Pharmacokinetics 3 (Elimination)

Question 1

drug needs to be _____ polar to be excreted out successfully

Answer 1

MORE

Question 2

GI tract draining all of absorbing material into

Answer 2

liver

Question 3

What is the advantage of GI tract draining all of absorbing material into liver

Answer 3

breaks bigger molecule into smaller molecules. then if molecules needs to go back into GI tract (e.g. if still too big).

Question 4

hepatic artery > liver >

Answer 4

hepatic vein

Question 5

s the name of the process when molecules goes back and fourth from GI to liver

Answer 5

hendro-hepatic recirculation

Question 6

Mesenteric artery > liver >

Answer 6

hepatic portal vein

Question 7

what is the most common site of action for drug metabolism

Answer 7

liver

Question 8

can lipophilic drug be polar?

Answer 8

no

Question 9

later on drug will be introduced in liver to make drug MORE

Answer 9

soluble and able to travel through liver

Question 10

gut > liver (> kidney) >

Answer 10

site of action

Question 11

Which enzymes facilitate the chemical process to make drugs more water soluble?

Answer 11

DMEs
Cytochrome P450
Alcohol dehydrogenase (ethanol)
Esterases

Question 12

What are the two step process of drug metabolism?

Answer 12

Phase I = oxidation, reduction, hydrolysis
Phase II = conjugation

Question 13

Phase 1 is catalysed by Cytochrome P450 (Haem-containing mono-oxygenase enzymes)

Answer 13

74 CYP gene families and multiple substrates
CYPs evolved to deal with environmental/nutritional toxins (e.g. plant alkaloids)
Some drugs or foods can increase the expression of specific CYPs (phenytoin, broccoli)
Some drugs or foods can inhibit the CYPs activity (grape fruit juice)
Metabolites could be more active than the drug (pro drugs)

Question 14

What does phase 1 require?

Answer 14

oxygen and NADPH

Question 15

Phase II is conjugation=

Answer 15

ADDITION of polar groups
(convert drugs more water soluble, that could most readily excreted by kidney)

Question 16

examples of polar groups that can be added to drugs

Answer 16

OH (glucuronyl, methyl, sulphate)
NH2 (glucuronyl, acetyl)
COOH (glucuronyl, glycine)

Question 17

the most common phase II catalysis is by…

Answer 17

Uridine-disphospho-glucuronyl transferases (UGTs)

Question 18

Drug Excretion/Elimination

Answer 18

Water soluble molecules:
Urinary system (Kidneys)- Major site of drug eliminations (3 stages)

Question 19

passive or not passive = glomerular filtration?

Answer 19

removal of [free] drugs

Question 20

Tubular secretion = what kind of transport?

Answer 20

active transport

Question 21

Reabsorption depends on _____ _______ & ___

Answer 21

lipid solubility & pH

Question 22

Biliary system (entero-hepatic recirculation)

Answer 22

Large molecule

Question 23

Describe the process of Drug Excretion/Elimination?

Answer 23

Active transport of large molecule into bile (glucuronides)
Excreted into gut
Redistribution of molecules into liver
Reabsorption can be blocked by activated charcoal (e.g. treatment method for drug poisoning)

Question 24

Drug in blood continually changes with time because of

Answer 24

ADME

Question 25

drug {dose} intravenous >

Answer 25

kelimination (Kel)

Question 26

higher absorbed drug

Answer 26

eliminated at a higher rate

Question 27

intravenously = advantage

Answer 27

drug is available in plasma immediately - 100% absorbed

Question 28

How to find out elimination rate?

Answer 28

[Drug]t = [Drug]0 e^-k el t

Question 29

Elimination measures (Half-life)

Answer 29

Half-life (t1/2) = time taken to reduce the plasma drug concentration by half from the administered [drug] or a time at which 50% of drug eliminated from plasma

Question 30

Half-life is calculated from the exponential curve (linear plot)

Answer 30

Slope of the log (best linear fit) = Kel

Question 31

Half-life is calculated from the exponential curve (linear plot)

Answer 31

Slope of the log (best linear fit) = Kel

Question 32

Elimination measures (Plasma clearance, CLp)

Answer 32

CLp is the volume of plasma (ml) that is cleared of drug in unit of time (min): e.g. xy ml/min

Question 33

CLp = CLliver + CLrenal

Answer 33

Interrelationships of measures (Vd, Kel, CLp and t1/2)

Question 34

kel = CLp / Vd

Answer 34

t1/2 = 0.693 / kel = 0.693d / CL p

Question 35

Summary of drug excretion/ Elimination:

Answer 35

Drugs are metabolised to more water soluble

Phase I process is catalysed by CytochromeP450 and Phase II process is by UDP glucuronyl transferases

The water soluble drug metabolites are excreted via kidneys and large molecules are processed through biliary (entero-hepatic recirculation process).

Renal excretion depends on filtration and active transport

Lipid solubility modulate the kinetics of drug reabsorption

Drug elimination (most) follow first order kinetics.

Half-life and plasma clearance rate are commonly used to determine drug elimination kinetics

Volume of distribution, plasma clearance and half-life are interrelated

Question 36

BNF pharmacokinetics profile

Answer 36

if lipophilic drug is higher, distribution?

Question 37

curve on graph tells you the

Answer 37

RATE of elimination