Basic Principles I

Question 1

pharmacology

Answer 1

-bio, biochem, phys, path, micro, psych, medicinal chem all go into pharmacology, which lead to pharmacodynamics, therapeutics and chemo, and tox (treatment of patients)

Question 2

pharmacodynamics

Answer 2

-given meds, leading to a response

Question 3

drug action

Answer 3

• molecular action

- invisible

Question 4

drug effect

Answer 4

• pharmacologic effect

- visible response

Question 5

selectivity

Answer 5

• property of drug to cause a specific effect
• few drugs produce a single effect
• primary effect is desired and second may or may not be
• can be one molecular action leading to multiple effects or two molecular action leading to combined effects

Question 6

pharmacokinetic

Answer 6

-drug and elimination

Question 7

pharmacodynamic

Answer 7

-how it works
-types of drug actions”
physiochemical and receptor interactions

Question 8

physiochemical actions

Answer 8

• simple chemical interactions
• antacids
• antiseptics
• not very specific

Question 9

receptor interactions

Answer 9

• interaction of drug with physiologic receptors-macromolecules
• most drugs

Question 10

drug receptors

Answer 10

• drug receptor interactions cause molecular events to occur in each cell
• enough of these events cause a change in cell function
• ultimately results in change in tissue function

Question 11

receptors

Answer 11

• macromolecules, particularly proteins
• may be on or in a cell or free in the plasma or extracellular fluid
• present as part of the normal biochemical and physiologic mechanisms and usually interact with endogenous compound
• function both as ligand binder and as an effector
• the natural ligand or a drug which resembles it can bind and modulate usual activity
• each receptor occupied might be stimulated or inhibited
• each cell in a tissue contains a large population of receptors that are easily accessible to drugs

Question 12

receptors 2

Answer 12

• each drug receptor interaction produces a small change in the biochemical or electrochemical homeostasis of the cell
• cumulative effects of many drug receptor interactions will lead to a change in the function of the cell and then the tissue
• when enough cells in a tissue are affected then the function of the tissue is altered and an observable pharmacologic response can be noted
• maximal response is eventually reached which is related to the number of drug receptor interactions and the physiologic capacity of the tissue

Question 13

types of receptors

Answer 13

• membrane bound-neural synapse, ion channels
• enzymes-intracellular or extra
• structural macromolecules- MT
• intracellular macro- steroid receptors, RNA
• cell membrane itself- change electrical potential, fluidity

Question 14

as subunit

Answer 14

-increases adenylyl cyclase and Ca currents

Question 15

ai subunit

Answer 15

-decreases adenylyl cyclase and increases K currents

Question 16

ao subinit

Answer 16

-decrease Ca currents

Question 17

aq subunits

Answer 17

-increases phospholipase CB

Question 18

a13 subunit

Answer 18

-increase Na/H exchange

Question 19

at subunit

Answer 19

-increases cCMP-phosphodiesterase (vision)

Question 20

aolf subunit

Answer 20

-increase adenylyl cyclase (olfaction)

Question 21

drug receptor bonds

Answer 21

• reversible are ionic, van der waals, hydrogen

- irreversible is covalent

Question 22

receptor amp and transduction

Answer 22

• aB together
• GDP off, interaction with receptor and ligand, GTP binds
• subunits split
• action
• GTPase on A gets rid of GTP
• back together

Question 23

G proteins

Answer 23

• regulate the activity of:
• distinct effector proteins in the cell- enzymes, channels, transport proteins
• can be multiple G proteins in a single cell
• act as switches that are turned on by the receptor and turn themselves off in a few seconds
• several drugs can stimulate different receptors but ultimately influence the same effector protein through the mediation of a G protein that is shared by different receptors
• stimulus averaging or modulation can be achieved

Question 24

second messenger

Answer 24

• also produce amplification of the drug receptor interaction
• converts an even that happens outside the cell into a change that happens inside the cell
• some second messengers can cause different effects in different tissues
• changing the biochemical balance of substrates in metabolic pathways and activating or deactivating enzyme systems can have a profound effects on the function of the cells in a tissue

Question 25

structure-activity relationships

Answer 25

• the structure of the drug determines how it will fit into the receptor
• the better the fit, the better the stimulation
• subtle changes in structure amongst a class of drugs can greatly influence effects

Question 26

quantitative descriptions of drug action

Answer 26

-attempts to take experimental data, combine it with certain assumptions and make a model that works for most systems

Question 27

interaction at eq

Answer 27

-drug + receptor equil with DR and leads to an effect

Question 28

dose response relationships

Answer 28

• dose to % max response

- log dose to % makes it easier to make comparisons to other drugs and find effective doses

Question 29

threshold

Answer 29

• beginning of the curve
• dose of agonist at which a response begins
• may relate to affinity of the agonist for the receptor

Question 30

slope

Answer 30

• rate of rise of response on the steep portion of the curve

- log of EC50 also relates to affinity

Question 31

maximal asymptote

Answer 31

-intensity of response is proportional to the fraction of receptors occupied
-effect = Emax x D / Kd + D
Kd is EC 50

Question 32

intrinsic activity

Answer 32

• ability to stimulate the receptor once bound
• relates to structure and influences efficacy and potency
• greater intrinsic activity=greater efficacy

Question 33

spare receptors

Answer 33

• not all receptors need to be occupied to achieve emax

- less efficacious agonists may need to occupy more receptors than highly efficacious agonists

Question 34

secondary receptors

Answer 34

• outside of the target tissues

- may mediate other effects of the drug side effects

Question 35

receptor regulation

Answer 35

• a cell can up or down regulate a population of receptors by changing the total number of receptors or their sensitivity
• homeostasis
• denervation hypersensitivity
• desensitization

Question 36

agonists

Answer 36

• bind to receptor and produce pharmacologic effect
• bind to receptor and activate
• can cause desensitization
• better fit results in better results at lower doses
• variations in intrinsic activity based on structure
• better agonists need lower doses
• can have same intrinsic activity- ability to achieve emax
• can have different intrinsic activity and same affinity- bind the same but dont reach emax the same
• can have different affinity and different intrinsic ability (different emax)

Question 37

antagonists 1

Answer 37

-can cause hypersensitivity if stopped suddenly

Question 38

efficacy

Answer 38

• stimulation after its bound
• ability of a drug to activate the effector protein of the receptor once the drug is bound to the receptor
• depends upon structure of drug

Question 39

potency

Answer 39

• relate to the amount of drug needed for an effect
• depends upon
  1. biologic system- receptor density, efficiency of stimulus response mechanisms of the tissue
  2. interaction of the drug with the receptor
• affinity, efficacy

Question 40

relative potency

Answer 40

• has horizontal relationship between two drugs

- increases EC 50 with different drug

Question 41

relative efficacy

Answer 41

• vertical relationships

- reach higher emax

Question 42

antagonists 2

Answer 42

• many things are learned about the structure and function of receptors from the use of antagonists
• block binding of agonists and prevent the pharmacologic repsonse

Question 43

competitive antagonists

Answer 43

• bind to same spot
• can be overcome by enough agonists
• just need more agonist
• antagonist has weak bond and is easily reversed
• two equilibriums-one to RL and one to RI
• increases L shifts eq that way and same for increasing I

Question 44

noncompetitive antagonists

Answer 44

• can’t be overcome by increasing doses of agonist
• receptors remain occupied by antagonist and not enough DR interactions occur to achieve emax
• strong bond and not easily reversed
• proton pumps
• inhibitor can either change effector or binding site
• if changes effector- ligand can bind but nothing happens- quad eq- bottom two inactive even after ligand binds (ligand plus inhibitor is inactive) - irreversible
• can also change binding site- bind to it or attaching to a different portion and altering site
• back to competitive eq- either ligand binds or inhibitor binds, but not both- reversible