M&R 11.1 Clinical significance of receptor regulation

Question 1

What is tachyphylaxis?

Answer 1

When excessive exposure to an agonist leads to reduced sensitivity to the agonist (so over time the agonist becomes less efficacious)

Question 2

What is suprasensitivity?

Answer 2

When agonist deprivation or excessive exposure to an antagonist leads to the response to an agonist becoming more sensitive

Question 3

What 4 main changes can lead to tachyphylaxis or suprasensitivity?

Answer 3

Change in receptor number
Change in receptor coupling to 2nd messengers
Change in availability of 2nd messengers
Change in cell responsiveness

Question 4

Describe a drug which has differential effects depending on which tissue it is acting in

Answer 4

Tamoxifen
Antagonises oestrogen receptor in breast tissue to reduce tumour growth
Agonist at oestrogen receptor in bone = beneficial effect (because oestrogen inhibits oestoclasts = reduced osteoporosis)
Agonist at oestrogen receptor in uterus = increased risk of endometrial cancer

Question 5

What is phaeochromocytoma?

Answer 5

A (usually) benign tumour of the adrenal medulla, which causes intermittent increased secretions of catecholamines (NA & adrenaline)

Question 6

What are they symptoms of phaeochromocytoma?

Answer 6

Intermittent signs/symptoms of SNS activity (usually lasting 30mins-1hr)
-> sweating, tremor, anxiety, high blood pressure

Question 7

Why does tachyphylaxis not develop in phaeochromocytoma?

Answer 7

Because the release of the catecholamines is intermittent

so doesn’t result in down-regulation of receptors/effector pathways

Question 8

What kind of antagonists are used to treat phaeochromocytoma?

Answer 8

Irreversible competitive antagonist at alpha and beta receptors

Prevents the high circulating levels of NA & adrenaline from displacing the drug from receptors

Question 9

What can be a complication of sudden cessation of beta blockers in angina, and why?

Answer 9

Beta blockers are antagonists at beta1 adrenoceptors, acting to decrease heart rate/force of contraction
Antagonism leads to beta receptor upregulation
So sudden cessation can lead to exacerbation of symptoms - because receptor numbers are increased so there is a relative increase in SNS action

Question 10

What is age-dependent catecholamine sensitivity?

Answer 10

Increasing age is associated with:

• > decreased sensitivity to endogenous catecholamines
• > reduced HR responsiveness to exogenous catecholamines
• > potential excess efficacy of administered drugs