Pharmacokinetics

Question 1

Give some examples of site of administration of drugs.

Answer 1

Focal (eye, skin, inhalation)
Systemic - enteral (sublingual, oral, rectal)
- parenteral (subcutaneous, intramuscular, IV)

Question 2

Why is the site of administration important when prescribing drugs?

Answer 2

Ease, practicality, localisation
Allows less systemic absorption and less off-target effects, as well as increasing the liklihood of proper use by the patient.

Question 3

What is oral bioavailability

Answer 3

The proportion of a dose which reaches the systemic circulation in an unchanged form.

Question 4

What does the amount of drug available after oral administration depend on?

Answer 4

Gut absorption, altered by food/disease.

First pass metabolism

Question 5

What does the rate of availability of a drug after oral administration depend on?

Answer 5

Pharmaceutical factors and gut absorption.

Question 6

How do you calculate bioavailability (%)?

Answer 6

AUC oral/AUC injected

AUC is the area underneath a plasma concentration curve.

Question 7

What is the therapeutic ratio for a drug?

Answer 7

The maximum tolerated dose over the minimum effective dose.

Question 8

What is first pass metabolism

Answer 8

The blood from the gut passes through the portal system so is delivered to the liver before systemic circulation, greatly reducing the concentration of the drug reaching the body.

Question 9

How can first pass metabolism be avoided?

Answer 9

Parenteral route (e.g. subcutaneous/IV)
Sublingual or rectal route

Question 10

What is volume of distribution for a drug?

Answer 10

The theoretical volume into which a drug has been distributed assuming this has occurred instantaneously.

amount given/plasma concentration at 0s

Question 11

The free level of a drug is what exerts an effect. When is this especially important for a drug? (i.e. a drug with specific properties)

Answer 11

If it is highly bound to albumin, has a small volume of distribution, has a low therapeutic index.

Question 12

Describe the difference between an object drug and a precipitant drug.

Answer 12

Object - class I. Used at a dose much lower than the number of albumin binding sites.

Precipitant - class II. Used at a dose much greater than the available binding sites.

Question 13

Give an example of an object drug and it’s corresponding precipitant drug.

Answer 13

Warfarin - sulphonamides, aspirin, phenytoin

Tolbutamide - sulphonamides, aspirin

Phenytoin - valproate

Question 14

What is first order kinetics when referring to a drug?

Answer 14

When the rate of decline of plasma drug level is proportional to the level of the drug. It’s half-life can be defined.

Question 15

What is zero order kinetics when referring to a drug?

Answer 15

When the rate of decline of a plasma drug level is constant.

Question 16

Where does metabolism and excretion of drugs take place?

Answer 16

Liver - metabolism

Kidney - excretion

Question 17

Describe phase I of liver metabolism.

Answer 17

Carried out by mixed function oxidases to oxidise, reduce or hydrolyse drugs.
- NADPH cytochrome P450 reductase
- cytochrome P450 in liver microsomes
They have low substrate specificity and have an affinity for lipid-soluble drugs.

The enzymes are inducible and inhabitable (competitive, non-competitive).

Question 18

Give an example of an enzyme inducer in the liver and the drug that it affects.

Answer 18

Phenobarbitone - warfarin, phenytoin

Rifampin - oral contraceptive

Cigarettes - theophylline

Question 19

Give an example of an enzyme inhibitor in the liver and the drug that it affects.

Answer 19

Cimetidine - warfarin, diazepam

Question 20

Give a drug which interacts with warfarin and how it does so.

Answer 20

Alcohol - inhibits metabolism
Aspirin/sulphonamides/phenytoin - displace from plasma proteins
Broad spectrum antibiotics - decrease vitamin K synthesis by bacteria in the gut
Aspirin - reduces platelet function
Barbituates/rifampicin - induce liver metabolism enzyme

Question 21

In liver disease, what drugs must you be careful administering?

Answer 21

Those with a low therapeutic ratio

Question 22

What feature of urine will affect how much of a drug is excreted?

Answer 22

pH

Question 23

For a weakly acidic drug, what effect will increasing alkalinity of the urine have on its excretion?

Answer 23

Decreases excretion because it ionises the drug, decreasing tubular absorption as the charged drug stays in the lumen of the blood vessel.

Question 24

For a weakly basic drug, what effect will increasing acidity of the urine have on its excretion?

Answer 24

Inceases excretion

Question 25

In renal disease, what effect does this have on the maintenance dose and loading dose of a drug?

Answer 25

Maintenance drug must be reduced

Loading dose remains unchanged unless the volume of distribution changes.