This document provides information about a pharmacogenomics course taught by Dr. Dalia A. Hamdy. The course covers basics of pharmacogenomics and its effects on drug metabolism and pharmacokinetics/pharmacodynamics. It will teach students how to apply pharmacogenomics in precision medicine using online resources for dosing guidelines. Students will also learn to integrate pharmacogenomics into clinical assessment and decision making to optimize drug therapy outcomes.
Pharmacogenomics is a new trending branch which has created enormous hopes in improving diagnostic methods, treatment outcomes and preventing adverse events and therapeutic failures. In this ppt basics of pharmacogenomics and pharmacogenetics has been discussed in simplest possible way along with two case studies. Clinical applications of pharmacogenomics has also been discussed in brief.
Pharmacogenomics is a new trending branch which has created enormous hopes in improving diagnostic methods, treatment outcomes and preventing adverse events and therapeutic failures. In this ppt basics of pharmacogenomics and pharmacogenetics has been discussed in simplest possible way along with two case studies. Clinical applications of pharmacogenomics has also been discussed in brief.
Pharmacogenomics is the branch of biochemistry in which study how an individual’s genetic inheritance affects the body response to drug. Pharmacogenomics is the intersection of genetics and pharmaceutical industry.
In this presentation a brief note is given about what is pharmacogenomics. Why different drugs work differently in different people. today pharmacogenomics, future of pharmacogenomics. also describe the future of pharmacogenomics. challenges which have to pharmacogenomics.
Pharmacogenetics and pharmacogenomics is an upcoming branch in therapeutics. Various pharmacogenomic tests are currently available to aid in actual clinical practice. It has shown to have promising results in personalized medicine It is my attempt to compile the basic concepts from various books, articles, and online journals. Please feel free to comment.
pharmacogenomics is a new drug discovry approach. It is the study of how genes affect a person's response to drugs, combining pharmacology and genomics
Pharmacogenomics: A new age drug technologyMahek Sharan
the pharmacogenomics require the pharmacology and genomic together to improve the drug responses and the new age drug potential according to individual need
This Presentation is about Pharmacogenomics and Pharmacogenetics , its Working , application, History.
It also contain a little bit info related to polypharmacy and its effects.
You can also see information regarding Drug Metabolism Phase, and drug Metabolizing Enzymes like CYPs, VKORC1, TPMT
Pharmacogenomics is the branch of biochemistry in which study how an individual’s genetic inheritance affects the body response to drug. Pharmacogenomics is the intersection of genetics and pharmaceutical industry.
In this presentation a brief note is given about what is pharmacogenomics. Why different drugs work differently in different people. today pharmacogenomics, future of pharmacogenomics. also describe the future of pharmacogenomics. challenges which have to pharmacogenomics.
Pharmacogenetics and pharmacogenomics is an upcoming branch in therapeutics. Various pharmacogenomic tests are currently available to aid in actual clinical practice. It has shown to have promising results in personalized medicine It is my attempt to compile the basic concepts from various books, articles, and online journals. Please feel free to comment.
pharmacogenomics is a new drug discovry approach. It is the study of how genes affect a person's response to drugs, combining pharmacology and genomics
Pharmacogenomics: A new age drug technologyMahek Sharan
the pharmacogenomics require the pharmacology and genomic together to improve the drug responses and the new age drug potential according to individual need
This Presentation is about Pharmacogenomics and Pharmacogenetics , its Working , application, History.
It also contain a little bit info related to polypharmacy and its effects.
You can also see information regarding Drug Metabolism Phase, and drug Metabolizing Enzymes like CYPs, VKORC1, TPMT
Drug Safety & Pharmacovigilance - Introduction - Katalyst HLSKatalyst HLS
Introduction to Drug Safety & Pharmacovigilance in Pharmaceuticals, Bio-Pharmaceuticals, Medical Devices, Cosmeceuticals and Foods.
Contact:
"Katalyst Healthcares & Life Sciences"
South Plainfield, NJ, USA
info@KatalystHLS.com
Personalized medicine involves the prescription of specific therapeutics best suited for an individual based on their genetic or proteomic profile. This talk discusses current approaches in drug discovery/development, the role of genetics in drug metabolism, and lawful/ethical issues surrounding the deployment of new health technology.
Personalized medicine involves the prescription of specific therapeutics best suited for an individual based on their genetic or proteomic profile. This talk discusses current approaches in drug discovery/development, the role of genetics in drug metabolism, and lawful/ethical issues surrounding the deployment of new health technology. I highlight some bioinformatic roles in the drug discovery process, and discuss the use of semantic web technologies for data integration and knowledge discovery..
Personalised medicines -pharmacogentics and pharmacogenomicsAlakesh Bharali
This seminar basically introduces and explains the learner about what is personalised medicines, what is the need for it, how personalised medicines work. For this, the concept of pharmacogenetics and pharmacogenomics are considered. After going through the presentation, the learner will be able to understand about the concept of pharmacogentics and pharmacogenomics. Certain examples of personalised medicines are included in this seminar.Although personalised medicines are specific and helpful, ins spite of having lots of advantages , it also have some disadvantages which are also specified in this seminar.Although , we speak about personalised medicines, we never saw personalised medicines in our local market. So here is an approach given that , when will we see personalised medicines at the local pharmacy. Again, certain marketed products are also listed in the seminar.Also, the future of personalised medicines is depeicted in the seminar. How medicines will be in a an around 2050 is shown in the seminar. After going through the seminar, the learner would be able to understand about personalised medicines and all its aspects in detail.
Soal dan Pembahasan Farmakogenomik dan Personalized MedicineNesha Mutiara
Materi farmakologi molekular farmakogenomik dan personalized medicine :
- penjelasan farmakogenomik, farmakogenetik, dan personalized medicine
- mekanisme kerja molekular warfarin dan clopidogrel terkait farmakogenomik
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
1. Pharm 503
4th November 2019
Dalia A. Hamdy
BSc.(Pharm), MSc., PhD, RPh., MBA, MRSC
Founder and Manager of AbEx Health Services LTD.
Clinical Assistant Professor, FoPPS, University of Alberta
dhamdi@ualberta.ca
2-142K Katz
2. i. Getting introduced to the basics of
pharmacogenomics and its effect on drug
metabolism/pharmacokinetics (PK) and/or
pharmacodynamics (PK-PD).
ii. Apply Pharmacogenomics in precision medicine
iii. Having a Hands-on experience on the online
resources used to help you find dosing guidelines
(CPIC & PharmGKb)
iv. Integrating pharmacogenenomics into your clinical
assessment and decision in resolving drug therapy
problems and optimizing pharmacotherapy outcomes
Dr. Dalia A. Hamdy (FS 19/20AY) 2
3. 1. Langman L, Dasgupta A. Pharmacogenomics in Clinical Therapeutics.;
Wiley-Blackwell 2012.
2. CPIC Guidelines for Simvastatin and SLCO1B1
https://www.pharmgkb.org/chemical/PA451363/guidelineAnnotation/
PA166105005
3. Roden D. Case Studies in personalized medicine. Vanderbilt University.
Online course through coursera.
https://www.coursera.org/lecture/personalizedmed/variability-in-drug-
therapy-spi4r
4. CPIC Guidelines for codeine and CYP2D6
https://www.pharmgkb.org/guidelineAnnotation/PA166104996
5. CPIC Guidelines for clopidogrel and CYP2C19
https://www.pharmgkb.org/guidelineAnnotation/PA166104948
6. CPIC Guidelines for voriconazole and CYP2C19
https://www.pharmgkb.org/chemical/PA10233/guidelineAnnotation/P
A166161537
7. Klein D. et al. PharmGKB summary: tamoxifen pathway,
pharmacokinetics. Pharmacogenet Genomics. 2013; 23(11): 643–647.
3Dr. Dalia A. Hamdy (FS 19/20AY)
4. 1. SLCO1B1 is a (transporter/enzyme/receptor) that is
found in the hepatocytes also known as
(OATP1B1/OAT1B1/OCT1B1). The following Allelle(s)
(*1a/*5/*14/*2) has normal function whereas
(*1a/*5/*14/*2) has decreased function and
(*1a/*5/*14/*2) has increased function.
2. A patient shows up in your pharmacy with a genotype of
(*1a/*1a) what would be the recommended dose? Can we
give 80 mg qd for this patient? Why? What is your
reference?
3. A patient carrying a genotype of (*1a/*5) came across
your pharmacy and his cholesterol levels were not
adjusted using the 20 mg /day dose of statin? What would
be your recommendation?
4Dr. Dalia A. Hamdy (FS 19/20AY)
10. “is the tailoring of medical treatment to the
individual characteristics of each patient”
The Age of Personalized Medicine
“The science of individualized prevention and
therapy”
National Institute of Health
10Dr. Dalia A. Hamdy (FS 19/20AY)
11. 11
One Size fits all
medicine
Vs.
Personalized
medicine
Dr. Dalia A. Hamdy (FS 19/20AY)
13. Pharmacogenetics:
The study of the effect of variations in DNA
sequence (genetic differences) on drug
response in terms of both the
metabolism/clearance (PK) and action (PD) of
the drug delivered
13Dr. Dalia A. Hamdy (FS 19/20AY)
15. 15Dr. Dalia A. Hamdy (FS 19/20AY)
1. What is DNA?
DNA (deoxyribonucleic acid),
the cell’s hereditary material.
DNA is a polymer of nucleotides
(sugar, phosphate and one of four
nitrogenous bases (A,T,G,C)
16. Human genome consists of
about 3.2 billion base pair (bp)
Every person has two copies of
each gene, one inherited from
each parent (6.4 billion bp)
DNA molecule is packaged into
thread-like structures called
chromosomes.
23 pairs of Chromosomes
Sex chromosome XX or XY
22 pairs autosomes
16Dr. Dalia A. Hamdy (FS 19/20AY)
17. 2. What is the gene function?
DNA
• 99-98% Non-coding : its job is to actually regulate the
process whereby genes are translated into proteins.
• 1-2% coding : acts like the blueprint that encodes
proteins (enzymes, structural elements, signaling
molecules)
17Dr. Dalia A. Hamdy (FS 19/20AY)
18. 3. Types of polymorphism
-SNPs (Single-Nucleotide Polymorphisms)
–Indels(Insertions & Deletions)
–VNTR (Variable Number Tandem Repeats)
–CNV (Copy Number Variants)
–Haplotypes (combination of alleles or to a set
of single nucleotide polymorphisms (SNPs) found
on the same chromosome
18Dr. Dalia A. Hamdy (FS 19/20AY)
19. Gene mutations
Inherited from a parent
Acquired during a person’s lifetime
Mutations range in size from
single base-pair mutation that occurs at a
specific site in the DNA sequence (SNV)
to a large segment of a chromosome (CNV)
19
SNP = SNV
which occur in
at least 1-2% of
the population
Dr. Dalia A. Hamdy (FS 19/20AY)
20. 3. Types of genetic variants
SNP can be in the coding or non-coding regions
of the DNA resulting in
different proteins that could be functional or
non functional
20Dr. Dalia A. Hamdy (FS 19/20AY)
22. • Polymorphism in enzymes, receptors and
transporters proteins can affect the PK and PD
of several medications
• In fact, 50–75% of medications are substrates of
the cytochrome P450 (CYP) 3A4 enzyme, 2C9,
and/or 2D6 metabolizing enzymes
• 50% of CPIC drugs guidelines involves 2C19, and/or
2D6
22Dr. Dalia A. Hamdy (FS 19/20AY)
26. 1. A patient appears with a T4 prescription in your pharmacy.
While discussing with him the use and checking his history you
realize that he has been on T3 and the pain is not manageable
and the dr. moved him to T4. In few days, he appears again
with a higher dose of codeine and still his pain is not in control.
-would you recommend a pharmacogenetic testing for this patient?
Why?
-If his PGX results came like that
CYP2D6 *4/*7, CYP2C19*1/*17, CYP2C9*1/*1, VKORC1 AA
What would you recommend and why?
2. What if the patient carried CYP2D6 *4/*9?
3. Knowing the mechanism of action of codeine, What other
information could be missing?
26Dr. Dalia A. Hamdy (FS 19/20AY)
28. 1. CYP 2D6
This had been determined using genotyping and
phenotyping. In phenotyping, a CYP2D6 specific probe
drug such as dextromethorphan is administered
the relative ratio between the concentration of probe
drug (dextromethorphan: DM) and its CYP2D6 specific
metabolite (dextorphan:DX)is obtained.
DM:DX ratios poor metabolizers.
DM:DX ratios extensive metabolizers
28Dr. Dalia A. Hamdy (FS 19/20AY)
31. 1. CYP 2D6
What is the effect of 2D6 on codeine?
Codeine
• Opiate analgesic
• Prodrug of morphine - is found naturally but
at low concentrations so usually synthesized
from morphine
31Dr. Dalia A. Hamdy (FS 19/20AY)
33. 33
1. Codeine is bioactivated to morphine, a strong opioid
agonist, by the hepatic cytochrome P450 2D6
2. The efficacy and safety of codeine are governed by
CYP2D6 activity.
3. Polymorphisms are a major cause of CYP2D6
variability.
Dr. Dalia A. Hamdy (FS 19/20AY)
35. 35
Similarly What about CYP2D6 and Tamoxifen?
Tamoxifen:
• a selective estrogen receptor modulator
• Used for the treatment and prevention of
estrogen receptor (ER)-positive breast cancer
• The drug is extensively metabolized by
CYP2D6 and other enzymes.
Dr. Dalia A. Hamdy (FS 19/20AY)
37. 37
Similarly What about CYP2D6 and Tamoxifen?
• 4-hydroxytamoxifen and endoxifen, are more
potent and considered the primary active
forms of the drug.
Dr. Dalia A. Hamdy (FS 19/20AY)
38. 38
Phenotype Genotype Therapeutic
recommendation for
tamoxifen
Ultrarapid metabolizer More than two copies of
functional alleles
None
Intermediate metabolizer One active allele and one
inactive allele, or two
decreased activity alleles,
or one decreased activity
allele and one inactive
allele
Increased risk for relapse of
breast cancer. Avoid
concomitant use of CYP2D6
inhibitors. Consider
aromatase inhibitor for
postmenopausal women
Poor metabolizer Two inactive alleles Increased risk for relapse of
breast cancer. Consider
aromatase inhibitor for
postmenopausal women
Dr. Dalia A. Hamdy (FS 19/20AY)
48. 48
1. What is expected to happen when I have
a. PM or IM CYP2C19?
b. UM or RM CYP2C19?
2. If we know that voriconazole is used for ttt
of invasive fungal infections in cancer patients.
Also that trough concentrations <2 mcg/ml is
associated with worse clinical outcomes? What
are the CPIC guidelines for a pt. with CYP2C19
*1/*17 or *2/*3?
Dr. Dalia A. Hamdy (FS 19/20AY)
52. 52
Using the CPIC guidelines how would you consider
carbamazepine therapy in the following pts.
1. A patient was using CBZ for 4 months and stopped
for problems with insurance coverage and
hospitalization periods. The dr. wants to restart him
again on CBZ. The dr. phones you and asks that he
heard about an available pharmacogenomic test
that is needed for this pt.? Would you strongly
recommend doing the test ? For what gene?
Why/why not?
2. The patient did the test and those were the results
CYP2D6 *4/*7, CYP2C19*1/*17, CYP2C9*1/*1, VKORC1
AA, HLA-B*15:02 negative
What would you suggest the dr. to do?
Dr. Dalia A. Hamdy (FS 19/20AY)
53. 53
Using the CPIC guidelines how would you
consider carbamazepine therapy in the
following pts.
3. A naïve pt. patient wants to start CBZ
therapy and his genetic testing shows HLA-
A*31:01 genotype
What would you suggest the dr. to do?
Dr. Dalia A. Hamdy (FS 19/20AY)
55. Pharmacists are expected to
1. Be the point of testing for the patients
2. Receive the patients reports and interpret
them in a meeting in lay language
3. Keep the results, consent and data in the
patient profile
4. Release the results or give results access to
patient
5. Communicate the results with other
healthcare professionals that the patient
chooses.
55Dr. Dalia A. Hamdy (FS 19/20AY)
56. Pharmacists are encouraged to communicate
with local physicians and introduce them to
report samples
Physicians are expected to act positively if
they are aware and familiar with the shape
or the results.
Pharmacists should encourage the patients to
contact their physicians if the results
warrants any change in therapy
56Dr. Dalia A. Hamdy (FS 19/20AY)
57. A pharmacist must prepare the dr. to the
referral . Surprises are not recommended!
57Dr. Dalia A. Hamdy (FS 19/20AY)
Transporter, oatp1B1
1a
5
14
Normal, check the recommendation, either through guidelines or through the imbedded results on website
The approach relies on scientific
breakthroughs in our understanding of how a person’s unique molecular
and genetic profile makes them susceptible to certain diseases. This same
research is increasing our ability to predict which medical treatments will
be safe and effective for each patient, and which ones will not be.
The approach relies on scientific
breakthroughs in our understanding of how a person’s unique molecular
and genetic profile makes them susceptible to certain diseases. This same
research is increasing our ability to predict which medical treatments will
be safe and effective for each patient, and which ones will not be.
Cnv copy number variations
Single nucleotide variants
CNV copy number variants
Alleles are forms of the same gene with small differences in their sequence of DNA bases. These small differences contribute to each person’s unique physical features
Missence: polymorphism changes amino acid
composition (missense)
Nonesense:induces premature stop
codons (nonsense), thereby affecting protein function.
although they may affect gene expression
(promoter SNPs) or RNA splicing
Discuss the cl and dose and auc and relationships and general expectations
3. The u receptor mutations
Uridine 5'-diphospho-glucuronosyltransferase (UDP-glucuronosyltransferase, UGT) is a cytosolic glycosyltransferase (EC 2.4.1.17) that catalyzes the transfer of the glucuronic acid component of UDP-glucuronic acid to a small hydrophobic molecule. This is a glucuronidation reaction.