19. The Clinical Significance of Receptor Regulation

Question 1

What does interaction between ligand and receptor depend on?

Answer 1

Molecular size, shape, and electrical charge.

Question 2

What is affinity?

Answer 2

A measure of the ability of a drug to form a drug receptor complex.

Question 3

What is efficacy?

Answer 3

A measure of the ability of the drug receptor complex to produce a response.

Question 4

How do the dose response curves differ is a drug is more potent?

Answer 4

It will shift left so the higher response will be possible at a lower log drug concentration (dose).

Question 5

What does excessive exposure to an agonist lead to?

Answer 5

Reduced sensitivity - tachyphylaxis.

Question 6

What does agonist deprivation or excessive exposure to an antagonist lead to?

Answer 6

Suprasensitivity.

Question 7

How can altered responsiveness be caused?

Answer 7

Change in receptor number, change in receptor coupling to second messengers, change in availability of second messengers, or change in cell responsiveness.

Question 8

What is the result of activation of u-opioid receptors?

Answer 8

Analgesia (suppression of pain), sedation, and euphoria.

Question 9

What is an example of an endogenous opioid?

Answer 9

Endorphin, used to relieve pain and increase relaxation.

Question 10

How does repeated use of an opioid cause opiate dependence?

Answer 10

Repeated use causes tachyphylaxis - u-opioid receptors are down regulated. This means more opioid is needed for the same response.

Question 11

What causes withdrawal symptoms in opioid use?

Answer 11

When opioid levels fall, the molecules leaves the receptor and are less likely to be replaced so second messenger activity falls and the patient will perceive pain.

Question 12

How does repeated use of an opioid affect the dose response curve and what is a repercussion of this?

Answer 12

It shift right so higher dose is needed to elicit the high response. This means the dose response curve is closer to the adverse drug reactions curve more side effects are present.

Question 13

What is tamoxifen used for?

Answer 13

In breast cancer, it is an anti-oestrogen.

Question 14

Why does tamoxifen not cause osterporosis?

Answer 14

It is only a selective oestrogen receptor modulator, so it has different effects at different site in the body - antagonises oestrogen receptors in the breast, but acts as an agonist in the bone and uterus.

Question 15

What is phaeochromocytoma?

Answer 15

A tumour of the adrenal medulla.

Question 16

What do phaeochromocytomas cause?

Answer 16

Increased secretion of catecholamines - adrenaline and noradrenaline.

Question 17

What are the symptoms of phaeochromocytomas?

Answer 17

Intermittent symtpoms and signs of sympathetic nervous system overactivity - sweating, tremor, anxiety, high blood pressure.

Question 18

Why does tachyphylaxis not occur with phaeochromocytomas?

Answer 18

They only cause intermittent release of catecholamines so there is no immediate need for down regulating receptors.

Question 19

How do beta antagonists alleviate symptoms in angina?

Answer 19

They decrease adrenergic stimulation, so decrease heart rate and decrease coronoary vasoconstriction.

Question 20

What is the effect on receptor number of continued use of beta antagonists?

Answer 20

Suprasensitivity - up regulation of beta receptors.

Question 21

Why must beta antagonists never be stopped suddenly?

Answer 21

There will be antagonist withdrawal due to the suprasensitivity. There are more receptors so there will be an increase in sympathetic actions so this leads to exacerbation of symptoms.

Question 22

How can antagonist withdrawal be avoided?

Answer 22

Slowly decrease dose rather than sudden cessation of treatment.

Question 23

How does age affect catecholamine sensitivity?

Answer 23

Decreasing sensitivity to endogenous catecholamines with age.

Question 24

How does decreasing sensitivity to endogenous catecholamines with age affect patients?

Answer 24

Reduced heart rate responsiveness to exogenously administered catecholines.