M&R Session 11 Flashcards
What can altered receptor responsiveness result from?
Change in receptor number
Change in receptor coupling to 2nd messenger
Change in availability of 2nd messenger
Change in cell responsiveness
Which changes causing altered receptor responsiveness are seen clinically?
Change in receptor number
Change in receptor coupling to 2nd messenger
How does suprasensitivity arise?
Agonist deprivation
Excessive antagonist exposure
What is tachyphylaxis?
Decreased sensitivity of a cell to a ligand
How does tachyphylaxis arise?
Excessive exposure to agonist
What is activation of mu-opioid receptors associated with?
Analgesia
Sedation
Euphoria
What is an example of an endogenous opioid?
Endorphins
When are endogenous opiates released?
Stress
How does repeated opioid use cause tachyphylaxis?
Repeated use –> receptors upregulated but amount of 2nd messenger is constant
What can be said about the level of opioid required to elicit a response in tachyphylaxis?
Increased
Why does a patient perceive pain when opioid levels fall?
Molecule leaves receptor and is less likely to be replaced –> 2nd messenger activity falls
What are the typical withdrawal S/S of opiate withdrawal?
Distressing, variable, poorly localised pain
Sweating
Anxiety
Constipation
Why is it preferable to use patient administered analgesia with opiate based treatment?
Will be administered irregularly so no tachyphylaxis hence dose will stay low
How is clinical opioid withdrawal treated?
Decrease dose of opioid Substitute w/ a different class of analgesia
What is phaechromocytoma?
Tumour of the adrenal medulla
What are the S/S of phaeochromocytoma?
Sweating
Tremor
Anxiety
High blood pressure
What is the characterising feature of the S/S of phaeochromocytoma?
Intermittent
What causes the S/S of phaeochromocytoma?
Intermittent increase of catecholamines causing intermittent overstimulation of the sympathetic nervous system
Why does a patient not get less symptomatic over time in phaeochromocytoma even though there is an increase in catecholamine release?
Intermittent release so no receptor regulation or secondary messenger alteration, therefore no tachyphylaxis
Do adrenoceptors tend to upregulate?
No
In which stage of life does asthma most commonly present?
1st-3rd
What is asthma associated with?
FHx of eczema, hayfever and allergies
What are the S/S of asthma?
Wheezing
What can initiate an asthma attack?
Infection
Allergy
Psychological factors
How can bronchoconstriction be caused by the nervous system?
Increased parasympathetic stimulation
Decreased sympathetic stimulation
Which receptors are involved in bronchoconstriction caused by increased parasympathetic stimulation?
mAChR
Which receptors are involved in bronchoconstriction caused by decreased sympathetic stimulation?
Beta-adrenoceptors
Treatments for which conditions can elicit asthma?
Hypertension
Angina
Heart failure
What happens to beta-receptors in heart failure?
Up-regulated
What can a decrease in beta-adrenoceptors in the lungs cause?
Asthma
Why is diagnosing an elderly patient with asthma risky?
They can be denied beta-blockers which they might need to treat a cardiac problem which is actually causing the apparent asthma
Describe what happens when long term beta-blocker treatment for angina is removed.
Beta-receptors initially upregulated –> withdraw Tx –> receptor number is high so there is increased sympathetic action
How is increased age linked to sensitivity to endogenous catecholamines?
Sensitivity is decreased
How does the HR responsiveness to exogenous catecholamines vary with age?
Decreases
What can happen to the pharmacological efficacy of a long term administered drug with increasing age?
It can potentially become excess
What can excess pharmacological efficacy in long-term beta-blocker treatment cause?
Symptomatic bradycardia
What does the interaction between a ligand and receptor depend on?
Molecular size
Molecular shape
Electrical charge
