Pharmacology for Nursing

1. Pharmacology for Nursing Munir Gharaibeh, MD, PhD, MHPE Department of Pharmacology School of Medicine The University of Jordan mgharaib@ju.edu.jo June 2019

2. Pharmacology • Is the science of drugs. It is the knowledge of history, source, physical and chemical properties, absorption, distribution, excretion, biotransformation, actions and therapeutic uses of drugs. Munir Gharaibeh MD, PhD, MHPE

3. Drug • A chemical that affects the living processes. It modifies an already existing function, and does not create a new function. Munir Gharaibeh MD, PhD, MHPE

4. Pharmacy • Is the branch of health sciences dealing with the preparation, dispensing, and proper utilization of drugs. Munir Gharaibeh MD, PhD, MHPE

5. Toxicology • Is the part of pharmacology which deals with adverse effects of drugs and the toxic effects produced by household, environmental and industrial chemicals. Munir Gharaibeh MD, PhD, MHPE

7. Drug-Body Interactions The interactions between a drug and the body are conveniently divided into two classes. • The actions of the drug on the body are termedpharmacodynamicprocesses. • The actions of the body on the drug are termedpharmacokineticprocesses. Munir Gharaibeh MD, PhD, MHPE

8. Drug-Body Interactions • Pharmacodynamicprocesses. These properties determine the group in which the drug is classified, and they play the major role in deciding whether that group is appropriate therapy for a particular symptom or disease. Munir Gharaibeh MD, PhD, MHPE

9. Drug-Body Interactions • Pharmacokineticprocesses. These processes govern the absorption, distribution, and elimination of drugs and are of great practical importance in the choice and administration of a particular drug for a particular patient, e.g., a patient with impaired renal function. Munir Gharaibeh MD, PhD, MHPE

10. Drug Receptors & Pharmacodynamics • Most drugs act by associating with specific macromolecules to alter their biochemical or biophysical activities. • Receptors المستقبلات)) are the components of the cell or organism that interact with a drug to initiate chain of events leading to the drug's effects. Munir Gharaibeh MD, PhD, MHPE

11. Drug Receptors & Pharmacodynamics • Many drug receptors have been isolated and characterized in detail, thus opening the way to precise understanding of the molecular basis of drug action. • The receptor concept has important practical consequences for the development of drugs and for arriving at therapeutic decisions in clinical practice. Munir Gharaibeh MD, PhD, MHPE

12. Drug Receptors & Pharmacodynamics Receptors largely determine the quantitative relations between dose (or concentration) of the drug and pharmacologic effects. • The total number of receptors limits the maximal effect a drug can produce. Munir Gharaibeh MD, PhD, MHPE

13. Relations between drug concentration and drug effect Munir Gharaibeh MD, PhD, MHPE

14. Relations between drug concentration and receptor-bound drug Munir Gharaibeh MD, PhD, MHPE

15. Drug Receptors & Pharmacodynamics Receptors are responsible for selectivity of drug action. • The molecular size, shape, and electrical charge of a drug determine how good it will bind to a particular receptor. • Accordingly, modifications in the chemical structure of a drug can dramatically increase or decrease a drug's affinities for different classes of receptors, with resulting alterations in therapeutic and toxic effects. Munir Gharaibeh MD, PhD, MHPE

16. Drug Receptor Interactions • Agonists act at the agonist binding site(Receptors) to initiate an action. • Competitive Antagonists or Inhibitors act at the agonist binding site, to produce no action, but can inhibit the binding and action of the agonist. • Allosteric Activators act at separate sites to increase the efficacy of the agonist or its binding affinity. • Allosteric Inhibitorsact at separate sites to decrease the efficacy of the agonist or its binding affinity Munir Gharaibeh MD, PhD, MHPE

17. Drug Receptor Interactions Munir Gharaibeh MD, PhD, MHPE

18. Agonist-Antagonist Relationships • Competitive (or reversible) antagonist: High agonist concentrations can overcome the inhibition by a competitive antagonist. Higher concentrations of agonist are required to produce a given effect • Irreversible (or noncompetitive) antagonist: Produces irreversible changes in the receptor to reduce the maximal effect of the agonist, although it may not change its EC50. Munir Gharaibeh MD, PhD, MHPE

19. Munir Gharaibeh MD, PhD, MHPE

20. Transmembrane Signaling Mechanisms 1. Lipid-soluble drug crosses the plasma membrane and acts on an intracellular receptor (which may be anenzymeor a regulator of gene transcription. 2. The drug binds to the extracellular domain of a transmembrane protein, thereby activating an enzymatic activity of its cytoplasmic domain 3. The drug binds to the extracellular domain of a transmembrane receptor bound to a separate protein tyrosine kinase, which it activates. 4. The drug binds to and directly regulates the opening of an ion channel 5. The drug binds to a cell-surface receptor linked to an effector enzyme by a G protein. Munir Gharaibeh MD, PhD, MHPE

21. Nicotinic Receptor Munir Gharaibeh MD, PhD, MHPE

22. Munir Gharaibeh MD, PhD, MHPE

23. Types of Dose-Response Curves • Gradede(متدرج) Dose-Response Curve. • Quantal Dose-Response Curve. Munir Gharaibeh MD, PhD, MHPE

24. Relations between drug concentration and drug effect Munir Gharaibeh MD, PhD, MHPE

25. Graded Dose-Response Curves Munir Gharaibeh MD, PhD, MHPE

26. Features of Graded Dose-Response Curves • Maximal Efficacy. • Potency. • Slope or Shape of the Curve. • Variability (Standard variation at each point) Munir Gharaibeh MD, PhD, MHPE

27. Quantal Dose-Response Curves Munir Gharaibeh MD, PhD, MHPE

28. Features of Quantal Dose-Effect Curves • Responses are all or non. • Follows the Normal Frequency Distribution. • If Cummulative-------- Sigmoid curve • Straight line for most of the line . • We can calculate the Therapeutic Index= LD50/ED50 Munir Gharaibeh MD, PhD, MHPE

29. Quantal Dose-Effect Curves • Median Effective Dose (ED50): is the dose at which 50% of individuals exhibit the specified quantal effect. • Median Toxic Dose (TD50): is the dose required to produce a particular toxic effect in 50% of animals. • Median Lethal Dose (LD50): is the dose required to produce death in 50% of the of the animals. Munir Gharaibeh MD, PhD, MHPE

30. Therapeutic and Toxic Effects of Drugs • Three posssibilities: • Both mediated by the same receptor-effector mechanism. • i.e. toxicity is a direct pharmacologic extension of the therapeutic action of the drug. • Mediated by identical receptors but in different tissues or by different pathways. • Each mediated by different types of receptors. Munir Gharaibeh MD, PhD, MHPE

31. Possibilities of Drug Combinations • Antagonistic Effects • Additive Effects. • Synergistic Effects. • No effect. Munir Gharaibeh MD, PhD, MHPE

32. Drug Antagonism • Pharmacologic Antagonism: • Drugs work on the same receptor. • Competitive Antagonism. • Noncompetitive antagonism. • Physiologic Antagonism: • Drugs work on opposite physiological processes. • E.g. Epinephrine in Anaphylaxis. • Chemical Antagonism: • A drug chemically neutralizes the other drug. • Antacid in heartburn. Munir Gharaibeh MD, PhD, MHPE

33. Variations in Drug Resposiveness • Hporeactive. • Hyperreactive or hypersensitivity. • Tolerance. • Tachyphylaxis. • Idiosyncrasy reactions: • Unusual, or rare, or unexpected responses. • Might be due to genetic differences or immunologic factors. Munir Gharaibeh MD, PhD, MHPE