ACE inhibitors and ARBs (Lecture 7) Flashcards
Explain the RAAS system
Renin is released by the kidney, cleaves angiotensinogen to form angiotensin 1 (is inactive) when it is cleaved by ACE on the endothelial cells it is formed to angiotensin 2 to cause the release of aldosterone from the adrenal cortex.
What is the purpose of the RAAS system?
Control of Na+ excretion and fluid volume.
Vascular tone.
What cells release renin?
What stimulation can they get to get the release?
Juxtaglomerular cells.
What are the two forms of ACE?
Angiotensin converting enzyme.
- They are on endothelial surface to convert Ang1 to Ang2.
- They are soluble and in the cytosol of the cell.
What receptors does Ang2 act on and what happens when these receptors are activated?
Angiotensin receptor 1 and angiotensin receptor 2.
What are the pathological down stream effects on stimulation of AT1 receptor?
- Powerful vasoconstriction
- Promotes Na+ and fluid retention by the nephron.
- Stimulates the release of aldosterone from the adrenal cortex.
- Enhances sympathetic activity: acts within the CNS and sympathetic nerve endings; stimulates noradrenaline release from synapse and inhibits reuptake.
- Stimulates cardiac hypertrophy and vascular hypertrophy.
- Stimulates collagen deposits promoting fibrosis.
- Stimulates the release of vasopressin (antidiuretic hormone from the posterior pituitary).
Explain the action of AT2 on the presynaptic AT1 receptor?
Cardio control centres in the medulla of the brain. Part of the autonomic nervous system.
NA to bind to receptors post synoptically and increase stimulation downstream.
Controlled by taking NA back up and storing it in nerve terminals.
Alpha 2 receptors are on the presynaptic terminals which when activated inhibits NA release.
Ang 2 binds to AT1R receptors causing further NA formation through dopamine pathways. Provokes inhibition of NA uptake thereby increasing the levels in the cleft, this increases the firing of the autonomic nervous system.
What are the suffix of ACE inhibitors and the ARBs? Give the examples on core drug list
ACE inhibitor: ‘pril’ drugs like Cilazipril.
ARBs: ‘sartan’ drugs such as Candesartan
What are the 4 main ways that ACE inhibitors cause decreased blood pressure in the vasculature?
- Decreased afterload (aterial vasoconstriction reduced)
- Decreased preload (venous dilation)
- Decreased bradykinin breakdown causing increased vasodilation.
- Downregulate Ang2 promoting sympathetic activation.
What effect does an ace inhibitor have on the kidney?
By reducing the effect of Ang2 and aldosterone release from the adrenal cortex it will promote Na+ and water excretion which will further reduce the blood pressure.
How is the ACE inhibitor which we need to know about taken and how is it excreted?
What are the theraputic uses of ACE inhibitors?
Essential and renovascular hypertension: diuresis and decreased blood pressure.
- However also useful for patients with normal renin levels (could be due to the effect of bradykinin). It will also reduce hypertrophic and pro-fibrotic consequences of RAS activation.
Would you use ACE inhibitors on someone who has chronic heart failure?
Especially useful because it reduces the supply demand ratio of O2.
Some adverse effects of ACE inhibitors?
What are the benefits of ARBs over ACE inhibitors?
The downsides?
It essentially does the same thing, however, there is no accumulation in bradykinin, therefore, no vasodilatory effects (however there is a reduction in cough related to bradykinin).
When would you use an ARB over an ACE inhibitor?
Used for the same reason but the person cannot tolerate an ACE inhibitor. ARBs generally have worse side effects and dont have vasodilatory effects.
How is ARB administered and secreted?
