Chapter 10 | Preclinical Studies

Question 1

An ideal drug is potent, efficacious, and specific

Answer 1

True

Question 2

The data for pharmacodynamics, pharmacokinetics, and toxicity enable the dose and dosing regimen to be set for the clinical trials

Answer 2

True

Question 3

The potency, efficacy, and safety of a drug depend on the chemical and structural specificity of drug-target interaction

Answer 3

True

Question 3

Pharmacokinetics

Answer 3

pharma=medicine; kinetic movement/motion) the study of drug movements throughout the body

Question 4

Pharmacodynamics:

Answer 4

(pharma=medicine; dynamics=change) refers to how a medicine changes the body

Question 5

Pharmacokinetics are grouped into four categories:

Answer 5

absorption
distribution
metabolism
excretion

pharmacokinetic variables depend on the ability of a drug to cross plasma membranes

Question 6

The Passage of Drugs Through Plasma Membranes

Answer 6

-Passive Diffusion
-Facilitated Diffusion
-Active Transport
-Pinocytosis

Question 7

Passive Diffusion

Answer 7

the random movement of molecules in fluid

Question 8

Facilitated Diffusion

Answer 8

from a region of high concentration to low concentration

Question 9

Active Transport

Answer 9

requires energy to drive the transportation of drugs against the concentration gradient, from low to high

Question 10

Pinocytosis

Answer 10

engulfing of fluids by a cell

Question 11

Absorption

Answer 11

the process involving the movement of a substance from its site of administration, across body membranes, to circulating fluids

Question 12

Factors that influence the absorption of medications:

Answer 12

• Drug formulation and dose
• Size of the drug molecule
• Surface area of the absorptive site
• Digestive motility or blood flow
• Lipid solubility
• Degree of ionization
• Acidity or alkalinity (pH)
• Interactions with food and other medications

Question 13

Distribution

Answer 13

involves the transport of drugs throughout the body

Question 14

Metabolism

Answer 14

also called biotransformation, is the process of chemically converting a drug to a form that is usually more easily removed from the body. It involves complex biochemical pathways and reactions that alter drugs, nutrients, vitamins, and minerals. The liver is the primary site of drug metabolism, although the kidneys and cells of the intestinal tract also have high metabolic rates.

Question 15

Drug-drug interactions

Answer 15

• Addition: the action of drugs taken together as a total
• Synergism: the action of drugs resulting in a potentiated (more than total) effect
• Antagonism: drugs taken together with blocked or opposite effects
• Displacement: when drugs are taken together, one drug may shift another drug at a nonspecific protein binding site, thereby altering desired effect

Question 16

Excretion of Medications

Answer 16

The rate at which medications are excreted determines the concentration of the drugs in the bloodstream and tissues. The concentration of drugs in the bloodstream determines their duration of action.
In an average-size person, approx 180L of blood is filtered by the kidneys each day.

Question 17

Factors that affect drug excretion:

Answer 17

• Liver or kidney impairment
• Blood flow
• Degree of ionization
• Lipid solubility
• Drug-protein complexes
• Metabolic activity
• Acidity or alkalinity (pH)
• Respiratory, glandular, or biliary activity

Question 18

Toxicology:

Answer 18

Toxicological studies show the functional and morphological effects of the drug. They are performed by determining the mode, site and degree of action, dose relationship, sex differences, latency, progression, and reversibility of these effects.
To determine toxicology: two studies: single dose and repeated dose.

Question 19

The therapeutic response of most drugs is directly related to their level in the plasma.

Answer 19

True

The plasma drug concentration between the minimum effective concentration and the toxic concentration is called the therapeutic range of the drug.

Question 20

single dose

Answer 20

purposes: the determination of repeated doses, identification of organs subjected to toxicity, and provision of data for starting doses in human clinical trials

Question 21

repeated dose

Answer 21

to evaluate the longer-term effects of the drug in animals

Question 22

carcinogenicity

Answer 22

carcinogenicity studies are carried out to identify the tumor-causing potential of the drug

Question 23

genotoxicity

Answer 23

genotoxicity studies determine if the drug compound can induce mutations of genes

Question 24

Onset of drug action represents the amount of time it takes to produce a therapeutic effect after drug administration.

Answer 24

True

Question 25

Peak plasma level occurs when the medication has reached its highest concentration in the bloodstream.

Answer 25

True

Question 26

Duration of drug action is the amount of time it takes for a drug to maintain its desired effect until termination of action.

Answer 26

True

Question 27

Variables that can affect the duration of drug action:

Answer 27

• Drug concentration
• Dosage
• Route of drug administration
• Drug food interactions
• Drug supplement interactions
• Drug herbal interactions
• Drug drug interactions

The most common description of a drugs duration of action is its plasma half life, defined as the length of time required for the plasma concentration of a medication to decrease by one-half after administration.

Question 28

The level of drug in the plasma is maintained continuously within the therapeutic range

Answer 28

plateau

Question 29

The plateau may be reached faster by administration of loading doses followed by regular maintenance doses

Answer 29

True

Question 30

Two fundamental ways to compare medications within therapeutic and pharmacologic classes:

Answer 30

• Potency
• Efficacy: magnitude of maximal response that can be produced from a particular drug

From a pharmacotherapeutic perspective, efficacy is almost always more important than potency

Question 31

A useful way to visualize the concept of potency is by examining dose-response curves

Answer 31

True

Question 32

Cellular Receptors and Drug Action:

Answer 32

Drugs act by modulating or changing existing physiological and biochemical processes. To exert such changes requires that drugs interact with specific molevules and chemicals normally found in the body. A cellular macromolecule to which a medication binds in order to initiate its effects is called a receptor.
The vast majority are proteins.

Question 33

The aim of preclinical pharmacological studies is to obtain data on the safety and effectiveness of the lead compound.

Answer 33

True

Question 34

Toxicity information in preclinical studies helps provide confidence about a drug’s safety.

Answer 34

True

Question 35

Pharmacological studies using animals are regulated under Good Laboratory Practice.

Answer 35

True

Question 36

Why do drugs administered to patients only contain APIs?

Answer 36

They don’t

Question 37

A drug’s vesicles affect it’s ability to permeate membranes.

Answer 37

True

Question 38

Through which barriers can lipid-soluble drugs usually pass?

Answer 38

cell membranes

Question 39

How are weak acid drugs generally absorbed by the stomach?

Answer 39

More quickly than weak basic drugs.

Question 40

Which route of administration does not completely bypass the liver?

Answer 40

rectal administration

Question 41

Why are intravenous drug dosages easier to control than drugs administered transdermally?

Answer 41

The entire dose is available in the bloodstream to be distributed to the target site.

Question 42

A drug’s lipid-solubility, polarity, and the __________ ___________ of the drug’s target tissue affect it’s distribution.

Answer 42

vascular nature

Question 43

What medical term means “to apply the drug on the surface of the skin”?

Answer 43

transdermal