Alpha receptors Flashcards
What are the neurotransmitters secreted by the sympathetic and parasympathetic systems?
Sympathetic - noradrenaline
Parasympathetic - acetylcholine
Adrenal medulla secrete adrenaline. True or false?
True
Where are B3 receptors mainly expressed?
Fat cells
How many isoforms of adrenergic receptors are there?
Four
Where are a1 receptors specifically expressed?
Vascular smooth muscle
Do a1 receptors mediate vasoconstriction or vasodilation?
Vasoconstriction
How do a1 receptors mediate vasoconstriction?
a1 receptors activate phospholipase C via Gaq
Phospholipase C hydrolyses PIP (lipid) into two product: IP3 and DAG.
DAG remains in the plane of the bilayer and activates PKC
IP3 is water solube and so diffuses to cytosol and activates ligand gated ion channels in the endoplasmic reticulum and sarcoplasmic reticulum
This leads to influx of calcium ions and an increased conc in them, which leads to contraction of smooth muscle
Which organs respond to adrenaline and noradrenaline?
Blood vessels, heart and lungs predominantly but also GI tract, salivary glands, bladder
Activation of a1 receptors can lead to relaxation of smooth muscle in GIT. True or false?
True
Which protein kinase is involved with mechanism of a1 receptors?
Protein kinase C
Which protein kinase is inhibited in mechanism of a2 receptors?
Protein kinase A
What is the mechanism of action of a2 receptors?
a2 receptors couple to Gai (inhibitory)
Gai inhibits activation of adenylyl cyclase
production of cAMP is inhibited and therefore PKA is not activated
this inhibits the release of neurotransmitters, including noradrenaline and acetylcholine
What is the importance of the negative feedback loop in a2 receptors?
Secretion of noradrenaline leads to activation of a1 receptors and therefore contraction of vascular smooth muscle.
As noradrenaline conc reach a high threshold, it feeds back onto a2 receptors, which inhibit further release of the neurotransmitter = negative feedback
This stops the smooth muscle from continuously contracting
Activation of a2 receptors also reduces insulin release. True or false?
True
Adrenaline acts differently on alpha receptors than it does on beta receptors. True or false?
False - acts in a similar way on all four receptors
Noradrenaline is an agonist of alpha receptors and B1 receptor. True or false?
True
Methoxamine is a beta agonist. True or false?
False - alpha agonist
Isoprenaline is an alpha agonist. True or false?
False - beta agonist
Phenylephrine acts on a2 receptors. True or false?
False - a1
Clonidine is selective for a2 receptors. True or false?
True
Dobutamine is selective for B1 receptors. True or false?
True
Which receptor is salbutamol selective for?
B2
Propranolol is a beta agonist. True or false?
False - antagonist
Name two drugs that are alpha antagonists
phentolamine
phenoxybenzamine
Parazosin is a selective _____ antagonist
a1 (competitive)
Yohimbine has no clinical use. True or false?
True
Atenolol is a b1 selective antagonist. True or false?
True
Butoxamine has no clinical use. True or false?
True
Which drug is used intravenously as an adjunct in cardiopulmonary resuscitation and why is it used?
Adrenaline as it causes arterial and venous vasoconstriction and increases BP as a result
Which drug is used in ventricular fibrillation and what is its purpose?
Adrenaline - coarsens ECG waveform
Which drug is used in the case of an anaphylactic shock and how is it administered and what is its purpose?
Adrenaline - IV slowly or IM every 10 mins
People who suffer an anaphylactic shock will experience hypotension and so the adrenaline will increase BP, restoring it to normal.
How is adrenaline in eyedrops used in treatment of chronic simple glaucoma?
It reduces intra-ocular pressure by reducing the production of aq humor and increasing drainage through trabecular meshwork
Why is adrenaline added to formulation of local anaesthetic?
Most local anaesthetic causes vasodilation and so facilitates its own distribution. Addition of adrenaline causes vasoconstriction and so prolongs the action and reduced systemic toxicity
Which drug is used to offset hypotension attributable to sympathetic block induced by spinal or epidural anaesthesia?
Phenyephrine
What is phenylephrine’s use in opthalmic examinations?
Used to produce short periods of mydriasis (pupil dilation) in examinations. It does this by causing contraction of the radial smooth muscle of the iris
Increasing agonist concentration has no effect on competitive antagonist. True or false?
False
Adding agonist to a non-competitive antagonist will not change anything. True or false?
True - non-competitive antagonist causes steric hinderance, preventing agonist from binding
Phenoxybenzamine is a non-competitive antagonist. True or false?
True
Phentolamine is a competitive antagonist. True or false?
True
What is phaeochromocytoma and how are antagonists used in the treatment?
Tumor of the adrenal medulla - secretes excessive amounts of adrenaline leading to episodes of hypertension. Phentolamine is used as treatment and phenoxybenzamine is used during surgery
Is phentolamine a selective or non-selective antagonist?
non-selective
How does phentolamine simultaneously blockade a1 and a2 receptors?
phentolamine reduces BP by blocking a1 receptors
this is sensed by baroreceptors which increase sympathetic outflow and so increase in noradrenaline
this results in increased BP = reflex tachycardia
Phentolamine is also an antagonist of a2 receptors and so this results in unacceptable reflex tachycardia as it blocks the autoinhibition of noradrenaline, so noradrenaline levels remain high
Phentolamine is therefore useless at treating hypertension
Why is prazosin more effective at reducing BP than phentolamine?
Because it is a selective a1 antagonist and so produces a more acceptable reflex tachycardia, as it doesn’t affect a2 receptors. Results in restoration of BP
Is prazosin used as first line therapy for hypertension?
No - used where other therapy has proved ineffective
Which specific type of alpha receptor is present in prostate smooth muscle and what does it do?
a1A - mediates contraction of smooth muscle
What is the role of tamsulosin in treatment of benign prostate hyperplasia?
It is an antagonist at a1A so can alleviate the contraction of smooth muscle and treat condition
