Chapter 4 - Drug Absorption Flashcards
true or false
ONLY free drug can get distributed to the target site/other tissues
true
3 routes of administration
intravascular
extravascular
topical
how can extravascular drug administration be further divided?
parenteral and non-parenteral
name the extravascular parenteral routes
IM and SUBQ
NOT IV!!!!!!!! IV is intravascular
true or false
extravascular parenteral is preferred over extravascular non-parenteral
FALSE
non-parenteral is preferred bc less expensive painless, can self-medicate, and more likely to comply
what is the first layer of the skin? is it more or less lipophilic than the dermis?
stratum corneum
3-5x more lipophilic than the dermis(hard to penetrate!)
compare the surface area for topical absorption vs through the small intestine
skin - 1.73 meters squares
small intestines - 150-200 meters squared
mechanism of topical absorption through the skin
passive diffusion
the stratum corneum can be considered ____ phase
what is continuous?
2 phase lipid/protein
lipid is continuous
5 DOSAGE FORM factors that affect topical absorption through the skin
-drug’s affinity for the vehicle
-surface area of the film
-thickness of the film
-permeation enhancers
-concentration of drug in the delivery system
true or false
the larger the surface area of the patch, the quicker the absorption rate
true
true or false
the thicker the film, the faster the drug will permeate
FALSE
if thinner, will permeate faster
true or false
we do not want the drug to have a very high affinity to the vehicle for topical absorption
true
otherwise will take forever to come out and absorb through the skin
rate limiting layer of skin permeation
the stratum corneum
true or false
skin permeation is an active process
FALSE - passive diffusion
*****4 advantages of topical absorption
-no 1st pass I
-long acting
-no degradation in GI
-can deliver potent lipophilic drugs with a short half life ***
what kinetics do we want for transdermal delivery
zero order
***major advantage of transdermal delivery is the type of drug we can deliver —-
potent, lipophilic drug with a short half life
if given orally - would need very frequent dosing! transdermal is a very good way to administer it - provides a long duration of action for it!!!!!!!!!!!
3 disadvantages of topical/transdermal absorption
metabolism of drug in skin
binding to the epidermis
blood supply
True or false
dosage form does not have an impact on bioavailability
FALSE
impacts absorption and thus impacts bioavailability
true or false
if a drug is rapidly absorbed, it is less likely to degrade in the GI fluids
TRUE - bc not there for that long
true or false
a disadvantage of rapid oral drug absorption is that it increases variability
FALSE - actually decreases variability
3 major factors that influence the release of the drug from the dosage form administered orally
physiochemical properties of:
-the drug
-the dosage form
-human body variations
true or false
the human body variations ONLY AT THE SITE OF ABSORPTION can affect absorption
FALSE - also at the site of administration
6 absorption mechanisms
what is the majority
passive diffusion (majority)
active transport
facilitated transport
convective (pore) transport
ion-pair transport
pinocytosis
explain facilitated transport
what is it similar to?
similar to active transport except there is NO ENERGY INPUT
goes through concentration gradient. must have concentration gradient for absortpion
true or false
active transport has NOTHING to do with concentration gradient
true
what is considered the “last chance” for absorption
pinocytosis
3 kinds of pinocytosis
corpuscular
vesicular
particulate
true or false
facilitated transport can be considered a mix of active and passive
true
only transport mechanism where the drug does not have to be in aqueous solution to be absorbed
pinocytosis
Fick’s first law:
for the SAME DRUG, dc/dt (rate of diffusion across membrane) only depends on what?
C (concentration)
in fick’s first law, what parameter is considered the most important
the concentration gradient
in fick’s first law, will any parameters be CONSTANT if it is changed to a different drug?
only h and A will be constant
(membrane thickness, available surface area)
K, D, C will be different
(partition and diffusion coefficient, concentration)
true or false
fick’s first law represents zero order kinetics
FALSE - FIRST ORDER!!!!
because diffusion through the membrane is highly dependent on the concentration!
true or false
the ionized form of a drug is better for absorption
FALSE
unionized is better. lipophilic diffuses and crosses membrane better
what is calcium taken with any why?
what mechanism of absorption is this?
vitamin D
helps absorption of calcium through timulating its protein carrier
active transport
active transport follows what equation
michaelis menten
dc/dt = C * vmax / Km + C
explain how active transport can either follow zero OR first order kinetics
-if the drug concentration is much lower than Km, will be first order.
-if drug concentration is much higher than Km, will be zero order. the max capacity will be carried each time. CONCENTRATION INDEPENDENT. if you increase the concentration, the rate will NOT CHANGE because it’s already saturated!
true or false
in active tranport, it is not possible to go from low to high concentration
FALSE - it is - uses energy
what is the “affinity constant”
Km
true or false
for a given drug-carrier complex, both Km and Vmax are considered CONSTANT
TRUE
when Km is much higher than C, what can the michaelis-menten equation be boiled down to
dc/dt = K’c
when C is much higher than Km, what can the michaelis-menten equation be boiled down to
dc/dt = vmax
whatever is the max - that will be the rate of transport! bc drug conc is high enough
explain the steps of active absorption/transport
-substrate + carrier complex in the membrane surface
-substrate-carrier complex moves through membrane
-substrate released from complex on other side of membrane
-the carrier molecule is now free and goes back to apical surface of the membrane to bind future substrates
true or false
active absorption always takes place regardless of the concentration inside or outside of the membrane
true
upper limit MW for:
-spherical
-chain-like
to pass pores in convective/pore transport
spherical - MW upper limit is 150
chain-like - MW upper limit is 400
explain ion-pair transport
organic cation + anion join to form a PHYSICAL complex.
this physical complex increases lipophilicity and can be absorbed better
NOT chemically combined
this is not a major absorption mechanism in our body
which molecules undergo endocytic processes for absorption (pinocytosis/phagocytosis)
large molecules
can large molecules passively diffuse
no
true or false
pinocytosis is a specific process
FALSE - nonspecific
endogenous molecule that undergoes endocytic absorption
amino acids and fat (typically solid fat)
liquid lipids like oil– use bile salts typically
where does pinocytosis occur
near the end of the small intestine. wait for the large molecules that can’t be absorbed through upper GI trac
explain what pinocytosis is
cell essentially swallows the molecule
what is the most dilated part of the GI tract
the stomach
when filled, what is the volume of the stomach
1.1-1.2 liters
in short, stout people, the stomach will be ___ and ___
in tall and thin people, it will be ___ and ___
short and stout - high and horizontal
tall and thin - elongated and vertical
in reality, the intestines are ___x as tall as their sitting height
7x
true or false
the intestines are shorter in vegetarians
false - longer
what is the longest part of the GI tract and how long is it
the small intestines
20-25 feet
which part of the GI tract contains villi and microvilli
small intestine
this organ absorbs water from digested food
what is the residence time in this organ?
large intestine
12-24 hours
3 regions of the small intestines
3 regions of the large intestine
small intestine - duodenum, jejunum, ileum
large intestine - cecum, colon, rectum
what is the reference volume amount of the stomach for in vitro studies
1.1-1.2 liters
what will happen if we can’t neutralize acid
peptic ulcer
true or false
if gastric emptying time is slowed, absorption is delayed
TRUE - bc most drug is absorbed through the small intestine, not the stomach
4 specific regions of GI tract where villi are present
duodenum
jejunun
ileum
cecum
3 things that affect the EXTENT of drug absorption through GI tract
(affect AUC)
-metabolism by intestines
-hydrolysis in GI
-metabolism as drug crosses GI wal
which part of the small intestine is the most major piece for drug absorption and why
the duodenum
has highest concentration available - Fick’s first law!
rank according to residence time (slowest to longest)
ileum
duodenum
jejunum
large intestine
duodenum (5 mins)
jejunum
ileum
large intestin (12-24 hours)
GI motility is an important factor that influences drug absorption.
name 2 GI motility patterns
-digestive motility pattern (when you have food in tummy)
-inter-digestive motility pattern - happens in fasting
changes in BLOOD FLOW to the GI tract affects absorption of drugs that….
high intestinal permeability
what is standard tummy volume
250mL
true or false
gastric emptying follows zero order kinetics
FALSE - first order
rate is volume intake-dependent
after a normal meal, how long does complete gastric emptying take
4 hours
should ALL be in small intestine at this point
if there’s no absorption within 4 hours - something isn’t right
true or false
a larger gastric volume = FASTER emptying
TRUE
FIRST ORDER - VOLUME DEPENDENT
TRUE OR FALSE
a liquefied meal results in slower emptying
FALSE - faster emptying
you drink a 500mL liquid, explain what will happen after 10 mins
250mL in small intestine and 250mL left in stomach
true or false
is viscosity of the food increases, the gastric emptying RATE increases too
false- rate decreases (so emptying time increases)
true or false
a WARM MEAL will empty slower than a cold meal
false - empties faster
name a drug that decreases the rate of gastric emptying
ethanol
true or false
ethanol increases gastric emptying time
TRUE (decreases rate means that emptying time is increased)
food stays in stomach longer
true or false
most drugs are largely absorbed by passive diffusion
true
true or false
acidic drugs are better absorbed from the stomach
TRUE - because unionized (HA)
HOWEVER, in reality the small intestine is the major site of absorption of acidic drugs because of very large surface area
true or false
basic drugs are better absorbed from the stomach
FALSE - the intestines - bc unionized
factors that decrease _____ will generally delay drug absorption
movement from the stomach to the small intestine - bc most absorption happens through the small intestine
true or false
the larger the volume of the meal, the faster the food empties from the stomach
TRUE
true or false
gastric emptying follows 1st order kinetics
true
as the volume of the ingested meal increases, there is initial increase in rate of gastric emptying
then as the volume in the stomach decreases, the rate of gastric emptying also decreases
volume of liquid ingested is less than 100mL
volume of liquid ingested is greater than 200mL
explain the mechanism
less than 100mL = inter-digestive motility pattern
over 200mL - first order kinetics. half life of 10 mins
true or false
large volume of liquids in the stomach helps the dissolution of drugs
true
true or false
increasing the viscosity of gastric contents REDUCES the rate of gastric emptying
TRUE
decreased rate = longer emptying time
true or false
increased viscosity enhances the dissolution of drugs
FALSE - hinders dissolution
the rate of gastric emptying depends primarily on….
the caloric content of the meal
rank the following according to the rate of emptying
proteins
fats
carbohydrates
carbohydrates empty the fastest
then proteins
then fats empty the slowest. (longest gastric emptying time)
effect of stress on the rate and motility of gastric emptying
increased rate and increased motility
true or false
depression decreases the rate of gastric emptying
true
true or false
exercise increases the rate of gastric emptying
FALSE - decreases the rate – bc all the blood is going to the muscles!
(prolonged time)
explain how body posture affects the rate of gastric emptying
laying on your left side decreases the rate
true or false
**liquids gastric emptying time is via zero order
true
liquids are zero order, solids are first order
acids and bases effect on gastric emptying time
acids - decrease rate
alkalies - increase the rate at low conc, and decrease the rate at high conc
effect of bile salts on the rate of gastric emptying
decreased rate of gastric emptying (prolonged time)
micelle formation takes time!!!!
true or false
a decreased rate of gastric emptying means decreased gastric emptying time
false - decreased rate means increased gastric emptying time
pH of the GI tract in the fasting state
2-6
pH of the GI tract DURING DIGESTION
pH of the GI tract at the VERY BEGINNING OF DIGESTION
during digestion - 1.5-2
beginning of digestion - 4-6
why does the pH of the stomach increase at the very beginning of digestion, and then decrease again during digestion?
bc of the buffering effect of food
GI secretions composition
aqueous and mucus components
as mentioned, GI secretions are composed of aqueous and mucus components
name the components of each of these
aqueous - main component is enzymes (for digestion)
mucus component - thick and gel-like at the SURFACE (for protection), and gets less viscous toward the lumen
true or false
disease states cannot affect GI motility and emptying
FALSE - they can
true or false
while the majority of weak acids are unionized in the stomach, weak acids are not well absorbed here
TRUE
bc of the thickness of the stomach wall, mucus protection, etc
5 functions of the mucus component of the GI tract
-surface protection
-lubrication of epithelium
-barrier to enzymes like pepsin
-hydration to the underlying tissue
-barrier to absorption!
” so like BHB”
true or false
a lot of drugs degrade in the stomach
true - rich in enzymes
**4 daily secretions from the stomach
pepsin
lipase
rennin
hydrochloric acid
liam hates pat’s retardness
**4 daily secretions from the duodenum
bile
trypsin
amylase
chymotrypsin
“act b”
true or false
food impacts absorption
true
viable count of gut flora per gram of wet sample
mouth and stomach:
small intestine:
rectum and feces:
mouth and stomach - 1 million
small intestine - 10 million
rectum and feces - 1 billion
rank the following according to the viable count per gram of wet sample
-small intestine
-rectum and feces
-mouth and stomach
most - rectum and feces ( 1 billion)
small intestine - 10 million
least - mouth and stomach ( 1 million)
recap: 5 factors that influence the bioavailability of oral drugs
API itself
pharm ingredients (excipients)
dosage form characteristics (route administration)
physiologic factors and patient characteristics
drug metabolism ( through gut and first past)
