SNS antagonists Flashcards
What are the 4 receptors of the SNS and where are they?
a1 (vascular-constrict, divert from GI)), a2(negative SNS on presynaptic neuron-inhbit active neuron-swift but short-NE), b1 (heart-CO, Divert from GI, Renin from kindey)), b2 (lungs-bronchodilate, vasodilate, SMC, glucneogenesis) (B3?lipolysis?)
What are the different drugs that bind different andrenoreceptors?
Some are non selective -Carvediol A1/2-Phentolamine a1-prazosin B1/2-propanolol B1-Atenol No need for a selective B2
Why use SNS antagonists for hypertension? Which are the organs to target with which drugs?
BP=COxTPR -mostly heart and blood vessel related (tiny bit brain and kidney)
Hypertensions is consistently over 140/90 - the body aims around there-issue. silent disease but main cause of stroke/HF, MI, CKD ->reduce mortality with SNS antagonists
Target SNS nerve releasing NE, Kidneys, Heart, arteriole and CNS (reduce blood volume, CO and vascular tone)
B blockers dont go to arterioles
Heart, SNS, Kidney, CNS - B1 -> Lower HR/Contractility, lower renin (Ang II down->less aldo and less vasocontrict)
(ps: can have B-adreno on presynaptic, and act to increase NE)
SNS, CNS - B2
B1 blocker-atenolol
B1/2-propanolol
Mixed a/B-carvediol (effect on vascular)
What are the unwanted side effects of Beta-Blockers?
Bronchoconstriction (asthma/COPD)-worse one-dont give B blockers to asthmatics (eve selective ones)
Cardiac failure-dont stop all SNS
Hypoglyceamia-SNS acts on liver glucose balance -and masks the symptoms
less dangerous:
B2-Fatigue-CO down and muscle perfusion down
B2-Cold extremites-loss of B receptor mediated vasodilation
Bad dreams
What are the 3 main types of B blockers?
non selective-propanolol
B1 selective-Atenolol (cardio selective)
Mixed B-a blocker-carvedilol-a1 provides extra vasodilation
Nebivolol-cardio selective but also makes NO (dilate)
Sotalol-non selective but inhbit K+ channels
Why use Atenolol over Propanolol? And Cavedilol over the others?
Atenolol is specific B1 (not 100% tho)
So reduce the B2 side effects-reduce bronchodilation and liver side effects
Should be better for asthmatics and diabetics-but not 100%-some are not fine
Cavedilol-more powerful hypotensive effect (also dilating arterioles)-but also means more side effects
What types of alpha blockers are there?
a1-block the Gq activating actions of a1 recepors-eg prazosin
a2-blocks the Gi imhbiting actions of a2 receptors
What are the clinical uses of alpha blockers?
non selective like phentolamine-phaechromacytoma (adrenal tumour producing tons of adrenal)-try and dilate
a1 specific-prazosin inhbits vasoconstriction of NE, but not a super good hypotensive
For some reason, Phentolamine works better than prazosin
What are the main side effects of a blockers?
SNS tends to decrease GI activity-ablockers can lead to diarrhoae
Why do alpha 2 receptors and baroreceptors reduce phentolamine effectiveness? Therefore why use prazosin?
Phento is for both a-means they are in competition
But blocking a2 means that NE can more likely bind a1 and act
For baroreceptors-a blockers reduce BP, which causes baroreceptors to fire less, meaning higher SNS drive and lower PSNS acting-rebound side effects (higher HR/SV)
Prazosin doesnt have the a2 side effects. But does have the baroreceptor problem
What is a false transmitter?
MethylDOPA-replaces DOPA in the NE pathway, but in the end becomes a-methyl-NE
Released fine in synapse, but cant bind a1/B1 - very selective to B2 and a2
AND not metabolised well by MAO (removed NE normally in peripheral tissue) - not broken down in cell, so conc gradient to reuptake NE is lower, and reuptake is lower
-> remains in synapse longer, bind B2 strong, a2 too->strong inhibitory
What are the uses of Methyldopa?
Improved blood flow-antihypertensivs
For CKD patients or people with cerebral heammorghage
What are the side effects of Methyldopa
Acts on all of SNS-can cause massive (way to big) hypotension, dry mouth
What are the uses of SNS Antagonists in Arrythmias?
Arrythmia usually results from damage to heart (any kind, valve, muscle, conductance,)
Increasing SNS drive exarcerbates the Arrythmia
Just want to slow heart down to try and help blood flow
B1 drives that, so B blockers make a great drug to treat it
eg: propanolol
What are the uses of SNS Antagonists in Angina?
Chest pain, blocked coronary vessels-not enough BF to heart
Usually starts as stable-pain on exertion (increased demande bad)-becomes unstable-culminating pain at rest, thrombus
Either increase blood flow to tissue/02 supply, or reduce HR to reduce the needs
B1 selective for the second one (better blood flow match)
