Chapter 2

Question 1

Preclinical stage

Answer 1

Early part of drug development.

Identification of promising drugs and their testing on animals occurs in this stage.

Question 2

Clinical stage

Answer 2

Pharmaceutical companies establish the safety and effectiveness of new products in humans during this stage.

Question 3

Phase I clinical trials

Answer 3

Establish biological effects, as well as safe dosages and pharmacokinetics in a small number of healthy people.

Question 4

Phase II clinical trials

Answer 4

New drugs are used to treat in small number of patients and to establish the potential of a drug to improve patient outcomes.

Question 5

Phase III clinical trials

Answer 5

Compares the new medication to standard therapy in a larger number of patients studied by at sites across the country.

Question 6

Post-marketing sureveillance

Answer 6

Surveillance during which health professionals are encouraged to report adverse events experienced while on the new drug.

Question 7

Clinical trial

Answer 7

Stage where several thousand patients receive a new drug.

Question 8

Post-marketing period

Answer 8

Larger population receives new drug. Additional adverse effects are identified, if they arise.

Question 9

Pharmacogenomics

Answer 9

Study of how individual variations in drug targets or metabolism affect drug therapy.
Helps identify factors that are responsible for beneficial or adverse effects in individual patients.

Question 10

Homeostasis

Answer 10

Cell, tissue, or body does not respond to drug, but instead maintains internal environment by adjusting physiological processes.

Question 11

Pharmacology

Answer 11

Study of substances that produce biological responses.

Question 12

Graded drug response

Answer 12

Biological effects that can be measured continually up to the maximum resounding capacity of the biological system.

• blood pressure
• heart rate
• diuresis
• bronchodilation
• FEV1
• pain
• coma

Question 13

Quantal drug response

Answer 13

Drug responses that may or may not occur.

• convulsions
• pregnancy
• rash
• sleep
• death

Question 14

Drug potency

Answer 14

How much drug is needed to produce a biological response.

Question 15

Drug efficacy

Answer 15

The maximum effect a drug can produce.

Question 16

Drug intrinsic activity

Answer 16

The ability of a drug to produce a response once it has occupied specific receptors.

Question 17

Drug selectivity

Answer 17

A ratio of the dose or concentration producing the undesired effect to the dose or concentration producing the desired effect.

Question 18

Therapeutic index

Answer 18

Ratio of lethal dose of the drug to the therapeutic dose of the drug.

Therapeutic index for drugs on the market is always greater than 1.

Question 19

Placebo effect

Answer 19

Pharmacological effect that is not due to the active ingredient.

Question 20

Structure-activity relationship (SAR)

Answer 20

Correlation of chemical structure with pharmacological activity.

Question 21

Ion channel receptors

Answer 21

Transmit signals across the cell membrane by increasing the flow of ions and altering the electrical potential or separation of charged ions across the membrane.

Produce responses with rapid onset and short duration.

• muscle movements

Examples:
ACh (nicotinic)
Gamma-aminobutyric (GABA)
Excitatory amino acids (glycine, aspartate, and glutamate)

Question 22

Receptors coupled to G proteins

Answer 22

Proteins that cross the cell membrane 7 times, creating a pocket in which drugs can interact. Bound drugs may stimulate the receptor to release G protein that can interact with various effector proteins to produce a physiological response.

•Heart beat

Examples:
Alpha
Beta
Gamma

Question 23

Transmembrane receptors

Answer 23

Receptors that consist of extra cellular hormone-binding domain and intracellular enzyme domains that phosphorylates the amino acid tyrosine.

Examples:
Receptors for insulin
Receptors for epidermal growth factor
Platelet-derived growth factor

Question 24

Intracellular receptors regulating gene expression

Answer 24

Liquid soluble hormones can pass through the cell membrane and bind to intracellular receptors. The receptor moves to the nucleus, where it controls the transcription of genes by binding to specific DNA sequences.

Example: 
Corticosteroids 
Mineralcorticosteroids
Sex steroids 
Vitamin D
Thyroid hormones

Question 25

Enzymes

Answer 25

Biological molecules that encourage specific chemical reactions in the body.

Example:
Acetylcholinesterase breaks a chemical bond in ACh to terminate its action and make acetic acid and choline.

Question 26

Agonists

Answer 26

Drugs that produce receptor stimulation and a conformational change every time they bind.

Question 27

Antagonists

Answer 27

Drugs that occupy receptors without stimulating them. Antagonists occupy a receptor site and prevent other molecules, such as agonists, from occupying the same site and producing a response.

Example: 
Beta blockers (lol)

Question 28

Non-receptor mechanisms

Answer 28

Drugs whose action is based on their physicochemical properties rather than interaction with receptors.

Example:
Sodium bicarbonate

Question 29

Pharmacokinetics

Answer 29

Branch of pharmacology dealing with absorption, distribution, through the body, metabolism, and excretion of drugs.

Question 30

Absorption

Answer 30

Once inside the body, depending on route of administration, drugs interacts with various receptors to produce physiological change that result in clinical effectiveness.

Question 31

Bioavailability

Answer 31

The percentage of the administered dose that does enter the blood stream

Question 32

Distribution

Answer 32

The process of drugs moving throughout the body.

Question 33

Passive diffusion

Answer 33

Process by which drugs cross some type of biological barrier, such as a cell membrane or through a layer of cells, based on the concentration difference on the two sides of the barrier.

Question 34

Protein binding

Answer 34

Drugs bind to a variety of proteins that are present in the bloodstream; called plasma proteins.

Example: 
Albumin
Alpha 1 glycoprotein
Cortisol-binding globulin 
Sex-binding globulin 
Lipoproteins

Plasma protein binding occurs in the plasma and encourages retention of drug in the systemic circulation.

Question 35

Influx of a drug

Answer 35

Transport of drugs into the cell.

Question 36

Efflux of a drug

Answer 36

Transport of drugs out of the cell.

Question 37

Metabolism

Answer 37

The process of changing one chemical into another, and the process usually either creates or uses energy.

Question 38

First-pass metabolism

Answer 38

Metabolism by the liver following oral administration.

Question 39

Phase I metabolism

Answer 39

Known as non synthetic reactions.

Involve oxidation, reduction, and hydrolysis reactions, which prepare the drug molecule for further metabolism.

Question 40

Phase II metabolism

Answer 40

Known as synthetic or conjugation reactions.

Drugs molecules are metabolized and something is added to the drug to synthesize a new compound.

Question 41

Cytochrome P450

Answer 41

Reaction that catalyze the metabolism of a large number of diverse drugs and chemicals that are highly lipid soluble.

Question 42

First order metabolism

Answer 42

Metabolism is related to drug concentration so that a fixed FRACTION of drug is metabolized per hour.
Characterized by a half-life.

Question 43

Zero-order metabolism

Answer 43

Ethanol is present at concentrations well above their Km for metabolism, causing enzymes to act to their maximal metabolic capacity and metabolize a CONSTANT amount of drug each hour.

Question 44

Enzyme induction

Answer 44

Drugs that increase the expression of drug-metabolizing enzymes.

Example:
Phenobarbital

Question 45

Excretion

Answer 45

Process in which drugs are transferred from inside the body to outside.

Some unique sites where drugs are excreted by not absorbed:

• Kidney
• gallbladder

Principle organs for drug elimination:

• kidneys
• lung
• biliary system
• intestines