designer drugs presented by: frank clark beth nendza
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Designer Drugs
Presented by:Frank Clark
Beth Nendza
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Overview Pharmaceuticals
History Ethical Code Interesting Cases Ethical Concerns Body response to
medicines Drug reactions Human Genome
Project Pharmacogenomics
Pharmacogenomics
SNPs Cancer/other
diseases Patient benefits Pharmaceutical and
consumer supports Funding Ethical concerns
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History
Oldest known medical book Natives of North and South America Aztecs in Mexico Aspirin
Creation of research based pharmaceutical companies
-Globalization and Health (Gentry and Webber 1999)
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Ethical Code
American Pharmaceutical Association 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 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
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Changing Ethics
Recently, many pharmaceutical codes of ethics have passed and added a “conscience” clause This gives pharmacists’ the right to
examine their own morals when filling prescriptions
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Interesting Cases How can this new clause effect you?
Utah, a pharmacist refused to fill the “morning after” pill for a patient
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
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Ethical Concerns
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?
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How Does The Body Respond To Medications?
What are drugs used for?
Fight infections Reverse a disease
process Relieve symptoms Restore normal
functions Aid in diagnosis Inhibit normal body
processes Maintain health
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Medications
How is it administered? Orally Intravenously Intramuscular Subcutaneous Rectal
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How do medicines work in the body? Administration of medications Absorption into blood stream Distribution throughout the body
Effected by: Blood supply Organ/compartment size Permeability of tissue membranes Binding of drug to various components of blood
and tissues
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Drug Reactions Journal of American Medical Association Pharmaceutical companies can’t predict
drug reactions All medications come with warning labels
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Heart DrugsDigitalis Thiazide diuretics Increased digitalis toxicityDigitalis Reserpine Increased digitalis toxicityDigitalis Barbituates Enhanced digitalis metabolismSeditivesBarbiturates Alcohol SynergismChloral hydrate Alcohol SynergismBarbiturates Oral anticoagulants Diminished anticoagulant effectBarbiturates MAO inhibitors Increased CNS depressionBarbiturates Male sex hormones Diminished activity of sex hormonesBarbiturates Oral contraceptives Inhibition of contraceptive actionBarbiturates Oral antidiabetic drugs Enhancement of barbiturate activity
Drugs and the Human Body (Liska 1997)
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Minor TranquilizersValium, Librium Alcohol Increased CNS depressionValium, Librium MAO inhibitors OversedationMajor TranquilizersPhenothiazines Alcohol OversedationMajor Tranquilizers Thiazide diuretics ShockMajor Tranquilizers Antihistamines Additive effect (CNS depression)Major Tranquilizers Morphine Enhanced SedationHaldol and Innovar Lithium Increased tranquilizer toxicity
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Parkinson's Treatments1-Dopa MAO inhibitors Hypertensive crisisArtane, Pagitane Phenothiazines Lowered blood levels of phenothiazinesOral Contraceptives Tegretol, Dilantin, antifungals Diminished contraceptive actionAntidepressivesProzac, Paxil, Zoloft MAO Inhibitors Nausea, shivering, confusion, muscle contractionsBronchodilatorPrimatene (asthma) Tagament or antibiotics Potential life-threatPain KillersAspirin Anticoagulants HemorrageAspirin Alcohol GI BleedingAspirin Probenecid Inhibition of probenecidDemerol MAO inhibitors Respiratory depression and Increased CNS depression
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AntibioticsTetracyclines and penacillin G Antacid or milk Reduced effectiveness of antibioticPenicillin Tetracycline Diminished activity of penicillinTetracyline Oral iron preperations Inhibited absorption of iron
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Why do some people experience drug reactions while others don’t? Dose-related effect Food/drink in stomach Biological variability Age
Fat content increases Liver metabolism Kidney excretion Blood protein decreases Increasing sensitivity
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Circadian rhythm Body temperature varies 2-4C Pulse and blood pressure
Not many drugs effected
Obesity Drugs that work with a build up of
time (Prozac)
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Genetic factors Genes are very similar
Ten fingers, etc Genes do have subtle differences
Makes you, you! These differences cause differences in your bodies
proteins Medications interact with the body’s proteins
Therefore, people will react differently to medications
This is why people suffer from nausea and even death from medicine toxicity
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Research One specific research by Dr. Erin
Schuetz of St. Jude Children’s Research Hospital
Discovered that CYP3A5 (protein) in some humans was not produced in sufficient levels to metabolize medications
Leads to build up and perhaps toxic levels of medication in human system
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Human Genome Project
What is the HGP? 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?
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Pharmacogenomics
Imagine 50 years down the road 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? Pharmacogenomics is the study of how an
individual’s genetic inheritance affects the body’s response to drugs
Pharmacogenomics= pharmaceuticals + genomics
Holds the promise of individual made drugs Keeping in mind that other factors effect drug
reaction Pharmacogenomics is believed to be the key to
creating medications that will reduce the harmful side effects of medication
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Single-Nucleotide Polymorphisms (SNPs)
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.) 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 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) Mass spectrometric methods to study
SNPs (self validating instrument) Scientists focusing on the changes in
the frequency of SNPs as the population ages
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Cancer and Other Diseases
Cancer and pharmacogenomics Pharmacogenomics more crucial to treatment
of cancer as opposed to other diseases Current cancer therapies
Suffer form low efficacy rates High rates of toxicity Adverse effects Significant consequences of incorrect therapy
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Variagenics inc Company that wants to use pharmacogenomic
pathway approach to develop cancer therapeutics
Markers SNPs and Haplotyping Haplotyping: identifies the groups of
polymorphism that occur together in each gene Additional genetic markers
Efficacy of cancer treatment depends on genetic properties of the tumor
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Loss of heterozygosity Measure of chromosomal loss Early phases of tumor formation
(DNA are lost) Affects gene copy number and
function
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Example: 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) 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
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
Tumors can undergo DNA hypermethylation
Occurs at CPG island in the promoter regions of specific genes
Poor expression of genes in the region
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Methylation analysis (cont.) 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 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)
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 Pain management Environmental medicine Depression HIV/AIDS
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Patient Benefits1. More powerful medicines Pharmaceutical companies, create drugs (proteins, enzymes,
etc.) Drug discovery Decrease damage to other healthy cells2. Better, safer drugs Investigate patient’s genetic profile, prescribe best drug
therapy Adverse reactions eliminated Speed recovery time3. Accurate methods of determining appropriate drug
dosages No more dosages on the basis of weight and age Solution: basis of person’s genetics Minimize the chance of overdose
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Benefits Cont.4. Advanced screening for disease Person can make lifestyle or environmental change at an early age
(basis of genetic code) Avoid severity of disease5. Better vaccines Made of DNA or RNA Activate immune system without causing infections Inexpensive, stable, easy to sore, etc6. Improvements in drug discovery and approval process Genome targets make it easier for companies to discover new therapies Reduce cost and risk of clinical trials7. Decrease in cost of health care Decrease in the number of adverse reactions Decrease failed rug trials Decrease time for drug to be approved More drug targets Decrease time period patient is on medication