Pharmacokinetics (flipped lecture) 2

Question 1

What are the two phases of drug metabolism in the body? (2)

Answer 1

Two biochemical reactions

-Phase 1 catabolic reactions
can produce more ‘reactive’ compound

-Phase 2 synthetic (anabolic) reactions, involve conjugation(coupling) to produce inactive product (Liver)

Question 2

Where does drug metabolism take place?

Answer 2

The liver

Question 3

When do ‘pro-drugs’ become activated?

Answer 3

After being metabolised

Question 4

What kind of enzymes are present in the liver and involved in metabolism?

Answer 4

‘Microsomal’ enzymes (intracellular)

Question 5

What is the biggest family of enzymes involved in the metabolism of drugs?

Answer 5

Cytochrome P450

Question 6

What are the two routes to the liver (where metabolism takes place)? (2)

Answer 6

portal system and plasma

Question 7

How can some drugs be excreted without metabolism?

Answer 7

They combine with bile and get excreted

Question 8

What happens to aspirin after phase 1 of metabolism?

Answer 8

After phase 1 become more reactive and now has altered structure so is larger and no longer bond to targets

Question 9

What could enzyme induction (results in increased activity of enzyme) do?

Answer 9

Increase drug toxicity and carcinogenicity of product of phase 1 reaction (eg. Paracetamol) are toxic

Question 10

How does increased drug metabolism affect plasma concentration of drug?

Answer 10

Lowers plasma concentration

Question 11

What are the routes of exertion of drugs in the body? (3)

Answer 11

-Renal excretion
-Gi excretion
-Lung excretion

Question 12

What are the 3 routes of renal (kidney) excretion? (3)
And what types of drugs use each route? (3)

Answer 12

-Glomerular Filtration (most drugs not bones that are bound to plasma)
-Active tubular secretion (weak acids and bases)
-Passive diffision (lipid soluble drugs)

Question 13

What is the time course of mono-exponential delay in drug concentration in body determined by rate of? (2)

Answer 13

-Rate of metabolism
-Rate of excretion

Question 14

What is type of decay does drug concentration in body follow?

Answer 14

mono-exponential decay

Question 15

Describe the single compartment model of drug concentration in body over time? (3)

Answer 15

-In such a situation the concentration of the drug in the plasma follows ‘first-order’ kinetics
-Rate of elimination is directly proportional to drug concentration
-Simple exponential decay, plasma half life is the same irrespective of drug concentration and can be easily calculated and only dependent on the rate of elimination (a constant).

Question 16

Describe the continuous model of drug concentration in body over time? (2)

Answer 16

Continuous infusion of drug

-Drug concentration in plasma increases overtime to a steady state level where rate of infusion is matched by rate of elimination.

-With repeated doses, get similar behaviour ie. reaches steady state at roughly the same time, but shows more fluctuations in getting there

(Steady state is usually reached in ~3.5 half lives of the drug)

Question 17

What kind of kinetics do drugs such as ethanol, phenytoin (anticonvulsant) and salicylate (aspirin metabolite) show?

Answer 17

zero order kinetics

(Get linear relationship where drug is eliminated at a constant rate independent of concentration)

Question 18

What is the maximum rate for zero order kinetics limited by?

Answer 18

So maximum rate at which drug can be administered should be limited to maximum rate at which it can be eliminated, otherwise start to get sharp increases in plasma levels…unpredicatable concentrations, behaviour and pharmacological consequences.

Question 19

Therapeutic window?

Answer 19

Just below dangerous level, enough to still produce effect