10/15 Flashcards
long-term diuretic administrarion
HR and CO = unchanged
TPR = dec (mechanism unknown)
plasma volume = dec or unchanged
plasma renin activity = inc
thiazide diuretic MOA
acts in distil convoluted tubule, blocks Na/Cl symport (from urine), Na stays in urine, water stays in urine
Ca reabsorption
may open Ca activated K channels leading to vasodilation
decrease in peripheral resistance may result from negative Na balance
thiazide like diuretics
chlorthalidone, indapamide, metolazone
any drugs that inc Na delivery to collecting tubule ___
will cause K wasting
Na tries to come back in, K goes out
thiazide toxicities
hypokalemia, hyperuricemia, hypercalcemia, impaired carbohydrate tolerance, hyperlipidemia, hyponatremia, ED
clinical uses of diuretics
HTN, edema, CHF, kidney disease, hepatic cirrhosis, hypercalcemia, diabetes insipidus
thiazides CI
sulfa allergy
loop diuretics examples
furosemide, bumetanide, ethacrynic acid
loop diuretics MOA
inhibit the Na/K/2Cl cotransporter in the thick ascending limb
K+ is still transported to urine, drives Ca2+ and Mg2+ to be reabsorbed because of charge difference
-in pts w normal renal fxn, thiazides are more effective antihypertensives
loop diuretic toxicites
dehydration, hypokalemia, ototoxicity, hyperuricemia, hypomagnesemia
loop CI
sulfa allergy
diuretics that act in the collecting tubule
amilioride and triamterine
amilioride and triamterine MOA
inhibit Na channels in the apical membrane of collecting tubule
reduced Na entry into these cells reduces K excretion (sparing)
amilioride and triamterine uses
amilioride - adjunct treatment w thiazide or loop in CHF or HTN
triamterene - edema associated w CHF, hepatic cirrhosis, nephrotic syndrome or hyperaldosteronism, does not lower BP alone
amilioride and triamterine toxicites and CI
hyperkalemia, hyperchloremic metabolic acidosis
CI: K+ supplements, ACEI, kidney stones (triamterene)
diuretics that act in the collecting tubule
aldosterone antagonists
aldosterone enters cell of collecting duct and transcribes proteins (AIP) that inc Na reabsorption
-spiranolactone (aldactone)
-eplerenone
spiranolactone actions
blocks production of Na channels (aldosterone action)
inhibits 5a reductase
clinical uses of spiranolactone
HTN or CHT w other diurects
spiranolactone toxicities and CI
hyperkalemia, gynecocomastia, impotence, BPH
CI: K+ supplements, ACEI, chronic renal insufficiency
eplerenone actions
selective antagonism of MC receptor in kidney, heart, BVs and brain
eplerenone toxicities and CI
hyperkalemia, hypertriglycemia
CI: K+ supplements, K+ sparing diuretics, ACEI, chrionic renal insufficiency, DM w microalbuminuria, CYP450 3A4 inhibitors
renin is responsible for
converting angiotensinogen to angiotensin I (not active)
Ang I is rapidly converted to ___ by ___
ang II by ACE
ANG II 2 actions
- vasoconstriction -> inc PVR
- aldosterone release -> inc Na and water retention
ARBs place in RA system
block ANG II from binding (no vasoconstriction or aldosterone secretion)
spironolactone and eplerenone place in RA system
blocks aldosterone actions (inc Na and water retention)
ACEI place in RA system
inhibit ACE (no ANG I -> ANG II, no bradykinin inactivation (vasodilation))
aliskiren place in RA system
inhibits renin (angiotensinogen will not be converted to ANG I)
ang II works on __ receptors
AT1
AT1 receptors are located:
in the BV, brain, adrenal, kidney and heart
activation of these receptors increases BP
3 pathways that control renin release
- nacl reabsorption at macula densa
- BP in pre-glomerular vessels
- activation of B1 adrenergic receptors on juxtula glomerulur cells
ACEI overview
“prils”
sulfhydryl-containing (captopril (Capoten))
dicarboxyl-containing (enalorpil (Vasotec))
phosphorus-containing (Cosinopril sodium (Monopril))
sulfhydryl-containing ACEI
captopril (Capoten)
active site inhibitor
short half life (
dicarboxyl-containing ACEI
enalapril (Vasotec):pro-drug, requires hydrolysis of ethyl ester to form diacid form (enalaprilat), 11 hour half life, parenteral availability
lisinopril (Prinvil, Zestril): active molecule, 12 hour half life
phosphate-containing ACEI
fosinopril (Monopril): prodrug, requires cleavage by hepatic esterases to the active form (fosinoprilat), 11.5 hour half life
uses of ACEI
HTN, left ventricular systolic dysfunction, myocardial infarction, diabetic neuropathy
ACEI AE
hypotension, dry cough, hyperkalemia, acute renal failure, skin rash (captopril), angioedema
ACEI drug drug interactions
Antacids: reduce bioavailability
NSAIDS: reduce effectiveness (interfere w bradykinin mediated vasodilation)
K+ supplements: hyperkalemia
digoxin and lithium: increased levels
ACEI CI
pregnancy - ANG II needed for normal growth and function
high doses CI in pts with renal insufficiency
ARB overview
the “sartans”
losartan (Cozaar)
Valsartan (Diovan)
ARB actions
do not effect bradykinin
selectively block effects on ANG II (pressor effects, stimulation of NE system, secretion of aldosterone, effects on renal vasculature, growth-promoting effects of cardiac and vascular tissue)
ACEI primarily excreted through hepatic metabolism
moexipril (use w compromised renal fxn)
ARB uses
HTN, CHF, diabetic nephropathy, stroke prophylaxis
ARB AE
hypotension, hyperkalemia, teratogenic potential (2nd or 3rd trimester)
renin inhibitors
aliskiren
direct inhibition of renin (dipeptide like mimetic)
SE: diarrhea
CI: pregnancy and nursing
