1. Dr. Steven I. Dworkin Pharmacology for the Health Sciences Lecture 3

2. Dr. Steven I. Dworkin How are Drugs Named? Chemical Name –Specifies chemical structure Pre patent or release name –Typically drug company letters and numbers Generic Name –Nonproprietary name (each drug has only one generic name) Brand or Trade Name –Market name for a particular company Common or Street Name –Users name

3. Dr. Steven I. Dworkin What’s in a Name Chemical NameGeneric NameTrade Name N-(4-hydroxyphenyl) acetamideAcetaminophenTylenol 7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H- 1,4-benzodiazepin-2-one DiazepamValium 4-[4-(p-chlorophenyl)-4-hydroxypiperidino]-4'- fluorobutyrophenone HaloperidolHaldol 5-thia-1-azabicyclo [4.2.0]-oct-2-ene-2 carboxylic acid, 7- [(aminophenylacetyl)amino]-3-methyl-8-oxo-, monohydrate CephalexinKeflex, Keforal, Keftabs DL-threo-2-(methylamino)-1-phenylpropan-1- ol PseudoephedrineSudafed N''-cyano-N-methyl-N'-[2-[[(5-methyl-1H- imidazol-4-yl) methyl]thio]ethyl]guanidine CimetidineTagamet

4. Dr. Steven I. Dworkin Rose Chemical Nameisobutylphenyl propionic acid In-house name Generic Nameibuprofen Brand NamesAdvil, Children's Advil/Motrin, Medipren, Motrin, Nuprin, Pediacare Fever etc StreetNon-asprin headache reliever ibuprofen (ī'byūprō'fən), nonsteroidal anti-inflammatory drug (NSAID) that reduces pain, fever, and inflammation. Along with naproxen and ketoprofen, ibuprofen belongs to the propionic acid class of NSAIDs. It was first made available in 1967. Like other NSAIDs, it acts by inhibiting the body's production of prostaglandins. Available over the counter in a variety of preparations (e.g., Advil, Motrin, Nuprin), it is commonly used to treat rheumatoid arthritis, gout, and painful menstruation. Side effects include rash, alteration of platelet function and bleeding, and intestinal upset, which can lead to gastritis. Like other NSAIDS, it appears to have no potential for abuse or physical dependence. It should not be used by those who are allergic to aspirin.naproxenketoprofen prostaglandins

5. Dr. Steven I. Dworkin Drug Resources

6. Dr. Steven I. Dworkin Classification of Drugs Grouping by chemical structure. Specific Examples Core StructureGeneric NameTrade Name TetracyclinesDoxycyclineVibramycine CorticosteroidsPrednisoneMeticorten BenzodiazepinesDiazepamValium

7. Dr. Steven I. Dworkin Classification of Drugs Mechanism of action –Serotonin uptake inhibitors antidepressants –beta blockers Anti-hypertensives –H 2 blockers Anti-histamines

8. Dr. Steven I. Dworkin Drug Classification Therapeutic Categories and Subcategories Therapeutic CategoryExamples of Subcategories AnalygesicsNSAIDs Opioids AntibioticsTetracyclines Penicillins Cephalosporins Antihypertensive   –Blockers Diuretics ACE Inhibitors Anti-inflammatory drugsNSAIDs Corticosteroids Asthma Drugs   –Blockers Corticosteroids Leukotriene modifiers

9. Dr. Steven I. Dworkin Drug Classification ClassificationCharacteristics OTC drugsDrugs that do not require a prescription. May contain a lower dose of a prescribed compound, Prescription drugsGreater potential for adverse effects. Untoward drug interactions may occur. Use is monitored by a physician. Controlled SubstancesSchedules drugs evaluated for abuse liability. More restrictive requirements regarding distribution, storage, and record keeping

10. Dr. Steven I. Dworkin The Feds YearActPurposeComment 1906Federal Pure food act Prohibit adulteration and misbranding of medications USP standards established for ingredients. Drug did not have to be safe or effective 1938Drug and Cosmetic Act Required safety of new drug approval by FDA Start of NDA process 1952Durham- Humphrey Amendment Differentiated prescription and nonprescription Drugs unsafe without medical supervision required prescription, refill restriction 1962Kefauver-Harris Amendment Required effectiveness of prescription and nonprescription approval by FDA Drugs developed between 1938- 1962 included 1970Comprehensive Drug Abuse Act Established Categories for drugs with abuse potential. DEA to enforce the act

11. Dr. Steven I. Dworkin

14. Pre Clinical Trials In vitro studies In vivo studies –Use of standard animal models Efficacy Potency Safety LD determination ED determinations –Therapeutic Ratio Abuse Potential or Liability –Drug self-administration

15. Dr. Steven I. Dworkin Clinical Trials Introduction –Before a pharmaceutical company can initiate testing in humans, it must conduct extensive preclinical or laboratory research. Preclinical research typically involves years of experiments in animal and human cells. The compounds are also extensively tested in animals. 100-300k compounds screens  100-300 compounds  1 or 2 lead compounds Pharmaceutical company provides selected data to the Food and Drug Administration (FDA) with a requesting approval to begin testing the drug in humans. This is called an Investigational New Drug application (IND). Typically this is when the clock starts clicking and the PC has the next 11 years of exclusive patent rights.

16. Dr. Steven I. Dworkin PhasePurposeSubjectsDurationOutcome Phase I how drug absorbed, metabolized, and excreted and side effects over range of doses healthy volunteers (20 to 100), who are usually paid for participating in the study. several months70 percent of experimental drugs pass this initial phase of testing Phase II determine relative safety of the new drug, and its effectiveness.. several hundred patients randomized trials, drug vs control often blinded. several months to two years33 percent of experimental drugs successfully complete both phase I and phase II studies Phase III provide drug company and the FDA with a more thorough understanding of the drug's effectiveness, benefits, and the range of possible adverse reactions. several hundred to several thousand patients., most phase III studies are randomized and blinded trials. several yearsSeventy to 90 percent of drugs that enter phase III studies successfully complete this phase of testing FDA approval for market ing the drug. Phase IV objectives: (1) studies often compare a drug with other drugs already in the market; (2) studies are often designed to monitor a drug's long-term effectiveness and impact on a patient's quality of life; and (3) many studies are designed to determine the cost-effectiveness of a drug therapy relative to other traditional and new therapies.

17. Dr. Steven I. Dworkin Issues The New Drug War (non-US markets) Involvement of Pharmaceutical Companies Involvement of Interest Groups Role of advisory panel Role of FDA officials Publication and disclosure of negative findings When things go wrong? – Cox-2 inhibitors Media –Steroids –Alternative Medications

18. Dr. Steven I. Dworkin Questions Why are drugs categorized? What are the major differences between name brand and generics drugs? Approximately how many drugs are tested for every drug that is approved ? What federal agency is responsible for determining the safety and efficacy of new pharmaceuticals? What federal agency is responsible for enforcing the regulations for scheduled compounds What are the basic differences between OTC and prescription drugs? Under what conditions can a schedule I drug be prescribed for a patient. Name 2 Schedule II and 3 Schedule III compounds, what is one major difference between these compounds (difference of Schedule II compared to Schedule III) ? Who is responsible for the appropriate use of a compound?