Drug Absorption

Question 1

drug absorption

Answer 1

absorption is the movement of a drug from its site of administrateion int o the central compartment of systemic circulation

achieves adequate plasma concentration at its site of action in order to produce its pharmacological effects

amount of absorption depends on routes of administration

Question 2

bioavailability

Answer 2

the fractional extent to which an administered drug reaches systemic circulation

the main criterion for choosing the route of administration

Question 3

routes of administration

Answer 3

intravenous

transdermal

subcutaneous

intramuscular

inhalational

sublingual and buccal

oral

rectal

Question 4

oral administration and the stages before therapeutic effect

Answer 4

most common because it is safest, most convenient, and most economical

phases - pharmaceutical, pharmacokinetic, pharmacodynamic, effect

Question 5

pharmaceutical phase

Answer 5

disintegration of dosage form, dissolution of active ingredients

Question 6

pharmacokinetic phase

Answer 6

absorption, distribution, metabolism, excretion

Question 7

pharmacodynamic phase

Answer 7

drug-receptor interaction, drug-drug interaction, individual sensitivity, pathophysiological conditions

Question 8

physiological parameters of human small intestines

Answer 8

gastric pH is 1.5 to 2.5

duodenum from 5 to 6

jejunum to ileum is 6 to 7 to 7.5

effective surface area 71-250m^2

gastric surface area 155cm^2

Question 9

direct interactions that affect drug absorption

Answer 9

physiological factors:

gastric emptying time is slowed by foods

drugs may be destroyed by the gastric pH or digestive enzymes

Question 10

didanosine intake

Answer 10

anti-HIV drug

most effective when taken 0.5-1 hour before or 2 horus after meals

acid-sensitive drug, prolonged gastric time will cause degradation

Question 11

nitrofurantoin intake

Answer 11

better taken with food because the drug is not very soluble and increased dissolution time in the intestine helps absorption

Question 12

first pass effect

Answer 12

drugs may be metabolized in the gut and subsequently in the liver before gaining access to the systemic circulation

Question 13

major drug metabolizing enzyme int he gut

Answer 13

P450 (CYP3A4)

Question 14

grapefruit jiuce and drug interactions

Answer 14

grapefruit juice could alter drug concentrations via two mechanisms:

inhibiting CYP3A4 drug metabolizing in the gut - irreversible (96 hours to replenish)

inhibiting uptake transporter OATPs - reversible (after 4 hours)

found to enhance antihypertensive effects of felodipine because metabolizing enzymes were inhibited

Question 15

controlled-release formulations

Answer 15

preparations of drugs designed to produce slow, uniform absorption for 8 or more hours, achieving a stable blood concentration

eliminates extreme peaks and troughs of blood drug concentration

Question 16

disadvantages of oral administration

Answer 16

first-pass effect and destruction of drug

onset of effect is too slow for emergencies

not able to administrate to unconscious patients or when vomiting is present

Question 17

rectal administration

Answer 17

alternative to oral when the patient is unconscious or when ovmiting

used to treat local conditions such as hemorrhoids

dosage may include solutions or suppositories

rectal absorption can be erratic

lowered potential for hepatic first-pass metabolism

50% bypasses the liver

Question 18

parenteral routes of drug delivery

Answer 18

interavenous, intramuscular, subcutaneous

Question 19

intravenous injection

Answer 19

100% bioavailability, bypass first-pass effects

results in potentially immediate effect, good for emergencies

permits titration of dose

suitable for large volumes, but may have adverse effects because of rapidly attained high concentrations

once the drug is injected, there is no retreat

Question 20

intramuscular injection

Answer 20

absorption of lipids through diffusion along concentration gradients

absportion of lipid-insoluble drugs goes through interendothelial loose junctions, macula occludens with pore size of 4-5 nm, or transcytosis

absorption may be made slow and sustained by using repository preparations

suitable for moderate volumes, oily vehicles, and some irritating drugs

may be pain at site of injection

Question 21

subcutaneous injection

Answer 21

similar to intramuscular injection

suitable for some water-insoluble suspensions and for implantation of solid pellets

not suitable for large volumes or irritating substances

concurrent administration of vasoconstrivtor will slow abosrption

Question 22

intrathecal injections

Answer 22

enhances the entrance of drugs into CNS, circumvents blood-brain barrier and blood-CSF barrier

uses extremely permeable ependymal cells lining ventricles

can be used to treat acute CNS infections with antibiotics

Question 23

inhalation

Answer 23

gaseous and volatile agents and aerosols are absorbed rapidly via lungs because of large surface area of alveoli, which is perfused by high blood flow

thin membranes separate alveoli from circulation

inhalation of volatile general anesthesia

Question 24

topical application

Answer 24

through skin or transdermal mucous membranes

skin is a pipoidal membrane barrier, so only highly lipid soluble drugs are absorbed

absorption is faster through mucous membrane than through skin

drugs can be administered sublingually or by dermal patch, avoid first-pass effect

Question 25

three criteria of generic drugs

Answer 25

pharmaceutical equivalent

bioequivalent

effective and safe

Question 26

pharmaceutical equivalents

Answer 26

same active ingredients

identical in strength or concentration

same dosage form

same route of administration

Question 27

bioequivalence

Answer 27

when two pharmaceutical equivalent drugs produce the same rates and extents of bioavailability of the same active ingredient, they are considered to be bioequivalent

Question 28

reasons why pharmaceutical equivalence does not equal bioequivalence

Answer 28

may have differences in crystal form, particle size, and manufacturing processes

Question 29

criteria for FDA to approve a generic drug

Answer 29

pharmaceutical equivalence

bioequivalence (80% to 125% of bioequivalence to the brand name drug)

safety and effectiveness for intended use

Question 30

drug distribution

Answer 30

after absorption, a drug distributes to interstitial and intracellular fluids

process influenced by a number of physiological factors and the particular physicochemical properties of the individual drug

Question 31

first phase of tissue distribution

Answer 31

rapid distribution to organs of high blood flow: brain, heart, liver, and kidneys

Question 32

second phase of tissue distribution

Answer 32

drug delivery to muscle, most viscera, skin, and fat which have moderate blood flow

Question 33

final tissue distribution

Answer 33

depends on the properties of the drug and its affinity for the tissue site

lipid soluble, nonionized drugs are readily distributed to all tissues, especially adipose tissue

ionized drugs in generall will remain in the plasma and intersitial compartments

Question 34

anitomical properties of the blood-brain barrier

Answer 34

lacks fenestration and vesicles in endothelial cells

tight junctions

limited extracellular spaces, covered by basal membrane, astrocyte end-foot processes and pericytes

Question 35

biochemical properties of the blood-brain barrier

Answer 35

ABC transporters on luminal surfaces of endothelial cells that pushes drugs back into the blood

Question 36

entry of drugs into the CNS

Answer 36

permeable to lipid-soluble drugs - entry of drug is proportional to its lipid solubility and concentration gradient

if both ionized and non-ionized forms exist, entry is proportional to the non-ionized form

Question 37

blood-cerebrospinal fluid barrier

Answer 37

resides in the epithelial cells of the choroid plexu, which have tight junctions

only lipid-soluble drugs get into the CSF from the blood

not as significant as the blood-brain barrier

ependymal cells lining ventricles are not connected by tight junctions an doffer unrestricted passage of drug molecules between CSF and brain cells

Question 38

pharmacologically inactive

Answer 38

describes a drug bound to a protein such as albumin and can no longer confer function

plasma proteins may be storage to prolong drug action

Question 39

localized distribution

Answer 39

uptake transporters and enterohepatic recirculation of drugs have been shown to achieve liver-specific distribution of statins, which enhance the therapeutic action of stains in the liver to reduce cholesterol synthesis and reduce the systemic drug level preventing myotoxicity

Question 40

phenytoin

Answer 40

narrow therapeutic index

hard to control because serum levels increase exponentially depending on albumin binding and other factors

Question 41

when are drug-drug interactions not of a concern

Answer 41

if the drug has high therapeutic index

if the drug response is slow