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Physiology and Pharmacology > Pharmacokinetics - AD > Flashcards

Pharmacokinetics - AD Flashcards

1
Q

What is pharmacokinetics?

A

Study of what the body does to a drug

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2
Q

What are the processes involved in drug entry to the body?

A

Absorption

Distribution

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3
Q

What are the processes involved in drug removal from the body?

A

Metabolism

Excretion

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4
Q

What are the routes of drug administration? What do they each mean?

A

Enteral - drug is delivered to the GI tract

Parenterel - drug is delivered through routes that are not the GI tract

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5
Q

What are some examples of enteral drug administration?

A

Oral

Rectal

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6
Q

What are some examples of parenterel drug administration?

A

Intravenous

Intramuscular

Subcutaneous

Inhalation

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7
Q

What is the most common route of drug administration?

A

Oral

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8
Q

Are drugs absorbed in the stomach? Why?

A

No

because it has a thick layer of mucous

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9
Q

Where does most of drug absorption occur? Why?

A

Small intestine

Has extremely large surface area
long transit time

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10
Q

What is the typical transit time of food in the small intestine?

A

3-5 hours

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11
Q

What does transit time of food in the small intestine depend on?

A

Motility - the contraction of smooth muscle in the small intestines to mix and propel the food along

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12
Q

What is the pH of the small intestine? What is the importance of this?

A

Slightly acidic, 6-7

Affects the proportion od drugs in ionised and unionised states

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13
Q

What are the different mechanisms of drug absorption in the small intestine?

A

Passive diffusion

Facilitated diffusion

Active transport, mostly secondary

Pinocytosis

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14
Q

What properties must a drug have in order to be absorbed by passive diffusion in the small intestine?

A

Lipophilic

Small, not ionic

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15
Q

How do drugs that are weak acids or bases exist in the small intestine?

A

Equilibrium between their ionised and unionised forms

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16
Q

How can drugs that are weak acids or bases be absorbed by passive diffusion in the small intestine?

A

Drug in unionised form is absorbed by passive diffusion
then because of the equilibrium, the ionised form is prontonated/deprotonated into the unionised form

Or by facilitated diffusion (later flashcards)

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17
Q

What properties do drugs absorbed by facilitated diffusion in the small intestine generally have?

A

Low lipid solubility, hydrophilic

Large

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18
Q

What is the name of the transporters responsible for facilitated diffusion of drugs in the small intestine?

A

Solute carrier transport proteins

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19
Q

What are the types of solute carrier transport proteins?

A

Organic anion transporters

Organic cation transporters

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20
Q

Where in the body are organic anion and cation transporters expressed?

A

Small intestine

Liver

Kidneys

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21
Q

What properties do drugs absorbed by secondary active transport in the small intestine generally have?

A

Low lipid solubility, hydrophilic

Large

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22
Q

What is the name of the transporters responsible for secondary active transport of drugs in the small intestine?

A

Solute carrier transport proteins

  • organic anion transporters
  • organic cation transporters
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23
Q

Which electrochemical gradients are used in the secondary active transport of drugs in the small intestine?

A

Sodium ions

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24
Q

What properties do drugs absorbed by pinocytosis in the small intestine generally have?

A

Extremely large

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25
Q

What are the groups factors affecting drug absorption in the small intestine?

A

Drug properties factors

GI properties factors

Drug metabolism in gut

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26
Q

What are the drug properties factors affecting drug absoprtion in the small intestine?

A

Lipophilicity

Size

Acid/base properties

Charge

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27
Q

What are the GI properties factors affecting drug absoprtion in the small intestine?

A

Total surface area

pH

Blood flow

GI motility, transit time

Density of transporters

Food

Enzymes

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28
Q

What inreases blood flow to the small intestine?

A

Eating

29
Q

What decreases blood flow to the small intestine?

A

Exercise

Heart failure

Shock

30
Q

What increases GI motility?

A

Diarrhoea

31
Q

What decreases GI motility?

A

Eating

32
Q

How can small intestine pH and enzymes affect drug absorption?

A

Can destroy some drugs

reducing their absorption

33
Q

How can the presence of food affect drug absorption?

A

Can both increase and decrease absorption for different drugs

34
Q

Where does most of the drug metabolism in the gut occur?

A

Liver

35
Q

How do drugs first reach the liver?

A

Absorbed into small intestine capillaries

travel through the hepatic portal vein to the liver

36
Q

What is the name of the drug metabolism occurring in the liver after it’s just been absorbed? Why?

A

Hepatic first pass metabolism

Because it occurs in the drug’s first passage into the body

37
Q

What happens in hepatic first pass metabolism?

A

Some drugs passing through veins and capillaries of the liver
enter cells and are metabolised by enzymes

38
Q

What are the types of enzymes involved in hepatic first pass metabolism?

A

Cytochrome P450s - Phase 1

Conjugating enzymes - Phase 2

39
Q

What is bioavailability?

A

Relative amount of drug that reaches systemic circulation

40
Q

What does bioavailability reflect?

A

Reflects all the barriers to absorption of the drug

in its particular route of administration

41
Q

What is the reference route of administration used in bioavailability? Why?

A

IV

because all of the drug reaches the systemic circulation

42
Q

What is oral bioavailability?

A

Relative amount of drug that reaches systemic circulation for drugs given via oral route compared to giving them via IV route

43
Q

How is oral bioavailability calculated?

A

Area under curve for oral route curve
______________________________
Area under curve for IV route curve

curve is y axis-plasma drug concentration against x axis-time

44
Q

What is the symbol for oral bioavailability?

A

F

45
Q

What are the range of values of oral bioavailability?

A

0 to 1

46
Q

What is drug distribution?

A

The process of drug molecules reaching their target sites in cells from the systemic circulation

47
Q

How are drugs distributed in the body?

A

In blood in arteries
then diffuse out of capillaries into intersitital fluid and then to their target cells and then to their target site on those cells

48
Q

What are the factors of drug distribution?

A

Blood supply to target tissue/capillary density to target tissue

Capillary permeability

Drug lipophilicity

Drug binding to plasma proteins, tissue proteins

49
Q

What are the different types of capillaries based on their permeability, in order from least permeable to most permeable?

A

Continuous

Fenestrated

Sinusoid

50
Q

What is the structure of continuous capillaries

A

Their endothelial layer and basement membrane doesn’t contain any holes or gaps

51
Q

What is the structure of fenestrated capillaries?

A

Their endothelial layer contains holes

52
Q

What is the structure of sinusoid capillaries?

A

Both the endothelal layer and the basement membrane have gaps

53
Q

What are some examples of organs that contain fenestrated capillaries?

A

Intestines

Kidneys

54
Q

What are some examples of organs that contain sinusoid capillaries?

A

Liver

Spleen

55
Q

What are some examples of organs that contain continuous capillaries?

A

Brain - blood-brain barrier

56
Q

How do lipophilic drugs distribute in the body?

A

Can passively diffuse across capillary walls, cell membranes etc. to target site

57
Q

How do hydrophilic drugs distribute in the body?

A

Leave the capillaries through fenestrations or sinusoids

may become uncharged by pH of tissue and then passively diffuse across cell membranes
or if remain charged, can be carried by organic anion or cation transporters across cell membranes if they’re present

58
Q

What are some examples of plasma proteins that drugs may bind to?

A

Albumin

Lipoproteins

Immunoglobulins

59
Q

How do plasma proteins affect the plasma drug concentration?

A

Reduce the free drug concentration

60
Q

What proportion of the drug is bound to plasma proteins in the blood? Why?

A

Equilibrium between

drug + protein protein-drug complex

61
Q

What form of the drug in the blood is able to bind to target sites and cause an effect?

A

Only the free drug molecules can do this

62
Q

What are the different body fluid compartments?

A

Plasma water

Extracellular water = plasma + interstitial water

Total body water = plasma + intersitital + intracellular water

63
Q

What is volume of distribution referenced to?

A

Plasma drug concentration

64
Q

How is volume of distribution calculated?

A

Total amount of drug in body
____________________________
Plasma drug concentration at time 0

65
Q

What do smaller volume of distribution values mean?

A

Higher drug concentration in plasma

less penetration of intersitital and intracellular fluid

66
Q

What do large volume of distribution values mean?

A

Lower drug concentration in plasma

more penetration of interstitial and intracellular fluid

67
Q

What are the units of volume of distribution?

A

Litres assuming standard body weight

Litres/kg for specific body weights

68
Q

What are the over-simplifications made by the volume of distribution?

A

That all the different body fluid compartments behave similarly

That the drug is evenly distributed throughout the whole body

That the drug is fully distributed at time 0

Physiology and Pharmacology (20 decks)

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