The House Always Wins ACE-inhibitors, ARBs, Aliskiren

1.2 – “The H House ouse Always Wins”: ACE-i -inhibitors, nhibitors, ARB ARBs, s, aliskiren RAAS (Ren (Renin-angiotens in-angiotens in-angiotensin-aldostero in-aldostero in-aldosterone ne system) • Renin is a protease released by kidney cortex in response to direct SNS β1 stimulation in juxtaglomerular apparatus (kidney shaped slot machines signs “raining” cash; winner with JGA). SNS stimulation can result from ↓renal arterial pressure, ↓renal Na delivery, direct SNS activation in other systems. • Renin stimulates angiotensinogen (loose tie gambler) cleavage to angiotensin-I (tense tie). Angiotensin-I has little biologic activity and is converted to angiotensin-II by angiotensin converting enzyme (ACE) (ACE = ace; tie-wearer is losing to suspender wearer – I going to II). ACE is distributed throughout the body, most notably in the vascular endothelium, particularly in the lungs (dealer with lung spots on uniform). • Angiotensin-II helps maintain arterial BP and electrolyte balance: • Acts on vascular smooth muscle → pressor effect (tight suspenders). Also acts on CNS & SNS → same effect. • Efferent arteriole constriction at glomerulus → increased pressure & blood back up → ↑ GFR (suspender-wearing patron pinching efferent side glomerulus-shaped straw; coffee ground filtration rate is way increased). This effect is especially important when there is ↓blood flow either d/t obstruction (as with atherosclerosis) or ↓CO (low coffee mug). • Acts at PCT to increase sodium bicarb resorption (suspender-wearer eating salty peanuts while watching Pro Cart Track) • Increases aldosterone (a mineralocorticoid) production & release (mineral crystal themed bar). Aldosterone acts at the collecting duct to ↑sodium & fluid retention at expense of potassium (peanut snacks on the bar; banana peels on the floor = ↓K) Meds • ACE-inhibitors & angiotensin receptor blockers (ARBs) reduce long-term M&M in HF & MI (guardian angel of April Shower’s Casino). • ACE-inhibitors o All end in -pril (April Showers Casino). Include captopril, enalapril, lisinopril, and several others o Effects result from prevention of angiotensin-I conversion to angiotensin-II (slumped gambler with floppy suspenders). Block vasopressor effects and aldosterone upregulation of angiotensin-II. ▪ ↓SVR. • When initiating treatment, significant hypotension can precipitate syncope d/t abrupt removal of constrictive effects (dude passed out at ACE-I table). To prevent, start low & slowly titrate up. ▪ ↓GFR by dilation of efferent arteriole. This commonly causes a transient bump in creatinine (up to 30%) within a few days of starting ACE-inhibitors (creatinine credit card). ▪ Promote natriuresis. Decreased Na retention at →↓Na & ↑K; may even precipitate hyperkalemia (raised banana daiquiri) ▪ Remember that if angiotensin-II is blocked, all the upstream products will increase o Indications ▪ First line agents for CHF (deflated heart shaped balloon) • Reduce afterload (↓SVR) & preload (salt & water loss). • Decrease SNS stimulation d/t ↓angiotensin-II effects. • Decreases mortality (angel over marriage); probably d/t attenuation of cardiac remodeling (remodeling behind couple). standard therapy post-MI d/t prevention of remodeling (heart banjo with broken strings). ▪ First line for primary HTN (“high pressure” candy pipes) ▪ Slow progression of diabetic nephropathy (kidney shaped lollipops) • Diabetic nephropathy classically defined by proteinuria, which may indicate glomerulosclerosis • Indication for starting ACE-inhibitors: persistent albuminuria + BP>130/80. Even in absence of HTN, recommend anyone with diabetes & any level of albuminuria start on ACE-inhibitors. Note that moderate albuminuria (30-300 mg/d) is not detectable on dipstick, only on urinalysis. o Side effects/toxicities ▪ Hyperkalemia (ACE-I winner with raised banana daiquiri) ▪ Mild dry coughing d/t ↑bradykinin (dealer with braids for bradykinin coughing; she’s inhibiting the ace because it’s in her pocket) (may also involve substance P or prostaglandins). Because ACE actually breaks down these other things too. • If this is bothersome to patient, change them to an ARB. ▪ Contraindicated with heredity angioedema (C1 esterase deficiency). Angioedema commonly manifests in face, lips, tongue (woman with C-shaped ring in lip). ▪ Contraindicated in pregnancy d/t risk of fetal hypotension, anuria, renal failure; can result in oligohydramnios and Potter’s sequence (pregnant woman with tarantula jacket) ▪ Coadministration with NSAIDs can cause AKI d/t NSAID mediated constriction of proximal afferent arteriole (fire extinguisher mounted in cracked kidney case). ▪ Can cause AKI in bilateral renal artery stenosis, where kidney function is reliant on angiotensin-II efferent constriction to maintain blood flow (constricted straps on kidney purse). Presents with persistent ↑Crt, more than a few days after initiation of therapy d/t renal insufficiency (woman with credit card). Indication for discontinuation of therapy. • Angiotensin receptor blockers (ARBs) o -sartan suffix. Include losartan, candesartan, valsartan. (“Sorry, taken” sign by PCT screens) o Competitive antagonists of angiotensin-I receptor (taken sign competing for a seat). o Effective in HTN, diabetic nephropathy (although fewer renal protective effects in diabetes than ACE-inhibitors), HF o Side effects/toxicities ▪ Hyperkalemia d/t aldosterone inhibition (Banana daiquiri on chair) • Aliskiren (High Risk Limit cash slots) o Direct renin inhibitor prevents conversion of angiotensinogen to angiotensin-I (gambler losing tie) o Treatment of HTN o Side effects/toxicities ▪ ↓BP ▪ ↓renal function ▪ ↑K (3 bananas)