Pharmacodynamics III: Intracellular Receptors & Receptor Regulation

Question 1

How long do Intracellular Receptors take to signal?

Answer 1

• Process takes minutes to hours
• Effects take hours to days

Question 2

What FOUR molecules do Intracellular Receptors mediate cells responses to?

Answer 2

1. Steroids (& Vit. D)
2. Thyroid Hormone
3. Lipids
4. Inducers of drug metabolism acting via the Ah receptor

Question 3

What molecules do PPARs (Peroxisome Proliferator-Activated Receptors) bind to?

Answer 3

Fatty acids and FA metabolites

Question 4

What is an Agonist of PPARα?

Answer 4

Fibrates

Question 5

What is an Agonist of PPARγ?

Answer 5

Thiazolidinediones (Type 2 diabetes)

Question 6

What is an Antagonist of PPARγ?

Answer 6

Bisphenol A

Question 7

Where are Ah (Aryl Hydrocarbon) Receptors located?

Answer 7

Cytosol

Question 8

What are Ah Receptors also known as?

Answer 8

Orphan Receptor

Question 9

What TWO types of molecules do Ah Receptors bind to?

Answer 9

1. Polycyclic Hydrocarbons (PHCs)
2. Halogenated Aromatic Hydrocarbons

Question 10

What genes do Ah Receptors stimulate expression of?

Answer 10

P450 genes

Question 11

How does long-term presence of an Agonist affect receptor numbers and what does this cause?

Answer 11

• DECREASE receptor number
• Causes DESENSITISATION / TOLERANCE

Question 12

How does long-term presence of an Antagonist affect receptor numbers and what does this cause?

Answer 12

• INCREASES receptor number
• Causes SENSITISATION

Question 13

What are the FIVE main mechanisms of drug Desensitisation / Tolerance?

Answer 13

1. Reduced drug at receptor (due to clearance)
2. Reduced receptor response (due to modification)
3. Reduced number of receptors (due to lower expression)
4. Depletion of mediators
5. Physiological adaption

Question 14

What may cause slower receptor density change?

Answer 14

Endocytosis