Pharmacokinetics

Question 1

What is pharmacokinetics?

Answer 1

how the body affects a specific substance after administration

Question 2

What is drug absorption?

Answer 2

the passage of a drug from the site of administration into the plasma

Question 3

What is bioavailability?

Answer 3

the fraction of the initial dose that gains access to the systemic circulation

Question 4

Name five sites of administration

Answer 4

Intra-venous
Oral
Inhalational
Dermal (Percutaneous)
Intra-nasal

Question 5

Which site of administration has 100% bioavailability?

Answer 5

Intra-venous

Question 6

How can drugs travel around the body?

Answer 6

Bulk flow transfer (through bloodstream)
Diffusional transfer (molecule by molecule across lipid membranes)

Question 7

What is pinocytosis?

Answer 7

Cell membrane forms vesicle which envelops drug and releases it on the other side of the membrane. Rarely used for drug transport

Question 8

How do most drugs move across cell membranes?

Answer 8

Across lipid membranes or through transport proteins

Question 9

Which drugs can diffuse across lipid membranes?

Answer 9

Lipid soluble drugs

Question 10

What are most drugs ?

Answer 10

Weak acids or weak bases

Question 11

What two forms can weak acids/bases exist as?

Answer 11

Ionised or unionised

Question 12

What happens to a weak acid in its ionised state?

Answer 12

Donates protons

Question 13

What happens to a weak base in its ionised state?

Answer 13

Accepts protons

Question 14

Which state is more lipid soluble: ionised or unionised?

Answer 14

Unionised

Question 15

What determines the state of the drug?

Answer 15

pKa (dissociation constant) and pH

Question 16

When will a weak acid be more unionised?

Answer 16

When pH decreases (below its pKa)

Question 17

When will a weak base be more unionised?

Answer 17

When pH increases (above it’s pKa)

Question 18

Is drug distribution uniform?

Answer 18

No - different tissues will be exposed to different amounts of the drug

Question 19

How does regional blood flow affect distribution?

Answer 19

Different tissues receive differing amounts of the cardiac output.

More drug will be distributed to those tissues that receive most blood flow

Question 20

What happens to drugs once they enter systemic circulation?

Answer 20

They bind to plasma proteins

Question 21

What determines the amount of drug bound to plasma proteins?

Answer 21

The free drug concentration
The affinity for the protein binding sites
The plasma protein concentration

Question 22

Which drugs are more heavily bound to plasma proteins?

Answer 22

Weak acids

Question 23

How does the concept of tissue localisation apply to drug distribution?

Answer 23

Lipid soluble drugs will localise in lipid environments and water soluble drugs will localise in aqueous environments due to the drug equilibrium

Question 24

What is drug metabolism?

Answer 24

The conversion of drugs to metabolites that are as water soluble as possible and easier to excrete

Question 25

What is the major metabolic tissue?

Answer 25

The liver

Question 26

What are the main enzymes responsible for metabolism?

Answer 26

P450 enzymes

Question 27

What are the two phases of drug metabolism?

Answer 27

Phase 1 - add a reactive polar group by reduction, oxidation or hydrolysis Phase 2 - add a substituent group to make the drug inactive and less lipid soluble

Question 28

What are prodrugs?

Answer 28

Drugs which require hepatic metabolism to become active

Question 29

What is an issue with oral drug administration?

Answer 29

They will be metabolised by the liver before they enter the systemic blood supply, leading to little active drug being circulated

Question 30

Name four routes of drug excretion

Answer 30

Via lungs Via breastmilk Via kidney (urine) Via liver (bile)

Question 31

What are the three phases of excretion via the kidneys?

Answer 31

Glomerular filtration Active tubular secretion Passive diffusion across the tubular epithelium

Question 32

Which drugs are excreted by glomerular filtration

Answer 32

drugs under 20,000

Question 33

What is the most important method of drug excretion through the kidney?

Answer 33

Active tubular secretion through the proximal tubule, 80% of blood passes through here

Question 34

What does passive diffusion often lead to?

Answer 34

Reabsorption of particularly lipid soluble drugs

Question 35

Which factors influence reabsorption?

Answer 35

Drug metabolism - phase 2 metabolites are reabsorbed less Urine pH - weak acids reabsorbed at low pH, weak bases reabsorbed at high pH

Question 36

How are drugs excreted through liver?

Answer 36

In faeces

Question 37

What is enterohepatic recycling?

Answer 37

Gut bacteria hydrolyse glucuronide metabolites making them more lipid soluble and increases their reabsorption. Leads to prolonged drug effects