Pharm I Drug Dispostion Part I

Front 1

Are the following attributes of pharmaco kinetics or dynamics? Therapeutic effect and toxic effect

Back 1

dynamic

Front 2

Are the following attributes of pharmaco kinetics or dynamics? Absorption, distribution, metabolism and excretion

Back 2

kinetic

Front 3

What are the two options for a drug to move from the blood to many tissues?

Back 3

through the cell or around it

Front 4

What determines drug transport through a lipid bilayer via passive diffusion? Is carrier-mediated transport active or passive?

Back 4

(1) concentration gradient… (2) can be either

Front 5

In passive diffusion across capillary endothelial membranes, which is the major factor determining diffusion? Capillary wall restraint or blood flow?

Back 5

blood flow

Front 6

Which two transport system are seen in Carrier-mediated transport?

Back 6

active transport and facilitated transport

Front 7

Can facilitated diffusion move againt a concentration gradient?

Back 7

no

Front 8

Which transport mediated transport includes these characteristics? Competitive inhibition, saturability, selectivity.

Back 8

both active transport and facilitated transport

Front 9

Which transport mediated transport includes these characteristics? seen in renal tube, neuronal membranes, choroid plexus and hepatocytes?

Back 9

active transport

Front 10

How do most drugs enter cells?

Back 10

passive diffusion through the lipid bilayer

Front 11

a) Show Flick's equation. b) Flick's law show that flux (passive movement) is dependent on which variables? b) What variable is not mentioned here but plays a big part in passive transport across a lipid bilayer?

Back 11

a) Flux = (C1-C2 X area X permeability coefficient) ÷ thickness… b) [drug] across membrane (C1-C2) and lipid solubility (permeability coefficient)… b) not addressed in Flick's law is the pH along the membrane and drug pka, but they play a big role in passive diffuse

Front 12

What are the 6 factors that determine absorption?

Back 12

solubility, rate of dissolution, concentration at site, blood circulation at site, area of absorbing surface, route of administration.

Front 13

For oral administration, what type of drug do you want lipid or aqueous soluble?

Back 13

it's a balance, since it must be lipid soluble to pass through the membrane, however, if its too lipid soluble it will be unstable in the aqueous environment in the intestine and therefore be unstable and eratically absorbed.

Front 14

Besides Flick's law and pH an pka, what other factors are important in absorption of an orally administerd drug?

Back 14

Intestinal blood flow and gastric emptying (food mental state, diseases, other drugs, and endocrine status)

Front 15

What does "extraction ratio" (a.k.a., Intrinsic clearance) mean?

Back 15

the extent of removal of a drug form the circulation by the liver

Front 16

What is the difference between "high" and "low" extraction drugs?

Back 16

High Extraction = drug extensively removed by the liver… Low Extraction: little drug removal by the liver

Front 17

Which type of drug is more sensitive to hepatic blood flow? High extraction or Low extraction

Back 17

High, where high extraction drugs have extensive removal of the drug by the liver. Thus, in high hepatic blood flow there will be greater extraction and vice versa… (the opposite is true of low extraction)

Front 18

What are two things that can decrease the first pass effect on high extraction drugs?

Back 18

aging and liver disease

Front 19

T/F sublingual administration bypasses the first pass effect.

Back 19

TRUE

Front 20

T/F Rectal administration of drugs is 100% absorbed into the system circulation

Back 20

False, it is subject it can be subject to less first pass since there is less blood floow… but some drugs do bypass first pass by this method

Front 21

Why are gaseous and volitale drugs ideal for rapid absorption through the pulmonary administration?

Back 21

they are lipid soluble, small molecular size and vast aveolar area

Front 22

Transdermal administration allows for slow and even absorption, what is the advantage of transdermal administration of drugs?

Back 22

compliance, risk of injection, no variability seen in oral administration, better control of drugs with short half-lives.

Front 23

When does the half-life start for transdermal administration?

Back 23

at absorption

Front 24

What are the requirements for transdermal drugs?

Back 24

requirements: both lipid and water soluble

Front 25

Which types (targets) of drugs are used in transdermal administration? Why?

Back 25

cardiac, CNS and endocrine drugs… because of their slow and sustained release

Front 26

What limits absorption of hydrophilic drugs via transdermal administration?

Back 26

Stratum Corneum

Front 27

List 6 advantages of transdermal administration.

Back 27

1. Sustained release --> Stable blood levels… 2. Avoid first pass (no hepatotoxic effects)… 3. Pt compliance… 4. No injection risks… 5. No variability as seen in oral absorption… 6. Better control of drugs with short half-lives.

Front 28

List 3 Disadvantages of transdermal administration.

Back 28

1. Too slow for therapeutic efficacy of some drugs… 2. Toxicity and disease to skin… 3. Metabolism by skin

Front 29

What is the criteria for transdermal drugs? (hint: potency, lipid soluble, water soluble, irritating, stability)

Back 29

high potency, lipid sol to penetrate skin, water sol to enter systemic circulation, non-irritating to skin, stable in reservoir.

Front 30

What percentage of IV drugs enter the liver during one circulation time?

Back 30

30%, vs. 100% for orally administered drugs

Front 31

What type of absorption is seen in IV drugs?

Back 31

none… it's directly in to the systemic circulation

Front 32

What are two of the dangers of IV administration of drugs?

Back 32

overdose and toxicity

Front 33

What are two of the advantages of IV administration of drugs?

Back 33

rapid access to systemic circulation and accuracy in dosage

Front 34

What factors determine the aborption of intramuscular and subcutaneous administration of drugs? Which type of drug would be a good candidate for subcutaneous injection?

Back 34

lipid solubility and blood flow at site… (2) weak soluble, slow release form of a drug when slow long action is required, e.g., steroids

Front 35

What are the disadvantages of transdermal administration?

Back 35

penetration is too slow for therapeuitc efficacy of some drugs, toxicity and dz of the skin, drug is metabolized by the skin

Front 36

What is the definition of bioavailability?

Back 36

1. the % of drug that enters the systemic circulation after first pass… 2. Relative amount received in the systemic circulation from different modes of administration (other than IV)

Front 37

a) What is represented in AUC (area under the curve)? (hint: Y/X coordinates)... b) What does the AUC reflect? c) What is the AUC used for?

Back 37

a) plama levels/time… b) it reflects total amount of drug entering the plasma (systemic circulation)… c) calculate bioavailability (comparing different modes of administration)

Front 38

Define Pharmaceutical equivalence

Back 38

Drug content identical, but inactive ingredience and manufacturing may not be the same.

Front 39

Define biological equivalence

Back 39

provides the same [drug] to blood and tissues

Front 40

Define therapeutic equivalence

Back 40

provides equal therapeutic benefit

Front 41

In which types of drugs is bioavailability a big factor?

Back 41

drugs with a narrow therapeutic index

Front 42

What does bioavailability measured by AUC NOT reflect?

Back 42

rate of absorption… thus even though a rapid absorption demonstrates a peak [plasma] faster a slower performing drug can still have the same AUC

Front 43

Does a "true" equivalent have the same rate of absorption? Are generic drugs necessarily equal in terms of bioavailability? What has the FDA done about BA?

Back 43

a) yes, they would be the same in all respects… b) no, generic drugs can differ with respect to BA… c) requires that all new generic drug have equal BA

Front 44

What is the FDA tolerance for a drug to be considered BA (AUC) and peak [plasma]? (hint: first order and zero order drugs)

Back 44

The FDA requires (+/-) 20% for first order drugs… and (+/-) 10% for zero order drugs

Front 45

What does the FDA classification of "A" or "B" indicate?

Back 45

A=therapeutically equivalent… B=equivalence is doubtful

Front 46

What is the main determinate of tissue distribution?

Back 46

organ perfusion

Front 47

Why is it that a response to a drug like thiopental terminates even though much of the drug remains in the body?

Back 47

redistribution to lesser perfused areas of the body

Front 48

What positive effects would a site-specific drug have?

Back 48

enhance therapeutic value and limited toxic side effects

Front 49

Name 4 drug reservoirs in the body

Back 49

1. Fat (for lipid sol drugs), 2. GI tract, where extensive enterhepatic circulation increase levels of drug hours or days after administration… 3. Intracellular macromolecules (in liver and muscle store Drug for extended periods)… 4. Bone and teeth, i.e., tetracycline