Pharmacokinetics

Question 1

What is the acronym for remembering the pathway of journey of a drug through the body?

Answer 1

ADME

Absorption

Distribution

Metabolism

Excretion

Question 2

What is the full journey of a drug through the body?

Answer 2

1. Administration
2. Absorption
3. Distribution
4. Metabolism
5. Excretion
6. Voided

Question 3

Name eight methods of drug administration:

Answer 3

1. Dermal
2. Intramuscular
3. Subcutaneous
4. Intravenous
5. Intraperitoneal
6. Inhalation
7. Ingestion

Question 4

What are the two ways routes of administration can be differentiated?

Answer 4

Whether they are local or systemic

Whether they are enteral or parenteral

(Enteral = via the GI tract
Parenteral = everything but the GI tract)

Question 5

What are the two main ways drug molecules move around the body?

What does this mean for the characteristics of a drug?

Answer 5

Bulk-flow transfer e.g. in bloodstream

Diffusion over short distances

They have to be able to transverse both aqueous and lipid environments

Question 6

What are the four main ways a drug can move across a membrane?

Answer 6

Simple diffusion

Diffusion across aqueous pores (Needs to be very small)

Carrier mediated transport (using energy)

Pinocytosis

Question 7

What is the normal pH of a drug?

What does this mean for their polarity?

Answer 7

Most are either weak acids or weak bases

Therefore they exist in ionised (polar) and non-ionised (non-polar) forms depending on the surrounding pH

Question 8

How does drug polarity affect its ability to move across membranes?

Answer 8

Non-polar substances can freely dissolve in lipid domains so can diffuse across a membrane

Question 9

What is ion-trapping?

Use asprin as an example:

Answer 9

The pH of a body compartment will effect the ratio of ionised:un-ionised drug so in different compartments, the drug will be able to cross a membrane more-easily/difficultly

Aspirin is very unionised in the acidic GI-tract so can easily pass into the blood from there, but in the blood is much more ionised, so will not leave the blood as easily.

Question 10

How does being a weak acid or base drug affect its ionisation in different body pHs?

Answer 10

Weak acids - more ionised in alkali environments

Weak bases - more ionised in acidic environments

Question 11

Why does IV Sodium Bicarbonate increase excretion of a weak acid drug like aspirin?

Answer 11

It increases the urine pH, so once the drug enters the urine, it is very ionised and therefore will be less likely to be reabsorbed.

Question 12

What are the 4 main factors affecting drug distribution?

Answer 12

Regional Blood Flow

Extracellular binding (e.g. plasma-protein binding)

Capillary permeability

Localisation in tissues

Question 13

What is regional blood flow and its impact on drug distribution?

Answer 13

The differing proportions of cardiac output that reach the target organ directly impact the amount of a dose of a drug that reaches that organ.

This can change during rest/activity/eating etc.

Question 14

What is extracellular binding, and how does it affect drug dosing?

Answer 14

Different drugs will bind to plasma proteins in a different ratio, so the level of binding will affect the dose given.

Different drugs can also unbind a drug from a protein increasing the ‘active’ dose, so this must be taken into account.

Question 15

Why does capillary permeability affect drug distribution?

Answer 15

Different tissues have different permeabilities of capillary:

• Continuous with gap junction
• Blood brain barrier with tight junctions
• Fenestrated
• Discontinuous

This will affect how drugs need to access different tissues, e.g. lipid soluble for brain.

Question 16

How does localisation in tissues affect drug distribution?

Answer 16

Sometimes a drug will localise in a specific tissue

e.g. Extremely Lipid soluble localise in adipose - General anaesthetics, which can then re-enter the blood later and cause a repeated effect

Question 17

What are the two major pathways of drug excretion?

Answer 17

Through the Kidneys

Or through the liver via bile

Question 18

How are drugs excreted via the kidneys?

Answer 18

Low molecular weight drugs through glomerular filtration

Bigger drugs (the majority) through active secretion in tubules using active transporters

Question 19

How does the liver excrete drugs?

Answer 19

Very large molecular weight lipophilic drugs can enter the bile ducts and be excreted into the GI system.

Active transport systems can also transport drugs into the bile

Question 20

What is Enterohepatic cycling?

Answer 20

Because the active transport systems into the bile are geared to transporting bile acids and glucuronides into the bile, drugs conjugate with glucuronides to enter the bile.

Once in the intestines, the gut bacteria breakdown the conjugate and so the drug can be reabsorbed back into the blood.

This leads to drug persistence

Question 21

What is bioavailability?

Answer 21

Proportion of the administered drug that is available within the body to exert its pharmacological effect

Question 22

What is apparent volume of distribution?

Answer 22

The volume in which a drug appears to be distributed - an indicator of the pattern of distribution

Question 23

What is Biological half-life?

Answer 23

Time taken for the concentration of the drug (in the blood/plasma) to fall to half its original value

Question 24

What is clearance?

Answer 24

Blood (plasma) clearance is the volume of blood (plasma) cleared of a drug (i.e. from which the drug is completely removed) in a unit time​