Case 3 GI

Question 1

Describe the control of bile secretion

Answer 1

1) Bile acid dependent - after fat digestion, bile salts are reabsorbed via enterohepatic circulation - This leads to enhanced bile secretion 2) Bile acid independent - (stimulus H+) Secretin stimulates duct cells to produce watery HcO3 rich fluid - (stimulus fat) CCK stimulates contraction of gall bladder - vagus nerve increases bile flow during cephalic phase - CCK -

Question 2

What is bile made up of?

Answer 2

1) Bile salts 2) others Bilirubin Alkaline fluid Cholesterol Phopholipid

Question 3

Otline bilirubin metabolism

Answer 3

See case 3 week 2 notes

Question 4

What is the role of phase 1 reactions in drug metabolism?

Answer 4

1) functionalisation , introducing a reactive group on drug .. 2) makes more chemically reactive, and exposes chemically reactive group 3) activates therpeutic activity of prodrugs 4) has unwanted side effects

Question 5

Name and give examples of phase 1enzymes

Answer 5

CYTOCHROME P450 ENZYMES 1) CYP3A4 - involves in half of phase 1 metabolism 2) CYPIA2 - metabolises caffein and theophylline 3) CYP2E1 - metabolises alcohol 4) CYP1A1 - metabolises theophylline

Question 6

What is the advantage of having isoforms of CYP enzymes overlapping?

Answer 6

Useful in the event of enzyme dysfunction or depletion

Question 7

What is the role of phase 2 enzymes in drig metabolism?

Answer 7

1) deactivate 2) made water soluble - replaces pharmacophoric regions with sugar/sulphate group

Question 8

Give an example of a phase 2 enzyme, and some characteristics

Answer 8

UDP GLUCURONSYL TRANSFERASES 1) conjugates glucuronic acid to make drug/ metabolite water soluble 2) has broad substrate specificity

Question 9

Name two conditions associated with UDP GLUCURONSYL transferase enzyme, what occurs?

Answer 9

In these two condition UGT1A1 gene gets mutated/ defected 1) cirggler najjar syndrome - Lack of UDP G transferase , unable to conjugate bilirubin, so build up of toxic unconjugated bilirubin (become jaundiced) 2) Gilbert’s syndrome - decreased UDP G transferase, common and become slightly jaundice during increased RBS breakdown

Question 10

What is the disadvantage of metabolism? (Presystemic)

Answer 10

Metabolism done so efficiently that levels of drug are subtherapeutic when reaching circulation 1) and a larger dose would need to be given 2) unpredictable …

Question 11

What are the two types of drug interactions?

Answer 11

1- Induction: Drug A causes drug B to be metabolised by activating an enzyme

2- Inhibition: Drug A causes inhibition of cytochrome enzyme, thus drug B is not metabolised. Leading to drug B build up and thus, adverse side effects

Question 12

Give an example of induction drug interaction

Answer 12

St John’s wort and oral contraceptive pill

1. St John’s wort activate CYP3A4
2. CYP3A4 metabolises ethinylestradiol (oral contraceptive pill)
3. Ethinylestradiol becomes subtherpeutic

Question 13

Give an example of an inhibition drug interaction

Answer 13

Erythromycin and oral contraceptive pill

1. Erythromycin inhibits CYP3A4
2. CYP3A4 unable to metabolise ethinyloestradiol
3. ethinylostradiol builds up, causing adverse drug reactions

Question 14

Outline normal paracetamol metabolism

Question 15

Outline when happens during a paracetamol overdose