(1.2+2.1) Pharmacokinetics

Question 1

Suggest 3 enteral administration routes.

Answer 1

• Oral
• Rectal
• Sublingual

Question 2

Suggest 4 parenteral administration routes

Answer 2

• IV
• IM
• Subcutaneous
• Submucosal

Question 3

Suggest 4 factors that affect Oral bioavailability.

Answer 3

• Age
• Drug formulation (liquid/tablets)
• Interactions (with tea/water)
• Lipophilicity - Lipid soluble better than water soluble

Question 4

Suggest 4 factors that may affect protein binding.

Answer 4

• Liver function
• Renal function
• Pregnancy
• Displacement by other drugs

Question 5

What does a high Volume of distribution indicate?

Answer 5

highly spread into other tissues

Question 6

Which parts of the body are Lipophilic drugs strongly attached to?

Answer 6

Areas of large amount of fatty tissue e.g. brain

Question 7

Suggest 4 factors that affect the Volume of distribution.

Answer 7

• Lipophilicity
• Regional blood flow
• Specific receptors in the tissues
• Protein binding sites

Question 8

Describe the role of the CYP450 enzyme.

Answer 8

• Used in Phase 1 Metabolism
• Oxidation/Reduction/Hydrolysis
• Make drug more reactive

Question 9

In which part of the nephron are drugs primarily excreted and how?

Answer 9

• PCT

- By Anion/Cation transporters

Question 10

How is the elimination rate calculated?

Answer 10

Clearance/Volume of Distribution

Question 11

How is the volume of distribution calculated?

Answer 11

Total drug in the body/[Drug] in plasma at time 0

Question 12

Approximately how many half lives does it take for a drug to become effectively removed?

Answer 12

5-6

Question 13

Why give a loading dose? What drugs should use a loading dose?

Answer 13

• Distribute drug across all of volume of distribution -> each steady state quickly when you start giving the actual dose
• Drugs with high Lipophilicity and large Volume of distribution

Question 14

How may the steady state concentration be calculated?

Answer 14

Dose rate / Clearance

Question 15

How is the loading dose calculated?

Answer 15

Vd x CpSS

Question 16

Which two organs are critical for the clearance of drugs?

Answer 16

• Kidneys (Excretion)

- Liver (Hepatic Portal System)

Question 17

What influence do CYP450 inducers have on drug effects? Give 6 drugs that are inducers of CYP450.

Answer 17

Inducer -> faster metabolism -> less active time -> reduced therapeutic effects
ABC PRS
- Alcohol (long term intake)
- Barbiturate
- Carbamazapine
- Phenytoin
- Rifampicin
- Sulphonylurea

Question 18

What influence do CYP450 inhibitors have on drug effects? Give 6 drugs that are inhibitors of CYP450.

Answer 18

Inhibitor -> slower metabolism -> long active time -> increased therapeutic effects
O-DEVICES
- Omaprazole
- Disulfirum
- Ethanol (acute intake)
- Valproic Acid
- Isoniazid
- Cimitidine
- Erythromycin
- Sulphonamide

Question 19

What is First Order Kinetic also called? Describe its kinetic. Plot a graph of [Drug] vs time.

Answer 19

First Order = Linear (Log[drug] vs time) = metabolism + elimination are proportional to drug level

https://www.google.co.uk/search?q=first+order+kinetics&espv=2&biw=1318&bih=673&source=lnms&tbm=isch&sa=X&ved=0CAYQ_AUoAWoVChMI0-eNgOyWyAIVAdgUCh23DQ69#imgrc=Zd0EUMCpFxq3PM%3A

Question 20

What is Zero Order Kinetic also called? Describe its kinetic. Plot a graph of [Drug] vs time.

Answer 20

Zero Order = Non-Linear = metabolism + elimination are constant at any drug levels

https://www.google.co.uk/search?espv=2&biw=1318&bih=673&tbm=isch&sa=1&q=zero+order+kinetics&oq=zero+order+kinetics&gs_l=img.3..0i19l6j0i7i30i19j0i30i19l2j0i8i30i19.74726.75266.0.75472.4.4.0.0.0.0.97.336.4.4.0….0…1c.1.64.img..0.4.334.V03r3S1Dkjw#imgrc=oryf-sy376UfVM%3A

Question 21

Which of Zero or First Order Kinetic drugs have a defined half life? How do you work it out from a graph?

Answer 21

First Order Kinetic has a defined half life (whereas Zero order’s half life decreases with drug levels)

By plotting a [Drug] vs time graph of First Order Kinetic
https://www.google.co.uk/search?q=first+order+kinetics&espv=2&biw=1318&bih=673&source=lnms&tbm=isch&sa=X&ved=0CAYQ_AUoAWoVChMI0-eNgOyWyAIVAdgUCh23DQ69#imgrc=Zd0EUMCpFxq3PM%3A

Question 22

• Most drugs have Zero or First Order Kinetics when at therapeutic does. If overdose they become Zero or First order.
• Why is this?
• Give some examples of this kind of drugs.

Answer 22

• Therapeutic level: First Order
• Overdose: Zero Order
• CYP enzymes and kidneys become saturated, therefore metabolism and elimination rates are constant (e.g. max, affordable rate)
• E.g. Aspirin, Verapamil, Phenytoin, Fluoxetine
• This means any drugs with Zero order kinetics need to be monitored