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									Designer Drugs

 Presented by:
  Frank Clark
 Beth Nendza
   Pharmaceuticals            Pharmacogenomics
       History                    SNPs
       Ethical Code               Cancer/other diseases
       Interesting Cases          Patient benefits
       Ethical Concerns           Pharmaceutical and
       Body response to            consumer supports
        medicines                  Funding
       Drug reactions             Ethical concerns
       Human Genome
       Pharmacogenomics
   Oldest known medical book
   Natives of North and South America
   Aztecs in Mexico
   Aspirin
       Creation of research based pharmaceutical
    -Globalization and Health (Gentry and Webber 1999)
                 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
   A pharmacist acts with honesty and
    'Integrity’ in professional relationships
   A pharmacist maintains professional
   A pharmacist respects the values and
    abilities of colleagues and other health
   A pharmacist serves 'Individual, community
    and societal needs’
   A pharmacist seeks justice in the
    distribution of health resources
   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
              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
                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
       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
   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?
   What are drugs used
       Fight infections
       Reverse a disease
       Relieve symptoms
       Restore normal functions
       Aid in diagnosis
       Inhibit normal body
       Maintain health
         How is it
             Orally
             Intravenously
             Intramuscular
             Subcutaneous
             Rectal
   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
                Drug Reactions
   Journal of American Medical Association
   Pharmaceutical companies can’t predict drug
       All medications come with warning labels
           Drugs and the Human Body (Liska 1997)

Heart Drugs
Digitalis          Thiazide diuretics        Increased digitalis toxicity
Digitalis          Reserpine                 Increased digitalis toxicity
Digitalis          Barbituates               Enhanced digitalis metabolism
Barbiturates       Alcohol                   Synergism
Chloral hydrate    Alcohol                   Synergism
Barbiturates       Oral anticoagulants       Diminished anticoagulant effect
Barbiturates       MAO inhibitors            Increased CNS depression
Barbiturates       Male sex hormones         Diminished activity of sex hormones
Barbiturates       Oral contraceptives       Inhibition of contraceptive action
Barbiturates       Oral antidiabetic drugs   Enhancement of barbiturate activity
Minor Tranquilizers
Valium, Librium       Alcohol              Increased CNS depression
Valium, Librium       MAO inhibitors       Oversedation
Major Tranquilizers
Phenothiazines        Alcohol              Oversedation
Major Tranquilizers   Thiazide diuretics   Shock
Major Tranquilizers   Antihistamines       Additive effect (CNS depression)
Major Tranquilizers   Morphine             Enhanced Sedation
Haldol and Innovar    Lithium              Increased tranquilizer toxicity
Parkinson's Treatments
1-Dopa                   MAO inhibitors                  Hypertensive crisis
Artane, Pagitane         Phenothiazines                  Lowered blood levels of phenothiazines
Oral Contraceptives      Tegretol, Dilantin, antifungals Diminished contraceptive action
Prozac, Paxil, Zoloft    MAO Inhibitors                Nausea, shivering, confusion, muscle contractions
Primatene (asthma)       Tagament or antibiotics       Potential life-threat
Pain Killers
Aspirin                  Anticoagulants                Hemorrage
Aspirin                  Alcohol                       GI Bleeding
Aspirin                  Probenecid                    Inhibition of probenecid
Demerol                  MAO inhibitors                Respiratory depression and Increased CNS depression
Tetracyclines and penacillin G Antacid or milk          Reduced effectiveness of antibiotic
Penicillin                     Tetracycline             Diminished activity of penicillin
Tetracyline                    Oral iron preperations   Inhibited absorption of iron
   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
   Circadian rhythm
       Body temperature varies 2-4C
       Pulse and blood pressure
            Not many drugs effected
   Obesity
       Drugs that work with a build up of time
   Genetic factors
       Genes are very similar
            Ten fingers, etc
       Genes do have subtle differences
            Makes you, you!
            These differences cause differences in your bodies
                  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
   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
        Human Genome Project
   What is the HGP?
       Identify all the 30,000 genes in human
       Determine the sequences of the 3 billion
        chemical base pairs that make up human
   How does HGP tie into
   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
   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
      Polymorphisms (SNPs)
   Markers that will indicate
    connection between drug
    response and genetic
   Definition: variation in DNA
    at a single base that is found
    in at least 1% of the
   Help understand and treat
    human diseases
   Help scientists find the
    position on a chromosome
    where a particular
    susceptibility gene is located
   SNP consortium:
      Non-profit organization,

      In the process of publishing a high-density

       SNP map of the human genome
      Goal: map 300,000 SNPs
   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
   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
   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
    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
   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
   Loss of heterozygosity
       Measure of chromosomal loss
       Early phases of tumor formation (DNA are
       Affects gene copy number and function
   Example:
       Patient’s cells contain
        two alleles for drug
       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
   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
   mRNA expression
       Expression levels of
        specific genes, good
        predictor of response to
       Comparison of mRNA
        expression patterns of
        responsive and
       Expression profiling:
        mRNA levels measure
        to determine which
        genes are turned on at
        a given time
   Methylation
       Tumors can
        undergo DNA
       Occurs at CPG
        island in the
        promoter regions of
        specific genes
       Poor expression of
        genes in the region
       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
   Heart disease
       High salt diet may result in high blood
       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
   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
       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
   Other applications
       Pain management
       Environmental medicine
       Depression
       HIV/AIDS
                 Patient Benefits
1. More powerful medicines
  Pharmaceutical companies, create drugs (proteins, enzymes, etc.)
  Drug discovery
  Decrease damage to other healthy cells
2. Better, safer drugs
  Investigate patient’s genetic profile, prescribe best drug therapy
  Adverse reactions eliminated
  Speed recovery time
3. 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
                   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 disease
5. Better vaccines
  Made of DNA or RNA
  Activate immune system without causing infections
  Inexpensive, stable, easy to sore, etc
6. Improvements in drug discovery and approval process
  Genome targets make it easier for companies to discover new
  Reduce cost and risk of clinical trials
7. 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

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