1. Pharmacodynamics Ed Bilsky, Ph.D. Department of Pharmacology University of New England

2. The New York Tomes, February 20, 2005 For Pain Management, Doctors Prescribe Caution By MARY DUENWALD "All of us have been reacting to the news as it comes forward, as to whether some of our tools will be taken off the market," said Dr. Raymond Gaeta, an anesthesiologist who directs Stanford's pain management clinic. "This is good news for patients over all. Clearly there are side effects with every medication, but it's really important to weigh the potential side effects versus the benefits for an individual patient."

3. Transmembrane Signaling Katzung, 2-8

4. Molecular Drug Targets TargetDrugs opioid receptorsmorphine, naloxone  receptorsalbuterol, metoprolol estrogen receptorsethinyl estradiol, tamoxifen voltage gated Na + channelslidocaine acetylcholinesteraseneostigmine, organophosphates cyclooxygenaseaspirin catecholamine reuptakecocaine

5. Downloaded from: StudentConsult (on 30 January 2006 03:27 AM) © 2005 Elsevier Drug/Receptor Interactions

6. Glucocorticoid Action Katzung, 2-9

7. Epidermal Growth Factor Receptor Katzung, 2-10

8. Ion Channels Katzung, 2-12

9. G-Protein Coupled Receptors Katzung, 2-12

10. Downloaded from: StudentConsult (on 30 January 2006 03:27 AM) © 2005 Elsevier Graded Responses

11. Downloaded from: StudentConsult (on 30 January 2006 03:27 AM) © 2005 Elsevier Concentration-Response Curve

12. Downloaded from: StudentConsult (on 30 January 2006 03:27 AM) © 2005 Elsevier Quantal Dose-Response Curve

13. Affinity and Potency How well does the drug bind to the receptor?

14. Potency

15. Efficacy How well is the receptor/transduction process activated?

16. Efficacy and Opioid Analgesics Severe Pain Moderate Pain Mild Pain

17. Therapeutic Index The relative safety of a drug is sometimes expressed as a therapeutic index (TI) Ratio of the dose of the drug lethal in 50% of a tested population (LD 50 ) to the dose of the drug therapeutically effective in 50% of the tested population (ED 50 ) TI= LD 50 ED 50

18. Therapeutic Index AnalgesiaDeath 3 mg 600 mg % Animals Showing Effect 0 50 100

19. Drug Interactions Antagonism –pharmacological (heroin and naloxone) –physiological (norepinephrine and acetylcholine) Additive effect –morphine and fentanyl Synergistic effect –alcohol and diazepam

20. Drug Interactions ABA+B Antagonism ABA+B Addition ABA+B Synergy Measured Effect

21. Downloaded from: StudentConsult (on 30 January 2006 03:27 AM) © 2005 Elsevier Competitive Antagonism

22. Downloaded from: StudentConsult (on 30 January 2006 03:27 AM) © 2005 Elsevier Partial Agonists

23. Some Drug Interactions are Favorable LeWitt P. N Engl J Med 2008;359:2468-2476

24. Tolerance Definition: –decreased effectiveness of a drug that results from repeated drug exposure –necessitates an increase in the dose of the drug in order to maintain a given level of effect Related Terms: –cross-tolerance (morphine/fentanyl) –tachyphylaxis

25. Different Types of Tolerance Metabolic: –Repeated administration of alcohol induces the enzyme alcohol dehydrogenase --> increased metabolism leads to a decreased drug effect Pharmacodynamic: –Repeated administration of morphine produces changes to opioid receptors and second messenger systems Behavioral: –Development of tolerance can be influenced by learning and conditioning processes

26. Drug Dependence and Withdrawal Definition: –Continual exposure to a drug produces physiological adaptations at the cellular level (physical dependence) –Cessation of drug administration can results in a rebound effect --> withdrawal syndrome (e.g., heroin withdrawal) Related Term: –psychological dependence