General Principles of Pharmacology

Question 1

What are the steps involved in the marketing of drugs?

Answer 1

Preclinical testing, clinical testing phases I, II & III, and Phase IV or post marketing surveillance

Question 2

What does a drug need to be approved for marketing by the Food and Drug Administration (FDA)?

Answer 2

Drug must be shown by studies to be “safe and effective”

Question 3

What is “indications?”

Answer 3

Conditions for the drugs use

Question 4

What is “unlabeled” uses for drugs?

Answer 4

Therapeutic utility for different purposes or in populations other than those described in the package insert

Question 5

Which group of people are considered “therapeutic orphans?”

Answer 5

Pregnant women, women of child bearing age, infants, and children

Question 6

What is Bioavailability?

Answer 6

is the percentage of the dose of the drug administered by any route reaches the systemic circulation

Question 7

What is bioequivalence?

Answer 7

equivalent release of the same drug substance from 2 or more drug products or formulations

Question 8

Are drugs with the same same active ingredient bioequivalent?

Answer 8

No; to be bioequivalent when they produce AUC, Cmax and Tmax values that are neither clinically nor statistically different

Question 9

What is Pharmacology?

Answer 9

The total knowledge of drugs including history, chemistry, source, biochemical & physical effects, pharmacodynamics (what the drug does to the body), pharmacokinetics (what the body does to the drug), therapeutics, site of action, interactions, distinctive features, etc.

Question 10

What is a Drug?

Answer 10

any substance which, when introduced into the body, produces a physiological change, a biological change, a decrease in population of resident or invading microorganisms, or a decrease in abnormal tissue development

Question 11

What are Orphan drugs?

Answer 11

development of drugs for treatment of diseases affecting fewer than 200,000 patients in the US, or for research using commonly available (nonpatentable) chemicals for treatment of specific diseases

Question 12

What is Clinical pharmacology?

Answer 12

The study of the effect of drugs in man

Question 13

What is Pharmacotherapeutics?

Answer 13

deals with use of drugs in prevention & treatment of disease, usually to alleviate symptoms or, sometimes, to alter the course of the disease. The emphasis is on the disease and the treatment thereof

Question 14

What is therapeutic index and how is it calculated?

Answer 14

The relative toxicity of a drug this is the ratio of the dose capable of killing 50% of animals (LD50) over that required to achieve a beneficial effect in 50% of the animals (ED50)

Question 15

What constitutes a “small therapeutic index?”

Answer 15

little difference between the therapeutic dose and the dose that causes toxicity

Question 16

What is Tolerance?

Answer 16

is hyporeactivity that occurs from chronic exposure to a drug

Question 17

What is CROSS TOLERANCE?

Answer 17

tolerance between drugs within a class; or between drugs of different classes that produce similar pharmacologic effects

Question 18

What is enzyme induction?

Answer 18

stimulate production of drug-metabolizing enzymes resulting in increased rate of metabolism and usually decreased blood level of the drug

Question 19

What is down regulation?

Answer 19

is a decrease in the number or sensitivity of receptor sites after continued dosing

Question 20

What is up regulation?

Answer 20

the body may either increase the number of receptors or increase the sensitivity of receptors

Question 21

What is Idiosyncrasy?

Answer 21

describes an unusual effect of a drug

Question 22

What is Side effect?

Answer 22

describes any action of the drug other than the desired (therapeutic) effect

Question 23

What is Adverse Effect?

Answer 23

is any noxious, unintended, and undesired effect that occurs at normal drug doses

Question 24

According to the Controlled Substances Act, addictive substances are categorized into?

Answer 24

schedules (I through V)`

Question 25

What drugs are Schedule I?

Answer 25

(Written C-i): Addictive substances with no approved use (e.g., heroin)

Question 26

What drugs are Schedule II?

Answer 26

C-ii: Highly addictive substances (e.g., morphine; amphetamine). Prescriptions must be written in ink or typed or submitted using electronic prescribing procedures and cannot be refilled. A DEA rule in 2007 allows a prescriber to write multiple prescriptions on the same day for the same patient and same drug to be filled sequentially for up a 90 day supply. (I did not see this but I assume C-ii prescriptions are limited to a 30 day supply.)

Question 27

What drugs are Schedule III and Schedule IV?

Answer 27

C-iii & C-iv: Less addictive; may be prescribed orally and may be refilled up to 5 times in 6 months (e.g., aspirin with codeine C-iii; diazepam C-iv)

Question 28

What drugs are Schedule V?

Answer 28

C-v: Low addictive potential. Texas law requires a prescription for C-v drugs so essentially, in Texas, there is no difference in prescribing or how schedules iii, iv & v are handled. See Lehne p. 434 for more comprehensive description of the various DEA schedules.

Question 29

What is Pharmacokinetics?

Answer 29

is the quantitative study of the absorption, distribution, metabolism and excretion of drugs and their metabolites. In simple terms, pharmacokinetics (often simply called “kinetics”) is what the body does to the drug.

Question 30

What factors affect Plasma membranes?

Answer 30

molecular size and shape, solubility at the site of absorption, the degree of differences in pH across the membrane, the electrochemical gradient for the lipid form of the drug, degree of ionization, vascularity of the tissue, and relative solubility of ionized and nonionized forms

Question 31

What substances cannot penetrate Plasma membranes?

Answer 31

Polar molecules (e.g., soluble in water) and ions cannot penetrate membranes and require transport systems.

Question 32

What substances are ionized or partially ionized?

Answer 32

``` Strong acids (e.g., HCl) and bases (e.g., NaOH) are completely ionized On the other hand, many drugs are weak acids or weak bases and are present in solution as both nonionized and ionized species ```

Question 33

What substances can penetrate Plasma membranes?

Answer 33

The nonionized is usually lipid soluble and able to penetrate the lipid membrane while the ionized moiety cannot. With a few drugs, the ratio of ionized to nonionized molecules is affected by change in pH

Question 34

What happens to salicylic acid in an acid environment?

Answer 34

a weak acid (such as salicylic acid, the active metabolite of aspirin), in an acid medium (such as the stomach or acid urine,) is predominantly in the nonionized state (hence lipid soluble and can be absorbed)

Question 35

What happens to morphine in an acid environment?

Answer 35

a weak base in an acid medium is predominantly in the ionized state; hence gets “trapped” in the more acidic fetus if morphine is given to a woman at term

Question 36

What is “ion trapping?”

Answer 36

A change in pH causing a change in a weak acid/base to a strong acid/base causing the medication to not be excreted

Question 37

What is the blood-brain barrier?

Answer 37

Tight junctions are characteristic of capillaries of the CNS, which, along with surrounding lipid glial cells

Question 38

What is Active transport?

Answer 38

characterized by selectivity, competitive inhibition by congeners (similar drugs or metabolites), a requirement for energy, saturability, and movement against an electrochemical gradient (usually polar or water soluble: e.g., levodopa)

Question 39

What is p-glycoprotein?

Answer 39

transporter; move chemicals out of cells. | is a drug efflux system also found in enterocytes, the kidney and brain

Question 40

What is Absorption?

Answer 40

is the transfer of a substance from the site of application to the blood stream (usually the systemic circulation)

Question 41

What is First pass effect?

Answer 41

refers to the rapid hepatic inactivation of certain oral drugs on their first pass through the liver

Question 42

What activates prodrugs?

Answer 42

prodrugs are inactive as such and are activated by metabolism in the liver

Question 43

What is Distribution?

Answer 43

is the process of a substance leaving the blood stream and moving to cells or tissues.

Question 44

What is volume of distribution (Vd)?

Answer 44

is a mathematical expression of the sum of the apparent volumes of the compartments that constitute the body. Vd relates the amount of drug in the body to the concentration of drug in the blood (or plasma).

Question 45

What is 1st order reactions?

Answer 45

rate of absorption and elimination is proportional to concentration

Question 46

What is zero order reactions?

Answer 46

rate of elimination is independent of concentration

Question 47

What is Half-life? How to calculate?

Answer 47

is the time it takes for 50% of the drug in the body to be eliminated from the body

Question 48

What is Clearance?

Answer 48

is the measure of the body's ability to eliminate a drug

Question 49

What is steady state?

Answer 49

reach a plateau in plasma concentration takes about four or five doses

Question 50

What are loading doses and what are they used for?

Answer 50

may be used to boost the drug concentration into the therapeutic range more quickly, especially if the drug has a large volume of distribution, a long half-life, or it is important to reach therapeutic concentration quickly

Question 51

What is Cmax, Tmax, and t 1/2?

Answer 51

peak (maximum) blood level; time to reach peak; half-life. βt½: elimination half-life

Question 52

What is the purpose of metabolism?

Answer 52

the primary purpose of metabolism is to change lipid soluble active compounds

Question 53

What is phase I metabolism and what occurs?

Answer 53

Phase I (termed "asynthetic") usually converts the parent drug to more polar metabolites by oxidation, reduction, hydrolysis, dealkylation, etc

Question 54

What is phase II metabolism and what occurs?

Answer 54

Phase II ("synthetic") involves coupling the drug or its phase I metabolite to endogenous water-soluble substrates, such as glucuronic acid, sulfuric acid, mercapturic acid, acetic acid, or an amino acid.

Question 55

What is cytochrome P-450 system (CYP 450)?

Answer 55

oxidizing enzyme system

Question 56

What does it mean if an enzyme is "inducible?"

Answer 56

certain compounds will increase enzyme activity

Question 57

What does it mean if an enzyme is "inhibited?"

Answer 57

certain compounds will decrease enzyme activity

Question 58

What is enterohepatic cycling?

Answer 58

drug may be reabsorbed

Question 59

What is he classical explanation of drug-receptor coupling?

Answer 59

is that the intensity of response produced by a drug is related to the number of receptors occupied thus is proportional to the dose of the drug

Question 60

What is Affinity?

Answer 60

attraction between a drug and its receptor

Question 61

What is Efficacy or Intrinsic activity?

Answer 61

ability of a drug to activate a receptor and produce an effect

Question 62

What is a drug agonist?

Answer 62

agonist binds to the receptor and cause a change in cellular activity. It has both affinity and efficacy.

Question 63

What is an antagonist?

Answer 63

An antagonist binds to the receptor, causes no change in cellular activity, and blocks the ability of endogenous substances or other drugs to bind to the receptor. It lacks efficacy.

Question 64

What is a partial agonist?

Answer 64

A partial agonist binds to the receptor, causes a low level of change in cellular activity, but blocks endogenous substances or other drugs from binding to the receptor.

Question 65

What is the cause of non-compliance?

Answer 65

the result of a misunderstanding, a failure of communication, the cost of the drug (I couldn’t afford it), or due to a patient's concern about the seriousness of the disease and their belief in the medication

Question 66

How does the FDA categorizes drug safety in pregnancy ?

Answer 66

A. No fetal harm in studies in women B. No fetal harm in animals; no studies in women C. Fetal harm in animals; no studies in women D. Fetal harm in studies in women; Weigh risk vs. benefit X. Definite fetal harm in studies in women. Contraindicated

Question 67

What is an Object drug?

Answer 67

drug whose action or kinetics is altered

Question 68

What is a Precipitant drug?

Answer 68

drug causing altered action

Question 69

What are important object drugs?

Answer 69

``` aminoglycoside antibiotics hypoglycemics antiarrhythmics lithium carbamazepine phenytoin cyclosporine theophylline digoxin warfarin ```

Question 70

What are characteristics of object drugs?

Answer 70

Narrow therapeutic index. Used chronically. Metabolized by hepatic microsomal enzymes

Question 71

What are Important precipitant drugs:

Answer 71

Absorption antacids, cholestyramine Enzyme Inducers carbamazepine, phenobarbital, phenytoin, rifampin, NNRTs Enzyme Inhibitors cimetidine, ciprofloxacin, erythromycin, isoniazid, azole antifungals, clarithromycin, verapamil, grapefruit juice, ritonavir + Transport inhibitors diltiazem, amiodarone, quinidine, ketoconazole

Question 72

How is grape fruit juice an enzyme inhibitor?

Answer 72

Grapefruit juice inhibits CYP 3A4

Question 73

What is the difference between drug misuse and abuse?

Answer 73

Abuse of a drug might be construed as any use of a drug for nonmedical purposes To misuse a drug might be to take it for the wrong indication, in the wrong dosage, or for too long a period

Question 74

What are the physiological factors on neonates when prescribing medication?

Answer 74

``` Small body mass Low body fat Low albumin Immature kidney and liver High body water Greater membrane permeability ```

Question 75

What physiological considerations are there for elderly?

Answer 75

Increase in body fat Decrease in most physiologic functions Multiple diseases Multiple medications

Question 76

Which drugs are Teratogenic?

Answer 76

Teratogenic drugs include phenytoin, carbamazepine, valproic acid, lithium, warfarin, retinoids, and danazol

Question 77

How does smoking affect theophyline?

Answer 77

decreasing the effectiveness of theophylline

Question 78

What does smoking and drinking do to enzymes?

Answer 78

enzyme inducer