9: SNS Antagonists Flashcards
Alpha 1 receptor stimulateion
vasoconstriction, relaxation of GIT
Alpha 2 receptor stimulation
inhibition of transmitter release, contraction of vascular smooth muscle (respond to NA), CNS actions
Beta 1 receptor stimulation
increased cardiac rate and force, relaxation of GIT, renin release from kidney
Beta 2 receptor stimulation
bronchodilation,
vasodilation,
relaxation of visceral smooth muscle,
hepatic glycogenolysis
these respond to circulating adrenaline levels- no direct input from SNS.
Beta 3 receptor stimulation
lipolysis
Which receptor does labetalol target
alpha 1 + beta1
SNS antagonist targeting alpha 1 + 2
phentolamine
SNS antagonist targeting alpha 1
prazosin
Which receptors does propanolol target
beta 1+2
atentolol targets
beta 1
Main clinical uses of SNS antagonists and false transmitters
- Hypertension
- Cardiac Arrhythmias
- Angina
- Glaucoma
Where do beta adrenoreceptor antagonist sgenerally work as antihypertensives
- Act in the CNS to reduce sympathetic tone
- Act on the beta 1 receptors in the heart to reduce HR + CO but this effect disappears with chronic treatment - the heart resets itself
- Acts on the kidneys: beta 1 receptors to reduce renin production. Blocking this kidney response is the primary anti-hypertensive effect. Reduced renin production results in reduced total peripheral resistance
Unwanted effects of beta antagonists
Most effects come from beta 2 blockade
- Bronchoconstriction: b2 in bronchial SM.
- Cardiac failure
- Hypoglycaemia: can mask symptoms of hypoglycaemia. Dangerous for diabetics bc blocks b2 breakdown of glycogen in liver.
- Fatigue: reduced CO + muscle perfusion
- Cold extremities: loss of beta receptor emdiated vasodilation of cutaenous vessels
Conditions in which you wouldnt give nonselective beta blocker
o ASTHMA
o COPD
o CARDIAC FAILURE
o DIABETES
How does propanolol work
blocks b1 and b2.
At rest, propranolol causes very little change in HR, CO or arterial pressure.
At exercise you see the effects of propranolol on these variables. As it is non-selective, it produces all the typical adverse effects, mainly caused by beta 2 antagonism
How does atenolol work
Beta-1 selective
. It mainly antagonises the effects of NA in the heart but will also affect any tissue with beta 1 receptor e.g. kidneys. This has less effect on the airways than non-selective drugs, but it’s still not safe with asthmatic patients
How does labetalol work
alpha1 + Beta 2 selective
Acts more on beta-1
This lowers BP by reducing TPR. Like beta-blockers, labetalol induces a change in HR/CO but this effect wanes with chronic use as the heart resets itself
Main cause of arrythmia
myocardial ischaemia. Damage to the heart muscle can result in re-entry of impulses that messes up the heart rhythm. Exercise increases the chance of arrhythmia.
How do class 2 anti-arrythmics work
- The refractory period of the AV node is increased by beta antagonists. This interferes with AV conduction in atrial tachycardias and slows down ventricular rate
- So, even if you have strange re-entry type electrical activity in the damaged tissue, it won’t stimulate another heart beat because it’s still in the refractory period decrease the chance of developing arrhythmias.
What is angina
PAIN OCCURRING WHEN O2 SUPPLY TO MYOCARDIUM IS INSUFFICIENT
3 types of angina
- Stable
- Unstable
- Variable
when feel pain in the 3 types of angina
Stable: on exertion
Unstable: less and less exertion
Variable: rest
Cause of stable angina
Due to a fixed narrowing of the coronary vessels e.g. atheroma
There is increased demand on the heart
Cause of unstable angina
The atheromatous plaque is starting to rupture and breaks away.
You get a platelet-fibrin thrombus associated with the ruptured atheromatous plaque but without complete occlusion of the vessel
High risk of infarction
Cause of variable angina
Caused by coronary artery spasm
It is associated with atheromatous disease
How do Beta adrenoceptor antagonists reduce myocardial oxygen demand
• Decrease HR + SBP + cardiac contractile activity. This loweres O2 demand. Decreases chance of angina attack
How is aq humour produced in eye
Aqueous humour is produced by the blood vessels in the ciliary body via the actions of carbonic anhydrase.
The amount of humour produced is directly related to the blood flow in the ciliary body
The production is indirectly linked to the BP and blood flow in the ciliary body
How do beta antagonists work to treat glaucoma
beta-1 receptors regulates the action of carbonic anhydrase.
It reduce the rate of aqueous humour formation by blocking the receptors on the ciliary body reducing OP
How do alpha adrenoreceptor antagonism work
Alpha-1 is the main mediator of TPR. If you block the alpha adrenoceptors you get a fall in TPR and hence a fall in BP.
• CO and HR will increase as a reflex response to the fall in arterial blood pressure - this is a baroreceptor mediated tachycardia
Why do u get postural hypotension if on alpha antagonist
When you stand up, the SNS kicks in to give a quick boost to your blood pressure and prevent you from fainting and falling over.
, this sympathetic drive is blocked and you get postural hypotension.
How does phenotolamine work
Non-selective alpha antagonist. Causes vasodilation and a fall in BP due to blockade of alpha-1 adrenoceptors. However, blockade of presynaptic alpha-2 receptors removes the inhibitory effect of the alpha-2 receptors on NA release and so you get an increase in NA release. This enhances the reflex tachycardia that you get with any BP lowering agent
How does prazosin work
Highly selective ALPHA-1 antagonist. This leads to vasodilation and a fall in BP. There is less tachycardia than non-selective antagonists since they don’t increase NA release from nerve terminals (no alpha-2 actions). You still get some reflex tachycardia because of the fall in BP.
Unlike other anti-hypertensives, alpha-1 antagonists cause a ….
decrease in LDL and an increase in HDL cholesterol.
Example of false transmitter
methyldopa
How is methyldopa use
Methyldopa is taken up by the noradrenergic neurons. It’s decarboxylated and hydroxylated to form the false transmitter: alpha-methyl noradrenaline. It is not deaminated within the neuron by MAO and tends to accumulate in larger quantities than NA. It displaces NA from the synaptic vesicles when taken up.
Mechanism of action of methyldope
alpha-methyl noradrenaline) is released in the same way as NA into the synapse etc.
• It is less active than NA on alpha-1 receptors. This means that it is less effective at causing vasoconstriction so there will be a fall in BP.
- Also it is more active on presynaptic alpha-2 receptors (the ones that mediate the negative feedback and release of NA shut down the synthesis and release).
- This means that the auto-inhibitory feedback mechanism operates more strongly and reduces noradrenaline release below normal levels
• It also has some CNS effects, it stimulates the vasopressor centre in the brainstem to inhibit sympathetic outflow
