Week 1: Pharmacodynamics and Pharmacokinetics

Question 1

Alignment of a drug with its receptor is aided by various bonding forces. Which bonding forces play a predominant role in this alignment?

Answer 1

-Van der Waals
-Hydrophobic
-Hydrogen
-Ionic
-Covalent

Question 2

The dosage range of a drug that provides safe effective therapy with minimal adverse effects is?

Answer 2

Therapeutic window

Question 3

Volume of distribution of a mathematical calculation which equals:

Answer 3

Vd= Dose of drug/Plasma
concentration of drug

Question 4

What the BODY does to a drug once administered

The study of the changes in the concentration of a drug during the process of ABSORPTION, DISTRIBUTION, METABOLISM, and ELIMINATION from the body (ADME)

Answer 4

Pharmacokinetics

Question 5

What a DRUG does to the body

The study of the biochemical, physiologic, and molecular effects of drugs on the body and involves receptor binding

Answer 5

Pharmacodynamics

Question 6

The extent to which a drug reaches its effect site after its introduction into the body; differs based on the route of administration

Answer 6

Bioavailability

Question 7

Factors affecting bioavailability of a drug (6)

Answer 7

-Solubility
-Molecular weight
-pH and pKa
-Blood flow
-Age/sex/pathology
-Temperature

Question 8

Quick tell-tale for bioavailability

Answer 8

Blood flow to region med is administered

ex: Lungs have good blood flow = good bioavailability

Question 9

What is essential for the delivery of drugs to various tissues?

Answer 9

The vascular system

Question 10

Which drugs enter organs, muscles, and fats and bind to receptors?

Answer 10

Unbound drugs

Question 11

What are most drugs salts of?

Answer 11

Weak acids
Weak bases

Question 12

As an acid or base, drugs exist in solution as?

Answer 12

Ionized form
Nonionized form

Question 13

Is an ionized form of a drug water or lipid soluble?

Answer 13

Water soluble; unable to easily penetrate lipid cell membranes

Question 14

Is a nonionized form of a drug water or lipid soluble?

Answer 14

Lipophilic; diffuses across cell membranes like blood-brain/gastric/placental barriers

ex: propofol (very fast acting medication

Question 15

What are acid and bases degree of ionization at a particular site determined by?

Answer 15

-pKa = dissociation constant
-pH gradient across the membrane

Question 16

The negative log of the equilibrium constant for the dissociation of the acid or base

The pH at which 50% of the drug is ionized, 50% is nonionized

Answer 16

pKa = dissociation constant

Question 17

A med had a pKa of 7.3. pH is 7.3. If inject med IV, how much of drug is ionized? nonionized?

Answer 17

50% ionized, 50% nonionized

Question 18

What is quantitatively the most abundant plasma protein?

Answer 18

Albumin

Question 19

What two other proteins bind basic drugs?

Answer 19

• Alpha 1-acid glycoprotein
  -Beta globulin

Question 20

_______ drugs are not free to act on receptors, and therefore influences how a drug is distributed

Answer 20

Protein-bound

Question 21

______ protein binding prevents drug from leaving blood to enter tissues

(High or low)

Answer 21

High

Question 22

High protein binding results in ______ plasma concentrations

(High or low)

Answer 22

High

Question 23

If a drug is highly lipid soluble, it tends to be ______ protein bound

(Highly, not as)

Answer 23

Highly

Question 24

Can adding more drug “overcome” protein binding?

Answer 24

Yes, because the number of protein binding sites for drugs is FINITE

Bond is usually weak and can dissociate as
-plasma concentrations of drug declines
-a second drug that bind to the same protein is introduced

Question 25

May occur when drug administered ORALLY or RECTALLY Occurs in the intestinal wall or liver prior to drug entering systemic circulation

Answer 25

First-pass hepatic metabolism -Venous drainage from most portions of GI tract enter portal circulation -Less bioavailability

Question 26

A protein or other substance that binds to an endogenous chemical or a drug Leads to a chain of events which ultimately results in an effect

Answer 26

Receptor

Question 27

Drug response occurs from a low concentration

Answer 27

Sensitivity

Question 28

Produced by structurally similar chemicals

Answer 28

Selectivity

Question 29

The response from a given set of receptors is always the same because the cells themselves determine the response

Answer 29

Specificity

Question 30

Receptors have 3 common properties

Answer 30

Sensitivity Selectivity Specificity

Question 31

Drug response equation

Answer 31

D + R <----> (DRC) <-----> TR D= drug R= receptor DRC= drug receptor complex TR= tissue response

Question 32

Complete saturation of available receptors with drug molecules is not necessary for a desired tissue response to be elicited (True or false?)

Answer 32

True d/t sensitivity Spare Receptor Concept ex: acetylcholine and its receptor at the neuromuscular junction; less than 1% of the cell surface binds drug to receptor protein to achieve tissue response

Question 33

Degree of attraction between a drug and its receptor on the cell's surface

Answer 33

Affinity or potency ex: different agonists can produce the same maximal response (efficacy) but at differing concentrations; the most potent drug of a series requires the lowest dose ex: High affinity/potency = less drug ex: Low affinity/potency = more drug; increase concentration gradient

Question 34

A drug's capacity to produce an effect

Answer 34

Efficacy ex: Propofol has a high efficacy for sleep ex: Reglan has a low efficacy for nausea, but high efficacy as a prokinetic

Question 35

Which is safer, a wide or narrow therapeutic index?

Answer 35

Wide Narrow = higher risk of giving a lethal dose

Question 36

Are similar in molecular structure to their corresponding agonist drugs They have receptor affinity, but lack intrinsic activity or efficacy

Answer 36

Pure antagonists

Question 37

Second major type of antagonist drugs Have receptor protein affinity and intrinsic activity, but often only a FRACTION of the potency of the pure agonist

Answer 37

Agonist-Antagonists ex: Nalbuphine (mixed narcotic agonist-antagonist)

Question 38

Involves two agonist drugs that bind to different receptors Both drugs bind to specific unrelated receptor proteins and initiate a protein conformational shift with elicited individual tissue response These responses however generate OPPOSING forces; won't see as dramatic of a change

Answer 38

Physiologic Antagonism ex: isoproterenol-induced vasodilation and norepinephrine-induced vasoconstriction

Question 39

Occurs when a drug's action is blocked and no receptor activity is involved

Answer 39

Chemical Antagonism ex: Protamine is a positively charged protein that forms an ionic bond with heparin, thus rendering it inactive ex: Sugammadex encapsulates rocuronium, rendering it inactive

Question 40

Useful for predicting serum concentrations and changes in drug concentrations in other tissues Depict the body as theoretic spaces with calculated volumes

Answer 40

Compartment models

Question 41

Two compartments of the two-compartment model

Answer 41

First compartment = central compartment -Intravascular fluid -Highly perfused tissues (heart, lungs, brain, liver, kidneys) -Vessel rich group; 75% CO Second compartment = peripheral compartment -Vessel-poor group; 25% CO -Muscle, fat, bone

Question 42

Single-compartment model is not sufficient to describe the action of many drugs, including ______ ______ anesthetic drugs

Answer 42

Lipid soluble

Question 43

Proportional expression that relates the AMOUNT OF DRUG in the body to the SERUM CONCENTRATION Calculated by dividing the dose of the drug administered intravenously by the plasma concentration before elimination occurs

Answer 43

Volume of distribution (Vd)

Question 44

Formula for Volume of distribution (Vd)

Answer 44

Vd = Dose of drug/Plasma concentration of drug

Question 45

A _____ Vd (>0.6 L/kg) implies that drug is widely distributed and likely ______ soluble (Large or small) (Water or lipid)

Answer 45

Large, lipid

Question 46

A _______ Vd (<0.4 L/kg) implies drug is largely contained in the plasma and likely ______ soluble (Large of small) (Water or lipid)

Answer 46

Small, water

Question 47

Enzyme-catalyzed change in chemical structure of agent

Answer 47

Metabolism

Question 48

Main organ of metabolism

Answer 48

Liver

Question 49

Other metabolism pathways

Answer 49

Plasma Lungs GI tract Kidneys Heart Brain Skin

Question 50

Increased enzyme activity created by enzymatic stimulation over a period of time System can therefore break down more agent that uses same enzymatic system for biotransformation (metabolism) Leads to reduced half-lives (drug doesn't work as long)

Answer 50

Enzyme induction ex: Alcohol

Question 51

Drug is cleared at a rate proportional to the amount of drug present in the plasma Most drugs administered in therapeutic doses follow this

Answer 51

First-Order Kinetics

Question 52

A constant amount of drug is cleared regardless of the plasma concentration ex: alcohol Drugs exceed body's ability to excrete or metabolize them; enzyme system is saturated

Answer 52

Zero-Order Kinetics

Question 53

Another name for metabolism

Answer 53

Biotransformation

Question 54

Phases of metabolism

Answer 54

PHASE I: Oxidation, reduction, hydrolysis; usually form more chemically reactive products, which can be pharmacologically active, toxic, or carcinogenic; often involve a monooxygenase system in which cytochrome P-450 plays a key role PHASE II: Conjugation of a reactive group usually leads to inactive and polar products that are readily excreted in urine

Question 55

Do all drugs need to go through both Phase I and Phase II of metabolism?

Answer 55

Many drugs already possess an appropriate functional group for conjugation and do not need to be modified by a prior phase I reaction to be conjugated; allows them to be metabolized quicker

Question 56

Time necessary for the plasma content of a drug to drop to half its prevailing concentration after a rapid bolus injection

Answer 56

Elimination Half-Life

Question 57

Amount of drug remaining is related to what?

Answer 57

The number of half-lives elapsed

Question 58

When is a drug regarded as fully eliminated?

Answer 58

When approximately 95% has been eliminated Usually occurs in 4-5 half-lives

Question 59

Time to halving of the blood concentration after termination of drug administered by an infusion designed to maintain a constant concentration Accounts for continuous infusions or repeated dosing-induced changes in drug behavior (repeated small boluses)

Answer 59

Context-Sensitive Half-Time

Question 60

The volume of plasma completely cleared of drug by metabolism and excretion per unit of time

Answer 60

Clearance

Question 61

What properties govern clearance

Answer 61

Properties of the drug and the body's ability to eliminate it: -Directly proportional to the dose -Inversely related to the agent's half-life and concentration in central compartment

Question 62

Two main organs for clearance

Answer 62

Hepatic Renal

Question 63

Formula for clearance

Answer 63

Clearance = Q X E Q= blood flow to organs E= Extraction ratio/ability to extract drug from bloodstream

Question 64

Drug is cleared at a constant PERCENTAGE; dosage INDEPENDENT; a constant fractions of total drug is metabolized in a set time period; greatest amount og drug eliminated per unit time occurs when concentration highest

Answer 64

First-order kinetics

Question 65

Drug is cleared in a CONSTANT amount regardless of plasma concentration

Answer 65

Zero-order kinetics