SNS Antagonists Flashcards
What does α1 Adrenoceptor do?
Vasoconstriction, Relaxation of GIT
What does α2 Adrenoceptor do?
Inhibition of transmitter release, contraction of vascular smooth muscle, CNS actions
What does β1 adrenoceptor do?
Increased cardiac rate and force, relaxation of GIT, renin release from kidney
What does β2 adrenoceptor do?
Bronchodilation, vasodilation, relaxation of visceral smooth muscle, hepatic glycogenolysis
What does β3 adrenoceptor do?
Lipolysis
How does α2 receptor-mediated negative feedback work?
NA released from synapse can bind to α2 receptor on the presynaptic bulb. This reduces synthesis and release of NA from the synapse
Name a non-selective adrenoceptor antagonist:
Carvedilol
Name an α adrenoceptor selective antagonist:
Phentolamine (α1+2)
What does Prazosin selectively antagonise?
α1
Name a β adrenoceptor selective antagonist:
Propanolol (β1+2)
What receptor does Atenolol antagonise?
β1
What are the main clinical uses of Adrenoceptor antagonists?
Hypertension
Cardiac Arrhythmias
Angina
Glaucoma
What is the definition of Hypertension, and what are the factors that contribute to it?
Sustained diastolic blood pressure greater than 90mmHg
(NICE: <140/90mmHg)
Blood Volume
Cardiac Output
Total Peripheral Resistance
What are the sympathetic controls of Blood pressure?
Controls heart via β1 receptors
Main controller: Renin release from kidneys via β1
What tissues can anti-hypertensives target?
The heart - cardiac output
Sympathetic nerves that release the vasoconstrictor noradrenaline
The kidney - blood volume/vasoconstriction
Arterioles - peripheral resistance
The brain - blood pressure set point
Which organs do beta-blockers target?
The heart and kidneys (β1)
Sympathetic nerves and CNS (β1 + 2)
How do beta-blockers work on the heart to lower BP?
Reduce HR and CO via β1 but this effect disappears with chronic treatment as the heart resets itself
How do beta-blockers work on the kidney to decrease HR?
β1 antagonism reduces renin production which results in decreased TPR
This leads to reduced production of Angiotensin II a potent vasoconstrictor
How do beta-blockers act on presynaptic β-adrenoceptors?
Blockade of the facilitatory effects (positive feedback) of presynaptic β-adrenoceptors on noradrenaline release may also contribute to the antihypertensive effect.
What are cardioselective beta-blockers?
Name one
More selective for β1 receptors
Atenolol
What are mixed β-α blockers?
(I would rather die lol)
Carvedilol - a1 blockade gives additional vasodilator properties
What is Nebivolol?
A β1 blocker that also potentiates NO
What is Sotalol?
A β-blocker that also inhibits K+ channels
What is the main side-effect of beta-blockers?
What group of patients must you therefore be careful when prescribing to?
Bronchoconstriction - Asthma/COPD can be dramatic and life-threatening
What are the two other main serious side-effects of Beta-blockers?
Cardiac Failure - need some sympathetic drive to the heart
Hypoglycemia - The use of b-antagonists mask the symptoms of hypoglycemia (sweating, palpitations, tremor). Use of non-selective b-antagonists are more dangerous in such patients since they will also block the b2- receptors driven breakdown of glycogen . b1- selective agents may have advantages since glucose release from the liver is controlled by b2- receptors.
What are three less serious side-effects of beta-blockers?
Fatigue - less cardiac output and less muscle perfusion.
Cold Extremities - Loss of β-receptor-mediated vasodilatation in cutaneous vessels.
Bad Dreams
What us the main advantage of Atenolol over propranolol?
Atenolol β1 selective
Propanolol β non-selective
Decreased side effects with Atenolol as they tend to be due to β2 receptors, however they are not fully selective so some side-effects may remain
What is the advantage of Carvedilol over Atenolol?
In reducing BP, both reduce Renin secretion and contractility, but Carvedilol also reduces vasoconstriction and therefore TPR due to alpha1 blockade
How do α1 receptors work?
Gq linked receptors
How do α2 receptors work?
Gi linked receptors
What is prazosin and how does it work?
Highly selective α1 antagonist
Hypotensive via inhibition of vasoconstriction
Also causes decrease in LDLs and increase in HDLs
What is Phentolamine and how does it work?
Non-selective α antagonist
Hypotensive via inhibition of alpha mediated vasoconstriction
Also blocks presynaptic α2 inhibitory effects so increased NA which enhances reflex tachycardia
What are the side-effects of α-blockers?
Postural Hypotension - when you stand up SNS kicks in to give boost to BP, which is blocked
Reflex Tachycardia
Increased GIT motility
Why does phentolamine have reduced effectiveness due to α2 receptors?
Blocks α2 inhibitory effect, so there is an increase in NA release which enhances the reflex tachycardia
What does methyldopa create?
A false-transmitter - alpha-methylnoradrenaline
How do false-transmitters work to reduce hypertension?
Methylnoradrenaline displaces NA from synaptic vesicles
Far less active on α1 receptors than NA therefore less effective at causing vasoconstriction
It is also more active on α2 receptors reducing NA release
What are the side-effects of Methyldopa?
Dry mouth, sedation, Orthostatic hypotension, Male sexual dysfunction
Why are Beta-blockers given to patients with arrhythmias?
An increase in sympathetic drive to the heart via b1 can precipitate or aggravate arrhythmias. Particularly after myocardial infarction there is an increase in sympathetic tone.
AV conductance also depends critically on sympathetic activity, and the refractory period of the AV node is increased by b-adrenoceptor antagonists, interfering with AV conduction in atrial tachycardia’s, and to slow ventricular rate.
Reduce heart rate so reduces the severity of arrhythmias
How do beta-blockers reduce angina?
Angina is pain that occurs when O2 supply to myocardium is insufficient
At low doses, b1-selective agents, metoprolol, reduce heart rate and myocardial contractile activity without affecting bronchial smooth muscle.
O2 demand is reduced whilst the same degree of effort is maintained
How do beta-blockers treat glaucoma?
They reduce the production of Aqueous humour by blocking the receptors on the ciliary body
