Pharmacokinetics and drug metabolism

Question 1

Outline the journey of a drug through the body

Answer 1

Absorption

Distribution

Metabolism

Excretion

(removal)

Question 2

Examples of routes of administration (6/7)

Answer 2

Dermal, Intramuscular, Subcutaneous, Intraperitoneal, Inhalation, Ingestion (Intravenous)

Question 3

Define systemic

Answer 3

The entire organism

Question 4

Define local

Answer 4

Restricted to one area

Question 5

Define enteral

Answer 5

Gastro-intestinal administration

Question 6

Define Parenteral

Answer 6

Outside the gastro-intestinal tract

Question 7

What are the 2 ways drugs enter the systemic circulation?

Answer 7

Bulk flow transfer = in the blood

DIffusional transfer = molecule by molecule over a short distance

Question 8

Examples of aqueous compartments

Answer 8

blood, lymph, extracellular fluid, intracellular fluid

Question 9

Example of lipid barriers

Answer 9

cell membranes (epithelium/endothelium)

Question 10

Outline area of bulk flow, diffusion and barriers (absorption)

Answer 10

Question 11

What substances can penetrate a lipid membrane and why?

Answer 11

Non-polar substance, they can dissolve in non-polar substances and won’t interact with the membrane

Question 12

True or False?

Most drugs are either strong acids or weak bases

Answer 12

False

They are weak acids or weak bases

Question 13

What does the ratio of polar and non-polar forms of a drug depend on

Answer 13

The pH

(ionised = polar, non-ionised = non-polar)

Question 14

What factors influence drug distribution? (4)

Answer 14

>Regional blood flow

>Extracellular binding (plasma protein binding)

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

>Localisation in tissues

Question 15

What do highly metabolically active tissues display?

Answer 15

Denser capillary networks

(Increase blood flow, increase removal of waste products and delivery of O2)

Question 16

Outline the effect of plasma protein binding on drug distribution

Answer 16

Acidic drugs = 50-80% bound to plasma proteins

If there is a high binding percentage, less is freely transported in the blood, therefore, there’ll be less of the drug available to have an effect

Question 17

Where are the 2 main areas of drug excretion?

Answer 17

Kidneys = responsible for the elimination of most drugs

Liver = some drugs are concentrated in the bile (large molecular weight conjugates)

Question 18

What is transported at the glomerulus, proximal tubule and the proximal/distal tubules

Answer 18

Glomerulus = drug-protein complexes are not filtered

Proximal = active secretion of acids and bases

Proximal/distal = lipid-soluble drugs

Question 19

Outline how drugs are excreted from the kidneys

Answer 19

Question 20

Why might intravenous sodium bicarbonate increase aspirin excretion?

Answer 20

IV sodium bicarbonate = increae urine pH = ionse aspirin = less lipid soluble = less reabsorption from tubules = INCREASE excretion

Question 21

Other than the liver and kidneys, what are other routes of excretion

Answer 21

Lungs, Skin, GI secretion, saliva, sweat, milk, genital secretions

Question 22

What is enterohepatic cycling and what is the result of this?

Answer 22

The drug is excreted into the gut (through bile) then reabsorbed and taken to the liver where its excreted again

This can lead to drug persistence (the drug has a continued effect)

Question 23

Define BIOAVAILABILITY

Answer 23

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

Links to absorption

Question 24

Define APPARENT VOLUME OF DISTRIBUTION

Answer 24

The volume in which the drug appears to be distributed, an indicator of distribution patterns

Links to distribution

Question 25

Define BIOLOGICAL HALF-LIFE

Answer 25

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

Links to metabolism and excertion

Question 26

Define CLEARANCE

Answer 26

Blood (plasma) clearance is the volume of blood cleared of a drug in a unit of time.

Related to the volume of distribution and the rate at which the drug is eliminated from the system

Links to excretion

Question 27

Which drugs will be least likely to penetrate the lipid membranes?

Ionised drug, non-ionised, protein-bound drug, lipophilic drug, a hydrophilic drug

Answer 27

Ionised drug

Protein-bound drug

Hydrophilic drug

Question 28

Which drugs will most likely be able to penetrate a lipid membrane?

Question 29

Drug elimination kinetics:

What is C₀?

Answer 29

concentration at time zero, this can’t be measured so it needs to be extrapolated

Question 30

Drug elimination kinetics:

What is V_d?

Answer 30

Volume of distribution (Dose/C₀)

This is the volume in which the drug is distributed and indicates the pattern of distribution

Question 31

Drug elimination kinetics:

What is t_0.5?

Answer 31

The half-life of the substance

Question 32

Drug elimination kinetics:

What is K_el?

Answer 32

The elimination rate constant (slope of the line)

Question 33

What is the order of the majority of drugs?

Answer 33

First order

Question 34

What is first-order kinetics?

Calculate clearance of a first-order drug

Answer 34

The amount of drug decreases at a proportional rate to the concentration of the drug remaining in the body

Clearance = V_d x K_el

(K_el = Log2/t_0.5)

Question 35

What is zero-order kinetics?

Calculate clearance of a zero-order drug

Answer 35

The amount of the drug decreases at a rate that is independent of the concentration of the drug within the body

Clearance = time x K_el

(K_el = ðC/ ðt)

Question 36

What does zero-order kinetic suggest?

Answer 36

Implies that there is a saturable (usually enzymatic) metabolic process