?
B.Explain approaches usedtodetect
andreportADRS.
6
3

64. Detection of adversedrug reactions...
•Since ADRs areunpredictable
difficult todetect
•Manytimesasignandsymptomare
sub-acuteanddonotformafamiliar
syndrome
ItisdifficulttoconfirmthattheADR
isduetoiatrogeniceffect.
64

65. •It is also difficult to differentiatebetween:
–Drug induceddisease
–Naturallyoccurringdisease
Solution:Methodofchallengeandre-challenge(re-
administrationofdruginducingADR)
canbeusedtoqualifyandquantifyADR.
65

66. •Approaches usedto detectADRS:
1.Drug-oriented system based on
cohort studies
2.Disease Oriented systemscalled
casecontrolstudies
3.Complication-orientedsystem
66

67. 1.Drug Oriented System or Cohortstudies:
•Thisinvolvestudyofindividuals
exposedtoaparticulardrugorselectedgroup
ofrecipienttothatdrug(Cohert).
HelptodetectfrequencyofADRattributedto
thatdrug
67

68. 1.Drug Oriented System or Cohortstudies:
Methodology:collectingpatientdataand
casereportsfromalargevarietyofpopulation
receivingparticulardrug
Reportarethananalysed
forprobabilityofcorrelationbetweenthedrug
anddisease.
68

69. Advantage:
•Link can be established between the
drug and adisease
Disadvantage:
•These studies areusually:
–short term multi-centrestudies
–Carried out at large no ofpatients
69

70. Disease Oriented SystemOr Case controlStudy
•Groupofpatientswithadisease
whichisthoughttobeduetodrug(case)
iscomapredwiththegroupwhodoesnot
receivethedrug.
70

71. ComplicationOriented System
•Thisapprochinvolvesthestudyof
individuals
whoaresufferingfromaclearlydefined
syndrome
whicharethoughttobedrugrelated.
•Ex.maternalthalidomideexposureand
phocomeliaofnewborn. 71

72. Complication-orientedsystems
qAdvantages: Particularvalueundercertain
circumstanceslike:
–event under investigation is a rarecondition.
–Theconditioniswelldefinedandrelatively
easy todiagnose
–the relationship between drug exposure and
disease detection isshort.
72

73. Q&A
Q.1 What is done to qualify and quantify ADR?
Q.2 Enlist approaches usedtodetect ADRS?
Q.3 Give examplesof complication oriented system.
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74. Pharmacovigilance and Post-marketing surveillance of medicines
qIt is concerned with:
–detection
–assessment
–and prevention of adverse effects or any
other possible drug-related problems
Goal:
–To achieve rationaland safetherapeutic
decisionsin clinical practice.

75. 1. Spontaneous reporting:
–Itcollectdata-->aboutsuspected
ADRsinacentraldatabase.
●Advantages:
–Itisrelativelycheaptoadminister
–canfollowaproductthroughoutitslife
–acceptreportstoover-the-counter
medicationandherbaltreatments.
Method of Reporting ADR:

76. ●Disadvantage:
–Such schemes are passive surveillance systems.
–Rely on the ability of health professionals:
●to recognise possible ADRs and to distinguish these
from symptomsrelated to underlying disease.

77. Important term in ADR Detection
●Signal detection:
–Asignalcanbedescribedasapossiblecausalrelationshipbetween
anadverseeventandadrugwhichwaspreviouslyunknown.
●Causalityassessment:
–Theassessmentofwhetheradrugisresponsibleforasuspected
ADR

78. 2. Yellow Card Scheme:
●The UK's Yellow Card Schemewas established in 1964 following the
thalidomide tragedy.
●It is operated by the Medicines and Health care products Regulatory
Authority (MHRA).
●Health care professionals can submit reportsof suspected ADRs --> using
a Yellow Cardor using an on-line form.

79. ●Anassociationbetweenthemedicineandtheevent
doesnothavetobeconfirmed.
●Asuspicionissufficient
forareporttobesubmitted.
●Newermedicinesunderintensivesurveillance-->areidentifiedwithaninverted
blacktrianglesymbolinproductinformation.
●Blacktrianglestatusisgenerallymaintainedforatleast2years.

80. ●InformationfromYellowCardreportsis
–enteredintoadatabase
–suspectedreactionsarecategorised-->usingthe
InternationallyAcceptedMedicalDictionaryforRegulatory
Affairs(MedDRA)
–andtheresultantsignalsgeneratedbythecombined
reports-->areassessedforcausality.

81. ●FurthertoconfirmADEitcouldalsoinvolve:
–requestingfurtherdetailsfromreporters
–contactingmanufacturers
–reviewingtheliteratureor
–conductingpharmacoepidemiologicalstudies.

82. 3. Direct patient reporting
–Patientshave been permittedto
report directly to MHRA.

83. 4. Published case reports:
–Case reportshave been described as a form of non-
systematic voluntary reporting.
–Disadvantage: Editors may demand
●a causal link
●higher standards of investigation
It can prevent case histories from reaching publicationand deter
many clinicians.

84. 4. Published case reports:
–Furthermore, the time it takes for a case
reportabout a suspected ADRto be
published could be Several months
during which time more patients may be
exposed.

85. Reference:
•RogerWalkerandCateWhittlesea.ClinicalPharmacyand
Therapeutics,5thedition.ChurchillLivingstoneElsever
PublicationPg.No:61-75.
85

86. 8
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87. Q&A
Quiz-Attendance/Feedback:
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7

88. Shaikh Abusufiyan
Part-05: Adverse Drug
Reactions
Pharma Learning Forever
88

89. At the end of this e-learning session you are able to…
A.Explain best practices in ADR reporting
and sample ADR reporting form?
B.Discuss Role of pharmacist in
preventing ADR.
8
9

90. Best Practices for Reporting ofADR:
qADR &medication errors shouldbereported-->
immediatelytothe physicians.
Hospital is encourage --> to report anyunexpected
ADR to the FDA/ Medical association/ Manufacturer.
90

91. 91
•Several practical approaches can be
initiated in the hospital setting
to increase effectiveness of detecting
and reportingADR.
-It include:
1. Retrospective
2. Activesurveillance

92. •Variousmethodofreportingcanbe
designedbyindividualpharmacistand
institutionsfortheiruse.
•Periodic publications can be utilised
to keep staff members
informed ofADR
92

93. SUSPECTEDADVERSEDRUG
REACTIONREPORTINGFORM(Link)
93

94. Role of pharmacist in preventing AdverseDrug Reaction
1. Detection of commonsyndromes:
A. Pharmacist may reduce the likelihood of
allergic and hypersensitivity reactionsby asking
the patient
whether or not he has ever experiencedan
allergic reaction todrug?
94

95. Role of pharmacist in preventing AdverseDrug Reaction
•IFanswerisYES-->thenpharmacist
should inquireabout
–type ofreaction
–and the drug that supposedly inducedit.
Ex. Skin reactionexhibited by the patient
inthe past by drugs likepenicillin.
95

96. Q&A
Q.1 What are two practical approaches in detecting
and reporting of ADR?
Q.2 What is use of periodic publications?
Q.3 How Pharmacist may reduce the likelihood of
allergic and hypersensitivity reactions?
9
6

97. 2. Overdosage:
–Pharmacist may prevent
over dosage which may result
of Physicianerror
By scrutinizing physician
prescription.
97

98. 2. Overdosage:
•or Patient voluntary administration ex.Sedatives
Pharmacistshouldattempttomaintainamountof such productshe
dispense
below toxiclevels.
•Two ways of limiting such productsare:
1. Request physician--> to limit prescriptionqty
2. Ask physician --> to Increaseno of refills ifpossible
98

99. 3. Patient monitoring/Counselling:
•Itcanbefocusedtowardscareful monitoring of
signs and symptom ofADR.
•Ex.Patientondailydiuretictreatment
--> experiences weakness &fatigue
Pharmacistshouldsuggestsupplemental
potassiumtherapy
99

100. 4. Patient Drug profilerecord:
•Patientprofileorcompletefamily
healthrecordmaintainbypharmacist
assistincontrollingADR.
•Italsohelppharmacist
Tomakeaccuratepredictionsof
potentialADRanddruginteraction.
100

101. 5. Otherprophylactic measures:
•Ex:
–Use of alert cards for those drugs with high incidence
of ADR
–Admission questionnaire regarding drugallergies
101

102. –Referencetopublished
data
canbeofgreatassistance
tothepharmacist
102

103. qHospital or community pharmacist can performthe
following services related to detection, prevention and
reporting ofADR:
•Patientinterview
•Dailyvisittonursingunittodiscusspossibleand
reportedADR
•Recognize potential of ADR based on patient history
ofhypertension
•Identify cause of ADR based on patientdescription
•Determining--> Withdrawalsymptoms.
103

104. Reference:
•RogerWalkerandCateWhittlesea.ClinicalPharmacyandTherapeutics,
5thedition.ChurchillLivingstoneElseverPublicationPg.No:61-75.
•Dr.H.P.TipnisandDr.AmritaBajaj.ClinicalPharmacy,3rdedition.Career
PublicationPg.No:330-342.
•Adverse drug reaction reporting form.
https://cdsco.gov.in/opencms/export/sites/CDSCO_WEB/Pdf-
documents/Consumer_Section_PDFs/ADRRF_2.pdf
104

105. Disclaimer (Images)
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useprincipleforeducationpurpose.
Copyright @ Presentation
•ThesaidpresentationiscopyrightunderCopyright@shaikhabusufiyan2021
•Thepresentationisforeducationpurposeonly,don’tusethesameforanylegal
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107. Q&A
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