RAAS system Flashcards
Why do we want to inhibit the RAAS system?
Hypertension - these patients likely have increased renin levels, aim to decreases peripheral resistance.
Heart failure - kidney think the volume is low, often have edema, so we want to decrease the extracellular volume.
Liver cirrhosis - used to treat edema as patients are unable to produce adequate amounts of albumin, so they have reduced capillary oncotic pressure.
Diabetic patients - they often get nephropathy (nyresygdom). Drugs can delay the reduction in the kidney function and reduce glomerular filtration pressure by dilation of efferent arteriole.
Direct renin inhibitors - aliskiren
MOA: inhibits the active site of renin, so it cannot cleave angiotensin 1 from angiotensinogen.
Effect: decrease blood pressure, decrease the production of aldosterone.
Indication: hypertension.
Side-effects: few. Hyperkalemia (bc decreased aldosterone, decreased potassium is secreted in the kidneys.
ACE inhibitor - enapril, captopril
MOA: binds to the active site of ACE, competes with angiotensin 1 for binding the enzyme. Less angiotensin 2 is produces, less binding of angiotensin 2 to AT1 receptor on vascular smooth muscle cells –> less contraction of vessel (dilation).
Effect: lowers blood pressure due to vasodilation.
Indication: hypertension, cardiac failure, nephropathy.
Side-effects: hypotension, reduced kidney function (due to vasodilation of the efferent arteriole, which leads to reduced GFR), dry cough (ACE normally breaks down bradykinin. When ACE is inhibited, there is more bradykinin. Bradykinin induce dry cough as it is a lung irritant), hyperkalemia.
Angiotensin receptor blockers - losartan
MOA: antagonist for the AT1 receptors on vascular smooth muscle cells. Reduced effect of the receptor, reduced contraction of vessels (vasodilation).
Effects: decrease blood pressure due to vasodilation.
Indication: hypertension, heart insufficiency.
Side-effects: hypotension, hyperkalemia.
