Drug Absorption #2 Flashcards
T/F Passive diffusion is uni-directional
FALSE: can move in either direction (the concentration gradient determines which direction the molecule moves)
What are the 2 routes in which blood can diffuse?
intracellular(transcellular)
-paracellular
intracellular transport
molecules move directly through the membrane
-this is the most common
paracellular transport
molecules move between cells
-has a limiting factor (size of the molecules)
What is the limiting factor of paracellular transport?
the size of the molecule
T/F Carriers are typically proteins
TRUE
What are the 2 types of carrier mediated transport?
- facilitated
- active
Carrier Mediated Transport (2)
- are specific (only move one type of molecule)
- typically located in specific areas of the GI tract
T/F Carriers CAN NOT be saturated
FALSE; there are only a certain number of carriers, which means they can be saturated
T/F Carriers can be inhibited
TRUE
T/F Carrier transport is one direction
TRUE (mucosal side –> to the blood)
Which transport system requires ATP energy?why?
Active transport b/c it can occur from a region of lower concentration to higher concentration
metabolism
chemical altering of the drug molecule by the body
What is the effect of metabolites on bioavailability?
although metabolites are inactive–> they decrease bioavailbility because there would be a reduced amount of drug that would get to the site of action
efflux transporters (2)
- going in the opposite direction than what we would like
- typically P glycoproteins
P glycoproteins (3)
- energy driven
- pump the drug back in the direction in which it came from
- not as specific as carrier proteins
_____ are thought to cause tolerance to cancer therapeutic agents
P glycoproteins
What would be the effect of P glycoproteins on the bioavailability of the drug?
it would DECREASE the bioavailability because its taking the drug molecules in the opposite direction than we want them to go–> not allowing them to ultimately get to the site of action
What part of the stomach is where most secretion occurs?
the middle of the stomach
Antrum
holds material in the stomach to control how it moves to the pylorus
T/F The stomach is very muscular
TRUE
What are the functions of the stomach? (4)
- reservoir
- site of the beginning of digestion
- regulate the delivery of nutrients
- bacteriostatic
The secretion of ____ typically destroys the bacteria that make it to the stomach
HCl
What are the secretion cells in the stomach? (4)
- mucoid cells
- chief cells
- parietal cells
- g cells
mucoid cells
secrete mucus
mucus provides ____ and ____ protection
chemical and physical
chief cells
secrete pepsinogen (gets converted to pepsin)
____ begins the digestion process in the stomach
pepsin
parietal cells
secrete primarily HCl and intrinsic factors
intrinsic factors are necessary for…
absorption of B12
G cells
secrete gastrin (which in turn controls the secretion of HCl)
About ___L/day of fluids are secreted by the stomach
3
Would you anticipate significant absorption from the stomach? Why?
- no, almost no drug is absorbed by the stomach
- drugs do not stay in the stomach long enough and the stomach has a small surface area
Where is the site of most absorption of drug?
small intestine due to the large membrane surface area
What is the pH of the stomach? with food?
~ 1-2
food neutralizes the stomach–> pH goes up to around 4,5, or 6
What are the 3 segments of the small intestine?
- duodenum: connected to the pylorus (upper)
- jejunum (middle)
- illeum (lower)
T/F Each segment of the small intestine have regional differences
TRUE. transporter proteins are located at specific sites in the intestine
What components help tribute to the large surface area of the small intestine?
- folds of kerckring (increase 3x)
- villi (increase 30x)
- microvill (increase 600x)
Bile:
Is stored in the _______; made by the _____
gall bladder; liver
gall bladder empties bile into the duodenum (ph ~6)
Why does the pH change from 2 when it leaves the stomach and go up to 6?
bicarbonate ion–>neutralize acidic fluid that is emptying from the stomach
What is the primary function of the large intestine? pH?
storage of waste; pH 5.5-7
T/F There are vili present in the Large Intestine.
FALSE; no villi present leading to absorption being poorer
_____ are present in the large intestine. What is a downfall of having this there?
microflora–> if a drug makes it to the large intestine it may destroy the bacteria that is already there and the bacteria could absorb the drug and metabolize it
As pH varies from a weak acid or base… so does
the degree of ionization
Summary of pH in GI tract
- stomach (fasting)
- stomach (fed)
- duodenum
- ileum
- large intestine
- stomach (fasting): less than 2
- stomach (fed): 2-6
- duodenum: 6-6.5
- ileum: 7-8
- large intestine: 5.5-7
T/F Solids and liquids are emptied the same way from the stomach
FALSE; emptied differently
What do you think is a major factor affecting stomach emptying?
food
Fed mode of the stomach (3)
- one type of pattern
- regular, frequent contractions
- grinding and mixing occurs as long as food is present
_____ and ___ will empty from the stomach and leave in a FIRST order process
liquids and particles less than about 5-10 mm
Liquids empty the stomach _____. High Volume–> _____
immediately; faster emptying
_____ leave in a ZERO order process, it is converted at a ______ rate
solids; constant
What are the 4 phases of the fasting mode in the stomach?
I: relaxation
II: increase in tone and activity (few contraction of different magnitudes)
III: strong contractions–> HOUSEKEEPER
IV: decline in activity
The housekeeping stage of the fasting mode….
sweeps anything left in the stomach out
How long does it take for material to move through the entire small intestine?
3-4 hours
T/F Solution, pellets, and single units move through the small intestine at about the same rate
TRUE-> it does not depend on the presence of food
Absorption _____ occur in the stomach–> but the ____ of emptying of the stomach does effect drug absorption
DOES NOT; RATE
What factors affect gastric emptying? (11)
- meal type
- hydrogen ion concentration
- volume
- osmolality
- emotional state
- exercise
- posture
- age
- gender
- disease state
- drug
Fats, proteins, and carbs typically have _____ emptying if they are the same caloric value. The presence of these _____ emptying
same; decrease
____ (food) have the greatest effect on emptying on a molar basis
fats: they are harder to digest
hydrogen ion concentration:
_____ concentration in intestine will INHIBIT emptying
Increased
Volume:
____ volume of liquid results in more RAPID emptying
increased; liquids in general empty very fast. they can empty even when there is food in the stomach (takes about 12-15 minutes)
Osmolality:
_____ contents empty FASTER than _____ liquids
iso-osmotic; hyper-osmotic
T/F There are receptors in the duodenum that detect increases in the osmotic pressure that use feedback mechanism
TRUE
_____ increases osmotic pressure
eating/food
Emotional state:
_______: increases gastric emptying
_______: decreases gastric emptying
aggression- increase
stress, anxiety- decrease
Exercise:
________: have no effect or slight increase in gastric emptying
_________: decrease gastric empyting
moderate intensity; vigorous
Posture:
If you are on your ____ side: increase gastric emptying
If you are on your _____ side: decrease gastric emptying
right;left
T/F Gastric emptying is FASTER in older people
FALSE: SLOWER
T/F Females have slower gastric emptying then males
TRUE
What disease states INCREASE gastric emptying? (3)
- hyperthyroidism
- duodenal ulcers
- cholecystitis (inflammation of the gallbladder)
Gastritis, GERD, Gastric Carcinoma, Pyloric stenosis, Gastric Ulcers, Diabetic Gastroparesis, Hypothyroidism, Migraine, Pregnancy_______ gastric emptying
decrease
What drugs DECREASE gastric emptying? (4)
- narcotic analgesic
- isoniazid–> used to treat TB
- antacids
- tricyclic antidepressants
What drugs INCREASE gastric emptying? (2)
- metoclopramide
- erythromycin
T/F Food has a great impact on gastric emptying
TRUE: general you would want a patient to take solid dosage form on an empty stomach with a full glass of water
Why do we want to get the drug out of the stomach ASAP?
because it is not being absorbed in the stomach and it needs to get in the intestine
What is considered an empty stomach with food?
- 30 minutes before a meal
- 2 hours after a meal
Why do some drugs need to be taken with food? (2)
- if drug is irritating
- food increase absorption of some drugs
T/F You CAN NOT decrease saturation if given with food
FALSE: you can
How could food affect absorption of a drug? (3)
- emptying
- change in pH
- interact with drug
Food ____ gastric emptying
slows
Food changing the pH could do what?
- increase/decrease absorption
- increase/decrease degradation
When the drug Nitrofurantoin was given with food, more excretion (unchanged drug) occurred. Why?
When you give with food emptying is SLOWED making the drug stay in the stomach longer which allows more of the drug to dissolve in the stomach before it is emptied into the intestine
T/F Blood flow is static.
FALSE: there is first blood flow through the membrane then the drug is being carried away by the blood
rate limiting step
slowest step in the overall process that controls how fast the process will proceed
perfusion rate limited (2)
- blood flow step is the slowest step (#2)
- drug freely passes through the membrane with little resistance
ex. water and ethanol
diffusion or permeability rate limited
- difficult to cross the membrane, slowly crosses the membrane
ex. ribitol (large polar molecule)
When a drug is administered through the muscle (IM), then it only has to cross…..
the blood capillaries
Capillary walls are very ______ compared to the GI tract. What type of rate limited is this?
permeable
- molecules with HIGH molar weights easily cross the capillary wall
- perfusion rate limited
Would you expect gentamicin, a large polar water soluble molecule to be absorbed well?
NO, because it is big and its polar but if administered into muscle tissue it is readily absorbed
The vascularity in the SQ tissue is less than that of muscle tissue, what would you expect to be the effect on absorption?
SQ would have a slower rate of absorption because of less blood flow
SQ administration: What would be the expected effect on the absorption rate following SQ administration in the following situation?
Application of heat or massage the site of administration
INCREASE because blood flow is increasing
o SQ administration: What would be the expected effect on the absorption rate following SQ administration in the following situation?
Co-administration of a vasodilator or hyaluronidase (destroy connective tissue)
INCREASE, vasodilator because blood flow is increasing
hyaluronidase will cause the drug to spread out (increasing the SA)
o SQ administration: What would be the expected effect on the absorption rate following SQ administration in the following situation?
Co administration of epinephrine that produces vasoconstriction
DECREASE
Feedback mechanism in the duodenum (3)
- receptors located in the duodenum, but control emptying in the stomach
- an increase hydronium ions cause SLOW rate of emptying
- osmotic pressure is related to colligative properties
