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PK > Lecture 2 Oral Dosing and Absorption Concepts > Flashcards

Lecture 2 Oral Dosing and Absorption Concepts Flashcards

1
Q

What does it means to have permeability rate-limits absorption?

A

Dissolution&raquo_space; Absorption

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2
Q

What does it mean when Dissolution&raquo_space; Absorption?

A

Drug is hydrophillic; forms a solution rapidly

most of the drug has dissolved in GIT before an appreciable fraction has bben absorbed

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3
Q

What does it mean to have dissolution rate-limits absorption?

A

Absorption&raquo_space; Dissolution

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4
Q

What does it mean when Dissolution &laquo_space;Absorption?

A

Drug is hydrophobic; very little drug in solution at absorption site; any drug that is dissolved is absorbed ASAP
more common

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5
Q

What is the difference between solubility and dissolution?

A

Solubility - intrinsic property

Dissolution - Overall system of drug; how fast the drug dissolves, etc.

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6
Q

3 ways that the drug can be transported across GI membrane:

A
  1. Passive transcellular
  2. Paracellular
  3. Facilitated transcellular
    no energy involved
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7
Q

What are some factors that affect the transportation of drug across the GI membrane?

A
  • Size of drug molecules

- Lipophilicity

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8
Q

Paracellular permeability drops off sharply with MWs above ___g/mol

A

350g/mol

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9
Q

Paracellular diffusion depends on the __ of the membrane

A

Rigidity of membrane

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10
Q

More lipophilic the drug molecules, the ____ its permeability

A

greater permeability when drug molecules are more lipophilic

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11
Q

What happens when the drug molecules are tooo lipophilic?

A
  • Poorer aqueous solubility

- Greater propensity to bind to membrane transporters

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12
Q

What is the pH-partition hypothesis?

A

pKa
Henderson-Hasselbalch equation
Drug molecules needs to be unionized in order to pass through

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13
Q

4 reasons why most drugs are absorbed via SI rather than in gastric

A
  1. SA 200m2 VS stomach 1m2
  2. Blood flow in SI 1L/min VS stomach 150ml/min
  3. Sink condition
  4. More permeable membrane
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14
Q

Since abs of all drugs is faster in intestine VS stomach, what is the controlling factor in the speed of drug abs even when it is given in solution?

A

Gastric emptying rate

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15
Q

Why is gastric emptying important?

A

control the rate at which the drug is presented to the major site of absorption (upper SI); controls the onset along with the rate of abs

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16
Q

What does intestinal motility determine?

A

Intestinal motility determines the residence time of the dosage form in the SI

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17
Q

What will changes in motility alter?

A

Changes in motility could alter drug bioavailability depending on whether dissolution or permeability is the rate-limiting step

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18
Q

How can we change the motility for dissolution rate limiting?

A

slow down motility (esp gastric emptying) allows for more complete dissolution and improves F (extent)

19
Q

How can we change the motility for permeability rate limiting?

A

Slow down motility to allow more time for absorption, thus compensates for poor permeability
Accelerated motility aggravates permeability problems

20
Q

GI motility when meal is taken

A

dec in GER (slow down)

21
Q

If solutions or suspensions of particles in GI motility

A

empty more rapidly, inc GER (speed up)

22
Q

If chunks of materials in GI motility

A

needs to be broken down before empyting, dec GER (slow down)

23
Q

If drugs are anticholinergic/narcotic analgesics, what happens to GER

A

Dec GER (slow down)

24
Q

If drugs like metoclopramide, what happens to GER?

A

Inc GER (speed up)

25
Q

Intake of food only affects

A

GER of stomach (transit time increases);

SI is unaffected by food, always 3-4h of absorption max

26
Q

When GER is reduced, what happens to the Cmax and T max

A

Cmax lowers, Tmax prolongs

reduction in systemic absorption

27
Q

Cmax and Tmax changes cannot conclude the extent of absorption is affected. Which term does?

A

AUCtotal

28
Q

How does the surface area per unit length changes along the intestine?

A

decreases from duodenum to rectum

29
Q

Where are the changes in tightness of junction (electrical resistance)

A

Higher in colon than SI

must be <350g/mol by paracellular mode

30
Q

How is the distribution like for metabolic enzymes and transporters in the GIT?

A

Distributed variably throughout GIT

e.g. PGP efflux pump’s activity increases along GIT

31
Q

Where are the anaerobic microbes abundant?

A

Colon

32
Q

How does the pH vary along the intestine?

A

pH 6.6 (proximal SI)
pH 7.5 (terminal ileum)
pH 6.4 (caecum)
pH 7.0 (descending colon)

33
Q

What is the mean transit time for SI and large bowel?

A

3-4hrs (SI)

10-36hr (large bowel)

34
Q

Where does the absorption of less permeable drugs occur?

A

within SI even though drugs spend longer time in colon

35
Q

What are the properties of drugs with low Foral?

A

F = 0.005 -0.14
Polar, MW >400g/mol
excessively variable oral abs, some given parenterally

36
Q

How do you define decrease in extent of abs?

A

dec Cmax, dec AUC

37
Q

GER impacts which term; Tmax or Cmax?

A

Tmax

38
Q

Formula for oral systemic bioavailability

A

Ff x Fg x Fh
Ff: enters intestinal tissues
Fg: reaches portal vein
Fh: reaches liver

39
Q

What are the factors involved in drugs which are entering low impedance by porous capillary membrane (large fenestrations) in muscle and SC tissues?

A
  1. Charge or uncharged
  2. Degree of ionisation
  3. Mol size (up to 5000g/mol)
40
Q

Which muscle group does more blood supply go to?

Deltoid or gluteal?

A

Deltoid&raquo_space; gluteal

41
Q

Which site of adm supply more blood? IM or SC?

A

Higher blood supply to muscles IM than SC fats

42
Q

What can reduce blood flow, thereby reducing rate of absorption?

A
  • Vasoconstrictor

- Shock

43
Q

What can increase blood flow, thus increasing rate of abs?

A
  • Heat, fever, exercise
44
Q

Absorption of drug in solution from muscle and SC tissue is what type of rate-limited?

A

perfusion rate-limited

PK (6 decks)

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