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Y1 - ICPP > Lecture 19 - Pharmacokinetics I > Flashcards

Lecture 19 - Pharmacokinetics I Flashcards

1
Q

What type of signalling molecule is a drug?
Exogenous or endogenous?

A

Exogenous signalling molecule

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2
Q

What are the 4 basics steps to a drugs lifecycle in the body?

A

Absorption
Distribution (around body)
Metabolism (producing its effect)
Excretion

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3
Q

What are the 2 stages which involve the drug going in?

A

Absorption
Distribution

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4
Q

What are the 2 stages which involve the drug going out?

A

Metabolism
Excretion

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5
Q

What mneumonic can be used to remember the 4 stages of the lifecycle of a drug?

A

ADME

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6
Q

What are the 2 classes of drug administration?

A

Enteral
Paraenteral

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7
Q

What is enteral drug administration?

A

When the drug is directly administered into the GI tract

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8
Q

What are the 3 methods of enteral drug administration?

A

Oral
Sublingual
Rectal

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9
Q

What is paraenteral drug administration?

A

Delivery via all other routes that are not the GI tract

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10
Q

What are some examples of paraenteral drug administration?

A

Intravenous
Subcutaneous
Intramuscular
Transdermal
Inhalation
Intranasal

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11
Q

What is the pneumonic to remember some drug administration routes?

A

Oi It is Sir

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12
Q

What does the mneumonic for remembering drug administration routes stand for?

A

Oi It Is Sir

Oral
Intravenous

Intramuscular
Transdermal

Intra -nasal
Subcutaneous

Sublingual
Inhalation
Rectal

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13
Q

What is the main site of drug absorption in the body?

A

Small intestine

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14
Q

Why is the stomach not an ideal target for drugs?

A

Has a thick mucus which acts as a barrier to drug absorption

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15
Q

How does the pH of the small intestine compare to the stomach?

A

Small intestine is much more weakly acidic (pH 6-7)

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16
Q

How is surface are of the small intestine for absorption maximised?

A

Villi
Microvilli on villi

Plica circularis (numerous folds of mucous membrane)

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17
Q

What are the 3 methods by which drugs can be absorbed into the body?

A

Passive diffusion
Facilitated diffusion
Secondary active transport

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18
Q

What type of drugs are absorbed by passive diffusion?

A

Lipophilic drugs like steroids
Weak acids and weak bases

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19
Q

What type of dissocation does a weak acid or base do?

A

Partial dissociation (not full)

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20
Q

What is an example of an anti-epileptic drug (weak acid)?

A

Valproate

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21
Q

What is the typical transit time of drug absorption in the small intestine?

A

Between 3-5 hrs

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22
Q

Will a drug be able to pass through a membrane if it’s charged or uncharged?

A

Pass through more readily when uncharged

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23
Q

Will a weakly acid drug pass through a membrane more easily if a higher proportion of it is Protonated or un-Protonated?

A

More Protonated = more easily absorbed due to it not being charged

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24
Q

What process must molecules with a net charge undergo in order too be absorbed across GI epithelia?

A

Facilitied diffusion (Solute Carrier (SLC) transport)

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25
Where are SLC 22 family like OATs and OCTss highly expressed?
GI epithelia Hepatic epithelia Renal epithelia
26
What is the general process of secondary active SCL transport across on OAT or OCT?
Transport driven by pre-existing electrochemical gradient drives against electrochemical gradient across GI epithelial membrane
27
What are some examples of negatively charged drugs that cross the GI epithelia via SLC transport?
Prozac/Fluoxetine Penicillins
28
What is Fluoxetine/Prozac co-transported with? What type of drug is it?
Co-transported with Na+ (drug is -Ve) Is an SSRI antidepressant
29
What does a SSRI antidepressant stand for?
Selective serotonin re up take inhibitor
30
What are penicillins co-transported with via secondary active SLC transport?
H+
31
What Physicochemical factors affect drug absorption?
GI length or surface Drug lipophilicty Density of SLC 22 OAT/OCT expression in GI
32
What GI Physiological factors affect drug absorption?
Blood flow (higher post meal) GI motility (slow post meal) Food/pH
33
What is first pass metabolism?
When the drugs begin to get metabolised/denatured before it gets absorbed
34
Which parts of the body does first metabolism occur?
GI (gut lumen and gut wall) Liver
35
What are the different types of Phase Enzymes?
Phase I Enzymes Phase II Enzymes
36
What is an example of Phase I Enzymes?
Cytochrome P450s
37
What is an example of Phase II enzymes?
Conjugating enzymes
38
Where are the majority of Phase I and II enzymes?
Liver
39
How does first pass metabolism affect therapeutic potential of a drug?
The more that a drug gets metabolise, the less of the drug that will actually get absorbed
40
What is Bioavailability?
The fraction of a defined dosewhich reaches its way into a specific body compartment
41
What is the most common reference body compartment for bioavailability?
CVS circulation
42
What is meant by the IV bolus = 100% for CVS compartment bioavailability?
No physical/metabolic barriers to overcome
43
What is intravenous bioavailability commonly compared with?
Oral bioavailability (O)/(IV)
44
What is the first stage of how drugs journey through the body?
Bulk flow Diffusion
45
What is bulk flow of a drug?
Large distance travelled by the drug via the arteries to the capillaries
46
What are some potential barriers to diffusion?
Certain interactions of substances with the drug may prevent diffusion Area may not be permeable
47
What are the 3 different types of capillaries with varying permeability?
Continous Fenestrated Sinusoid
48
What endogenous transporters do capillary membranes express?
OATs OCTs
49
Where are continuous capillaries typically found?
CNS (Blood Brain Barrier)) PNS Cochlea Muscle Skin Fat
50
Where are fenestrated capillaries typically found?
Intestine Endocrine/exocrine Kidney Glomeruli
51
Where are sinusoid capillaries typically found?
Liver Bone marrow Spleen Lymph
52
Compare lipophilic and hydrophiliic drugs ability to cross membrane barriers:
Lipophilic = freely move across membrane barriers Hydrophilic = can journey across membrane barriers dependant on factors for Absorption: Capillary permeability Drug pKa + local pH Presents of OATs/OCTs
53
What is an example a plasma protein which a drug may bind to?
Albumin
54
Can a drug bind to its target site when bound to a tissue protein?
No Drug must be dissociated from the plasma/tissue protein
55
How may multiple drugs affect there binding to tissue proteins?
2 drugs might bind to the same site on albumin so there may be competition for binding site affecting free plasma concentration of the drug
56
What are the 3 main body fluid compartments in the body?
Plasma Extracellular water Total body water
57
How much total body water in the average 70kg male?
42 litres
58
How does a drug move from between the 3 body fluid compartments?
Plasma —> Interstitial fluid —> Intracellular
59
When increasing penetration by a drug into interstitial and intracellular fluid compartments, how does this affect: Plasma drug concentration? Vd?
Decreasing Plasma Drug Concentration Increasing Vd
60
What is Vd?
Apparent Volume of Distribution It summarises the movement of drug from plasma —> interstitial —> intracellular compartment It is referenced to plasma concentration
61
What does a small Vd value for a drug indicate?
Less penetration of Interstitial/Intracellular fluid compartment
62
What does a Larger Vd value indicate?
Greater penetration of interstitial/intracellular fluid compartment
63
What are the units for Apparent Volume of Distribution (Vd)?
Litres (assuming the standard 70kg male)
64
What can affect Vd?
Changes in regional blood flow Hypoalbunimea - affecting protein binding Drug interactions Pregnancy Cancer patients Anaesthetics

Y1 - ICPP (23 decks)

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