11 - Drugs

Question 1

What are xenobiotics?

Answer 1

A foreign chemical or substance

Question 2

What is the consequence of them being lipophillic?

Answer 2

Readily cross biological membranes (passive diffusion)
Absorbed with dietary fats
and can accumulate in adipose tissue

Question 3

What are the 4 principle stages in processing a foreign chemical?

Answer 3

Absorption, Distribution, Metabolism, Excretion

Question 4

What limits some drugs from being taken orally?

Answer 4

Food interactions
interactions with physiology of digestive tract
Rapid metabolism

Question 5

Why should tetracycline be taken several hours between eating, and never with milk?

Answer 5

Reacts with components in food, especially polyvalent cations like Mg2+ and Ca2+ found in milk, forming insoluble complexes and reducing absorption by 50-90%

Question 6

What’s a derivative of tetracyline, often used as a more stable alternative with increased availability?

Answer 6

Doxycycline

Question 7

In humans, how many families and subfamilies are there of cytochrome P450
Where are these enzymes mostly expressed?

Answer 7

18 families and 43 subfamilies

Mostly expressed in hapatic microsomes

Question 8

CYP450 enzymes react with xenobiotics to alter their chemical structure. What can the result be? (4)

Answer 8

Increased activity
Reduced activity
Toxic properties

Question 9

Why are the products of CYP450 enzyme reactions usually attached to another compound?

Answer 9

Makes the xenobiotic more water soluble

Makes it more easily excreted

Question 10

What is the major route for xenobiotic excretion?

Answer 10

Urine

Question 11

What are the enzymes that metabolise diazepam?

Answer 11

CYP3A4

CYP2C19

Question 12

What are some possible consequences of diet:drug interactions?

Answer 12

• Faster clearance from body
• Increased rate of toxic product formation
• Decreased rate of metabolism
• increased rate of toxic product clearance

Question 13

How does St Johns Wort interfere with drug metabolism? (incl active ingredient, what it inhibits, etc..)

Answer 13

Active ingredient Hyperforin increases expression of CYP3A4

Results in faster clearance of theraputic drugs metabolised by this enzyme, including statins and the contraceptive pill

Question 14

What is the active ingredient in grapefruit and how does it interfere with drug metabolism?

Answer 14

Bergamottin is a potent inhibitor or CYP3A4
Effect is largely in intestinal epithelial cells
Reduction in rate of metabolism of drug acted upon by this enzyme
Incl. statins, blood pressure and anti-diabetic drugs and antihistamines

Question 15

What vitamin is associated with metabolism by CYP450 enzymes, out-competing warfarin

Answer 15

Vitamin K

Question 16

What compounds do charred meats contain, which could be metabolised into carcinogens?

Answer 16

Hetrocyclic amines and polycyclic aromatics

Question 17

Why should smokers eat brussels sprouts or watercress?

Answer 17

High in phenyl isothiocynate, which blocks CYP2A1 and 2E1, which are involved in activation of tobacco-related carcinogens

Question 18

Monoamine oxidase inhibitors can lead to an increase in tyramine levels. What is tyramine usually metabolised into? What are the benefits and potential side effect?

Answer 18

Metabolised to monoamine oxidase
Treatment of depression, anxiety, mood
Can lead to hypertension

Question 19

What are the four genetic categories for metabolism types?

Answer 19

Ultra-rapid metaboliser
Extensive metaboliser (normal)
Intermediate metaboliser
Poor metaboliser

Question 20

What is 5-10% of codeine metabolised into? What is the enzyme that metabolises it?

Answer 20

Morphine

By CYP2D6