#2 absorption

Question 1

Factors affecting drug absorption

Answer 1

a. chemical composition of drug and delivery formulation (tablet, capsule, solvent, etc) b. regional differences in blood flow c. transport mechanisms d. permeability characteristics (lipid solubility) e. ion-trapping f. nonspecific binding g. surface area

Question 2

Factors affecting drug distribution

Answer 2

a. regional differences in blood flow b. tissue mass c. transport mechanisms d. permeability characteristics e. ion trapping f. binding to protein

Question 3

4 aspects of pharmokinetics

Answer 3

Absorption Distribution Metabolism Excretion

Question 4

2 uses for Area Under the Curve (AUC)

Answer 4

1. To compare the amount of a drug that enters systemic circulation from different routes of administration. (bioavailability (F)) 2. To compare the clearance of a drug in different individuals. (after the same does)

Question 5

DRUG ABSORPTION

Answer 5

The processes by which drugs move from their site of administration to the plasma.

Question 6

what must happen after oral administration for a drug to be absorbed

Answer 6

1. it must dissolve in the fluids of the GI tract 2. it must pass between or through cells to enter circulation

Question 7

Ion- Trapping

Answer 7

The non-ionized drug will equilibriate freely across membranes but if one compartment favors the ionized form then the drug will convert once it has crossed the membrane and the drug will be unable to leave bc ionized forms cannot pass through the membrane. Therefore basic drugs tend to become trapped in acidic compartments while acidic drugs in basic compartemtns

Question 8

main location of absorption of orally administered drugs

Answer 8

small intestine

Question 9

First-pass effect

Answer 9

Drugs taken orally pass through the liver prior to entering circulation. Some drugs may become metabolized in the liver, inactivating a fraction of the drug.

Question 10

Enterohepatic circulation

Answer 10

In the liver some drugs may be secreted into the bile which is transported back into the small intestine and therefore must pass back through the portal system. Therefore it takes longer to enter systemic circulation and may reduce bioavailability

Question 11

Bioavailability

Answer 11

The fraction (F) of the administered dose that reaches the systemic circulation in its active form.

Question 12

ways bioavailability can be reduced

Answer 12

1. if its not completely absorbed 2. if it is metabolized in the liver

Question 13

Salt Factor

Answer 13

The fraction of total drug that will be delivered as active drug to the systemic circulation is called the “salt factor” (S). not very common

Question 14

Advantages/disadvantages of sublingual administration

Answer 14

1. By-passes portal circulation 2. higher pH may be beneficial for more basic drugs 3. bad taste-disadvantage

Question 15

Advantages/disadvantages of rectal administration

Answer 15

Advantages: ~50-60% of absorbed drug by-passes portal circulation and therefore avoids first pass metabolism. useful in cases of nausea and vomiting. Disadvantages: discomfort, inconvenience, etc.

Question 16

how does transdermal drug administration work

Answer 16

passive diffusion of drugs across the skin—driven by concentration gradient.

Question 17

advantages of transdermal

Answer 17

1. controlled release of the drug into the patient—enables a steady blood-level profile 2. user-friendly, convenient, painless, multi-day dosing—improved patient compliance 3. bypassing the gastrointestinal (GI) tract obviates GI irritation that occurs with some drugs and avoids partial first-pass inactivation by the liver

Question 18

advantages of Parenteral Administration

Answer 18

greater degree of reliability and precision of administered dose fewer problems with absorption not affected by food in the stomach no “first-pass effect”

Question 19

Disadvantages of parenteral administration

Answer 19

Disadvantages: sight of the needle pain tissue damage and irritation drugs must be in solution limited volume

Question 20

advantages and disadvantages of Subcutaneous parenteral administation

Answer 20

Advantages a. slow, even absorption b. may be used as a depot c. rare of absorption may be modified by altering blood flow Disadvantages a. not effective when peripheral circulation is impaired (e.g. in shock) b. limited volume

Question 21

advantages and disadvantages of intramuscular parenteral administation

Answer 21

Advantages more rapid absorption than subcutaneous rate of absorption may be modified by altering blood flow Disadvantages potential for infection and nerve damage risk of inadvertent i.v. administration

Question 22

advantages and disadvantages of IV parenteral administation

Answer 22

Advantages Fastest and most reliable means of achieving a defined blood level Disadvantages Risk of overdose by “bolus effect”

Question 23

Protein binding

Answer 23

Many drugs bind to plasma proteins. a. albumin binds acidic drugs b. α1 acid glycoprotein binds basic drugs Protein-bound drugs are retained in the plasma.(do not enter tissues and become distributed)

Question 24

One compartment distribution

Answer 24

rapid equilibrium is achieved between plasma and tissue distribution. Plasma concentration-time profiles declines mono-exponentially

Question 25

Two compartment distribution

Answer 25

rapid distribution to a central compartment (plasma) followed by slow distribution to other tissues/binding sites (second compartment). Gives a bi-exponential plasma concentration-time profile

Question 26

VOLUME OF DISTRIBUTION (Vd)

Answer 26

A measure of how evenly distributed a drug is in the body.

Vd is how much blood (theroretical) would be required to contain the entire administered does at the concentration of drug in the plasma at time t=0 (C0)

Vd= Dose/C0

Question 27

large volume of distribution indicates

Answer 27

the drug is widely distributed to the tissues (majority not in the plasma)

Question 28

how does protein binding affect the volume of distribution

Answer 28

increasing the unbound fraction of total [drug] will increase the apparent volume of distribution. Bc the unbound drug can be distributed to the tissues while the bound drug will remain in the plasma

Question 29

what kinds of drugs have the greatest volume of distribution

Answer 29

lipid-soluble drugs bc they can easily accumulate outside the plasma compartments (reach all compartments especially fat). Vd may be greater than body volume

Question 30

DRUG RESERVOIRS

Answer 30

Fat and muscle in particular can act as drug reservoirs.

More drug may be stored in these tissues than remains in the systemic circulation.

Gradual release of drug from these sites can prolong the therapeutic effect or result in toxicity.

Plasma proteins can also serve as a drug reservoir.

Sulfonamides may compete for protein binding and increase the unbound fraction of other drugs.

Question 31

sulfanamides

Answer 31

can compete with other drugs for protein binding in the plasma. Results in more of the other drug being unbound and available for distribution to the tissues