drug metabolism

Question 1

the first organ that oral drugs will encounter to be metabolised is

Answer 1

liver

Question 2

what is the key role of the liver

Answer 2

protect the body from toxins (esp drugs/xenobiotics)

Question 3

list the course of a drug as it is taken in orally

Answer 3

1. GI = initial concentration
2. portal system
3. liver
4. either in blood (systemic concentration) or metabolised and excreted

if you want a certain concentration of systemic circ you need to provide repeat dosage

initial concentration>/= systemic concentration

Question 4

what is pre-systemic metabolism

Answer 4

metabolism prior to entering the systemic circulation
- first pass: when drugs enter the liver and get metabolised immediately after absorption from GIT
- drugs with high first pass metabolism require higher oral doses to achieve therapeutic effects

Question 5

hydrophilic/polar drugs are secreted via:

Answer 5

main routes = kidneys, hepatobiliary system, lungs
secondary: milk, sweat

Question 6

if a drug is normally excreted in the kidneys but kidney failure occurs, how does the drug get out

Answer 6

excretion not a fixed process, if renal failure occurs drug will take a different route out (fecal etc)

Question 7

describe enterohepatic circulation

Answer 7

in liver, drugs will be recollected with bile = recirculation. part gets excreted, part recirculates in bile

Question 8

how do lipophilic/nonpolar drugs get excreted

Answer 8

• non-polar drugs have a tendency to accumulate in areas where water is excluded (fat)
• therefore these chemicals are a lot more difficult to excrete in the urine (dont like water)
• liver must convert lipophilic drugs into water soluble form
• liver uses enzyme (CYP450) to convert into water soluble form

Question 9

what is CYP450 and how does it work

Answer 9

cytochrome P 450
- metabolises lipophilic drugs into hydrophilic form

Question 10

if the liver is trying to convert a lipophilic drug into a hydrophilic drug, but CYP450 isnt adequate, what will it do

Answer 10

drug transformation uses a 2 phase reaction.
- phase 1 = catabolic through CYP enzymes = oxidation, reduction or hydrolysis
- if drug derivative from phase 1 is not enough to be excreted have phase 2
- phase 2 = anabolic leads to synthetic conjugation
- excretion possible

Question 11

is there only one CYP

Answer 11

no there are multiple they all do different things
- oxidative
- reductive
- hydrolytive

make drug derivatives

Question 12

what happens if a drug is not metabolized properly

Answer 12

remains active and will become toxic as it accumulates in the body

Question 13

why do patients respond differently to drugs

Answer 13

• different genes that code for different metabolism of a drug
• inter species differences of CYP enzyme activity
• some CYP enzymes may be expressed in certain species compared to others (why not all animals can be given the same drugs)

Question 14

describe how drug interactions occur

Answer 14

Enzyme Inhibition: One drug can inhibit the activity of a CYP enzyme, leading to reduced metabolism and increased plasma levels of another drug metabolized by the same enzyme, potentially causing toxicity.
Enzyme Induction: Conversely, a drug can induce the production of CYP enzymes, increasing the metabolism of co-administered drugs, which may reduce their efficacy.