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Implementation of Pharmacogenomic services in community pharmacies and its potential uses in management of PTSD
1. IMPLEMENTATION OF
PHARMACOGENOMIC
SERVICES IN COMMUNITY
PHARMACIES AND ITS
POTENTIAL USES IN
MANAGEMENT OF PTSD
Dalia A. Hamdy
BSc.(Pharm), MSc., PhD, RPh., MBA, MRSC
Founder and Manager of AbEx Health Services LTD.
Assistant Clinical Professor, FoPPS, University of Alberta
dhamdi@ualberta.ca
2 5 t h M a y 2 0 2 3
2. Presentation
Outline:
DALIA A. HAMDY (25 MAY 2023) 2
Define pharmacogenetics, pharmacogenomics, personalized
medicine and the related nomenclatures.
Introduction to its available resources and how to integrate
into clinical assessment to solve drug therapy problems
Steps taken to Identify the current status of
pharmacogenomic implementation in community
pharmacies in Alberta.
The outcomes of PGX applications in community pharmacy in
Alberta
PGX potential uses for management and treatment of PTSD
3. PGX AND PRECISION MEDICINE
āŖPharmacogenomics is a new discipline
that studies
Effect of DNA variations on medications
metabolism/clearance (PK) and
activity/effectiveness (PD)
Drug-Gene Interaction!!
DALIA A. HAMDY (25 MAY 2023) 3
Empiric therapy
Personalized
(Precision) medicine
4. PGX AND PRECISION MEDICINE
Genotype
The genetic makeup of an individual.
Phenotype
The observable physical or biochemical
characteristics of an organism.
Determined by genotype and
environment.
DALIA A. HAMDY (25 MAY 2023) 4
Empiric therapy
Personalized
(Precision) medicine
5. POLYMORPHISM AND DRUG-GENE INTERACTION
Different types of genetic variants/polymorphism or mutations
DALIA A. HAMDY (25 MAY 2023) 5
Single Nucleotide Polymorphism (SNP)
=SNV that exist in 1-2% of the population
6. IMPLEMENTATION OF PGX IN
THERAPY MANAGEMENT
Guidelines and Resources
PharmGKB
āŖClinical Pharmacogenetics Implementation
Consortium (CPIC)
CPIC (cpicpgx.org)
āŖDutch Pharmacogenetics Working Group
(DPWG)
āŖCanadian Pharmacogenomics Network for
Drug Safety (CPNDS)
DALIA A. HAMDY (25 MAY 2023) 6
7. PGX ETHICAL AND LEGAL CONSIDERATIONS
North America!
GNA 2017 (Canada)
The Genetic Non-Discrimination Act: critical for promoting health and science in
Canada
https://www.cmaj.ca/content/cmaj/190/19/E579.full.pdf
GINA 2008 (USA)
The Genetic Information Nondiscrimination Act of 2008
https://www.eeoc.gov/statutes/genetic-information-nondiscrimination-act-2008
DALIA A. HAMDY (25 MAY 2023) 7
8. IMPLEMENTATION OF PGX SERVICES
1. Choosing a company offering commercial PGX testing
2. Getting the company training (education program)
3. Starting the documentation system in pharmacy and consent forms etc.
4. Identifying eligible patients
5. Pre-test counselling and post-test counselling
6. Results interpretation and communication with other health care provider
7. Ethical and legal considerations
8. Data storage
9. Incorporation in current pt therapy management plans
DALIA A. HAMDY (25 MAY 2023) 8
New Services
only in limited
places!
Precision Medicine
9. ~ 15-20 companies are available in the Canadian and US Market
DALIA A. HAMDY (25 MAY 2023) 9
IMPLEMENTATION OF PGX SERVICES
11. Research Map! (2016-2023)
1. What is the current status of PGX knowledge and applications?
2. Change the current status
A. Education of undergrads
B. Education of practicing pharmacists
C. implementation in community pharmacy
D. Increase awareness of patients and better communication with other healthcare providers
3. Digging deeper into the possible applications of PGX in different
diseases (screening, diagnosis, prognosis, therapy)
A. Covid therapy (repurposed drugs)
B. PTSD
DALIA A. HAMDY (25 MAY 2023) 11
13. CURRENT STATUS IN ALBERTA
From a study in 2018
McMurdo A., Abou Alwan R., Mayo PR. and Hamdy DA
Implementation of Pharmacogenomics in Community
Pharmacies in Alberta: Perceptions and Challenges.
Published as poster Pharmaceutical Sciences World
Congress, Virtual, October 2020.
Abstracts - FIP - International Pharmaceutical Federation
DALIA A. HAMDY (25 MAY 2023) 13
14. CURRENT STATUS IN ALBERTA
From a study in 2018
McMurdo A., Abou Alwan
R., Mayo PR. and Hamdy
DA Implementation of
Pharmacogenomics in
Community Pharmacies in
Alberta: Perceptions and
Challenges. Published as
poster Pharmaceutical
Sciences World Congress,
Virtual, October 2020.
DALIA A. HAMDY (25 MAY 2023) 14
15. CURRENT STATUS IN ALBERTA
From a study in 2017
McMurdo A., Abou Alwan R., Mayo
PR. and Hamdy DA Implementation
of Pharmacogenomics in
Community Pharmacies in Alberta:
Perceptions and Challenges.
Published as poster
Pharmaceutical Sciences World
Congress, Virtual, October 2020.
DALIA A. HAMDY (25 MAY 2023) 15
16. CURRENT STATUS IN ALBERTA
Hamdy DA. The Future of
Pharmacogenomics application
in Alberta Community
Pharmacies. Pharmaceutical
Sciences World Congress,
Virtual, October 2020.
Abstracts - FIP - International
Pharmaceutical Federation
DALIA A. HAMDY (25 MAY 2023) 16
17. CURRENT STATUS IN ALBERTA
Actions taken at University level
Hamdy DA. The Future of
Pharmacogenomics application in Alberta
Community Pharmacies. Pharmaceutical
Sciences World Congress, Virtual, October
2020.
Abstracts - FIP - International
Pharmaceutical Federation
DALIA A. HAMDY (25 MAY 2023) 17
18. CURRENT STATUS IN ALBERTA
Actions taken at University level
Hamdy DA. The Future of
Pharmacogenomics application in Alberta
Community Pharmacies. Pharmaceutical
Sciences World Congress, Virtual, October
2020.
Abstracts - FIP - International
Pharmaceutical Federation
DALIA A. HAMDY (25 MAY 2023) 18
Competencies based on the blue
print
Initiated in 2016
Revised on 2022
https://www.ajpe.org/content/ajpe/86/4/86
34.full.pdf
19. CURRENT STATUS IN ALBERTA
Actions taken at University level
Hamdy DA. The Future of
Pharmacogenomics application in Alberta
Community Pharmacies. Pharmaceutical
Sciences World Congress, Virtual, October
2020.
Abstracts - FIP - International
Pharmaceutical Federation
DALIA A. HAMDY (25 MAY 2023) 19
20. CURRENT STATUS IN ALBERTA
Actions taken at Research and
Practice
Hamdy DA. The Future of
Pharmacogenomics application in Alberta
Community Pharmacies. Pharmaceutical
Sciences World Congress, Virtual, October
2020.
Abstracts - FIP - International
Pharmaceutical Federation
DALIA A. HAMDY (25 MAY 2023) 20
21. Actions taken at Research and
Practice
Meagan Hayashi, Sherif Hanafy Mahmoud,
Dalia A. Hamdy. Pharmgenomics Pers Med.
2022 Apr 23;15:409.
DALIA A. HAMDY (25 MAY 2023) 21
CURRENT STATUS IN
ALBERTA
22. Actions taken at Research and
Practice
Meagan Hayashi, Sherif Hanafy Mahmoud,
Dalia A. Hamdy. Pharmgenomics Pers Med.
2022 Apr 23;15:409.
DALIA A. HAMDY (25 MAY 2023) 22
CURRENT STATUS IN
ALBERTA
23. CURRENT STATUS IN ALBERTA
āŖ2 days workshops were held
June 2021
āŖ36 participants between
synchronous and asynchronous
DALIA A. HAMDY (25 MAY 2023) 23
Meagan Hayashi, Sherif Hanafy Mahmoud, Dalia A. Hamdy. Pharmgenomics Pers Med. 2022 Apr 23;15:409.
24. CURRENT STATUS IN ALBERTA
āŖ7 PGX professors
participated in the
course from
Canada, USA,
Egypt and Qatar
DALIA A. HAMDY (25 MAY 2023) 24
Meagan Hayashi, Sherif Hanafy Mahmoud, Dalia A. Hamdy. Pharmgenomics Pers Med. 2022 Apr 23;15:409.
25. CURRENT STATUS
IN ALBERTA
āŖKnowledge
improvement for
course participants
DALIA A. HAMDY (25 MAY 2023) 25
Meagan Hayashi, Sherif Hanafy Mahmoud, Dalia A. Hamdy. Pharmgenomics Pers Med. 2022 Apr 23;15:409.
29. CURRENT STATUS IN ALBERTA
Lectures and Cases were recorded to be utilized by all Alberta
Pharmacists to increase their PGX knowledge and confidence
I encourage you to access the course materials through the following
google drive link:
https://drive.google.com/drive/u/0/folders/1oXh4qPV_LRdmUvqrkj5plnTpOkSuNYvC
DALIA A. HAMDY (25 MAY 2023) 29
RxA Innovation grant fund
30. CURRENT STATUS IN ALBERTA
Implementation in Community
pharmacies!!
āŖ15 Pharmacies recruited across Alberta
āŖ3 opted out due to time constraints and lack of
pharmacists
āŖCurrently 12 pharmacies enrolled
āŖEach pharmacy expected to recruit between
10-30 patients
DALIA A. HAMDY (25 MAY 2023) 30
Preliminary data!
Ongoing project! RxA Funded!
Dareen ElSayed , Meagan Hayashi, Sherif Hanafy Mahmoud, Dalia A. Hamdy
31. CURRENT STATUS IN
ALBERTA
Implementation in Community
pharmacies!!
Inclusion/Exclusion Criteria
DALIA A. HAMDY (25 MAY 2023) 31
Meagan Hayashi, Dareen ElSayed, Sherif Hanafy Mahmoud, Dalia A. Hamdy
Dareen ElSayed , Meagan Hayashi, Sherif Hanafy Mahmoud, Dalia A. Hamdy
32. CURRENT STATUS IN ALBERTA
DALIA A. HAMDY (25 MAY 2023) 32
Implementation in Community pharmacies!!
116 patients recruited
96 patients results completed
20 patients awaiting results
Preliminary data!
Ongoing project! RxA Funded!
21
21
1
7
17
9
33
3
4
0 5 10 15 20 25 30 35
Edmonton
Fort saskatchewan
Hinton
St. Paul
Calgary
Redcliff
Vulcan
Beaumont
Smokey lake
Number of Patients
Dareen ElSayed , Meagan Hayashi, Sherif Hanafy Mahmoud, Dalia A. Hamdy
33. CURRENT STATUS IN ALBERTA
DALIA A. HAMDY (25 MAY 2023) 33
Implementation in Community
pharmacies!!
116 patients recruited
96 patients results completed
20 patients awaiting results
Median age : 18 (18-82) years
Preliminary data!
Ongoing project! RxA Funded!
Male, 41%
Female, 59%
Dareen ElSayed , Meagan Hayashi, Sherif Hanafy Mahmoud, Dalia A. Hamdy
34. CURRENT STATUS IN ALBERTA
DALIA A. HAMDY (25 MAY 2023) 34
Implementation in Community
pharmacies!!
116 patients recruited
96 patients results completed
20 patients awaiting results
Preliminary data!
Ongoing project! RxA Funded!
Caucasian
79%
Aboriginal
5%
South Asian
5%
Black
3%
Middle eastern
6%
Filipino
1%
Latin America
1%
Dareen ElSayed , Meagan Hayashi, Sherif Hanafy Mahmoud, Dalia A. Hamdy
35. CURRENT STATUS IN ALBERTA
DALIA A. HAMDY (25 MAY 2023) 35
Implementation in Community
pharmacies!!
116 patients recruited
96 patients results completed
20 patients awaiting results
Identified medications
Antidepressant or antipsychotic 121
Any proton pump inhibitor 54
Tramadol or codeine 47
Atorvastatin or simvastatin
(ā„ 40mg daily)
22
Clopidogrel 14
Atomoxetine 2
Warfarin 1
Preliminary data!
Ongoing project! RxA Funded!
Dareen ElSayed , Meagan Hayashi, Sherif Hanafy Mahmoud, Dalia A. Hamdy
36. CURRENT STATUS IN ALBERTA
DALIA A. HAMDY (25 MAY 2023) 36
Implementation in Community
pharmacies!!
116 patients recruited
96 patients results completed
20 patients awaiting results
Reason for enrollment
Inefficacy 49
Side effects 29
History of inefficacy or side effects to a
medication in the same class
29
Assess stable therapy (monitoring) 22
Planning to start medication 6
New prescription (within 28 days) 5
Preliminary data!
Ongoing project! RxA Funded!
Dareen ElSayed , Meagan Hayashi, Sherif Hanafy Mahmoud, Dalia A. Hamdy
37. CURRENT STATUS IN ALBERTA
DALIA A. HAMDY (25 MAY 2023) 37
Preliminary data!
Ongoing project! RxA Funded!
Implementation in Community
pharmacies!!
116 patients recruited
96 patients results completed
20 patients awaiting results
Common alleles
Diplotype Frequency Diplotype Frequency
*3/*3 1
*1/*1 8 *1/*2 17
*1F/*1F 39 *1/*1 54
*1/*1F 34 *1/*3 9
*1/*1 22 *1/1 12
*1/*2 25 *1/2 10
*2/*2 5 *2/2 5
*2/*17 7 *2/4 4
*1/*17 20 *2/5 2
*17/*17 3 *1/4 8
*4/4 2
A/G 14 *2/41 8
G/G 11 *1/41 3
A/A 3 *4/41 1
*1/*1 74 T/C 24
*1/*22 7 T/T 52
*22/*22 1 C/C 5
CYP3A4
SLCO1B1
2D6
CY2C9
CYP 1A2
CYP2C19
VKORC1
Dareen ElSayed , Meagan Hayashi, Sherif Hanafy Mahmoud, Dalia A. Hamdy
38. CURRENT STATUS IN ALBERTA
DALIA A. HAMDY (25 MAY 2023) 38
Preliminary data!
Ongoing project! RxA Funded!
Implementation in Community
pharmacies!!
116 patients recruited
96 patients results completed
20 patients awaiting results
Dareen ElSayed , Meagan Hayashi, Sherif Hanafy Mahmoud, Dalia A. Hamdy
0
20
40
60
80
VKORC1 OPRM1 SLCO1B1
Genetic Polymorphism in Alberta
Normal Gene
variant
0
10
20
30
40
50
60
70
80
CYP1A2 CYP2C19 CYP2D6 CYP3A5 CYP3A4 CYP2C9
Genetic Polymorphism in Alberta
Normal gene
Variant
40. CURRENT STATUS IN ALBERTA
DALIA A. HAMDY (25 MAY 2023) 40
Preliminary data!
Ongoing project! RxA Funded!
Implementation in Community
pharmacies!!
116 patients recruited
96 patients results completed
20 patients awaiting results
Gene PM IM NM RM UM
CYP1A2 n/a n/a 42 (52.0) n/a 39 (48.0)
CYP2C9 2 (2.4) 26 (31.7) 54(65.9) n/a n/a
CYP2C19 5 (6.1) 32 (39.0) 22 (26.8) 20 (24.4) 3 (3.7)
CYP2D6 4 (4.9) 24 (29.6) 52 (64.2) n/a n/a
CYP3A4 1 (1.2) 7 (8.5) 74 (90.2) n/a n/a
CYP3A5 64(78.0) 13 (15.9) 5(6.1) n/a n/a
Phenotype Assignment [n (%)]
Gene
Low
Function
Intermed
iate
Function
Normal/
High
Function
VKORC1 2 (7.2) 14 (50.0) 12 (50.0)
OPRM1 2 (2.4) 19 (23.2) 61 (74.4)
SLCO1B1 5 (6.1) 25 (30.5) 52 (63.4)
Phenotype Assignment (n, %)
Phenotype Assignment
Dareen ElSayed , Meagan Hayashi, Sherif Hanafy Mahmoud, Dalia A. Hamdy
41. CURRENT STATUS IN ALBERTA
DALIA A. HAMDY (25 MAY 2023) 41
Implementation in Community
pharmacies!!
116 patients recruited
96 patients results completed
20 patients awaiting results
Direct Interventions?
Indirect interventions?
Preventive? Future? Interventions
(PS: old data needs update based on 50 samples)
Preliminary data!
Ongoing project! RxA Funded!
Dareen ElSayed , Meagan Hayashi, Sherif Hanafy Mahmoud, Dalia A. Hamdy
42. CURRENT STATUS IN ALBERTA
DALIA A. HAMDY (25 MAY 2023) 42
Implementation in Community
pharmacies!!
116 patients recruited
96 patients results completed
20 patients awaiting results
Direct Interventions?
Indirect interventions?
Preventive? Future? Interventions
(PS: old data needs update based on 50 samples)
Preliminary data!
Ongoing project! RxA Funded!
Dareen ElSayed , Meagan Hayashi, Sherif Hanafy Mahmoud, Dalia A. Hamdy
Antidepressants, 17,
36.7%
Proton pump
inhibitors, 12, 24.5%
NSAIDs/OPIODS , 7,
14.3%
Statins, 3, 6.1%
clopidogrel, 2, 4.08%
antipsychotics, 2, 4.08%
0thers , 4, 6.1%
MEDICATIONS IMPLICATED IN DRUG-GENE INTERACTIONS
43. IMPLEMENTATION OF PGX IN THERAPY
MANAGEMENT
Potential Applications?
1. Pharmacogenomic Considerations in Proposed COVID-19 Treatment and Management: A Systematic
Review -498 research outcome (2021)
2. Applications of PGx in Post-Traumatic Syndrome Disease Patients: A scooping Review (2022-2023)
3.
DALIA A. HAMDY (25 MAY 2023) 43
44. Application of PGX in COVID-19 Treatment
Regimens
DALIA A. HAMDY (25 MAY 2023) 44
1. How can pharmacogenomics be applied to treatment management of COVID-19? (we only looked at therapy management)
2. What are the common drugs used in COVID-19 treatment protocols worldwide? (Canada, USA, Qatar, Egypt)
3. Do COVID-19 treatment protocols consider pharmacogenomics in their recommendations? NO
4. What is the level of strength of the current PGX recommendations related to its application to medications used in the setting
of COVID-19 treatment? PHARMGKB
5. What are the drugs used for the treatment of COVID-19 with potential need for pharmacogenomic testing?Repurposed drugs
Jennifer Young, Dalia A. Hamdy. Pharmacogenomic Considerations in Proposed COVID-19 Treatment and Management: A Systematic Review. AFPC CPERC June 2022
Systematic Review!
Research Questions! PHARM498
45. Application of PGX in COVID-19 Treatment
Regimens
DALIA A. HAMDY (25 MAY 2023) 45
ā Five databases usedā¦ā¦. 20 keywords were determined
collaboratively with Health Sciences Librarian Janice
Kung
ļ Databases
ļ MEDLINE, EMBASE, Scopus, CINAHL, Cochrane
ā Search limits:
ļ English language
ļ Date range (2019 to April 2, 2021)
Jennifer Young, Dalia A.
Hamdy. Pharmacogenomic
Considerations in Proposed
COVID-19 Treatment and
Management: A Systematic
Review. AFPC CPERC June
2022
46. Results
DALIA A. HAMDY (25 MAY 2023) 46
PRISMA diagram of literature search and screen results
Jennifer Young, Dalia A. Hamdy. Pharmacogenomic Considerations in Proposed COVID-19 Treatment and Management: A Systematic Review. AFPC CPERC June 2022
Covidence Software
47. Number of publications discussing medication classes
used in COVID-19 treatment with possible PGx
intervention
Figure 4. Number of publications discussing
gene polymorphisms affecting COVID-19
treatment
Repurposed Drugs!
Dalia A. Hamdy (25 May 2023) 47
Jennifer Young, Dalia A. Hamdy. Pharmacogenomic Considerations in Proposed COVID-19 Treatment and Management: A Systematic Review. AFPC CPERC June 2022
48. Results
DALIA A. HAMDY (25 MAY 2023) 48
Jennifer Young, Dalia A. Hamdy. Pharmacogenomic Considerations in Proposed COVID-19 Treatment and Management: A Systematic Review. AFPC CPERC June 2022
ā¢ HCQ/CQ:
Glucose-6-phosphate dehydrogenase (G6PD) deficient variants hemolytic anemia
Doses used in COVID-19 ttt
CQ has been administered orally at a dose of 300 mg for adults, twice daily (bid) for a maximal duration of
10 days.
HCQ therapy is started at a loading dose of 400 mg bid on day 1 and then lowered to 200 mg bid (10 days
average)
1. FDA and CDC recommending a lower
dose of 300 mg in cases of malaria
prophylaxis and treatment for G6PD
deficiency patients
2. The Swiss drug label for chloroquine
that states that chloroquine is
contraindicated in patients with
G6PD deficiency
49. Results
DALIA A. HAMDY (25 MAY 2023) 49
Jennifer Young, Dalia A. Hamdy. Pharmacogenomic Considerations in Proposed COVID-19 Treatment and Management: A Systematic Review. AFPC CPERC June 2022
ā¢ Ribavirin:
Originally used for HCV
Ribavirin and peg-
interferon alfa 2a/2b
Intestinal uptake
via CNTs (encoded
by SLC).
IFNL3
(IL28B)
CT, TT PharmG
Kb
CPIC
1A Only 30% positive
response rate
HLA-B HLA-
B*44-
negative
PharmG
Kb
DPWG
3
SLC28A2,
SLC28A3,
SLC29A1
AA, AG PharmG
Kb
clinical
annotati
on
3 Less likely to have
rapid virological
response
ITPA AA PharmG
Kb
clinical
annotati
on
2B Hemolytic
anemia/thrombocyto
penia
Repurposed Drug Metabolism/Trans
porter
Biomar
ker
Actionab
le
Phenoty
pe
PGX
Guidelin
es
Level
of
eviden
ce
Adverse
events/effecacy
50. Results
DALIA A. HAMDY (25 MAY 2023) 50
Jennifer Young, Dalia A. Hamdy. Pharmacogenomic Considerations in Proposed COVID-19 Treatment and Management: A Systematic Review. AFPC CPERC June 2022
lopinavir/ritonavir
Repurposed Drug Metabolism/Tra
nsporter
Biomark
er
Actiona
ble
Phenot
ype
PGX
Guideli
nes
Level of
evidence
Adverse
events/effecacy
Orginal
label
(use)
references
lopinavir/ritonavir Inactivation via
CYP3A4
CYP3A4/
5
CC, CT PharmGK
b clinical
annotati
on
3 have increased trough
concentrations of
lopinavir in patients of
European descent, and
not in African American
or Hispanic patients.
HIV 1, 2, 4,
14, 20,
22
ABCB1 AG, GG 3 increased risk of
virological failure when
receiving highly active
antiretroviral therapy
(HAART)
AC, CC 3 have a increased ritonavir
intracellular/plasma
trough concentration as
compared to patients
with the AA genotype
ABCC1 CC, CT 3 increased risk of
virological failure when
receiving highly active
antiretroviral therapy
(HAART)
SLCO1B1 CT, TT 3 The CT genotype may
have decreased plasma
levels of lopinavir as
compared to patients
with the CC genotype, but
increased plasma levels as
compared to patients
with the TT genotype
UGT1A1 GG 3 increased risk of
nephrolithiasis when
treated with ritonavir
APOC3 CT, TT 3 increased risk of
Hypertriglyceridemia)with
ritonavir therapy
51. Results
DALIA A. HAMDY (25 MAY 2023) 51
Jennifer Young, Dalia A. Hamdy. Pharmacogenomic Considerations in Proposed COVID-19 Treatment and Management: A Systematic Review. AFPC CPERC June 2022
Azithromycin
Repurposed Drug Metabolism/Trans
porter
Biomark
er
Actiona
ble
Phenoty
pe
PGX
Guidelin
es
Level of evidence Adverse
events/effecacy
)
Azithromycin Efflux transport
via P-glycoprotein
ABCB1 AA PharmG
Kb
variant
annotati
ons
NA Approx. 2 fold
lower peak in
healthy volunteers
QTc
prologation
is more
likely in
personnel
carrying the
GG Allelle.
No
recommend
ation and
further
evidence
required
Non significant
substrate for those
enzymes/
transporters
CYP3A4,
SLCO1B1
,
SLCO1B3
No current
correlations
found
52. Results
DALIA A. HAMDY (25 MAY 2023) 52
Jennifer Young, Dalia A. Hamdy. Pharmacogenomic Considerations in Proposed COVID-19 Treatment and Management: A Systematic Review. AFPC CPERC June 2022
NSAIDS
Repurposed Drug Metabolism/Trans
porter
Biomark
er
Actiona
ble
Phenoty
pe
PGX
Guidelin
es
Level of evidence Adverse
events/effecacy
)
NSAIDs
(ibuprofen, meloxicam,
celecoxib etc)
CYP2C9 IM, PM
CYP2C9
*2/3
*3/3
*1/3
*2/2
PharmG
Kb CPIC
1A CPIC Dosing
Guideline for
celecoxib,
flurbiprofen,
ibuprofen and
lornoxicam
recommends
initiating
therapy with
25-50% of the
lowest
recommende
d starting
dose for
CYP2C9 poor
metabolizers
and initiating
therapy with
lowest
recommende
d starting
dose for
CYP2C9
intermediate
metabolizers
with activity
score of 1
Pai
ma
nt
CYP2C8 CYP2C8
*1
*3
*4
3 *1 and *3 show slow
metabolism whereas
diplotype *1/*1
shows rapid
metabolism
53. Results
DALIA A. HAMDY (25 MAY 2023) 53
Jennifer Young, Dalia A. Hamdy. Pharmacogenomic Considerations in Proposed COVID-19 Treatment and Management: A Systematic Review. AFPC CPERC June 2022
ā¢ Limitations
ā¢ Repurposed drugs are sometimes used at different doses from originally prescribed
ā¢ Most drug-gene interactions identified do not have an accompanying guidelines of intervention
ā¢ Most level of evidence found were level 3 (weak )
ā¢ We donāt have the PGX data for pt. readily available for use in ICU
ā¢ Conclusion
Further investigations are required before considering the possibility of utilizing PGX in COVID-19 therapy
management
54. Application of PGX in PTSD therapy
DALIA A. HAMDY (25 MAY 2023) 54
Post Traumatic Syndrome Disease (PTSD)
-complex, chronic and highly debilitating stress-related psychiatric disorder
ā¢ Occupational (Health care workers, first responders, Police, fire fighters, military..etc)
ā¢ After natural disasters (earthquakes, fires, etc)
ā¢ Family Violence
ā¢ Wars, genocides..etc
-Although the majority of individuals experience traumatic event, only small number of which develop
PTSD
Systematic Review!
Research Questions! International
Collaboration
Mahmoud M. Khalil, Shaimaa A. Abel-mougood, Dalia A. Hamdy. Applications of Precision Medicine in Post-Traumatic Syndrome Disease Patients: A scooping Review-ongoing research
,
55. Application of PGX in PTSD therapy
DALIA A. HAMDY (25 MAY 2023) 55
Post Traumatic Syndrome Disease (PTSD)
Patients symptoms:
ā¢ re-experiencing the traumatic event
ā¢ intrusive thoughts, nightmares, flashbacks
ā¢ dissociation(detachment from oneself or reality)
ā¢ intense negative emotional (sadness, guilt)
ā¢ physiological reaction on being exposed to the traumatic reminder
ā¢ insomnia
ā¢ concentration problems
ā¢ irritability, increased reactivity
ā¢ increased startle response, hypervigilance
ā¢ avoidance of traumatic triggers.
Systematic Review!
Research Questions! International
Collaboration
Mahmoud M. Khalil, Shaimaa A. Abel-mougood, Dalia A. Hamdy. Applications of Precision Medicine in Post-Traumatic Syndrome Disease Patients: A scooping Review-ongoing research
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56. Application of PGX in PTSD therapy
DALIA A. HAMDY (25 MAY 2023) 56
1. who are the Populations that are more prone to developing PTSD? (Genetically, environmentally, veterans,
refugees, war crime victims, genocidal victimsā¦etc)
2. what is the effect of gender and age on susceptibility to PTSD? From a genetic polymorphism perspective
3. what are the Inheritable genes affected by PTSD?
4. What are the non-inheritable gene polymorphisms affected by PTSD ?
5. What are the applications of PGX in PTSD therapy management? (Effect of ethnicity and personal SNPs of
drug PGX)
Systematic Review!
Research Questions! International
Collaboration-ongoing research!
Mahmoud M. Khalil, Shaimaa A. Abel-mougood, Dalia A. Hamdy. Applications of Precision Medicine in Post-Traumatic Syndrome Disease Patients: A scooping Review-ongoing research
,
57. Application of PGX in PTSD therapy
DALIA A. HAMDY (25 MAY 2023) 57
ā Two databases were selected and 31 keywords
ļ Databases
ļ PubMed, Scopus
ā Search limits:
ļ English language
ļ Date range (2013 to August 23rd , 2022)
ļ Grey literature was not included
ļ Peer-reviewed publications only
Systematic Review!
Research Questions! International
Collaboration-ongoing research!
58. Results
DALIA A. HAMDY (25 MAY 2023) 58
PRISMA diagram of
literature search and
screen results
Mahmoud M. Khalil, Shaimaa A. Abel-mougood, Dalia A. Hamdy. Applications of Precision Medicine in Post-Traumatic Syndrome Disease Patients: A scooping Review-ongoing research
,
Covidence Software
59. Results
DALIA A. HAMDY (25 MAY 2023) 59
Effect of Gender of PTSD Prevelence, Prognosis and Therapy
ā¢ After an exposure to a traumatic incident females are twice as likely to develop PTSD than males
ā¢ many of these findings have been thought to be related to estrogen regulation in females
ā¢ Among the genes responsible in gender differences in PTSD
Retinoid-related orphan receptor alpha (RORA) gene polymorphisms
Estrogen receptor alpha gene rs9340799
NGFI-A (nerve growth factor-induced protein A) binding site of the NR3C1 promoter
The pituitary adenylate cyclase-activating polypeptide (PACAP) and its PAC1 receptor (PAC1R)
Mahmoud M. Khalil, Shaimaa A. Abel-mougood, Dalia A. Hamdy. Applications of Precision Medicine in Post-Traumatic Syndrome Disease Patients: A scooping Review-ongoing research
,
Systematic Review!
Research Questions! International
Collaboration-ongoing research!
60. Results
DALIA A. HAMDY (25 MAY 2023) 60
Effect of Age on PTSD Prevelence
PTSD was reported to be
6% in ages 18-29
8% in ages 30-44
9% in ages 45-59
3% in ages 60 and older
On the other hand
PTSD is associated with advanced cellular aging and DNAm age, and that advanced DNAm age is related to reduced
neural integrity and cognitive ability.
PTSD with shortening of telomere length, which is also used as a marker of aging and related to reduced brain
volume
PTSD patients show higher GrimAge acceleration indicating the effect of PTSD on lifespan
Mahmoud M. Khalil, Shaimaa A. Abel-mougood, Dalia A. Hamdy. Applications of Precision Medicine in Post-Traumatic Syndrome Disease Patients: A scooping Review-ongoing research
,
Systematic Review!
Research Questions! International
Collaboration-ongoing research!
US
Population
61. Results
DALIA A. HAMDY (25 MAY 2023) 61
The inheritable genes polymorphisms affected by PTSD
ā¢ Many studies found evidence that the effect of PTSD exposure can be passed to offspring trans-generationally via the
epigenetic inheritance mechanisms of DNA methylation alterations and has the capacity to change the expression of
genes.
ā¢ Most studies focused on the hypothalamic-pituitary adrenal (HPA) axis and its correlation to stress
ā¢ Mainly through alteration of Two genes related to glucocorticoid signaling pathway and to HPA axis:
ā¢ NR3C1, encoding the glucocorticoid receptor
ā¢ FK506 binding protein 5 (FKBP5), encoding a glucocorticoid receptor co-chaperone
Mahmoud M. Khalil, Shaimaa A. Abel-mougood, Dalia A. Hamdy. Applications of Precision Medicine in Post-Traumatic Syndrome Disease Patients: A scooping Review-ongoing research
,
Systematic Review!
Research Questions! International
Collaboration-ongoing research!
62. Results
DALIA A. HAMDY (25 MAY 2023) 62
The non-inheritable genes polymorphisms affected by PTSD
PTSD affects the brain resulting in changes in
Fear response
Sleeping
Cognitive functions
Decreased cerebral blood flow
Higher resting metabolic activities
Mahmoud M. Khalil, Shaimaa A. Abel-mougood, Dalia A. Hamdy. Applications of Precision Medicine in Post-Traumatic Syndrome Disease Patients: A scooping Review-ongoing research
,
Systematic Review!
Research Questions! International
Collaboration-ongoing research!
63. Results
DALIA A. HAMDY (25 MAY 2023) 63
The non-inheritable genes polymorphisms affected by PTSD
The neurochemical changes involved
Mahmoud M. Khalil, Shaimaa A. Abel-mougood, Dalia A. Hamdy. Applications of Precision Medicine in Post-Traumatic Syndrome Disease Patients: A scooping Review-ongoing research
,
Systematic Review!
Research Questions! International
Collaboration-ongoing research!
64. Results
DALIA A. HAMDY (25 MAY 2023) 64
The non-inheritable genes polymorphisms affected by PTSD
The major suggested genes involved are
Mahmoud M. Khalil, Shaimaa A. Abel-mougood, Dalia A. Hamdy. Applications of Precision Medicine in Post-Traumatic Syndrome Disease Patients: A scooping Review-ongoing research
,
Systematic Review!
Research Questions! International
Collaboration-ongoing research!
65. Results
DALIA A. HAMDY (25 MAY 2023) 65
PGX in treatment of PTSD
ā¢ SSRI/SNRI (Sertraline and Paroxetine )
ā¢ Trazodone (insomnia)
ā¢ Clonidine and prazosin (trauma related nightmares)
ā¢ Risperidone
Mahmoud M. Khalil, Shaimaa A. Abel-mougood, Dalia A. Hamdy. Applications of Precision Medicine in Post-Traumatic Syndrome Disease Patients: A scooping Review-ongoing research
,
Systematic Review!
Research Questions! International
Collaboration-ongoing research!
PharmGKB
CPIC guidelines
Dutch Group Guidelines
CYP P450 Alleles
66. Results
DALIA A. HAMDY (25 MAY 2023) 66
Mahmoud M. Khalil, Shaimaa A. Abel-mougood, Dalia A. Hamdy. Applications of Precision Medicine in Post-Traumatic Syndrome Disease Patients: A scooping Review-ongoing research
,
Systematic Review!
Research Questions! International
Collaboration-ongoing research!
More to come!
67. REFERENCES
1. Meagan Hayashi, Sherif Hanafy Mahmoud, Dalia A. Hamdy. Pharmacogenomics and Personalized
Medicine. Pharmgenomics Pers Med. 2022 Apr 23;15:409-427.
https://pubmed.ncbi.nlm.nih.gov/35496350/
2. Meagan Hayashi, Dalia A. Hamdy, Sherif Hanafy Mahmoud. Application. Res Social Adm Pharm. 2021
Aug 20:S1551-7411(21)00313-2 https://doi.org/10.1016/j.sapharm.2021.08.009
3. McMurdo A., Abou Alwan R., Mayo PR. and Hamdy DA . Pharmaceutical Sciences World Congress,
Virtual, October 2020 https://www.fip.org/abstracts?page=abstracts&action=item&item=23209
4. Dalia A. Hamdy. Pharmaceutical Sciences World Congress, Virtual, October 2020.
https://www.fip.org/abstracts?page=abstracts&action=item&item=23187
5. Haga SB. Front Genet. 2021 Oct 1;12:741395. https://pubmed.ncbi.nlm.nih.gov/34659361/
6. Haga SB, Mills R, Moaddeb J, Liu Y, Voora D. Pharmgenomics Pers Med. 2021 Jul 15;14:877-886.
https://pubmed.ncbi.nlm.nih.gov/34290521/
7. Meagan Hayashi, Sherif Hanafy Mahmoud, Dalia A. Hamdy. Free Access PGX Online course materials
developed for Alberta Pharmacists. June 2021. https://drive.google.com/drive/folders/1-
agZrI1xp8K9aGqpdN0xMUL38NmIquUY?usp=sharing
DALIA A. HAMDY (25 MAY 2023) 67
68. ACKNOWLEDGEMENTS
DALIA A. HAMDY (25 MAY 2023) 68
Research team members
ā¢Prof. Dr. Patrick Mayo
ā¢Prof. Dr. Sherif Mahmoud
ā¢Meagan Hayashi, RPh. , MSc.
ā¢Mahmoud M. Khalil, RPh. ,MSc.
ā¢Shaimaa A. Abdel-mougood, RPh., MSc.
ā¢Amy McMurdo, RPh.
ā¢Riad Abou Alwan, RPh.
ā¢Jennifer Young, RPh.
ā¢Dareen ElSayed, Pharmacy student
Funding agency:
RxA Innovation Grant 2020
Faculty of Pharmacy and Pharmaceutical Sciences, University
of Alberta
Educational Course providers:
ā¢Prof. Dr. Corey Nislow, Canada
ā¢Dr. Dalia Hamdy, Canada
ā¢Prof. Dr. Sherif Mahmoud, Canada
ā¢Meagan, Hayashi, Canada
ā¢Dr. Jai Patel, USA
ā¢Dr. Susanne Haga, USA
ā¢Dr. Hazem Elewa, Qatar
ā¢Dr. Wafaa Rashed, Egypt
University of Alberta RedCAP
Alberta Pharmacists and Pharmacies enrolled in study