Lecture 20

Question 1

What is the purpose of phase. And phase 2 reactions in first pass metabolism?

Answer 1

Phase 1- make drugs more reactive (oxidation, hydrolysis etc)

Phase 2- make drugs more soluble for excretion in the kidney (form conjugates using glucuronide, glutathione etc)

Question 2

What is one problem of a drug with a high Vd?

Answer 2

Elimination is harder as little of the drug will be in the blood.

Question 3

What’s the name of drugs that are activated by phase 1 metabolism?

Answer 3

Pro drugs eg codeine to morphine

Question 4

Phase 1 metabolism?

Answer 4

Cytochrome p450 enzymes, low specificity, affinity for lipophilicity molecules. Aim to make them more reactive

Question 5

Cytochrome P450 enzymes?

Answer 5

Can be induced or inhibited by drug interactions.

Three super families

Question 6

Phase two enzymes?

Answer 6

Conjugation such as sulphation and glucoronidation to increase hydrophilicity and enhance renal elimination

Question 7

First order vs zero order kinetics?

Answer 7

First order more common and involves rate of elimination being proportional to drug level. Good for safety if too high a dose is given

Zero order shows a constant elimination rate and is more dangerous

Question 8

How can drug elimination kinetics change?

Answer 8

First order at low dose and zero order at high dose when enzymes saturated. Eg alcohol

Question 9

Give an example of a drug with zero order kinetics?

Answer 9

Alcohol, first order at first then zero order when Saturated

Question 10

When are drug interactions important when it comes to elimination?

Answer 10

Low therapeutic ratio

When drug working at minimum effective concentration eg contraceptive pill

When drug metabolism follows zero order kinetics

Question 11

What is drug clearance?

Answer 11

Rate of elimination of active drug from the body in ml/min

Question 12

What is drug half life?

Answer 12

Time for concentration of drug in body to reduce by half

Question 13

How many half lives to reach steady drug concentration in body?

Answer 13

Five half life’s

Question 14

Why is a bolus loading dose used?

Answer 14

To get to therapeutic concentration quickly and then use a maintenance dose

Question 15

How does pH of urine affect renal excretion?

Answer 15

Weak acids- acidic urine increases reabsorption (cooh can cross membrane)

Weak bases- acidic urine will decrease reabsorption (NH3+) charged

Question 16

Acids and bases?

Answer 16

Acid and hydrogen= uncharged

Base and hydrogen= charged

Question 17

Prescribing in renal disease?

Answer 17

If kidney excretion longer half life’s- lower maintenance dose of drug

Longer half lives mean longer time to reach steady state

Alter loading dose

Protein binding can be altered