Transcript DESIGNER DRUGS

Designer Drugs
Presented by:
Frank Clark
Beth Nendza
Overview
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Pharmaceuticals
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History
Ethical Code
Interesting Cases
Ethical Concerns
Body response to
medicines
Drug reactions
Human Genome
Project
Pharmacogenomics
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Pharmacogenomics
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SNPs
Cancer/other diseases
Patient benefits
Pharmaceutical and
consumer supports
Funding
Ethical concerns
History
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Oldest known medical book
Natives of North and South America
Aztecs in Mexico
Aspirin
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Creation of research based pharmaceutical
companies
-Globalization and Health (Gentry and Webber 1999)
Ethical Code
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American Pharmaceutical Association
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A pharmacist respects the relationship
between the patient and pharmacist
A pharmacist promotes the good of every
patient in a caring, compassionate, and
confidential manner
A pharmacist respects the dignity of each
patient
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A pharmacist acts with honesty and
'Integrity’ in professional relationships
A pharmacist maintains professional
competence
A pharmacist respects the values and
abilities of colleagues and other health
professionals
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A pharmacist serves 'Individual, community
and societal needs’
A pharmacist seeks justice in the
distribution of health resources
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There are many other codes of ethics
for those in the pharmaceutical industry
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Depends on what association they are a
part of
Theme of these codes of ethics are acting
with honesty and integrity, maintaining a
personal and confidential relationship with
a client and working with professional
competence
Changing Ethics
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Recently, many pharmaceutical codes of
ethics have passed and added a
“conscience” clause
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This gives pharmacists’ the right to
examine their own morals when filling
prescriptions
Interesting Cases
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How can this new clause effect you?
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Utah, a pharmacist refused to fill the “morning
after” pill for a patient
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Pharmacist was fired, but with this clause,
pharmacists will now be able to refuse such
prescriptions
Wal-Mart has announced that their pharmacy
will not carry this pill
Kmart has announced that if a doctor
prescribes any medication, then their
pharmacists will be expected to fill it
Ethical Concerns
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Does a pharmacist have the right to
pick and choose what medications are
allowed to be filled?
Is it right for a patient to have to
call/stop by a pharmacy until they find
one that will fill their prescriptions?
How Does The Body Respond
To Medications?
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What are drugs used
for?
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Fight infections
Reverse a disease
process
Relieve symptoms
Restore normal functions
Aid in diagnosis
Inhibit normal body
processes
Maintain health
Medications
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How is it
administered?
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Orally
Intravenously
Intramuscular
Subcutaneous
Rectal
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How do medicines work in the body?
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Administration of medications
Absorption into blood stream
Distribution throughout the body
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Effected by:
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Blood supply
Organ/compartment size
Permeability of tissue membranes
Binding of drug to various components of blood and
tissues
Drug Reactions
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Journal of American Medical Association
Pharmaceutical companies can’t predict drug
reactions
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All medications come with warning labels
Drugs and the Human Body (Liska 1997)
Heart Drugs
Digitalis
Digitalis
Digitalis
Seditives
Barbiturates
Chloral hydrate
Barbiturates
Barbiturates
Barbiturates
Barbiturates
Barbiturates
Thiazide diuretics
Reserpine
Barbituates
Increased digitalis toxicity
Increased digitalis toxicity
Enhanced digitalis metabolism
Alcohol
Alcohol
Oral anticoagulants
MAO inhibitors
Male sex hormones
Oral contraceptives
Oral antidiabetic drugs
Synergism
Synergism
Diminished anticoagulant effect
Increased CNS depression
Diminished activity of sex hormones
Inhibition of contraceptive action
Enhancement of barbiturate activity
Minor Tranquilizers
Valium, Librium
Valium, Librium
Major Tranquilizers
Phenothiazines
Major Tranquilizers
Major Tranquilizers
Major Tranquilizers
Haldol and Innovar
Alcohol
MAO inhibitors
Increased CNS depression
Oversedation
Alcohol
Thiazide diuretics
Antihistamines
Morphine
Lithium
Oversedation
Shock
Additive effect (CNS depression)
Enhanced Sedation
Increased tranquilizer toxicity
Parkinson's Treatments
1-Dopa
Artane, Pagitane
Oral Contraceptives
Antidepressives
Prozac, Paxil, Zoloft
Bronchodilator
Primatene (asthma)
Pain Killers
Aspirin
Aspirin
Aspirin
Demerol
MAO inhibitors
Hypertensive crisis
Phenothiazines
Lowered blood levels of phenothiazines
Tegretol, Dilantin, antifungals Diminished contraceptive action
MAO Inhibitors
Nausea, shivering, confusion, muscle contractions
Tagament or antibiotics
Potential life-threat
Anticoagulants
Alcohol
Probenecid
MAO inhibitors
Hemorrage
GI Bleeding
Inhibition of probenecid
Respiratory depression and Increased CNS depression
Antibiotics
Tetracyclines and penacillin G Antacid or milk
Penicillin
Tetracycline
Tetracyline
Oral iron preperations
Reduced effectiveness of antibiotic
Diminished activity of penicillin
Inhibited absorption of iron
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Why do some people experience drug
reactions while others don’t?
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Dose-related effect
Food/drink in stomach
Biological variability
Age
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Fat content increases
Liver metabolism
Kidney excretion
Blood protein decreases
Increasing sensitivity
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Circadian rhythm
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Body temperature varies 2-4C
Pulse and blood pressure
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Not many drugs effected
Obesity
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Drugs that work with a build up of time
(Prozac)
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Genetic factors
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Genes are very similar
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Ten fingers, etc
Genes do have subtle differences
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Makes you, you!
These differences cause differences in your bodies
proteins
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Medications interact with the body’s proteins
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 This is why people suffer from nausea and even death
from medicine toxicity
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Research
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One specific research by Dr. Erin Schuetz of
St. Jude Children’s Research Hospital
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Discovered that CYP3A5 (protein) in some
humans was not produced in sufficient levels to
metabolize medications
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Leads to build up and perhaps toxic levels of
medication in human system
Human Genome Project
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What is the HGP?
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Identify all the 30,000 genes in human
DNA
Determine the sequences of the 3 billion
chemical base pairs that make up human
DNA
How does HGP tie into
pharmaceuticals?
Pharmacogenomics
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Imagine 50 years down the road
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Gene test for what medication is suitable
for you
Pharmacists being able to look at your
genome and help figure out what OTC
drugs are best for you
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What is Pharmacogenomics?
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Pharmacogenomics is the study of how an
individual’s genetic inheritance affects the body’s
response to drugs
Pharmacogenomics= pharmaceuticals + genomics
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Holds the promise of individual made drugs
Keeping in mind that other factors effect drug reaction
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Pharmacogenomics is believed to be the key to creating
medications that will reduce the harmful side effects of
medication
Single-Nucleotide
Polymorphisms (SNPs)
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Markers that will indicate
connection between drug
response and genetic
makeup
Definition: variation in DNA
at a single base that is found
in at least 1% of the
population
Help understand and treat
human diseases
Help scientists find the
position on a chromosome
where a particular
susceptibility gene is located
(reeves)
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SNP consortium:
 Non-profit organization,
 In the process of publishing a high-density
SNP map of the human genome
 Goal: map 300,000 SNPs
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Orchid bio sciences (Princeton, N.J.)
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Collaboration with SNP consortium (two projects)
Confirms many of the SNPs in the public database
Confirmation of SNP: pull together an ethnically diverse
panel of DNA, assay for presence or absence of that SNP
(rakestraw)
Allele frequency determination
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Allele: alternative form of a gene
What is the frequency of occurrence of that SNP within the
members of ethnically diverse populations?
Formula: # of times SNP appears within each of the
populations/total = allele frequency
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Sequenom (San Diego)
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Mass spectrometric methods to study SNPs
(self validating instrument)
Scientists focusing on the changes in the
frequency of SNPs as the population ages
Cancer and Other Diseases
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Cancer and pharmacogenomics
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Pharmacogenomics more crucial to treatment of
cancer as opposed to other diseases
Current cancer therapies
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Suffer form low efficacy rates
High rates of toxicity
Adverse effects
Significant consequences of incorrect therapy
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Variagenics inc
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Markers
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Company that wants to use pharmacogenomic
pathway approach to develop cancer therapeutics
SNPs and Haplotyping
Haplotyping: identifies the groups of
polymorphism that occur together in each gene
Additional genetic markers
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Efficacy of cancer treatment depends on genetic
properties of the tumor
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Loss of heterozygosity
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Measure of chromosomal loss
Early phases of tumor formation (DNA are
lost)
Affects gene copy number and function
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Example:
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Patient’s cells contain two
alleles for drug target
1 highly expressed and 1
with low expression
LOH leaves low
expression allele
Drug target will be
present at small amounts
in the tumor
Less target protein to be
inhibited
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Study (Cairncross et al., J. Natl.
Cancer institute, 1998)
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100% (24/24) of oligodendrogliomas
carrying specific markers for LOH
responded well to chemotherapy
25% (3/12) lacking the marker responded
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mRNA expression
analysis
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Expression levels of
specific genes, good
predictor of response to
chemotherapy
Comparison of mRNA
expression patterns of
responsive and
unresponsive
Expression profiling:
mRNA levels measure
to determine which
genes are turned on at
a given time
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Methylation
analysis
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Tumors can
undergo DNA
hypermethylation
Occurs at CPG
island in the
promoter regions of
specific genes
Poor expression of
genes in the region
Methylation analysis (cont.)
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Methylation could affect how tumor
respond to drug treatment, if genes are
related to drug action
Comparison of Normal vs. Methylation
patterns in tumor tissue and non
responsive and responsive patients
Goal: investigate the significance of
methylation patterns to drug response
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Heart disease
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High salt diet may result in high blood
pressure
Coronary artery disease and stroke
Reduce salt intake
Problem: everyone cannot reduce their
salt intake by eating a low sodium diet
Solution: find genes that link high blood
pressure to high sodium
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University of Minnesota study (American
journal of hypertension)
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Correlating variation in angiotensin-converting enzyme (ACE)
gene with sodium sensitivity
24/35 patients with high blood pressure were sodium
sensitive
Three alleles of ACE correlated with sodium sensitivity
Sodium resistant allele: 25% were sodium sensitive
71% with sodium sensitive allele and 83% with both alleles
were sodium sensitive
Study is useful because it allows scientists to see which
individuals are in need of more salt management treatment
Physicians help manage their patients health more efficiently
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Other applications
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Pain management
Environmental medicine
Depression
HIV/AIDS
Patient Benefits
1. More powerful medicines
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Pharmaceutical companies, create drugs (proteins, enzymes, etc.)
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Drug discovery
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Decrease damage to other healthy cells
2. Better, safer drugs
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Investigate patient’s genetic profile, prescribe best drug therapy
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Adverse reactions eliminated
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Speed recovery time
3. Accurate methods of determining appropriate drug dosages
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No more dosages on the basis of weight and age
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Solution: basis of person’s genetics
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Minimize the chance of overdose
Benefits Cont.
4. Advanced screening for disease
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Person can make lifestyle or environmental change at an early age
(basis of genetic code)
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Avoid severity of disease
5. Better vaccines
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Made of DNA or RNA
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Activate immune system without causing infections
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Inexpensive, stable, easy to sore, etc
6. Improvements in drug discovery and approval process
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Genome targets make it easier for companies to discover new therapies
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Reduce cost and risk of clinical trials
7. Decrease in cost of health care
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Decrease in the number of adverse reactions
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Decrease failed rug trials
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Decrease time for drug to be approved
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More drug targets
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Decrease time period patient is on medication