19. Pharmacokinetics 1

Question 1

What does ADME stand for?

Answer 1

Absorption
Distribution
Metabolism
Elimination

Question 2

What are the 2 subtypes of drug administration and give examples?

Answer 2

Enteral (via GI tract) - oral, sublingual, rectal

Parenteral (not via GI tract) - intravenous, subcutaneous, intramuscular

Question 3

What is the typical transit time through the small intestine?

Answer 3

3-5 hrs

Question 4

What are the 4 ways drugs are absorbed?

Answer 4

Passive diffusion
Facilitated diffusion
Primary/secondary active transport (mainly secondary)
Pinocytosis

Question 5

What kind of drugs use passive diffusion?

Answer 5

Lipophilic drugs and weak acids/bases

Diffuse down concentration gradient into GI capillaries

Question 6

What are SLC?

Answer 6

Solute carrier transport - facilitated diffusion
Molecules with charge within GI pH range can be carried across GI epithelia
Uses electrochemical gradient

Question 7

What are the 2 types of SLC?

Answer 7

OAT - organic anion transporters
OCT - organic cation transporters
Highly expressed in GI, hepatic and renal epithelia

Question 8

What is secondary active transport?

Answer 8

SLC can enable drug transport in GI by secondary active transport
It means ATP is not used, ions such as Na+ and H+ used instead
E.g. penicillin, Prozac

Question 9

What are the physio chemical factors affecting drug absorption?

Answer 9

GI length/SA
Drug lipophilicity
Density of SLC expression in GI

Question 10

What are the GI physiology factors affecting drug absorption?

Answer 10

Blood flow - increase post meal, drastically reduce shock/anxiety exercise
GI motility - slow post meal, rapid with severe diarrhoea
Food - can reduce or increase uptake
pH - low pH destroys some drugs

Question 11

What are the first pass metabolism by GI and liver factors that affect drug absorption?

Answer 11

Gut lumen - enzymes can denature some drugs
Gut wall/liver - some drugs metabolised by two major enzyme groups (phase I and II)
Much larger expression of phase I and II enzymes in liver
Reduces availability of drug reaching systemic circulation

Question 12

What is bioavailability?

Answer 12

Fraction of a defined dose which reaches its way into a specific body compartment
CVS (circulation) is most common reference compartment

Question 13

What is the first stage of drug distribution?

Answer 13

Bulk flow - rage distance via arteries to capillaries
Diffusion - capillaries to interstitial fluid to cell membranes to targets
Barriers to diffusion - interactions/local permeability/non-target binding

Question 14

Where are continuous capillaries mainly found?

Answer 14

CNS
Muscle
Skin
Fat

Question 15

Where are fenestrated capillaries found?

Answer 15

Intestine
Endocrine/exocrine
Kidney
Glomeruli

Question 16

Where are sinusoid capillaries found?

Answer 16

Liver
Bone marrow
Spleen
Lymph

Question 17

Give 2 examples of drugs binding to proteins in the blood

Answer 17

Albumin - globulins

Lipoproteins - acid glycoproteins

Question 18

What is a dynamic reservoir?

Answer 18

When plasma/tissue protein (e.g. albumin) is bound to a drug

Question 19

Where does protein binding occur?

Answer 19

Plasma, interstitial fluid, intracellular fluid

Question 20

What does increasing penetration by drug into interstitial and intracellular fluid compartments lead to?

Answer 20

Decreases plasma drug concentration

Increases Vd

Question 21

What is Vd?

Answer 21

Apparent volume of distribution

Summarises movement out of plasma to interstitial to intracellular compartment

Question 22

What does a smaller Vd value mean?

Answer 22

Less penetration of interstitial/intracellular fluid compartment

Question 23

What are the units for Vd?

Answer 23

Litres or litres/kg

Question 24

How can Vd be affected?

Answer 24

Changes in regional blood flow
Drug interactions
Renal failure
Pregnancy
Paediatrics
Cancer patients
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