Pharmacology and the liver

Question 1

what is metabolism?

Answer 1

process by which enzymes chemically convert a drug into a less active more polar form that is more readily excreted from the body

Question 2

understand this drug overview

Question 2

what is the minimum effective concentration MEC of a drug?

Answer 2

minimum concentration in the plasma that a drug must reach to achieve an effect

Question 3

what is the minimum tolerated concentration MTC of a drug?

Answer 3

concentration before significant unwanted side effects occur

Question 4

what is the therapeutic window of a drug?

Answer 4

MTC - MEC

Question 5

what does a larger therapeutic window for a drug tell you about its safety?

Answer 5

safer

Question 6

what is the therapeutic ratio?

Answer 6

MTC/MEC

Question 7

what does a higher therapeutic ratio mean for a drugs safety?

Answer 7

higher the ratio the safer the drug

Question 8

what is steady state?

Answer 8

rate of drug administration = rate of drug elimination

Question 9

put these into an equation
Steady state plasma conc. , Cl , maintenance dose rate

Answer 9

Steady state plasma conc. = maintenance dose rate / Cl

Question 10

what is Cl?

Answer 10

the sum of all clearance processes

Question 11

what is the equation to calculate the rate of elimination at a steady state?

Answer 11

steady state plasma conc. x Cl

Question 12

what is the equation to calculate the rate of administration at a steady state?

Answer 12

steady state plasma conc. x Cl

Question 13

what does it mean if a drug exhibits first order kinetics?

Answer 13

the steady state plasma conc. is linearly related to infusion rate

Question 14

The time to reach steady state plasma conc. is determined by what?

Answer 14

half life

Question 15

Steady state plasma conc. is reached in approximately how many half life’s ?

Answer 15

5

Question 16

what is a leading dose?

Answer 16

initial higher dose given at the beginning of course treatment before stepping down to a lower maintenence dose

Question 17

what is the aim of a leading dose?

Answer 17

to get the patient to reach a steady state quicker

Question 18

what is the main organ of metabolism?

Answer 18

liver

Question 19

what is metabolism in the liver called?

Answer 19

hepatic metabolism

Question 20

what is first pass metabolism?

Answer 20

when a drugs concentration is reduced drastically at a specific site e.g. liver before reaching circulation

Question 21

what are 2 important effects of metabolism?

Answer 21

drug is more hydrophilic so quicker excretion from kidney

metabolites are usually more inactive than parent drug

Question 22

what are prodrugs?

Answer 22

drugs that are inactive until metabolised in the body to active drug

Question 23

liver metabolism involves what 2 reactions?

Answer 23

phase 1 reactions

phase 2 reactions

Question 24

what happens in phase 1 reactions in liver metabolism?

Answer 24

Transform drug to a more polar metabolite by introducing or unmasking a functional group e.g. -OH
Oxidations are most common using enzymes called cytochrome P450s with low substrate specificity

Question 25

what are phase 2 reactions in the liver used for?

Answer 25

For drugs/metabolites that are not polar enough to be excreted quickly by the kidneys

Question 26

what happens in phase 2 reactions in liver metabolism?

Answer 26

Makes them less active and more polar by conjugating with an endogenous substance

Question 27

link metabolism to drug toxicity

Answer 27

occasionally reactive products of drug metabolites are toxic to various organs e.g. paracetamol