lectures 8 & 9

Question 1

the science of interactions of chemical compounds with biological systems

Answer 1

pharmacology
i.e. how drugs act, where they act, mechanisms of drug action

Question 2

the study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of their actions and effects with their chemical structure

Answer 2

pharmacodynamics (what the drug does to the body)

Question 3

the study of the absorption, distribution, biotransformation, and elimination of xenobiotics

Answer 3

pharmacokinetics (what the body does to the drug)

Question 4

The ________ is the cornerstone of pharmacology.

Answer 4

drug receptor

Question 5

The ___________ explains how the organism reacts with a drug and initiates a chain of biochemical events which results in observed effects.

Answer 5

drug receptor

Question 6

The _________ is the drug whose interaction with the receptor stimulates a biological response.

Answer 6

agonist

Question 7

orthosteric binding examples

Answer 7

agonist, antagonist, partial agonist, and inverse agonists

Question 8

allosteric binding examples

Answer 8

positive (PAM) and negative (NAM)

Question 9

Inhibitors of ________ or inhibitors of ________ of endogenous ligands have drug like responses (MAOIs and SSRIs)

Answer 9

metabolism
reuptake

Question 10

Duration of drug action can be influenced by _________ and _________.

Answer 10

receptor (ex: steroid)
drug (ex: buprenorphine)

Question 11

What are the two purposes of drug therapy?

Answer 11

1. To produce the characteristic effect(s) of the drug being used. To do so, the drug must achieve adequate concentrations at its site(s) of action.
2. To achieve the maximal positive effect of the drug while minimizing undesired effects. No drug will have only one effect.

Question 12

Factors modifying drug therapy: prescribed dose

Answer 12

medication errors
patient compliance

Question 13

Factors modifying drug therapy: administered dose

Answer 13

rate and extent of absorption
body size and composition
distribution of body fluids
binding in plasma and tissues
rate of metabolism and excretion

Question 14

Factors modifying drug therapy: concentration at site(s) of action

Answer 14

physiological variables
pathological factors
genetic factors
interaction with other drugs
development of tolerance and desensitization

Question 15

Factors modifying drug therapy: drug effects

Answer 15

drug-receptor interaction
functional state of targeted system
selectivity of drug, propensity to produce unwanted effects
placebo effects
resistance (anti-microbial agents)

Question 16

Factors effecting drug specificity

Answer 16

affinity for target receptor
distribution of target receptor
multiple target receptors
enantiomers
acute vs chronic effects

Question 17

Drugs modify the normal __________ or _________ function of an organ, tissue, or cell.

Answer 17

physiological or biochemical

Question 18

A ______ effect is usually desirable from a therapeutic point of view. (________)

Answer 18

single
“therapeutic effect”

Question 19

Most drugs also have other _________ effects, usually at higher doses. (_______)

Answer 19

unwanted
“toxic/side effects”

Question 20

The __________ is where the drug acts to initiate the chain of events leading to an effects (ex: ________)

Answer 20

sites of drug action
extracellular, intracellular, on the drug surface)

Question 21

Extracellular sites of drug action examples

Answer 21

neutralization of excessive gastric acid by antacids
cholestyramine resin in reducing cholesterol absorption

Question 22

Intracellular sites of drug action examples

Answer 22

drug used to treat infections, drugs used for cancer chemotherapy, hormones such as estrogen

Question 23

Cell surface sites of drug action examples

Answer 23

steroid receptors (lipophilic and unionized)
cytokine receptors
tyrosine kinase receptors
ion channels
GPCRs

Question 24

Most receptors are _______.

Answer 24

proteins (regulatory, enzymes, transport, structural)

Question 25

Receptors largely determine the quantitative relationship between _________ and _________.

Answer 25

dose or concentration of drug pharmacologic effects

Question 26

Receptors are responsible for _________ of drug action, including _____, ______, and _______ of a drug molecule.

Answer 26

selectivity size shape charge

Question 27

Changes in the ____________ of a drug can affect receptor binding.

Answer 27

chemical structure

Question 28

______ are drugs that bind to a receptor and stimulate a biological response.

Answer 28

agonists

Question 29

_______ are drugs that bind to a receptor without altering receptor function (do not stimulate response); alter the interaction of the receptor with another drug

Answer 29

antagonists

Question 30

_____________ uses biochemical or biophysical approach. It typically measures a static event, not function

Answer 30

receptor binding/target engagement

Question 31

___________ assesses signaling events associated with receptor activity (ion flux/second messenger/gene regulation/substrate change)

Answer 31

functional assay

Question 32

Concentration effect curves and receptor binding and function of agonists: Responses to low concentrations of drug ___________. As ______ increase, the incremental response decreases. Concentrations may be reached at which ____________ in response can be achieved with increasing concentration.

Answer 32

increase proportionally doses no further increase

Question 33

________, measured by the value ____, is the ability of the drug to interact with the receptor and is one of the determinants of potency.

Answer 33

affinity KD

Question 34

A single drug may have different affinities for ___________. The _______ among drugs typically differs from receptor to receptor.

Answer 34

different receptors relative affinities

Question 35

The effect of a drug is directly proportional to ______________.

Answer 35

the amount of drug-receptor complex formed.

Question 36

The lower the KD, the _______ the affinity. The higher the KD, the _______ the affinity.

Answer 36

higher lower

Question 37

KD equation

Answer 37

KD= ([D][R]) / [DR] KD= K(off) / K(on)

Question 38

When the ligand/drug [D] occupies half of the receptors, the concentration of unoccupied receptors is ________ the concentration of occupied receptors.

Answer 38

equal to

Question 39

Saturation binding analysis: Bmax

Answer 39

total number of receptors on given cell or tissue (may be changed by drug or pathology)

Question 40

Saturation binding analysis: Kd

Answer 40

affinity of ligand for the receptor (typically constant for antagonists) readily identified at 1/2 Bmax

Question 41

Cheng-Prusoff equation

Answer 41

Ki= IC50 / [1 + L/KD]

Question 42

The _____ is an indirect measure of affinity.

Answer 42

Ki

Question 43

Considering the Cheng-Prusoff equation, which perameter is NOT required to calculate Ki from these data? A. KD of radioligand B. Bmax value C. IC50 value of test compound D. concentration of radioligand [L]

Answer 43

B

Question 44

Which of the following is not true? A. Pharmacology is the science of interactions of chemical compounds with biological systems. B. The drug receptor is the cornerstone of pharmacology. C. Drugs are defined by their actions (e.g. agonists or antagonists) D. Antibodies are in increasing use as drugs. E. Pharmacodynamics is the study of the absorption, distribution, biotransformation, and elimination of xenobiotics

Answer 44

E this is the definition of pharmacokinetics

Question 45

Which of the following is not true? A. Most drugs have a single effect. B. Agonists and antagonists have overlapping binding sites. C. The magnitude of drug response is influenced by its pharmacokinetics and pharmacology. D. Drug receptors are located intracellularly as well as on the cell surface. E. Allosteric modulators can have both positive and negative effects on agonists.

Answer 45

A most also have side effects

Question 46

Which of the following statements regarding Bmax is not true? A. Bmax is an estimated number of receptors in a given tissue. B. Bmax values are determined through saturation binding studies. C. Bmax values are not regulated by drug treatment. D. Bmax values are independent of the ligand. E. Bmax can influence downstream signaling events.

Answer 46

C can be downregulated or upregulated