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Cardio Quiz 1c

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eem8u's version from 2016-12-05 10:57

Heart Failure Pharmacology

******General // Overview
Question Answer
2 general approaches to treating HF & assc. curve shift1- inotropic (moves line up) / 2- vasodilation (left shift, slightliy upward) by reducing filling pressures
Furosemide - typeLoop diuretic (inhibitors of Na/K/2Cl symportor)
***drug that can induce arrhythmia’s in susceptible patients (such as MI/CHF)furosemide (b/c of hypokalemia)
****spironolactone - typeK+ saparing Diuretic - aldosterone R ANTAGonist
****drug w/ proven mortality benefit in CHF**ACE-I, **beta blocker (and spironolactone in certain subgroups, aldosterone antagonist) (also from Lec 5: ARB's)
****drug w/ proven mortality benefit in MIACE-I
***drugs that are teratogenicAliskirin (REN-in inhibitor), ACE-I’s (-pril), Losartan (ARB)
Nesiritide - typenatriuretic peptide (recombinant human BNP) BuMP the GruMP --> turn the tide
****aliskirin - typerenin inhibitor
lisinopril - typeACE Inhibitor
captopril - typeACE Inhibitior
enalapril - typeACE Inhibitior
Losartan - typeangiotensin receptor blocker
Sacubitril/Valsartan - typecombination angiotensin receptor/ Neprilysin inhibitor
Dopamine - typecatecholamine - receptors = d1 > b1 > a1 agonist >> positive inotrope
Dobutamine - typecatecholamine - receptors = b1 agonist >> positive inotrope
digoxin - typeinhibits intracellular NA/K channels>> increase intracellular Ca2+ >> positive inotrope
****milrinone-typephosphodiesterase inhibitor (PDE3) >> positive inotrope "one in a million"
****DOC for HTN tx in diabetic patients w/ chronic kidney diseaseACE-inhibitors
drug w/ NARROW therapeutic windowdigoxin (concern w/ calcium toxicity)
metoprolol-typebeta blocker (B1 selective)
contraindicated in unstable / acute CHFbeta blockers (b/c negative inotropic effect)
which drug improves symptoms before full mechanism taken placefurosemide b/c increased systemic venous capacitance >> decreases preload and edema before diuresis occurs
2 actions of aldosterone(collecting tubule) 1- increase synthesis and activity of ENac 2- basolateral na/k atpase >>> increasing Na+ reabsorption
drug w/ improved action (risk of toxicity) in HYPOkalemiadigoxin
****digoxin - mechanism of bradycardia**direct PS stimulation of baroreceptors**
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****Diuretics
Question Answer
general effectincrease rate of urine formation (usually by increasing solute load)
describe normal fx of Na/K/2Cl symporter in TALohall three solutes *INTO* cell (block = more Na+ outside of cell)
****Furosemide - clinical indication (2)1- acute pulmonary edema // 2- CHF edema
Furosemide - type / mechanism / locationLoop diuretic / inhibitors of Na/K/2Cl symportor / *thick ascending
****Furosemide - indirect effectincreased systemic venous capacitance >> decreases preload and edema before diuresis occurs
****Furosemide - adverse effects (3)1- volume depletion/hypotension (with too big of a dose) / 2- hypokalemia / 3-hypomagnesia
****Furosemide - explain mechanism of hypokalemia (3)direct inhibitor of Na/K/2Cl channel // ****stimulation RAAS system, via relative volume depletion - more Na+ reabsorbed = more negative lumen >> more K+ excretion in collecting tubule // increased delivery of Na to distal collecting duct >> Na reabsorbed via ENac >> larger negative luminal charge >> more K+ exertion (see 7.18)
***Furosemide - explain mechanism of hypomagnesiaNa/K/2Cl symporter into cell powered by ROMK channel that leaks K+ into lumen >> block = less K+ in lumen >> less positive charge at TAL >> less paracellular absorption of Mg2+
calculate GFRGFR = = Kf x [(Pgc –πgc )– (Pbs–πbs )] = Kf x Net filtration pressure
Furosemide - effect on GFRvolume depletion lowers Pgc >> GFR down
Furosemide - brandnameLasix (lasts for six hours in body b/c half life is about 2 hours)
Spironolactone - type / mechanism / locationdiuretic / cytoplasmic aldosterone receptor antagonist / @ Late Distal & Collecting Tubules
aldosterone - receptor & effect (2)1- increase activation/synthesis of lumen renal epithelial Na+ Channel (ENaC) // 2- activates basolatera Na/K ATPase >>> increase Na+ (and h20 absorption)
****aldosterone effects @ heart (3)fibrosis, LV hypertrophy, excitability/arrhythmia
****aldosterone effects @ vasculature (3)fibrosis, endothelial dysfunction, ****inhibit NO synthesis
Spironolactone - clinical indication (and what classes)CHF *decreased morbidity and mortality ** / Class II - IV in NYHA
Spironolactone - adverse effectHYPERkalemia (K+ sparing) >> b/c blocks Na+ reabosprotion >> more positive lumen >> K+ does not leak
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****Vasoactive Peptides
Question Answer
ANP - sourceatrial myocytes (released by atrial stretch)
BNP - sourceLV myocardium ( response to stretch)
****ANP/BNP mechanism of action (4)(opposite to AT II actions) 1- ****decreases proximal tubular sodium reabsorption > natriuresis and diuresis // 2- decrease renin, aldosterone and ADH // 3- arterial, venous and coronary vasodilation // 4- May prevent cardiac remodeling. (Nesiritide also)
ANP/BNP-mechanism of decrease blood pressure (2)1- increase cGMP in vasc. sm. musc. > vasodilation 2- decrease sympathetic tone > vasodilation
****ADH effect at collecting ductADH increases permeability to water back into body >> small volume of concentrated urine (this is counteracted by ANP/BNP
****Nesiritide - clinical indicationsshort-term tx of acute CHF >> improves C.O. (no consistent date on morbidity / mortality)
****Nesiritide - 2 mechanisms of increased cardiac output1- vasodilation (increase GMP) / 2- lower wedge pressure (b/c of natriuresis > decreases preload)
Nesiritide - adverse effecthypotension - due to vasodilation
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Question Answer
****renin produced wherejuxtaglomerular cells (b/t afferent and distal tubule) in kidney
renin regulation - sodium delivery to macula densadecrease NaCl *stimulates* (increase delivery > inhibits)
renin regulation - intrarenal baroreceptordecreased renal perfusion >> increase renin (and vs versa)
renin regulation - Beta-adrenergic receptorB1 receptors on JG cells sense HYPOTENSION >> activates sympathetics >> renin release
renin regulation - direct feedbackATII on the AT1 receptor —> INHIBITS renin release
Aliskiren - mechanismrenin inhibitor >> decrease BP
Aliskiren - plasma renin vs renin activity levelsplasma iNCREASE b/c of lack of negative feedback/ activity level decrease
****Aliskiren - angiotensin I / II levelsno A1, a little AII (b/c of alternate pathways
Aliskiren - AE’s (3)1- hyperkalemia (less aldosterone = less K+ excreted at collecting tubule) / 2- increased creatinine / 3- teratogenic angioedema
Aliskiren - mechanism of GFR changeAT-II is vasconstrictor in kidney efferent > afferent/// with aliskiren --> block = efferent DILATION > Pgc decrease b/c less hydorstatic P > decreased GFR/increased creatinine
****Angiotensin II - mechanism at bowman’s capsule (normal)constricts efferents > afferents (when blocked dilates EFFERENTS more than afferents >> low Pgc)
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****ACE Inhibitors
Question Answer
ACE - mechanism of action (2)1- converts ATI —> ATII / 2- bradykinin >>> inactive
***ACE-inhib - side effects (4) **COUGH** b/c of bradykinin increase, hyperK (b/c of less aldosterone >> less K+ wasting at collecting tubule) / hypotension / decreased GFR (b/c of dilation at Efferent > afferent arteriole
***ACE-inhib - adverse effects1) angioedema 2) teratogenic
ACE-inhib - AT I / AT II / renin levels renin increased b/c less feedback / AT i increased (b/c more renin) / AT II decreased
ACE-inhib - clinical indications (5)HTN / DM / CHF / ACUTE MI / ***CAD - coronary artery disease
shortest half-life / benefitsCaptopril (good for titation / but most dose frequently)
prodrugEnalapril
only available IVEnalapril
most commonly usedlisinopril
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Angiotensin Receptor Blockers (ARB)
Question Answer
general mechanismAngiotensin II (AT II) Receptor Antagonists
selectivity of ARB’sAT1 >>>>>>> AT2 (10000x more)
Losartan- clinical indications (4)(cf ACE-I’s) HTN / CHF / MI / Diabetic nephropathy
Losartan - Side Effects (4)Teratogen / Hypotension (because of vasodilation) / decreased GFR (change in Pgc) /Hyperkalemia (less A-II >> less aldosterone >> less Collecting Tubule Na+ reabsorption >> less negative charge in lumen >> more K+ leak)
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Inotropic Agents
Question Answer
dobutamine - receptorB1 agonist >> increase contractility
dopamineD1/ B1 /a agonist >> increase contractility
digoxin - mechanism inhibits Na/K ATPase >> increased intracellular Na+ >> reduces driving force for Na+ to enter cell via sodium-calcium exchanger (NCX) >> less Ca++ is extruded from the cell >> increased contractile force
digoxin - effect on ANSDECREASES sympathetic / increase PS outflow @ baroreceptor
digoxin -hypokalemaIMPROVED fx of drug b/c competes for K site of ATPase **also risk for TOXICITY)
digoxin - electricalal effect*shorter action potential (esp plateau) >> probably b/c of increased K+ conductance through Ca2+activate K channel
digoxin - toxicity riskOVERlOADED intraCa2+ stores >> DADs > premature depolarization > tachycardia > ventricular fibrillation >> heart arrest
digoxin - clinical indications (2)CHF (increased CO)/ atrial fib (why?(
digoxin - adverse effects (4) ***yellow/green vision** / GI nausea, vomit, pain / Cardiac **sagging ST = digitalis effect** / psych fatigue/delusion
digoxin - therapeutic window0.5-1 ng/mL (very narrow!!)
digoxin - treatment of OD(NO dialysis, b/c of large Vd) —> Digiband (digoxin immune fab)
milrinone - mechanism (2)Phosphodiesterase Inhibitor PDE 3 >> increase cAMP >> 1- increase contractility and 2- VASODILATION —> decrease preload and afterload
cAMP mechanism in vasculaturecAMP inhibits MLCK > inhibits vasoconstriction of smooth muscle
milrinone - clinical indication acute/severe CHF (ICU)
milrinon- adverse effects (2)a-fib/arrhtyhmias and hypotension
+/- of metoprolol(beta blocker) — negative chronotrope (good) / negative inotrope (bad)
metoprolol - mechanismb1 selective ANTAGONIST
metoprolol - contraindicationBRONCHOCONTRIVE disorders (b/c b1 selective, but might still affect b2
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Summary - Drug Effects on RAAS
drug / Plasma renin activity / pl renin concentration / angiotensiogen / AT i / AT ii
Question Answer Column 3 Column 4 Column 5 Column 6
Beta blockers downdownnanana
renin inhibitordown*** upNAdowndown
ACE inhibitorupupdown***updown
ARBsupupdownupup
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