1-41 Drug Absorption and Distribution

Question 1

Drug absorption

Answer 1

transfer of a drug from its site of administration to the systemic circulation depends on:

route of administration

• intravenous administration does not require absorption

bioavailability: how well a drug is absorbed, how much of drug reaches systemic circualation

bioequivalence: related to generic drug manufacturing/approval

Question 2

Routes of drug administration

Answer 2

• enteral: via GI tract (oral, rectal)
• Intrathecal: (spinal fluid)
• Intraarticular: inside joint
• Parenteral: intravenous, intrasucular, subcutaenous
• Transdermal: topical
• Intraosseous: bone marrow
• Intraperitoneal: into peritoneal cavity
• Intraocular: includes subretinal

Question 3

Time to effect vs Route of drugs

Answer 3

Question 4

Advantages/Disadvantage of drug routes

Answer 4

Also: tablets orally have a “disintigration phase” and a “dissolution phase”

Question 5

Factors affecting oral absorption

Answer 5

Ex. Ibuprofen:

• Better pH based absorption in the stomach BUT surface area of small intestine far outweighs and drive sthe majority of absorption there!

Question 6

Bioavailability

Answer 6

fraction of an administered dose of unchanged drug that reaches the systemic circulation

acute metabolism in gut wall & p glycoprotein efflux: work against bioavailablity

high first pass metabolism (transport and metabolism in the intestinal wall or liver before drug can reach systemic circulation) results in lower bioavailability, this is sometimes good and interferring with first pass metabolism can make some drugs more potent and toxic!

Question 7

BIoequivalence

Answer 7

drug preparations that exhibit the same bioavailability nd pharmacokinectices: ex is generic drugs, we look at AUC to compare and hight/time of maximal plasma concentration

Question 8

Drug distribution

Answer 8

reversible transfer of a drug between the system circulation and extraascular fuilds (interstilial) and tissues

Persuion-limited tissue distribution: initial rate of drug distrituion to various sites depends on blood flow to the tissue

• first phase: rapid sitribution to organs of high blood flow: brain, heart, liver, kidneys
• second phase: slower drug delivery, muscles, organs, skin, fat

Permability limited tissue distribution: central compartments with resitricted access, CNS, placenta

Question 9

Drug distirubiton to tissue sites

Answer 9

tissue distribution affects the apparent:

Vd (volume of distritubiton, in Liters) = total amount of drug administered/ plasma concentration

• mininmum Vd is 3L because that is how much plasma adults have

redistribution can alter the time course and the Vd

Question 10

Drug binding to plasma proteins

Answer 10

• many drugs bound and pharamcologically inactive
• protein binding lowers the effective concentration of drug
• slows distribution to extravascular sites (longer half life)
  
  • reversible binding may serve as a storage depot to prolong action

Question 11

Drug distribution to CNS

Answer 11

Less accessible to drugs despite high blood low, lipid soluble drugs are most permeable to CNS, BBB + cerebrospinal fluid interface

p-glycoprotein involved in effluxing drugs that do pass into brain capillary back out into blood vessel, discover this through KO mouse studies

Question 12

Blood-cerebrospinal fluid interface

Answer 12

epithelial cells of choroid plexus have tight junctions but less resitve than BBB capillaries, lipid soluble drugs can penetrate CSF, choroid plexus capillaries are fenestrated, epitherlial cells lining brain ventricles are leaky and allow paracellular transport

intrathecal drug delivery of cetain drugs successfully bypasses the BBB