1. Pharmacodynamics

2. * The study of the biochemical and physiologic effects of drugs and the molecular mechanisms by which those effects are produced * The study of what drugs do to the body and how they do it

3. To accomplish the therapeutic objective, nurses must have a basic understanding of pharmacodynamics * Educating patients about their medications * Making PRN decisions * Evaluating patients for drug responses (both beneficial and harmful) * Collaborating with prescribers about drug therapy

4. * Dose-response relationships * Drug-receptor interactions * Drug responses that do not involve receptors * Interpatient variability in drug responses * The therapeutic index

5. Relationship between the size of an administered dose and the intensity of the response produced Determines * The minimum amount of drug we can use * The maximum response a drug can elicit * How much we need to increase the dosage to produce the desired increase in response

6. * As the dosage increases, the response becomes progressively larger. * Tailor treatment by increased/decreased dosage until desired intensity of response achieved. * Three phases occur

8. These two characteristic properties of drugs are revealed in dose-response curves. Maximal efficacy * The largest effect that a drug can produce (height of the curve; see Figure 5-2, A). * Match the intensity of the response with the patient’s need. * Very high maximal efficacy is not always more desirable. Do not hunt squirrels with a cannon.

9. Potency * The amount of drug we must give to elicit an effect * Rarely an important characteristic of the drug * Can be important if lack of potency forces inconveniently large doses * Implies nothing about maximal efficacy – refers to dosage needed to produce effects * (see Figure 5-2, B)

11. Drugs * Chemicals that produce effects by interacting with other chemicals Receptors * Special chemicals in the body that most drugs interact with to produce effects

13. * Receptors are normal points of control of physiologic processes. * Under physiologic conditions, receptor function is regulated by molecules supplied by the body. * Drugs can only mimic or block the body’s own regulatory molecules. * Drugs cannot give cells new functions.

14. * Drugs produce their therapeutic effects by helping the body use its preexisting capabilities * In theory, it should be possible to synthesize drugs that can alter the rate of any biologic process for which receptors exist.

15. * Cell membrane-embedded enzymes * Ligand-gated ion channels * G protein–coupled receptor systems * Transcription factors

17. * The more selective a drug is, the fewer side effects it will produce. * Receptors make selectivity possible. * Each type of receptor participates in the regulation of just a few processes.

18. * Lock and key mechanism * Does not guarantee safety * Body has receptors for each: Neurotransmitter Hormone All other molecules in the body used to regulate physiologic processes

19. * Simple occupancy theory * Modified occupancy theory Affinity  Strength of the attraction Intrinsic activity  Ability of the drug to activate a receptor upon binding

21. Agonists, antagonists, and partial agonists Agonists Antagonists Noncompetitive versus competitive antagonists Partial agonists

22. * Agonists are molecules that activate receptors. * Endogenous regulators are considered agonists. * Agonists have both affinity and high intrinsic activity. * Agonists can make processes go “faster” or “slower.” * e.g. Dobutamine mimics NE at cardiac receptors.

23. * Produce their effects by preventing receptor activation by endogenous regulatory molecules and drugs * Affinity but no intrinsic activity * No effects of their own on receptor function

24. * Do not cause receptor activation but cause pharmacologic effects by preventing the activation of receptors by agonists. * If there is no agonist present, an antagonist will have no observable effect.

25. Noncompetitive antagonists * Bind irreversibly to receptors * Reduce the maximal response that an agonist can elicit (fewer available receptors) * Impact not permanent (cells are constantly breaking down “old” receptors and synthesizing new ones)

26. Competitive antagonists * Compete with agonists for receptor binding * Bind reversibly to receptors * Equal affinity – receptor occupied by whichever agent is present in the highest concentration

28. * These are agonists that have only moderate intrinsic activity. * The maximal effect that a partial agonist can produce is less than that of a full agonist. * Can act as antagonists as well as agonists.

29. * Receptors are dynamic cell components * Number of receptors on cell surface and sensitivity to agonists can change in response to: Continuous activation Continuous inhibition

30. * Continuous exposure to agonist Desensitized or refractory  Down-regulation * Continuous exposure to an antagonist Hypersensitive

31. * Simple physical or chemical interactions with other small molecules * Examples of receptorless drugs Antacids, antiseptics, saline laxatives, chelating agents

32. * The dose required to produce a therapeutic response can vary substantially among patients * Measurement of interpatient variability * The ED50

34. * Clinical implications of interpatient variability The initial dose of a drug is necessarily an approximation. Subsequent doses must be “fine tuned” based on patient’s response. ED50 in a patient may need to be increased or decreased after evaluating the patient response.

35. * Measure of a drug’s safety * The ratio of the drug’s LD50 (average lethal dose to 50% of the animals treated) to its ED50 * The larger/higher the therapeutic index, the safer the drug * The smaller/lower the therapeutic index, the less safe the drug