Designer Drugs

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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 cant predict drug
  reactions
• All medications come with warning labels

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Drugs and the Human Body (Liska 1997)
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• Why do some people experience drug reactions
  while others dont?
• 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 2-4?C
• 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 bodys 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 Childrens 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
  individuals genetic inheritance affects the
  bodys 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
• Patients 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 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 patients 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 persons 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 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 therapies
• 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