Pharmacokinetics

Question 1

What are pharmacokinetics?

Answer 1

What the body does to a drug

Question 2

What are pharmacodynamics?

Answer 2

What the drug does to the body

Question 3

From a pharmacological perspective, what 4 factors should we consider about a drugs efficacy?

Answer 3

1. Pharmaceutical process. Is the drug getting to the patient?
2. Pharmacokinetic process: is the drug getting to the site of action?
3. Pharmacodynamic process: is the drug producing the desired effect?
4. Therapeutic process: is the pharmacological effect producing the desired therapeutic effect?

Question 4

What is the difference between focal and systemic sites of administration? give examples of each.

Answer 4

Focal - eyes, skin, inhalation etc
Systemic: enteral - sublingual, oral, rectal
Systemic: parental - subcut, intramuscular, intravenous, inhalation, transdermal

Question 5

What is meant by the term ‘oral bioavailability’?

Answer 5

the proportion of a dose given orally that reaches the systemic circulation in an unchanged form. It can be expressed as amount (depends on gut absorption and first pass) and rate (pharma factors and rate of gut absorption)

Question 6

How would you calculate a therapeutic ratio?

Answer 6

the maximum tolerated dose/ minimum effective dose

LD50/ ED50

Question 7

Explain LD50/ ED50

Answer 7

Lethal dose/ minimal effective dose = therapeutic dose

Question 8

What is first pass metabolism and how can we avoid it?

Answer 8

Blood from the gut reaches the liver from the portal system. Here, the liver can metabolise drugs before they enter the systemic circulation. This is known as the first pass. We can avoid this by using different routes of administration e.g. sublingual, subcut, IV etc.

Question 9

What is the volume of distribution?

Answer 9

The THEORETICAL volume at time 0, calculated by dividing dose given/ total plasma concentration

Question 10

Would a drug still be effective if protein binding interactions occurred?

Answer 10

No, it is the free level of a drug which exerts an effect, not the total level. These are important if a drug is highly bound to albumin (90%), the drug has a small volume of distribution, or if it has a low therapeutic index. An example of this is warfarin and tolbutamide.

Question 11

Define an Object (class I) drug and a Precipitant (class II) drug. How might they interact?

Answer 11

Object drug: used at a dose much LOWER than the number of available albumin binding sites.

Precipitant drug: used at a dose which is HIGHER than the number of available albumin binding sites.

If a patient is on an object drug which has taken up, say, 80% of albumin, then adding on a precipitant drug may compete for the albumin sites and create higher circulating levels of free object drug. This could become a toxic level.

Question 12

Explain Km and Vmax

Answer 12

Vmax: concentration of substrate which fills all of the binding sites on a population of enzymes, i.e. they have saturated the enzymes.

Km: The concentration of substrate which occupies half of the enzyme binding sites. If there is a strong attraction then fewer substrate molecules will be needed to achieve this. It therefore has high affinity.

Question 13

Explain first order and zero order kinetics.

Answer 13

First order: amount of drug given does not saturate the enzymes responsible for metabolising it. It is less than Km. This means that there will always be enzymes present to clear the drug, the rate of which will depend on drug concentrations. Therefore, you get a curve with predictable half lives.

Zero

Question 14

When is a loading dose required?

Answer 14

During drug administration, a steady state will be reached within 5 half-lives of that drug. If an immediate effect is necessary, then a loading dose is required.

Question 15

What are the two main ways a drug can be eliminated from the body?

Answer 15

Metabolism (liver)

Excretion (kidney)

Question 16

Explain how the liver eliminates drugs from the body

Answer 16

This occurs in II phases. Phase I is carried out by mixed function oxidases in the liver. These consist of cytochrome P450 reductases with low substrate affinity. They can be induced or inhibited and work by oxidation, reduction and hydrolysis.

Phase II occurs through conjugation with glucuronide, acetyl, methyl, sulphate.

Care must be taken with drugs that either inhibit or enhance the effects of other drugs.

Question 17

Explain how the kidney eliminates drugs from the body

Answer 17

Only the free unbound drug is filtered through glomerular tuft. Urine pH can determine how much of a drug is eliminated via this route. For weak acids, making the urine alkaline will ionise the drug and therefore keep it within the tubule lumen. For weak bases, acidic urine increases excretion.