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Pharmacokinetics > Absorption > Flashcards

Absorption Flashcards

1
Q

Biopharmaceutics

A

Relationship between the physical and chemical properties of a drug in a dosage form and the pharmacologic response after administration

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2
Q

What 5 factors is biopharmaceutics dependent upon?

A

1) chemical nature
2) physical state
3) type of dosage form
4) presence/absence of excipients
5) pharmaceutical process

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3
Q

Pharmacokinetics

A

Study and characterization of the time course of the drug absorption, distribution, metabolism, and excretion (ADME). The relationship of these processes to the intensity and time course of the therapeutic and adverse effects of drugs.

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4
Q

Bioavailability

A

Rate and extent (amount) to which a drug is absorbed from a drug product into the body or to the site of action

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5
Q

Clinical Pharmacokinetics

A

The application of pharmacokinetic methods in drug therapy. It involves a multidisciplinary approach to individually optimized dosing strategies based on the patient’s disease start and patient-specific considerations

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6
Q

Pharmcodynamics

A

Refers to the relationship between drug concentration at the site of action (receptor) and pharmacologic response

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7
Q

Absorption

A

factors affecting drug absorption (transport processes, pH, lipophilicity, particle size, first-pass effect); factors affecting dissolution rate

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8
Q

Distribution

A

body fluid compartments, tissue distribution, protein-binding

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9
Q

Metabolism

A

phase 1 and 2 reactions, Michaelis-Menton (phenytoin), genetics, age, disease states, drug interactions

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10
Q

Excretion

A

renal clearance (filtration, secretion, reabsorption), enterohepatic circulation, biliary clearance

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11
Q

Bioavailability and Bioequivalence

A

methodology for measuring (experimental design, statistical considerations), relative and absolute bioavailability

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12
Q

Read chart on page 4

A

okay

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13
Q

Excretion is done by the _____

A

kidneys

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14
Q

Metabolism is done by the ______

A

liver

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15
Q

How do lipophilic drugs get across the membrane?

A
  • use diffusion to cross membrane

- once it passes, it’s in an aqueous environment

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16
Q

How do hydrophilic drugs get across the membrane?

A

-transport proteins to cross the membrane

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17
Q

______ = plasmid protein that binds a lot of drugs

A

albumin

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18
Q

Overall rate of absorption is faster in capsule or tablet?

A

capsule

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19
Q

Relative pH of stomach?

A

1-3

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20
Q

Relative pH of small intestine?

A

5-7

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21
Q

Relative pH of large intestine?

A

7-8

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22
Q

Tablet has _____ dissolution rate.

A

very limited

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23
Q

Granules have ____ dissolution rate.

A

limited

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24
Q

Very small particles from a capsule have _____ dissolution rate.

A

optimal

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25
Q

Why don’t suppositories work if you put them up to far?

A

You defeat the purpose, it will reach mesenteric vein which feeds into the portal vein and will go through first-pass metabolism (which is what you are trying to avoid by using suppositories).

If you insert it correctly, it goes straight to inferior vena cava and you bypass the first-pass metabolism.

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26
Q

______ drugs are better at crossing membranes

A

unionized

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27
Q

pH partition theory:

Absorption depends on?

A

pKa, lipid solubility, pH of solution

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28
Q

What 2 equations do you need to know?

A

AH A- + H+

Ka = [A-][H+]/[HA]

**Also know henderson hasselbach equation

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29
Q

Liver sinusoids have holes in them called _________

A

fenestrations

*only plasma proteins and things that are blood-soluble will pass through these holes

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30
Q

Sinusoid has how many zones?

A

3 zones

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31
Q

If you are putting a big liver into a smaller body, apoptosis happens on Zone __ cells

A

3

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32
Q

Which Zone gets all the nutrients first?

A

Zone 1

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33
Q

Liver has ___ blood supply

A

dual

  • portal vein which feeds mesenteric (low in oxygen)
  • hepatic artery which is high in oxygen but doesn’t originate from gut

*portal vein and hepatic artery meet

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34
Q

Drug uptake is highest in which zone?

A

Zone 1

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35
Q

Drug uptake is lowest in which zone?

A

Zone 3

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36
Q

Describe the fluid-mosaic model of the cell membrane

A

A) Pericellular aqueous pathway

B) Transcellular lipophilic pathway
-Lipid-soluble agents

C) Transport proteins
-Glucose, amino acids, nucleosides

D) Efflux pump

E) Receptor-mediated transcytosis
-insulin, transferrin

F) Adsorptive transcytosis
-albumin, other plasma proteins

**See slide 10

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37
Q

Exocytosis

A

Materials are exported outside of the cell

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38
Q

Endocytosis

A

Is a form of active transport in which a cell transports molecules into the cell by engulfing them in an energy-using process.

39
Q

Budding

A

a form of growth? idfk

40
Q

What do drug transporters control?

A
  • Controls intracellular drug concentrations and access to drug metabolizing enzymes
  • Controls systemic drug concentrations - absorption and excretion
  • Controls drug concentrations at the site of action
41
Q

What are the two groups of transporters?

A

1) SLC Uptake Transporters

2) ABC Efflux Transporters

42
Q

List some SLC Uptake Transporters

A 
OATPs
OATs
OCTs
PEPTs
MATEs
43
Q

List some ABC Efflux Transporters

A

P-gp (ABCB1)
BCRP (breast cancer resistant protein)
MRPs (multidrug resistant protein
BSEP (bile salt export protein)

44
Q

What can “Drug as a Substrate of Transporter” do?

A
  • Determinant of drug disposition (ADME)

- Prediction of potential drug-drug interactions (DDI)

45
Q

What can “Drug as an Inhibitor of Transporter” do?

A
  • Affects intracellular/systemic concentrations of affected drugs
  • DDI potential with other substrate drugs
46
Q

Describe P-gp

A
  • important efflux transporter
  • kicks stuff out of the cell
  • P-gp can work against you if you want something in the cell
47
Q

As a general rule, the SLC transporters are responsible for _____ of molecules into cells

A

uptake

48
Q

Most SLC transporters are located in the ____ ______ although there are some members located in mitochondria or other intracellular organelles

A

cell membrane

49
Q

SLC transporters are named using the format SLCnXm:

n = ?

A

family number (1-52)

50
Q

SLC transporters are named using the format SLCnXm:

X = ?

A

letter for the subfamily

51
Q

SLC transporters are named using the format SLCnXm:

m = ?

A

number representing the individual family member

52
Q

One exception is SLC family 21 (OATPs) which have what format?

A

SLCOnXm

53
Q

As a general rule, the ABC transporters are responsible for _____ of macromolecules from cells

A

efflux (removal)

54
Q

ABC transporters are transmembrane proteins that use ___ ________ as an energy source to translocate substrates across membranes.

A

ATP hydrolysis

55
Q

ABC transporters are named using the format ABCxN:

X = ?

A

family (A-G)

56
Q

ABC transporters are named using the format ABCxN:

N = ?

A

a number representing the individual family member

57
Q

ABC transporters can be very _____ proteins

A

large

58
Q

Transporters are everywhere! List a few locations

A
  • intestinal epithelia
  • hepatocytes
  • kidney proximal tubules
  • blood brain barrier
59
Q

Diffusion correlates with ______

A

temperature (proportional to degrees K)

60
Q

Will diffusion be stopped by a 30 degree temperature drop?

A

No - decreasing temp will decrease production of ATP, but since diffusion is a passive process and does not require ATP, it will not be slowed down by this temperature drop

61
Q

Will transport be stopped by a 30 degree temperature drop?

A

Yes, because when you lower the temp you decrease production of ATP (which transport depends on) so you will slow transport

62
Q

Active transport:

Can move a substrate ______ a concentration gradient

A

against

63
Q

Active transport:

Requires expenditure of _____

A

energy

64
Q

Active transport:

At low [drug] rate is proportional to _____

A

[drug]

65
Q

Active transport:

At high [drug] carrier mechanism is _______

A

saturated

66
Q

Active transport:

shows ______

A

specificity

67
Q

Active transport:

Subject to competitive ______

A

inhibition

68
Q

Active transport:

Shows site ______

A

specificty

69
Q

Active transport:

Is inhibited non competitively by ??

A

substances that interfere with the respiration of cells

70
Q

How do you tell the difference between diffusion or transport?

A

Transporters require energy

71
Q

How does volume influence gastric emptying?

A

The larger the starting the volume the grater the initial rate of emptying. After this initial period the rate slows

72
Q

How does physical state influence gastric emptying?

A

Solutions or suspensions empty more rapidly than chunks

73
Q

How do fatty acids influence gastric emptying?

A

Reduction in proportion to chain length

74
Q

How do triglycerides influence gastric emptying?

A

Reduction in rate of emptying, unsaturated more effected linseed and olive oils most effective

75
Q

How do carbohydrates influence gastric emptying?

A

Reduction

76
Q

How do amino acids influence gastric emptying?

A

Reduction, proportional to concentration

77
Q

How does osmotic pressure influence gastric emptying?

A

increase at lower concentrations, decrease at higher concentrations

78
Q

How do acid chemicals influence gastric emptying?

A

reduction

79
Q

How do alkali chemicals influence gastric emptying?

A

increase

80
Q

How do anticholinergic drugs influence gastric emptying?

A

decrease in emptying

81
Q

How do narcotic analgesics influence gastric emptying?

A

decrease

82
Q

How does metoclopromide influence gastric emptying?

A

increase

83
Q

How does ethanol influence gastric emptying?

A

reduction

84
Q

How does body position influence gastric emptying?

A

lying on left side reduces emptying

85
Q

How does viscosity influence gastric emptying?

A

increase viscosity reduces emptying

86
Q

How does emotional state influence gastric emptying?

A
  • aggressiveness increases contractions and emptying

- depression reduces

87
Q

How do bile salts influence gastric emptying?

A

reduces

88
Q

How do disease states influence gastric emptying?

A

rate is reduced in some hypothyroidism, pyloric lesions

89
Q

How does exercise influence gastric emptying?

A

vigorous exercise reduces it

90
Q

How does gastric surgery influence gastric emptying?

A

emptying difficulties can be a serious problem

91
Q

Facts affecting absorption of drugs across the gut?

A
  • age
  • blood flow
  • pH
  • food
  • other drugs
92
Q

Drugs can either _____, ______, or _______ the absorption of other drugs.

A

reduce, delay, or increase

**or not affect it

93
Q

Time vs. Plasma Drug Concentration Graph:

higher slope = ?

A

faster absorption

94
Q

Time vs. Plasma Drug Concentration Graph:

lower slope = ?

A

slower absorption

Pharmacokinetics (12 decks)

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