Pharmacokinetics

Question 1

What are the 5 stages of a drugs journey through the body?

Answer 1

Absorption

Distribution

Metabolism

Excretion

Removal

Question 2

List some routes of drug administration.

Answer 2

Inhalation, ingestion, dermal, intravenous, subcutaneous, intraperitoneal, intramuscular.

Question 3

Why might different administration routes be more appropriate?

Answer 3

If you want a systemic or local effect.

Speed of action.

Time period within body.

Question 4

Give some examples of local effect drugs.

Answer 4

Salbutamol (ventolin)

Antacids

Betnovate (betamethasone)

Question 5

Give some examples of drugs with systemic effects.

Answer 5

Aspirin
Cannabis

Nicotine.

Question 6

What is the difference between enteral and parenteral.

Answer 6

Parenteral = outside the GI tract (i.e. not orally administered)

Enteral = via GI tract.

Question 7

What two ways to drug molecules move around the body?

Answer 7

Bulk flow transfer, i.e. in the blood stream.

Diffusional transfer = over short distances.

Question 8

What key characteristic must drugs have?

Answer 8

Have to be able to transverse both hydrophilic and lipophilic environments.

They travel in aqueous compartments (e.g. bloodstram, lymph, etc.)

Must cross lipophilic barriers (e.g. cell membranes).

Question 9

Name 4 ways drugs can cross lipid barriers?

Answer 9

1. simple diffusion
2. diffusion across aqeous pores.
3. carrier mediated transport
4. pinocytosis

Question 10

Outline the route of aspirin and the barriers it must cross.

Answer 10

Ingested. Cross stomach lining to blood. Cross capillary wall to extracellular fluid. Cross from extracellular fluid into organs.

Question 11

Which one of two characteristics will most drugs have? Why is this significant?

Answer 11

Weak acid or weak base.

Drugs exist in polar/non-polar (ionised/non-ionised) forms depending on pH.

Question 12

How do aspirin and morphine differ at phyisological pH?

Answer 12

Morphine = basic. Proton acceptor.

Aspirin = acidic. Proton donor.

Question 13

Give the Henderson-Hasselbalch equation for the dissaciation constand of weak acid and weak base.

Answer 13

Question 14

How can the proportion of ionised:unionised molecules of a species be calculated?

Answer 14

Question 15

What is ion trapping? Explain with aspirin as an example.

Answer 15

Localisation of a drug in certain body compartments. High ionisation of aspirin in the blood (pKa = 3.5) gives it difficulty crossing lipid membranes.

Question 16

Why does IV Sodium Bicarbonate increase aspirin excretion.

Answer 16

Basic conditions –> increased aspirin ionisation –> reduced ability to pass back into blood after kidney ultrafiltration.

Question 17

Give 4 factors that influence drug distribution.

Answer 17

Regional blood flow

Extracellular binding (Plasma-protein binding)

Capillary permeability (tissue alterations – renal, hepatic, brain/CNS, placental)

Localisation in tissues

Question 18

What parts of the body receive the greatest regional blood flow?

Answer 18

Liver 27%

Heart 4%

Brain 14%

KIdneys 22%

Muscles 20% (when exercising)

Question 19

What is the effect of plasma protein binding on drugs (e.g. 50-80% aspirin)? Why is this important?

Answer 19

It remains in the blood. Dose must be adjusted.

Question 20

Why is it difficult for drugs to cross the BBB

Answer 20

tightly controlled substance transport. Tight continuous capillaries: difficult for ionised substances to pass through.

Question 21

Why does adipose tissue pose a problem for lipid soluble drugs?

Answer 21

Despite low blood supply, lipophilic drugs contained within it.

Question 22

What are the two major routes of drug excretion?

Answer 22

Kidney (urine)

Liver (bile in stool)

Question 23

How are drug molecules too large for ultrafiltration moved into the kidney tubules?

Answer 23

Active secretion using transport proteins (lipophilic drugs can be reabsorbed)

Question 24

How do hepatocytes move large metabolites into the bile?

Answer 24

active transport of the water soluble conjugates they create.

Question 25

Outline enterohepatic cycling.

Answer 25

Gut bacteria break down watersoluble metabolite leading to reabsorption and drug persistence.

Question 26

List some minor ways drugs can be excreted.

Answer 26

Lungs, skin, gastrointestinal secretions, saliva, sweat, milk, genital secretions.

Question 27

Define bioavailability.

Answer 27

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

Question 28

Define the apparent volume of distribution?

Answer 28

The volume in which a drug appears to be distributed

• an indicator of the pattern of distribution

Question 29

Define clearance.

Answer 29

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