Drug Disposition: Absorption

Question 1

(1) Define “therapeutic window.”

Answer 1

therapeutic window is the plasma drug concentration above which there is a therapeutic response but below which there is a toxic response

Question 2

(2) Contrast absorption and distribution of a

Answer 2

absorption is the process in which the drug moves into the blood stream, distribution is the the process where the drug moves from the blood stream to the tissue

Question 3

(2) What variables affect drug absorption? (6)

Answer 3

dissolution time (solid forms)
solubility
concentration at site of admin
perfusion rate v. diffusion rate
area of absorbing surface
membrane permeability

Question 4

(2) Describe difference in perfusion rate effecting drug distribution.

Answer 4

organs receive different blood flow (perfusion) and that effects how much of the drug they can be delivered and how fast

Question 5

(3) Describe how a drug can be diffusion limited.

Answer 5

a drug whose transport rate is limited by diffusion rate will not be changed by the perfusion rate

Question 6

(3) Describe how a drug can be perfusion limited.

Answer 6

a drug whose transport is limited by perfusion will show a different rate of transport when perfusion is increased or decreased

Question 7

(3) Drug molecules move through membranes by a process of ________, through various sized pores in the membranes.

Answer 7

diffusion

Question 8

(2) What factors effect the rate of simple diffusion of a drug?

Answer 8

concentration gradient
chemical nature of the compound (lipid,polar etc)
area and permeability of the membrane
thickness of the membrane
(Described by Flux and Fick's Law)

also local pH

Question 9

(4) Define weak acid and weak base.

Answer 9

weak acid = proton donator

weak base= proton acceptor

Question 10

(5) When are weak bases/acids charged… when protonated or unprotonated?

Answer 10

weak acids when protonated are neutral

weak bases when protonated are charged (+)

Question 11

(5) What is unique about the situation when the pH is equivalent to an acid’s pka?

Answer 11

the species will be 50/50 protonated/unprotonated

Question 12

(5) What is ion trapping?

Answer 12

depending on whether a drug is charged or not (based on protonation and pH) it may stay within a give compartment because it is unable to cross the cell membrane due to its charge (body fluids/compartments vary in pH)

Question 13

(6)State the Henderson-Hasslebalch equation.

Answer 13

pKa-pH= log( protonated/unprotonated)

Question 14

(6) Would you consider both facilitated diffusion and active transport as specific and able to be saturated

Answer 14

yes, both facilitated diffusion and active transport are molecularly specific and can be saturated.

Question 15

(7) What are the 3 enteric routes of drug administration?

Answer 15

oral (PO); sublingual (SL); and rectal (PR)

Question 16

(7) Name important considerations when admin drug PO.

Answer 16

safe, easy and economical but slower and variable absorption which is subject to the 1st pass effect and pH partitioning

Question 17

(7) What is important to remember when administering drugs SL or PR? (concerns are distinct for each)

Answer 17

sublingual provides quick absorption that avoids the first pass effect, great for lipophillic substances; rectal in the form of suppositories or enemas reduces the 1st pass effect and is useful if the patient is vomiting or unconscious

Question 18

(7) Describe advantages and disadvantages of admin via parenteral routes.

Answer 18

rapid onset with predictable action and bypasses gut enzymes, gut flora and liver (more control); drugs must be sterile, more expensive and less self-admin, danger of thrombus or embolism

Question 19

(7) Name 7 parenteral routes for drug administration.

Answer 19

subcutaneous (SC), intramuscular (IM), intravenous (IV) and topical, intraarterial, intrathecal, pulmonary

Question 20

(7) What are the characteristics and limitations of SC admin?

Answer 20

slow absorption can provide sustained effect or depots (oil or pellet) for long duration of action; not suitable for large volumes or irritating substances

Question 21

(7) What are the characteristics and limitations of IM admin?

Answer 21

rapid absorption of aqueous solution with high blood flow, can inject more irritating substances but soreness my result with injection (note- some anipsychotics given this way in long acting form to help with patient compliance

Question 22

(7) Describe indications and benefits for IV drug admin.

Answer 22

highly accurate dosing, absorption dependent only on rate of infusion, suitable for large volumes and irritating substances; not suitable for oily solution or insoluble drugs

Question 23

(7) Where and why are topical admins used?

Answer 23

where: skin, eyes, mucous membranes
why: to deliver drug at or immediately beneath the point of application

Question 24

(7) Name one reason the following parenteral routes are used: intraarterial, intrathecal, pulmonary

Answer 24

intraarterial: chemotherapeutics or diagnostic agents
intrathecal: spinal anesthesia or to bypass BBB
pulmonary: admin gaseous, volatile or aerosols; rapid absorption (**important to consider the size of particles in pulmonary admin)