Flashcards in 19. The Clinical Significance of Receptor Regulation Deck (24):
What does interaction between ligand and receptor depend on?
Molecular size, shape, and electrical charge.
What is affinity?
A measure of the ability of a drug to form a drug receptor complex.
What is efficacy?
A measure of the ability of the drug receptor complex to produce a response.
How do the dose response curves differ is a drug is more potent?
It will shift left so the higher response will be possible at a lower log drug concentration (dose).
What does excessive exposure to an agonist lead to?
Reduced sensitivity - tachyphylaxis.
What does agonist deprivation or excessive exposure to an antagonist lead to?
How can altered responsiveness be caused?
Change in receptor number, change in receptor coupling to second messengers, change in availability of second messengers, or change in cell responsiveness.
What is the result of activation of u-opioid receptors?
Analgesia (suppression of pain), sedation, and euphoria.
What is an example of an endogenous opioid?
Endorphin, used to relieve pain and increase relaxation.
How does repeated use of an opioid cause opiate dependence?
Repeated use causes tachyphylaxis - u-opioid receptors are down regulated. This means more opioid is needed for the same response.
What causes withdrawal symptoms in opioid use?
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.
How does repeated use of an opioid affect the dose response curve and what is a repercussion of this?
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.
What is tamoxifen used for?
In breast cancer, it is an anti-oestrogen.
Why does tamoxifen not cause osterporosis?
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.
What is phaeochromocytoma?
A tumour of the adrenal medulla.
What do phaeochromocytomas cause?
Increased secretion of catecholamines - adrenaline and noradrenaline.
What are the symptoms of phaeochromocytomas?
Intermittent symtpoms and signs of sympathetic nervous system overactivity - sweating, tremor, anxiety, high blood pressure.
Why does tachyphylaxis not occur with phaeochromocytomas?
They only cause intermittent release of catecholamines so there is no immediate need for down regulating receptors.
How do beta antagonists alleviate symptoms in angina?
They decrease adrenergic stimulation, so decrease heart rate and decrease coronoary vasoconstriction.
What is the effect on receptor number of continued use of beta antagonists?
Suprasensitivity - up regulation of beta receptors.
Why must beta antagonists never be stopped suddenly?
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.
How can antagonist withdrawal be avoided?
Slowly decrease dose rather than sudden cessation of treatment.
How does age affect catecholamine sensitivity?
Decreasing sensitivity to endogenous catecholamines with age.