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Absorption in GI tract Flashcards

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1
Q

Why are oral doses designed to make solutions in the small intestine and not, say, the stomach or large intestine?

A

Because the small intestine is made for absorption and is good at it

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2
Q

What is the main barrier to absorption in the stomach?

A

Thick layer of mucin (mucopolysaccharide)

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3
Q

Why is the pH in the stomach higher in “fed state” than in “fasted state”?

A

In fed state the acid in the stomach is being absorbed and used to digest food, so the pH is higher

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4
Q

When a drug is sensitive to low pH, what should you tell the patient?

A

Take it with food (keeps pH up)

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5
Q

What is a disadvantage of taking drugs with food?

A

Some drugs may be ionized at low pH but not at higher pH (ionized molecules enter solution faster)

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6
Q

What is the average range of gastric emptying time?

A

0-3 hours

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7
Q

What is the definition of gastric emptying time?

A

amount of time between deposition of material into stomach and its movement out of the stomach

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8
Q

What are two things that extend gastric emptying time?

A

Large chunks of food and fats

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9
Q

What is the “housekeeping wave”?

A

Gastric emptying that occurs every 15-20 minutes in fasted state in order to clear out mucin and acid

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10
Q

How can the housekeeping wave be utilized in regards to drug absorption?

A

If drug taken in fasting state, may enter intestine quicker by “riding” the housekeeping wave as opposed to waiting for gastric emptying

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11
Q

What is a disadvantage to taking the drug under fasted conditions (in regards to drug absorption)?

A

There is a limited, shorter amount of time for the drug to disintegrate/rupture before entering the intestines

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12
Q

Where do all the blood vessels of the small intestine drain?

A

Into portal circulation (portal vein)

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13
Q

What makes the small intestine so good at absorption?

A

Rich supply of nerves and blood vessels, strong blood flow, length

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14
Q

Approximately what percentage of cardiac output goes to small intestine circulation?

A

25-30%

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15
Q

What are the three parts of the small intestine?

A

Duodenum, Jejunum, Ileum

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16
Q

The pH of the intestine _______ as you move farther along

A

increases

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17
Q

What is the pH range in the duodenum?

A

4.9-6.4

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18
Q

What is the pH range in the jejunum

A

4.4-6.6

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19
Q

What is the pH range in the ileum?

A

6.5-7.4

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20
Q

What is the pH range in the large intestine?

A

6.4-8

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21
Q

What molecule is used to neutralize stomach acid in the intestines?

A

Bicarbonate

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22
Q

What cause the pH increase moving along the intestines?

A

Bacteria byproducts

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23
Q

Why does drug absorption decrease when a patient has diarrhea?

A

Because material is moving through the intestines much more quickly

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24
Q

What is the average time material spends going through the small intestine?

A

2-5 hours

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25
While most drugs are typically absorbed throughout the whole length of the small intestine, some drugs are only absorbed in a specific region, called the ________ for that drug.
Window of Absorption
26
Where does entero-hepatic recycling take place?
The small intestine
27
Explain the process of entero-hepatic recyling.
When drug in the small intestine is absorbed into the blood, it is transported through the portal vein where it is pulled out by the liver; the liver then deposits the drug into the bile duct, and when the bile is secreted back into the intestine, the drug can be reabsorbed back into the system.
28
What do goblet cells secrete?
A thin layer of mucin
29
What is another name for the basement membrane?
Lamina propria
30
What is the difference between the transcellular and paracellular pathways?
In the transcellular pathway, the drug must be able to interact with the cell membrane and pass through it while traveling from cell to cell; in the paracellular pathway, the drug never interacts with the membrane and instead passes through the small junctions between cells in an entirely aqueous pathway
31
If a drug can pass passively through the cell membrane in diffusion, what does that say about the cell?
It has a hydrophobic (lipophillic) portion that is able to interact with the nonpolar tails in the membrane
32
How do drug "hitch a ride" on nutrients being actively transported into the cell?
By having a size and shape similar to the nutrient
33
Efflux pumps can exist on either or both the _____ and _____ membranes.
Apical (lumen), basolateral (basal)
34
Are efflux pumps very specific? Why?
No, because that way they can transport a wider variety of foreign substances
35
For drugs using the paracellular pathway, what is an approximate size limit for the drug?
8 angstroms
36
Why is it said that the transcellular route is more "important" to absorption than the paracellular route?
The transcellular route has greater surface area available for absorption and allows larger drugs to be absorbed
37
What is a limit for drugs using the transcellular pathway?
Must be able to "dissolve" (partition) through lipid membrane
38
What are limiting factors for paracellular movement?
Size of drug and solubility in water
39
What is permeation?
The movement of a drug in solution through a biological membrane
40
What is the definition of drug solubility?
The maximum amt of drug that can be held in solution
41
The dose number refers to the total volume of ______ needed to solubize entire drug dose
water
42
It is said that a dose number less than what volume confirms that the drug going into solution will NOT be a limiting factor in absorption?
250 mls
43
Of the four types of drug molecules (based on biopharmaceutical classification system) which has the best bioavailability? Why?
Type 1, because it enters into solution easily and permeates membrane quickly
44
What are some factors that the BCS type system does NOT take into account?
1st pass metabolism, chemical stability, therapeutic range/effectiveness
45
What is the difference between BCS Type II and Type III drugs?
Type II easily permeate the membrane but take a long time to enter solution, while Type III enters solution quickly but takes a while to permeate the membrane
46
Why are Type II, III, and IV drugs still be used in treatment if their bioavailability is low?
Because they can still be effective if they are potent drugs (not much gets in, but not much needed to work)
47
What are some common Type I drugs?
Acetominophen, Propranolol, Valproic Acid
48
What are some common Type II drugs?
Cyclosporin, Digoxin, Ketoconazole
49
What are some common Type III drugs?
Cimetadine, ranitadine
50
What are some common Type IV drugs?
Chlorthiazide, furosemide
51
The Km (or Ko/w) value is the...
partition coefficient (measure of drug lipophillicity)
52
The pathway of diffusion is _______ movement characterized by Brownian motion
random
53
The diffusion coefficient is ________ proportional to the radius of the drug trying to diffuse
inversely (larger radius=slower diffusion)
54
As the diffusion coefficient _______, the diffusion rate decreases
decreases
55
Because it takes longer for larger drugs to diffuse, what molecular weight do most drugs try and stay under?
500
56
Flux describes...
mass of drug that moves through membrane per unit time
57
In terms of permeability, flux can be expressed as...
P(C1-C2) per unit area of membrane, where P is permeabilty, C1 is concentration of drug outside cell, and C2 is concentration of drug inside cell
58
________ C1 and ________ C2 makes the diffusion gradient bigger and results in faster flux
Increasing, decreasing
59
Why do we say that practically speaking, C2 goes to 0?
Because the body almost immediately clears away substances that get into the cell
60
Properties that ______ Km seem to ______ maximum value of C1.
increase, decrease
61
A ______ value of Km means higher lipophillicity and ______ rate of flux
higher, faster
62
What happens when the Km value becomes incredibly high?
The flux severely drops because the drug affinity for the membrane is so high it doesn't want to diffuse back out into the cell
63
What are the four components of Lipinski's "Rule of 5"
Expect poor absorption if the Log Ko/w is greater than 5, the molecular weight is greater than 500, there are more than 5 hydrogen bond donor sites (Hs on O or N), and there are more than 10 hydrogen bond acceptor sites (O, N, F)
64
What is the theory behind why hydrogen bonding affects absorption?
Drug can hydrogen bond with the lipid head groups in the membrane and the water outside, and since it costs energy to break the bonds in order to diffuse through the membrane, many drugs don't go
65
What are the two primary mechanisms of absorption inhibition?
Insoluble Complex formation and adsorption to an insoluble surface
66
What are the two kinds of Insoluble Complexes?
Ionic and macromolecule
67
The interaction in solution that leads to an insoluble complex is so strong it is said to be essentially ______
irreversible
68
Where does an insoluble complex form?
in solution
69
What is the definition of an insoluble complex?
A non-covalent interaction between a drug/ion or drug/highly charged organic molecule
70
What time period should separate taking drugs at risk for forming drug/ion complexes and taking antacids?
At least 2 hours
71
What is a drug/metal ion complex called?
Chelate
72
Why and how do drugs and multivalent cations react to form chelates?
They react when drugs have a highly conjugated pi bond system that results in extensive pi electron delocalization which gives the drug an overall strong partial negative charge and usually makes the molecule planar; this allows the multivalent cation and drug to form alternating "stacks" of cation and drug held together with ionic bonds
73
What are three common multivalent cations found in antacids?
Ca2+, Mg2+, Al3+
74
When dealing with drugs that are at risk for forming insoluble complexes, what is it best to tell the patient?
Take them on an empty stomach
75
What are two common macromolecules that can form complexes with drugs?
Xanthan gum and Sodium Alginate
76
Why do macromolecule complexes form?
Macromolecules that have an overall negative charge can interact with drugs that have a positive or partial positive charge (most drugs are weak bases w/ positive charges, so this big problem)
77
What does adsorption mean?
Binding of drug to another surface
78
Why would you want to encourage inhibition of drug absorption?
In the case of poisonings (accidental or otherwise)
79
What is the main substance used for adsorption?
Activated charcoal
80
What does it mean to say charcoal has a high affinity and high capacity?
High affinity refers to the extreme hydrophobic quality of charcoal that attracts hydrophobic drug regions, while high capacity refers to charcoal's porous nature that gives it an incredibly large surface area
81
Why is the effect of charcoal so time-dependent?
Because the longer it takes to administer charcoal, the more likely the drug will be cleared out of the stomach into the intestines; charcoal works better in the stomach before drug absorbed
82
What is the main solute that inhibits charcoal's action?
Ethanol
83
If ethanol or a sweetener such as sorbitol present when activated charcoal present, what should be done?
Charcoal dose increased
84
Why is charcoal administration difficult?
Bad taste
85
What is a side effect of activated charcoal?
Constipation

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