Drugs acting on adrenoceptors (3) Flashcards
What are agonists?
Agents that bind to a receptor and elicit a response.
What are the names of the agonists of sympathetic alpha and beta receptors?
Sympathetic agonist, adrenergic agonists or sympathomimetic agonists.
What is a sympathomimetic agonist?
Agonists that mimic the effects of the sympathetic nervous system.
What are some common catecholamine adrenoceptor agonists?
Noradrenaline, adrenaline, dopamine and isoprenaline.
What is significant about noradrenaline and adrenaline?
They are non-selective and are naturally occurring.
What is significant about isoprenaline?
It is beta selective and synthetic, but does not discriminate against the different types of beta receptors.
What receptors do noradrenaline favour?
Alpha - mostly alpha 1.
What receptors does adrenaline favour?
Beta over alpha.
What receptor does phenylephrine favour?
Alpha 1.
What receptor does clonidine favour?
Alpha 2.
What is the function of the alpha 1 receptors?
It constricts smooth muscle due to increased calcium levels intracellularly.
What is the function of alpha 2 receptors?
In the heart they presynaptically inhibit release as they are coupled with Gi which decreases the amount of cyclic AMP in the nerve terminal.
What is the effect of alpha 1 agonists?
Vasoconstrictors - increase blood pressure due to restricted blood flow. They can also be used to prolong the activity of an anaesthetic in the local area.
What is the effect of alpha 2 agonists?
They prevent noradrenaline release and therefore reduce blood pressure due to overall reduced sympathetic tone.
What effects does clonidine have and what receptor does it act on?
Alpha 2 agonist - central and peripheral effects.
What can adrenaline be used for clinically?
Cardiac arrest and anaphylactic shock. This is because blood pressure decreases and the heart struggles to pump blood around the system.
Why can adrenaline be used for cardiac arrest and anaphylactic shock?
As beta1 agonists can increase cardiac contractility.
What else can be used to treat cardiogenic shock?
Dobutamine.
What is cardiogenic shock?
When your heart can’t pump enough blood to meet your body’s needs - it happens in some types of heart attacks.
What is dobutamine more selective at?
Beta1 receptors.
What can beta2 agonists be used to treat?
Asthma - they relax bronchial smooth muscle.
Give an example of a beta2 agonist.
Salbutamol.
What else can beta2 agonists be used in?
They increase lean protein mass and lipolysis - there is abuse in the sport and food industry.
If too much beta2 agonist is given to an asthmatic, what may happen?
Stimulation of the heart as there are beta2 receptors in the heart as well as the airways.
Where are beta3 receptors found?
Adipose tissue.
What is associated with beta3 receptors?
Fat breakdown, which is associated with thermogenesis.
What have beta agonists been proposed to be used as?
Slimming drugs.
What are the mechanisms in which NA can be removed from the synaptic cleft?
Neuronal epinephrine transporter (NET) on the presynaptic membrane, Extraneuronal monoamine transporter (EMT) on the postsynaptic neuron.
What happens after NA has been taken back up into the presynaptic neuron?
It is transported actively back into nerve varicosities and VMAT (vesicular monoamine transporter) repackages NA into vesicles.
What happens after NA has been taken into the postsynaptic terminal?
It is metabolised by COMT.
How can drugs indirectly act as sympathomimetics?
They have similar structures to NA but do not activate receptors - they have other mechanisms that cause amine release.
How can drugs indirectly act to increase NA levels?
Substrates for VMAT and NET that cause a rapid increase in cytosolic NA and increase NA in the synapse.
How does amphetamine act to increase NA levels?
It reverses NET and VMAT transport.
What can amphetamine be used to treat?
Narcolepsy and ADHD.
What can be used as nasal decongestants?
Ephedrine, pseudoephredrine.
What is the mechanism of nasal decongestants?
They cause vasoconstriction, as in colds there is vasodilation - leaky blood vessels with lots of plasma going into the tissues.
What is the mechanism of cocaine on NA?
It inhibits NA to cause an increase of NA in the synapse.
What are some unwanted effects of NA?
Hypertension, vasoconstriction, tachycardia, dysrhythmia.
What are some unwanted side effects of adrenaline?
Same as noradrenaline - hypertension, vasconstriction, tachycardia, dysrhythmia.
What are some unwanted effects of isoprenaline?
Tachycardia, dysrhythmia.
What can isoprenaline be used to treat?
Asthma.
What are some unwanted side effects of isprenaline?
Tachycardia, dysrhythmia.
What is dysrhythmia?
Abnormality in the rhythm of the heart.
What are some unwanted side effects of dobutamine?
Dysthythmia.
What are some unwanted side effects of salbutamol?
Tachycardia, dysrhythmia, tremor.
What are some unwanted side effects of phenylephrine?
Hypertension, reflex bradycardia.
What are some unwanted side effects of clonidine?
Drowsiness, oedema.
What is the action of tyramine?
It releases NA.
What is the function of amphetamine?
It releases NA from vesicles.
What can amphetamine be used for?
Narcolepsy, appetite suppressant, drug of abuse.
What are some of the unwanted effects of amphetamine?
Hypertension, tachycardia, insomnia, psychosis and dependence.
What effect does ephedrine have?
NA release - beta agonist.
What effect does cocaine have?
Blocks NET - synaptic NA increase.
What is an unwanted effect of cocaine?
Hypertension.
What is an antagonist?
Binds to the receptor but elicits no response - it prevents the binding of an agonist.
What is an alpha selective antagonist?
Prazosin.
What is a beta selective antagonist?
Propanolol.
How else can NA activity be antagonised?
Indirectly by interfering with its synthesis.
What effects do alpha adrenoceptor antagonists have?
They cause hypotension, postural hypotension due to alpha1 blockade. They increase cardiac output and cause tachycardia. Alpha2 blockage leads to increased sympathetic output.
Give examples of alpha adrenoceptor antagonists.
Phenoxybenzamine, phentolamine.
What is the action of phenoxybenzamine?
It is a long lasting alpha adrenoceptor antagonist that is covalently binding. It also blocks other types of receptor such as 5HT, ACh and histamine.
How does phentolamine differ from phenoxybenzamine?
(both alpha antagonists) - phentolamine is more selective but is shorter acting.
What are labetalol and carvedilol?
Mixed alpha and beta antagonists that can be used to treat hypertension.
-alol at end?
Beta blockers.
-azosin at end?
Selective alpha1 antagonists.
What is the effect of selective alpha1 antagonists?
Cause vasodilation and a fall in arterial pressure.
What are alpha1 antagonists used as clinically?
Antihypertensive drugs.
Give examples of alpha1 antagonists.
Prazosin, doxazosin.
What are the benefits of selective alpha 1 antagonists?
They cause less tachycardia than non-selective antagonists, but still cause postural hypotension.
What else do alpha1 antagonists do?
They relax bladder neck smooth muscle and prostate capsule.
What can alpha1 antagonists be used to treat?
Urinary retention that is associated with prostatic hypertrophy - enlarged prostate.
Give an example of an alpha1 antagonist used to treat urinary retention.
Tamsulosin.
Give examples of selective alpha2 antagonists.
Yohimbine and idazoxan.
What can yohimbine be used to treat?
Male impotence, aphrodisiac and may increase fat burn when combined with exercise. It increases blood flow via vasodilation.
What is an aphrodisiac?
Increases blood flow - can be used to increase sexual desire.
What is phenoxybenzamine?
An alpha antagonist and a NET inhibitor.
What can phenoxybenzamine be used for?
Phaeochromocytoma - tumour of the adrenal tissue.
What are some of the adverse effects of phenoxybenzamine?
Hypotension, flushing, tachycardia, nasal congestion and impotence.
What are some adverse effects of tamsulosin?
Failure of ejaculation.
What are beta-adrenoceptor antagonists also known as?
Beta blockers.
What was the first pure antagonist blocking beta1 and beta2 receptors equally?
Propranolol.
What is a beta1 selective drug?
Atenolol.
What are the most desired effects of beta antagonists?
Effects on the cardiovascular system - they reduce the effect of exercise/excitement such as lowering the oxygen demand on the heart.
What effects do beta antagonists have in heart disease?
Antidysrhythmic effects - help maintain normal heart rhythm.
What other effects do beta antagonists have?
Unexpected antihypertensive effects - in hypertensive patients arterial pressure drops over several days. They can also prevent tremor as they are skeletal muscle beta receptors.
What are some unwanted effects of beta antagonists?
Bronchoconstriction (b2 antagonism), cardiac failure, bradycardia, hypoglycaemia, fatigue, cold extremities, erectile dysfunction and lucid dreams.
Why is bronchoconstriction a side effect of beta antagonists?
There are some beta1 receptors in the airways, so even selective beta1 antagonists can cause this effect.
Why is hypoglycaemia a side effect of beta antagonists?
Glucagon release and glycogenolysis is normally stimulated by circulating adrenaline via the b2 receptor, however this is blocked by antagonists.
What is hypoglycaemic unawareness?
The idea that the symptoms of hypoglycaemia such as tremor and tachycardia are blocked by beta antagonists so the sufferer is unaware of their condition.
Why is fatigue a side effect of beta antagonists?
There is reduced cardiac output and muscle perfusion during exercise.
Why is cold extremities a side effect of beta antagonists?
There is a loss of beta 2 induced dilatation of subcutaneous blood vessels.
What are some of the clinical uses of beta antagonists?
Hypertension, angina, cardiac dysrhythmias, glaucoma, hyperthyroid disease, anxiety, tremor and migraine.
What are some common beta antagonists?
Propranolol, atenolol, other -olol drugs, timolol.
