Introduction to Pharmacokinetics (ADME)

Question 1

Define pharmacokinetics.

Answer 1

Pharmacokinetics is essentially “what the body does to the drug”.
It describes the movement of the drug throughout the body - Absorption, Distribution, Metabolism and Excretion.

Question 2

Define pharmacodynamics.

Answer 2

Pharmacodynamics is essentially what the drug does to the body.
It involves the relationship between concentration of the drug at the site of action and the therapeutic effects (pharmacological response).

Question 3

Define “safe and effective” in relation to medication.

Answer 3

For safety to be imminent in a drug there must be a balance between safety and efficacy.
It is also important that the therapeutic index is identified.
When required, risk assessments and rational dosing regimens should be considered.

Question 4

Define therapeutic index.

Answer 4

This is the ratio between the largest non-toxic dose and the minimum effective dose.
When these values are close together - the drug has a narrow therapeutic index.

Question 5

Describe, in general terms, absorption of drugs.

Answer 5

Absorption refers to the transfer of drugs from their sire of administration to the blood.
This is dependent on
-Their route of administration (e.g. IV administration does not partake in absorption).
-Their chemical and physical properties.

Question 6

Define biophase

Answer 6

This is the effect site of the drug (the physical region in which the drug site is located).

Question 7

Define bioavailability

Answer 7

The extent and rate at which the drug reaches its site of action - systemic circulation plasma compartment).

Question 8

Describe, in general terms, the distribution of drugs.

Answer 8

The distribution and transport of drugs to tissues depends on:
- Ease of filtration
- Lipophilicity
- Extent of ionisation - ion trapping (pH)
- Transport mechanisms; active transport; endocytosis; facilitated diffusion.
- Perfusion (blood supply)

Question 9

Describe, in general terms, the metabolism of drugs.

Answer 9

Metabolism aka Biotransformation is used to facilitate the excretion of drugs.
This occurs primarily in the liver, where the drugs are converted to more water soluble forms to be secreted by the kidneys or bile.
2 phases: Phase 1 & Phase 2

Question 10

Describe, in general terms, the elimination of drugs.

Answer 10

Elimination is a protective mechanism - the body is trying to limit its exposure to xenobiotics (alien molecules).
The liver and kidneys are primary sites of elimination within the body.

Question 11

List the main routes of administration.

Answer 11

Intravenous
Oral
Subcutaneous
Intramuscular
Other GI
Nasal
Inhalation
Transdermal

Question 12

Define quantitative aspect

Answer 12

This is how many molecules make it into the plasma.

Question 13

Define rate aspect.

Answer 13

This is how quickly drugs make it to the plasma and leave (distribution : elimination).

Question 14

Describe the importance of the liver in drug elimination.

Answer 14

The liver is the main site of metabolism in the body.
The Cytochrome P450 enzyme family of enzymes in the liver catalyse reactions that prepare the (lipophilic) drug for Phase 2 of metabolism - by making them more polar.

The health of the liver is important for the rate of excretion.

Question 15

Describe the importance of the liver in drug toxicity.

Answer 15

The health of the liver is important in managing toxicity.
Liver disease means there is an increased risk of toxicity.
During metabolism in the liver, the CYP450 enzymes create metabolites - some may be toxic.

Question 16

Describe the importance of the kidney in drug elimination.

Answer 16

The kidneys are another primary site of drug excretion, particularly for more water-soluble drugs.
The kidney removes drugs from the bloodstream and eliminates them in the urine.
There are 3 processes involved in this.

Question 17

Describe the importance of the kidney in drug toxicity.

Answer 17

The kidneys work to prevent drug toxicity, but are susceptible to it for many reasons:
- High blood flow
- Concentration of drugs
-etc.
If the kidneys are faulty and are excreting slower, then this could cause accumulation of drugs at potentially toxic levels - (possibly leading to drug-induced nephrotoxicity).