SNS antagonists Flashcards
Name some sympathetic effects
- Pupil dilation
- Bronchi relaxation
- heart acceleration
- Stimulation of HGO
- Secretion of adrenaline and NA from kidney
- Contracts rectum
What do alpha 1 receptors do?
Alpha 1 receptors are present on blood vessels and when NA/ A binds to them, they cause vasoconstriction and relaxation of GIT.
What do alpha 2 receptors do?
Inhibition of transmitter release, contraction of vascular smooth muscle, CNS actions- suppress sympathetic activity.
What do beta 1 receptors do?
They are present in the heart.
They cause increased cardiac rate and force, relaxation of GIT, renin release from kidney.
What do beta 2 receptors do?
They are present in the lungs.
Causes bronchodilation, vasodilation, relaxation of visceral smooth muscle, hepatic glycogenolysis- drives the sympathetic effect in the liver.
Describe the negative feedback mechanism of the alpha 2 adrenoreceptor
NA produced from tyrosine (upstream), packaged into vesicles and leaves pre-synapse into the synaptic cleft. NA activates the receptor on the post synapse (alpha 1). Alpha 2 switches off this effect and stops NA being released.
NA release is fast in response to stimulus, but you don’t want a prolonged response. Swift response but quickly switched off too.
Name a non-selective SNS antagonist
Carvedilol
Name an alpha-1 and alpha-2 selective SNS antagonist
Phentolamine
Name an alpha-1 selective antagonist
Prazosin
Name an SNS antagonist which is selective to beta 1 and beta 2 over alpha receptors?
Propanolol
Name a beta-1 selective antagonist?
Atenolol
What do you need to think about if someone has hypertension?
You’re probably thinking that there is something wrong with the physiology in mechanisms to control BP.
Think CO X TPR = MAP
CO- there is probably something wrong with the heart (and the brains control of it)
TPR- to do with the blood vessels and the kidney’s ability to produce renin
Above which BP is considered hypertensive?
140/90
What are the main physiological contributors to BP?
- Blood volume
- cardiac output
- vascular tone
What are the tissue targets for anti-hypertensives?
- The heart- CO
- Arterioles- controls and determines TPR
- Kidneys- blood volume and vasoconstriction
- Sympathetic nerves that release NA (vasoconstrictor)- the CNS determines BP set point and regulate some systems involved in Bp control and autonomic nervous system.
how to spot a beta-blocker from the name?
They end in “olol”
What are the 2 main effects of beta blockers?
Beta-blockers will act on the heart (beta 1), on the kidney (beta 1) and sympathetic nerves that release the vasoconstrictor NA (beta1 and 2).
There are some beta receptors in the brain which regulate BP and to reduce sympathetic tone. Arterioles do not have beta-adrenoreceptors so will not be affected (vessels have alpha 1 receptors).
Action of beta-blockers specifically to reduce HR and BP
Decrease in HR & FOC and a decrease in cardiac output
The heart does not have to work as hard - reduced blood pressure. Reduction in cell activity.
Decrease in renin and therefore angiotensin II (Ang II) release-
lost vasoconstricting effect (positive TPR effect) and reduce aldosterone production.
Ang II - potent vasoconstrictor & increased aldosterone production. There are a number of stimuli for renin production (sympathetic nerves, sodium plasma level).
Blockade of the facilitatory effects of presynaptic β-adrenoceptors on noradrenaline release may also contribute to the antihypertensive effect.
Minor effect: Adrenaline increases the ability to create NA in the pre-synaptic neuron.
What does Nebivolol bind to? and why is it special?
Beta-1 adrenoreceptors and it also potentiates NO release.
NO is a vasodilator
What does sotalol do?
It binds to both beta-adrenoreceptors and it also inhibits potassium channels
what are the unwanted side effects of beta-blockers?
- Bronchoconstriction- should not be given to people with asthma/COPD
- Cardiac failure- should not be given to heart failure patients if you slow CO down too much, the heart cannot keep up with demand and worsen heart failure
- Hypoglycaemia- the symptoms are masked. There is usually a sympathetic response to hypoglycaemia, so you won’t notice it. Glucose is released from the liver it is stimulated via the beta 2 receptors.
- Fatigue - Reduced cardiac output and muscle perfusion
- Cold extremities- they are the vasodilating receptors and are present on muscles. Sympathetic nervous system activates the beta 2 receptors but if they are blocked, then the muscles will not get blood- leading to fatigue and cold extremities (limited capacity to dilate blood flow to the skin).
- Bad dreams
Why do you have to be careful when using propranolol?
Propranolol is non-selective Beta 1 and Beta 2. In a subject at rest causes very little effect but during exercise, can reduce HR, CO and ABP. As it is non-selective, it produces all the typical adverse effects.
why would you use atenolol over propranolol?
Atenolol is b1-Selective, antagonises the effects of noradrenaline on the heart but will affect any tissue with b1 receptors e.g. Kidney.
Less effect on airways than non-selective drugs, but still not safe with asthmatic patients. Selectivity is concentration-dependent.
Reduce the side effects that are beta 2 mediated. Given to asthmatics and diabetics to reduce the negative side effects.
Why use carvedilol over atenolol or propranolol?
There are beta mediated effects with carvedilol but there is blocking of vasoconstriction of arterioles (due to the alpha 1 selectivity). It is a more powerful anti-hypertensive but can have more potent side effects.
