PHRC 4210 Pharmcodynamics I

CO01: Describe the essential physico-chemical properties of drugs. CO01.01: Identify the chemical composition (atoms and/or functional groups) that confer water or lipid solubility upon a molecule CO01.02: Describe a hydrogen bond and identify hydrogen bond donators and hydrogen bond acceptors

CO01.03: Define the term “amphipathic” CO01.04: Calculate the formal charge on any atom CO01.05: Describe the lipid bilayer that makes up biological membranes CO01.06: Discuss the basis of the “hydrophobic effect” CO01.07: Define the terms “tight junction,” “desmosome”, and “fenestrae” and identify the anatomical sites where each of these are found CO01.08: Identify the various types of bonds in drug-receptor interactions and cite the relative strengths of these bonds CO02: Identify various functional groups present in drug molecules. CO02.01: Identify acidic or basic functional groups commonly encountered in drug chemistry CO03: Identify acidic and basic functional groups commonly found in drug molecules. CO03.01: Use the “Law of Mass Action” to write the equilibrium equation for an acid or base CO03.02: Define “Keq” and discuss how it differs from “Ka” and “Kb” CO03.03: Write the general (short-hand) equation for any monoprotic acid or base CO03.04: Identify the “conjugate acid” (protonated) and conjugate base” (unprotonated) specie in an acid (or base) equation CO03.05: Use the Huckle rule to identify whether or not a nitrogen atom within an aromatic ring is basic CO03.06: Discuss the use of salts of acids and bases in Drug formulations CO03.07: Explain qualitatively why decreasing the pH of the medium shifts the equilibrium toward the conjugate acid (protonated) specie, while increasing the pH shifts the equilibrium toward the conjugate base (unprotonated) specie CO03.08: Explain how resonance or inductive effects can strengthen or weaken the acidity (or basicity) of a given functional group CO03.09: Explain why aromatic bases (ArNR1R2) are less basic than aliphatic ones CO04: Explain drug solubility, lipophilicity, ionizability, passive diffusion and active transport mechanisms. CO.04.01 Describe the process of passive diffusion (absorption) of a molecule from the GI tract into the bloodstream, and from the renal tubule back into the bloodstream (reabsorption) CO04.02: Discuss the anatomical basis of the “blood-brain barrier” and describe intrathecal administration of a drug CO04.03: Describe the process of “ion trapping” in the urine, and recognize its usefulness in treating drug overdose CO05: Describe how pH influences the ionizability of acidic and basic functional groups in a drug. CO05.01: Define “pKa”, “pKb” and “pH” CO05.02: Derive the Henderson-Hasselbalch equation from the equilibrium expression of an acid or base CO05.03: Utilize the Henderson-Hasselbalch equation to calculate the ratio of the ionized to unionized specie of an acid or base CO05.04: Explain why it is appropriate (and convenient) to use the “pKa” value when referring to a base CO06: Describe the basic principles involved in drug absorption, distribution and elimination. CO06.01: Explain at the electronic level why a given functional group can (or cannot) serve as an acidic (or basic) functionality CO06.02: Describe the principles of drug absorption, distribution, metabolism and elimination CO06.03: Describe how the physicochemical properties of drugs may affect drug absorption and distribution CO06.04: Define “first-pass metabolism” and “oral bioavailability” CO06.05: Define renal excretion CO06.06: Describe the different factors that may affect renal excretion that are drug or patient related CO06.07: Describe how drugs can interact and compete for renal PHRC 4210 Pharmcodynamics I

CO06.08: Define excretion pathways: biliary excretion, enterohepatic circulation, fecal excretion, breast milk excretion, excretion through sweat, saliva, and tears CO06.09: List the different routes of administration (oral, sublingual, transdermal, parenteral, rectal, pulmonary, topical, etc.) including their advantages and disadvantages. CO06.10: Compare different routes of administration CO06.11: Describe different factors that may affect the bioavailability of drugs CO06.12: Define Enterohepatic circulation CO06.13: Describe first-pass metabolism CO06.14: Describe protein binding and how it may affect drug plasma concentrations CO06.15: Describe the unique properties of the central nervous system and the factors that may affect drug absorption and distribution into this tissue CO07: Define Phase I and Phase II metabolic pathways for drug molecules. CO07.01: Define “Phase I” and “Phase II” metabolism and state what is accomplished after each CO07.02: Identify sites in the body where drug metabolism commonly occurs CO07.03: Recognize that the 3 major Phase I processes are “oxidations”, “reductions” and “hydrolytic reactions”’ CO07.04: Define each of the above processes CO07.05: Recognize that Phase I metabolites may be inactive, more active, less active, or more toxic than the parent drug CO07.06: Identify functional groups that can undergo hydrolytic processes CO07.07: Illustrate using electron movement the mechanism by which a serine esterase can hydrolyze certain drugs and physiological substrates CO07.08: Rank in ascending order the ease of hydrolysis of esters, amides, carbamates, and ureas and explain the chemical basis of this ranking CO07.09: Define “prodrug” and discuss various reasons (advantages) to using the prodrug approach CO07.10: Provide some specific examples of clinically-useful prodrugs CO07.11: Identify common Phase II reactions, including the enzymes and their co-factors involved in these metabolic processes CO07.12: List specific types of Phase II conjugative processes and match each to (a) functional groups(s) that commonly undergo that form of conjugation CO07.13: Recognize that Phase II metabolism usually terminates the physiological activity of a drug CO08: Identify the relationship between physicochemical properties of drugs and their disposition pathways CO08.01: Describe the metabolic pathway by which benzapyrene and aflatoxin B can be metabolized to carcinogenic species CO08.02: List other common oxidative enzymes Involved in drug metabolism and illustrate via electron movement how prosthetic groups (co-factors) within these enzymes can function as oxidizing agents CO08.03: Identify functional groups that can undergo oxidative processes and illustrate electronically the mechanism behind these oxidations CO09: Define the enzymatic cycle of the Cytochrome P450 mixed function oxidase system and its clinical CO09.01: Describe the cytochrome P450 family of enzymes and illustrate the common pathway whereby the highly reactive “oxene” is formed by these enzymes CO09.02: State the role of cytochrome P450 reductase in the above process CO09.03: Illustrate how cytochrome P450 interacts with double bonds to form reactive epoxides CO09.04: Identify the four different processes that can occur subsequent to the formation of reactive epoxides by CYP450 CO09.05: Describe how CYP450 reductase & other reducing enzymes participating in reduction of drugs are able to do so. If the enzyme has a prosthetic group that participates in the reduction, show by electron movement the mechanism of the reduction CO09.06: Identify functional groups that can undergo reductive processes CO09.07: Describe the theoretical basis of the “Mickey Finn” effect CO09.08: Describe the CYP450 location and function CO09.09: Classify the CYP450 families and subfamilies (isoforms) CO09.10: Define CYP450 induction and inhibition CO09.11: Know the differences between active and inactive metabolites PHRC 4210 Pharmcodynamics I

CO09.12: List the different factors that may affect CYP450s enzymatic reactions: Genetic, race, physiological CO09.13: Describe how drugs can interact with the CYP450 and affect other drugs’ metabolism CO09.14: Describe examples of clinically relevant race/genetic/disease variations that may affect drug therapy success Warfarin, trastuzumab, omeprazole, plavix, abacavir CO09.15: Describe drugs that are inhibitors or inducer of the major CYP450 isoforms CO10: Define drug potency, efficacy and safety CO10.01: Explain therapeutic window and how it may affect the safety of some drugs CO11: Describe and apply basic pharmacokinetic principles. CO11.01: Describe zero and first order kinetics and how they relate to drug absorption, metabolism and elimination CO11.02: Define: Half-life, volume of distribution and clearance CO11.03: Describe the different factors that may affect pharmacokinetic parameters CO11.04: Define bioequivalence, dosing regimens and loading dose CO12: Identify the most common mechanisms of drug-drug and drug-food interactions. CO12.01: Describe examples of drug-drug interactions via protein binding and how this may affect drug plasma concentrations CO12.03: Define placental transfer of drugs CO12.04: Recognize the clinical relevance of drug metabolism and interactions CO12.05: Drug-drug interactions CO12.06: Drug-food interactions CO12.07: Drug-herbal interactions CO13: Describe specific facts about physiological targets of drugs including enzymes, nucleic acids, CO13.01: Describe drug-receptor interaction and its characteristics CO13.02: Define the lock and key model and the induced-fit model for drug-receptor interaction CO13.03: Recognize a drug-response curve: semi-log vs. arithmetic scale CO14: Identify different classes of receptors and their signal transduction pathways. CO14.01: Define xenobiotics, endogenous substances and signaling molecules (Local, hormone, neurotransmitter) CO14.02: Define affinity and intrinsic activity CO14.03: Know how to identify maximal response and EC50 in a dose-response plot CO14.04: Define efficacy and potency CO14.05: Summarize the two receptor theory and the concept of inverse agonists CO14.06: Explain how to compare drugs based on relative potency and relative efficacy (Dose-response curves) CO14.07: Define the criteria for receptor-mediated events CO14.08: Describe regulation of receptors: desensitization and up-regulation; autoreceptors CO14.09: Classify the different types of the following receptors and their properties: ligand-gated ion channels, G-protein coupled receptors, receptors as enzymes, nuclear receptors CO14.10: Describe ligand-gated ion channels and their functional properties. CO14.11: Recognize the different mediators of each major second signaling pathway CO14.12: Define the different second messenger systems and G-proteins: G-protein, adenylate cyclase signaling system, phosphatidylinositol phosphate signaling system, protein kinase signaling system CO15: Define agonists, antagonists, partial agonists, and receptor modulators. CO15.01: Define competitive and noncompetitive antagonism CO15.02: Describe the different types of receptor mediated allosterism: antagonism and potentiation CO15.03: Define agonist, partial agonist, antagonist and spare receptors CO15.04: Recognize full and partial agonists in dose-response curves CO16: Define the quantitative relationships between drug-receptor concentrations and the extent of drug- CO16.01: Describe dose-effect relationships: Benefit vs. toxicity CO16.02: Explain therapeutic index CO17: Describe antihistamines and their pharmacology including complementary and alternative medicines CO17.01: Describe the biological actions of histamine CO17.02: Classify the histamine receptors and their biological functions CO17.03: Explain the concept of “Physiological Antagonism” PHRC 4210 Pharmcodynamics I

CO17.04: Recognize drugs that can act as agonists or antagonists of the histamine receptors CO17.05: Define the drugs that can inhibit histamine release CO17.06: Describe the therapeutic applications of drugs that act on histamine receptors CO17.07: Describe the side effects and drug-drug interactions of drugs that act on histamine receptors CO17.08: Recognize complementary and alternative medicines used in the treatment of allergic reactions CO18: Define the pharmacological properties of local anesthetics. CO18.01: Recognize the unique chemical properties of local anesthetics and how this may affect their actions: esters and amides CO19: Describe local anesthetics their mechanism of action, side effects, drug-drug interactions and important CO19.01: Describe the mechanism of action of local anesthetics CO19.02: Describe the pharmacokinetics of local anesthetics CO19.03: Define the clinical applications of local anesthetics: Topical, Infiltration, field block, nerve block, intravenous regional anesthesia (Bier’s Block), spinal anesthesia and epidural anesthesia CO19.04: Describe the major side effects of local anesthetics CO19.05: Recognize the toxic effects of local anesthetics and what factors may affect the incidence of these toxic effects