MPP lecture 2 LO.pdf

1.Define the general terms of pharmacology as it relates to drug-receptor interactions and pharmacokinetics - Antagonists - inhibit the ability of their targets to be activated/inactivated - Competitive antagonists - drugs that bind to same sites on the target molecule...

1.Define the general terms of pharmacology as it relates to drug-receptor interactions and pharmacokinetics - Antagonists - inhibit the ability of their targets to be activated/inactivated - Competitive antagonists - drugs that bind to same sites on the target molecule - Competitve antagonists affect a drugs potency by reducing it - Noncompetitive antagonists - drugs that bind to other sites on the target molecule - Noncompetitve antagonists affect a drugs efficacy by reducing it - What are the 3 things the 4 properties of pharmacokinetics effect in a drug - Onsent, intensity, and duration of drug action - What are the 4 properties of pharmacokinetics - ADME, Absorption, distribution, metabolism, elimination - For drugs to have the same effect in the presence of an antagonist, what needs to happen to the drug concentration? - increase - Inverse agonist - Bind and cause active targets to become inactive - Partial agonist - Bind and activate target to partial extent - Full agonist - Bind and activate target to maximum extent - Agonist - Bind and cause a change in activity of target - Define Pharmodynamics - What the drug does to the body, the effect it exerts on the body - Define Pharmokinetics - What the body does to a drug, the movement of a drug in the body - Drugs and Drug receptors cause what two types of changes? - biochemical and physiological changes - What type of cell are Drug Receptors - macromolecules - Define Drugs - molecules that interact with specific molecular components of an organism 2.Characterize pharmacodynamics properties Binding site - The site on the receptor at which the drug binds What two chemical interactions allow drug-receptor binding to take place? - Van der waals forces (weak) and covalent bonding (strong) The favorability of a drug–receptor interaction is referred to as the affinity of the drug for its binding site - affinity Drug–receptor binding effects the Conformation of the receptor What affect do conformational changes in the receptor have on the drug? - Improve binding quality and alter action of the receptor What are two types of drug-receptor binding - Lock and key theory, active site inducted fit model Insulin analogues are an example of drug-receptor binding and all stimulate the insulin receptor to the same extent, however they exhibit slightly different Amino acid sequences. 4.Discriminate the four pharmacokinetic properties that determine the onset, intensity, and duration of drug action Absorption - Route of administration, permits entry of drug into circulation either directly or indirectly Distrubution - The drugs reversible dispersion into and out of the blood stream (vascular space and extravascular space) Metabolism - Biotransformation of the drug by the liver or other tissues Elimination - Drug is eliminated and excreted by the body via renal or kidney What are the two obstacles presented by the human body for drug absorbtion? - Integument, mucous membranes The human body has nonspecific _________ ____________ to present barriers to ALL drug absorption The rate and extent of absorption can limit the drugs ___________ at target organs Bioavailability refers to the _____ and ______ to which an administered drug reaches the systemic circulation - Rate, extent Bioavailability is important for calculating drug ________ for nonintravenous administration - Dosages Define first-pass metabolism and the property that it influences - The metabolism of the drug before it reaches the blood stream, usually by the liver or GI tract, influencing the drugs bioavailablity When a drug is absorbed from the GI tract it enters the ______ ______ before entering the systemic circulation - portal circulation Drugs with HIGH first pass metabolism need (HIGHER/LOWER) doses to increase bioavailability - Higher List the 4 mechanisms of absorption - Passive diffusion, facilitated diffusion, active transport, endocytosis What 4 factors influence absorption? - 1. Blood flow 2. Surface area available 3. Contact time 4. Expression of p-glycoprotein Define the role of P-Glycoprotein - responsible for transporting various molecules, including drugs, across cell membranes into the blood P-glycoprotein pumps drugs (in/out) of the cells from tissues to blood - out P-Glycoprotein is classified as a ___________ ___________ protein - Transmembrane transporter Areas of high P-glycoprotein expression have what kind of impact on drug absorption? - Limits absorption When a drug leaves the blood stream, it enters the ________ and the ________ - Interstitum, tissue Distribution of a drug from the plasma to the interstitum depends on what 4 aspects? - 1. cardiac output and local blood flow 2. capillary permeability 3. tissue volume 4. the degree of binding of the drug to plasma and tissue proteins 5.Predict Vd in a given clinical scenario 6.Compare and contrast the routes of drug administration 3 route categories of drug absorption - Enteral, Parenteral, Other Enteral - Oral - Most complicated and low gastric pH inactivates some drugs - Sublingual - Placement under tongue, directly enter blood stream (no stomach acid) Two preparations of oral drugs - Enteric-coated, extended-release Function of enteric-coated drugs - Protect from stomach acid Extended relasese oral prepreations of drug allower for _______ absorption and a _______ duration of action - Slower, longer Parenteral - Drugs directly into systemic circulation, for drugs poorly absorbed in the stomach What drug administration route has the highest bioavailability? - Parenteral (intravenous) Intravenous (IV) - Rapid effect and maximum degree of control over drug amount Intramuscular (IM) - Can be absorbed rapidly or slowly, example is epipens Subcutaneous (SC) - Absorption via simple diffusion and slower than IV route, example is insulin Other - Oral/Nasal Inhalation - Rapid, large surface area, avoid 1st pass - Intrathecal/Intraventricular - BBB, directly into CSF, example is meningitis - Transdermal - Drugs to the skins, varying absorption rate, example is nicotine patches - Rectal - Good for use if patient is vomiting or having tremors, prevents damage to the stomach