Week 3: Pharmacokinetics - Distribution + Metabolism

Question 1

What are 3 factors affecting distribution?

Answer 1

1. Blood flow to tissues
2. Exit of drug from vascular system
3. protein binding
   see page 21

Question 2

Why does exit of drug from vascular system affect distribution? (2)

Answer 2

• ions have to find a pore to exit the vascular system
• BBB has no pores so only lipid soluble drugs can pass

Question 3

Why does blood flow to tissues and protein binding affect distribution? (3)

Answer 3

• Blood has albumin where drugs bind to
• free drug is the only part that can do the job
• you need protein for binding

Question 4

Case study: ramanpreet was prescribed levothyroxine 50 mcg orally daily. Do you thyroxin is 99.97% protein found in the body. Does that mean levothyroxine is highly bioavailable or poorly bioavailable after administration? Will this drug work fast or slow in the body based on its protein binding percentage?

Answer 4

0.03% of the drug is usable
- therefore poorly bioavailable
- slow to work

Question 5

What occurs to the drug during metabolism?

Answer 5

• alters the drug in order for it to be removed

Question 6

Metabolism involves the P450 System, which are hepatic enzymes. What 6 things does this system do to the drug?

Answer 6

1. Accelerated renal excretion of drugs (lipid, non-ionized)
2. Drug inactivation
3. Increased therapeutic action (ie. codeine can turn to morphine after metabolism)
4. Activation of prodrugs
5. Increased toxicity (ie. acetaminophen toxic in liver if a lot)
6. decreased toxicity

Question 7

What are prodrugs?

Answer 7

• inactive but can be turned active

Question 8

What are enzyme inducers vs inhibitors? (2)

Answer 8

• inducers increase action of enzymes
• inhibitors inhibit metabolism and cause toxicity

Question 9

What are some factors that may alter the way a patient metabolizes drugs?

Answer 9

1. age (function of liver gets worse)
2. Induction and inhibition of liver enzymes
3. First-pass effect
4. Nutritional status (ie. vegan and hypoalbumenia)
5. Competition between drugs

Question 10

Which drugs undergo the first pass effect?

Answer 10

• drugs that are going into the stomach and broken down
• therefore oral drugs

Question 11

What are the steps in breaking down a drug if it is undergoing the first pass effect? (5)

Answer 11

1. Absorption
2. Metabolism to liver
3. Distribution
4. Metabolism to liver
5. Excretion
   see page 26 for diagram

Question 12

Why should we be mindful of the FPE? (2)

Answer 12

• some drugs get broken down so much because of the first pass effect
• which is why some drugs are not always taken orally anymore, like nitroglycerine which is now a spray