Designer Drugs

Presented by:Frank Clark

Beth Nendza

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

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)

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

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

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 competence

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

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

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 for?

Fight infections Reverse a disease

process Relieve symptoms Restore normal

functions Aid in diagnosis Inhibit normal body

processes Maintain health

Medications

How is it administered? 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 tissues

Drug Reactions Journal of American Medical Association Pharmaceutical companies can’t predict

drug reactions All medications come with warning labels

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)

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

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

AntibioticsTetracyclines and penacillin G Antacid or milk Reduced effectiveness of antibioticPenicillin Tetracycline Diminished activity of penicillinTetracyline 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 2-4C Pulse and blood pressure

Not many drugs effected

Obesity Drugs that work with a build up of

time (Prozac)

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

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 DNA Determine the sequences of the 3

billion chemical base pairs that make up human DNA

How does HGP tie into pharmaceuticals?

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

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

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)

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 (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

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 lost) Affects gene copy number and

function

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

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 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

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

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

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

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

Other applications Pain management Environmental medicine Depression HIV/AIDS

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

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