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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
What are the groups factors affecting drug absorption in the small intestine?
Drug properties factors GI properties factors Drug metabolism in gut
26
What are the drug properties factors affecting drug absoprtion in the small intestine?
Lipophilicity Size Acid/base properties Charge
27
What are the GI properties factors affecting drug absoprtion in the small intestine?
Total surface area pH Blood flow GI motility, transit time Density of transporters Food Enzymes
28
What inreases blood flow to the small intestine?
Eating
29
What decreases blood flow to the small intestine?
Exercise Heart failure Shock
30
What increases GI motility?
Diarrhoea
31
What decreases GI motility?
Eating
32
How can small intestine pH and enzymes affect drug absorption?
Can destroy some drugs | reducing their absorption
33
How can the presence of food affect drug absorption?
Can both increase and decrease absorption for different drugs
34
Where does most of the drug metabolism in the gut occur?
Liver
35
How do drugs first reach the liver?
Absorbed into small intestine capillaries | travel through the hepatic portal vein to the liver
36
What is the name of the drug metabolism occurring in the liver after it's just been absorbed? Why?
Hepatic first pass metabolism Because it occurs in the drug's first passage into the body
37
What happens in hepatic first pass metabolism?
Some drugs passing through veins and capillaries of the liver enter cells and are metabolised by enzymes
38
What are the types of enzymes involved in hepatic first pass metabolism?
Cytochrome P450s - Phase 1 Conjugating enzymes - Phase 2
39
What is bioavailability?
Relative amount of drug that reaches systemic circulation
40
What does bioavailability reflect?
Reflects all the barriers to absorption of the drug | in its particular route of administration
41
What is the reference route of administration used in bioavailability? Why?
IV | because all of the drug reaches the systemic circulation
42
What is oral bioavailability?
Relative amount of drug that reaches systemic circulation for drugs given via oral route compared to giving them via IV route
43
How is oral bioavailability calculated?
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
What is the symbol for oral bioavailability?
F
45
What are the range of values of oral bioavailability?
0 to 1
46
What is drug distribution?
The process of drug molecules reaching their target sites in cells from the systemic circulation
47
How are drugs distributed in the body?
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
What are the factors of drug distribution?
Blood supply to target tissue/capillary density to target tissue Capillary permeability Drug lipophilicity Drug binding to plasma proteins, tissue proteins
49
What are the different types of capillaries based on their permeability, in order from least permeable to most permeable?
Continuous Fenestrated Sinusoid
50
What is the structure of continuous capillaries
Their endothelial layer and basement membrane doesn't contain any holes or gaps
51
What is the structure of fenestrated capillaries?
Their endothelial layer contains holes
52
What is the structure of sinusoid capillaries?
Both the endothelal layer and the basement membrane have gaps
53
What are some examples of organs that contain fenestrated capillaries?
Intestines Kidneys
54
What are some examples of organs that contain sinusoid capillaries?
Liver Spleen
55
What are some examples of organs that contain continuous capillaries?
Brain - blood-brain barrier
56
How do lipophilic drugs distribute in the body?
Can passively diffuse across capillary walls, cell membranes etc. to target site
57
How do hydrophilic drugs distribute in the body?
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
What are some examples of plasma proteins that drugs may bind to?
Albumin Lipoproteins Immunoglobulins
59
How do plasma proteins affect the plasma drug concentration?
Reduce the free drug concentration
60
What proportion of the drug is bound to plasma proteins in the blood? Why?
Equilibrium between | drug + protein protein-drug complex
61
What form of the drug in the blood is able to bind to target sites and cause an effect?
Only the free drug molecules can do this
62
What are the different body fluid compartments?
Plasma water Extracellular water = plasma + interstitial water Total body water = plasma + intersitital + intracellular water
63
What is volume of distribution referenced to?
Plasma drug concentration
64
How is volume of distribution calculated?
Total amount of drug in body ____________________________ Plasma drug concentration at time 0
65
What do smaller volume of distribution values mean?
Higher drug concentration in plasma | less penetration of intersitital and intracellular fluid
66
What do large volume of distribution values mean?
Lower drug concentration in plasma | more penetration of interstitial and intracellular fluid
67
What are the units of volume of distribution?
Litres assuming standard body weight Litres/kg for specific body weights
68
What are the over-simplifications made by the volume of distribution?
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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