Pharmacokinetics

Question 1

Why is the ideal system not true for biological systems?

Answer 1

• Not a homogenous structure leading to a non-continuous distribution of data
• Drugs are metabolised, absorption and excretion (transformation) affect biological availability

Question 2

Name 5 methods of administration along with an advantage and disadvantage?

Answer 2

• oral (non-intrusive but many steps away from the blood stream)
• injection (quick and precise but easy to overdose)
• inhalation (quick but possible lung irritation)
• intramuscular (slow and even but irritation risk)
• Subcutaneous (slow and even, variable dependent on site)

Question 3

What are the 3 ways by which drugs travel across membranes?

Answer 3

• Diffusion across lipids
• Diffusion across aqueous channel
• Carrier protein

Question 4

What determines lipid solubility?

Answer 4

ionisation (most drugs are weak acids/bases), drugs can move across membranes more easily when protonated

Question 5

What determines whether a drug is ionised?

Answer 5

It’s pKa and the pH of the environment where:
log [A-]/[HA] = pH - pKa
A COMBINATION OF THE PROPERTIES OF THE MOLECULE AND THE ENVIRONMENT

Question 6

What is the prime site of metabolism?

Answer 6

The liver

Question 7

What is phase I metabolism?

Answer 7

• Non-synthetic (oxidation, reduction an hydrolysis)

- Can produce more/less active metabolite

Question 8

What is phase II metabolism?

Answer 8

• Synthetic, involving the conjugation of of chemical moitys
• Almost always less active and more water soluble for excretion

Question 9

What is first order drug kinetic clearance?

Answer 9

• Described in terms of half life where rate = c[drug]

- Number of enzymes activated is drug concentration dependent

Question 10

When does drug clearance have zero order kinetics?

Answer 10

• When there is a very high concentration of drug and so all enzymes are occupied, hence rate is determined by enzymatic activity

Question 11

What 7 factors determine drug half-life?

Answer 11

• Rate of biotransformation
• Rate of excretion
• Enzyme type (efficiency)
• Enzyme induction (drugs can induce increase in activity/enzyme level)
• Enzyme inhibition (drugs can inhibit the actions of enzymes)
• Enzyme competition (drugs compete for the same metabolic system)
• Metabolic variation between patients (due to age, sex, ethnicity or random effects)
• Binding to inactive sites (can be stored in fat and bone)

Question 12

How are drugs excreted?

Answer 12

• More heavily ionised drugs are readily filtered out by the kidneys

Question 13

What is an ideal pharmacokinetic system?

Answer 13

Where concentration = quantity/volume

And the action of drugs is concentration dependent

Question 14

Using pH and pKa explain why ibuprofen can enter the body more easily than aspirin?

Answer 14

• Aspirin has a low pKa of 3.5 and so exists in a mostly protonates state in saliva but mostly ionisedi in the stomach which has a much lower pH
• Ibuprofen has a high pKa of 9.5 and therefore exists in a mostly protonated state and can move in the body more easily

Question 15

What is CYP450 and give examples of how it can be affected by a) enzyme induction, b) inhibition and c) competition

Answer 15

Cytochrome P450 is a group of enzymes which functions to clear toxic compounds (and drugs)

a) Consistent drug use can raise its levels, reducing drug effect
b) Can be inhibited by grapefruit juice
c) Alcohol competes for drugs with CYP450 therefore there is lower metabolism