Pharmacology 3 (Pharmacokinetics)

Front 1

how do nonsynthetic reactions differ from synthetic reactions in their type?

Back 1

both are determined by functional group

there are a limited number of synthetic reactions, but a wide variety of nonsynthetic reactions

synthetic reactions are relatively predictable, whereas nonsynthetic reactions are unpredictable

Front 2

how do the metabolites differ between synthetic and nonsynthetic reactions?

Back 2

synthetic - almost always less lipid soluble, almost always pharmacologically inactive

nonsynthetic - usually less lipid soluble, may have less/equal/greater/different activity

Front 3

what biotransformations are catalyzed by nonmicrosomal enzymes (occur in the cytoplasm)?

Back 3

synthetic - all except glucuronidation

nonsynthetic - most hydrolyses

Front 4

what biotransformation reactions are catalyzed by microsomal enzymes (occur in the ER)?

Back 4

synthetic - only glucuronidation

nonsynthetic - most oxidations and reductions

Front 5

when is the rate of reaction of synthetic reactions affected by drugs?

Back 5

in the ER, the rate of reaction of microsomal enzymes is stimulated by drugs

in the cytoplasm, the rate of reaction of nonmicrosomal enzymes is not stimulated by other drugs

Front 6

when is the rate of biotransformation reactions of nonsynthetic reactions stimulated by other agents?

Back 6

in the ER, the rate of reactions of nonsynthetic reactions is stimulated by many agents

in the cytoplasm, the rate of reactions of synthetic reactions is not stimulated by other drugs

Front 7

what are the classic enzyme inducers?

Back 7

barbiturates

Front 8

define enzyme induction

Back 8

process in which a drug induces (enhances rate of synthesis or reduces degradation of) an enzyme

important enzyme for our discussion - P-450

Front 9

how do toxins affect metabolism of drugs?

Back 9

can damage the tissue where the enzymes are located leading to an irreversible inhibition of activity

Front 10

how does age affect metabolism/excretion of drugs?

Back 10

in the elderly, generally expect to see a decreased excretion rate

Front 11

what is a bimodal distribution?

why does isoniazid have a bimodal distribution?

Back 11

continuous probability distribution with two local maxima

in a plot of number of patients vs. plasma [isoniazid], there is a bimodal distribution because some people are genetically programmed to acetylate efficiently, and others do it inefficiently

Front 12

how is isoniazid metabolized?

Back 12

acetylated

Front 13

what are first order kinetics?

Back 13

a first-order reaction depends on the concentration of only one reactant

Front 14

what is an elixir?

Back 14

mixture of alcohol, a drug, and water; alcohol is used to dissolve the drug

Front 15

what is a suspension?

Back 15

preparations containing finely divided drug particles (clumps) distributed throughout a vehicle in which the drug is insoluble

Front 16

what is used in a suspension to help prevent the drug from settling to the bottom of the container?

Back 16

thickening agents (often carboxymethylcellulose)

shaking the container before dosing

Front 17

what is the old way of creating sustained release drug preparations?

Back 17

clumps of drug particles were coated with coatings differing in their solubility

easily soluble coatings release the drug quickly for immediate absorption, and slowly dissolving coatings release the drug at a later point in time

Front 18

what is the new way of creating sustained release drug preparations?

Back 18

drug is contained in a membrane that is semipermeable to water, and has a laser drilled delivery orifice in it

as water enters the membrane, the drug goes into solution and the solution is pushed out the small hole at a controlled rate

Front 19

how are depository (depot) forms of drug administration used?

Back 19

IM use (NOT IV)

Front 20

what is a depository (depot) form of drug administration?

Back 20

suspension of poorly water-soluble drug is injected into muscle, slowly dissolves, and is absorbed into the plasma

Front 21

how can a water soluble drug be made into a depository form of drug administration?

Back 21

a long hydrocarbon chain can be esterified to an OH group, making the complex weakly water soluble

the complex is slowly absorbed and broken apart by enzymes in the plasma, thus liberating free drug

Front 22

what is bioequivalence?

Back 22

a term in pharmacokinetics used to assess the expected in vivo biological equivalence of two proprietary preparations of a drug

if two products are said to be bioequivalent it means that they would be expected to be, for all intents and purposes, the same

Front 23

what three factors are considered by the FDA when approving a generic as bioequivalent to to its brand name counterpart?

Back 23

peak height concentration

time of peak concentration

area under the serum concentration time curve (yields extent of absorption)

Front 24

what was the effect of the Pure Food and Drugs Act of 1906?

Back 24

prohibited interstate commerce of misbranded and adulterated foods, drinks, and drugs, and provided the remedies of seizure and prosecution

Front 25

what inspired the Pure Food and Drugs Act of 1906?

Back 25

Upton Sinclair's book, The Jungle

Front 26

what was the effect of the sherley amendment to the FD&C act of 1906?

Back 26

prohibited false or fraudulent statements regarding the effectiveness of a drug

Front 27

what was the effect of the federal food, drug, and cosmetic act of 1938?

Back 27

drugs must be safe but not necessarily effective

FDA cannot interfere with practice of medicine (approved drugs can be used for unapproved uses)

Front 28

what was the effect of the 1962 kefauver-harris drug amendments?

Back 28

drug manufacturers were required to PROVE to the FDA that their product was effective before marketing them

FDA could deny or approve a new drug application based on the studies submitted to them by the majufacturer

FDA required that drug safety be shown to their satisfaction before marketing

Front 29

what event initiated the Federal Food, Drug, and Cosmetic Act of 1938?

Back 29

100 die due to ethylene glycol as solvent in elixir of sulfanilamide in 1938

Front 30

what event initiated the Kefauver-Harris Drug Amendments of 1962?

Back 30

thalidomide causes severe birth defects in thousands of babies in western Europe in 1962

Front 31

how does the new mission of the FDA differ from the old mission?

Back 31

in old mission, FDA was risk averse, focusing solely on safety

new mission puts emphasis on balancing the safety aspect with the potential benefit of the new drug

Front 32

what is an Investigational New Drug (IND) Application?

Back 32

request for an exemption from the federal statute that prohibits an unapproved drug from being shipped in interstate commerce

permission to test in humans

Front 33

what is a New Drug Application (NDA)?

Back 33

the vehicle through which drug sponsors formally propose that the FDA approve a new pharmaceutical for sale and marketing in the U.S.

Front 34

what is the purpose of a new drug application (NDA)?

Back 34

FDA examines:

Whether the drug is safe and effective in its proposed use(s), and whether the benefits of the drug outweigh the risks.

Whether the drug's proposed labeling (package insert) is appropriate, and what it should contain.

Whether the methods used in manufacturing the drug and the controls used to maintain the drug's quality are adequate to preserve the drug's identity, strength, quality, and purity.

Front 35

what is an Abbreviated New Drug Application?

Back 35

application for a generic drug, in which the company only has to show bioequivalence to the brand name drug (peak concentration, time to peak concentration, area under the curve) in order to sell their generic

Front 36

what happens in preclinical testing?

Back 36

testing in animals

IND is filed

Front 37

what happens in Phase I Clinical Testing?

Back 37

human testing (first time the drug is used in a human body)

emphasis on safety

Front 38

what happens in Phase II Clinical Testing?

Back 38

human testing

emphasis on efficacy

limited number of people (about 100)

Front 39

what happens in Phase III Clinical Testing?

Back 39

human testing

emphasis on side effects and long-term use

500-3000 patients

catch early toxicities; miss infrequent/delayed toxicities

NDA is submitted

Front 40

what is Phase IV of clinical testing?

Back 40

postmarketing

MD reporting

Front 41

when does a drug enter phase IV of clinical testing?

Back 41

after NDA approval

Front 42

what is the definition of pharmacokinetics?

Back 42

study of the time course of drug action; involves the factors that influence the appearance and disappearance of the drug in plasma

Front 43

by what order kinetics are most drugs absorbed and eliminated?

Back 43

first-order kinetics

(rate is proportional to the concentration of one reactant although the process may have several reactants)

Front 44

describe zero-order kinetics

Back 44

process occurs at a constant rate

rate is independent of concentration

Front 45

describe first-order kinetics

Back 45

process occurs at a decreasing rate as drug concentration declines

rate is proportional to concentration

Front 46

why is glucose an exception to the rule that reabsorption is always first-order?

Back 46

reabsorption of glucose is carrier mediated whereas reabsorption of most drugs, etc. is via passive diffusion

Front 47

by what order of kinetics does glomerular filtration operate?

Back 47

ALWAYS first-order

Front 48

by what order of kinetics does reabsorption operate?

Back 48

almost always first-order

glucose is different because it is carrier-mediated

Front 49

by what order of kinetics does tubular secretion operate?

Back 49

zero-order above the saturation concentration

Front 50

when are biotransformation/biliary transport first-order?

Back 50

only if enzymes or transporters are not saturated

Front 51

why is a first-order elimination process not linear when graphed?

Back 51

the body is better at getting rid of something when there's more of it

Front 52

what is a half life?

Back 52

time required for 50% of the drug to be excreted

Front 53

what is the rule of thumb for how long it takes to eliminate a drug from the body?

Back 53

4 half-lives

Front 54

how long does it take for a drug to reach steady-state?

Back 54

4 half-lives

Front 55

why does the level of drug in a patient's system level off after four half-lives?

Back 55

the rate of absorption of the drug becomes equal to the rate of elimination of the drug

Front 56

what is the equation for rate of absorption?

Back 56

Rate of Absorption = [Drug]GI x k

Front 57

what is the equation for rate of elimination?

Back 57

Rate of Absorption = [Drug]plasma x k

Front 58

what is the equation for absorption and elimination at steady state?

Back 58

[Drug]GI x k = [Drug]plasma x k1

k is not equal to k1

Front 59

on what factors is the point where a plateau concentration is reached in a drug administration curve dependent?

Back 59

half life
dosing rate

NOT:
dosage given

Front 60

how does dosing administration affect peak-trough difference?

Back 60

the more frequently a dose is given, the smaller the peak-trough difference

Front 61

what is a peak-trough difference?

Back 61

difference between drug concentration at peak blood concentration and at minimal blood concentration during a dosing schedule

more doses per half-life means smaller peak-trough differences