Diuretics act on ___ surface
Luminal
___ interact with membrane transport proteins
Thiazides, Furosemides, Triamterene
___ interact with enzyme and ___ interact with hormone receptors
acetazolamide, apironolactone
___ osmotic effect
Mannitol
___ is a carbonic anhydrase inhibitor
acetazolamide
CA inhibitors causes ____ in ____ (what and where)
decrease NaHCO3 reabsorption
PCT
Loop of henle water removal in ___ limb and Na ___ in ___limb
descending
NaCl Reabsorption in accending
Na reabsorpted in ascending limb via ______?
NKCC2 (NaK2Cl co transporter
Loop diuretics do what?
inhibit NKCC2
Mg/Ca excretion (K intracell high, difuse back to lumen (K channel) drives Mg/Ca reabsorption)
Increase RBF
Uses of Loop Diuretics
CHF (volume overload)
Refractory edema (+thiazide, aldosterone antagonists)
Hypercalceimia
Acute Pul Edema
HF have ___ diuretic response due to:?
decreased
Decrease drug delivery to kidney, decrease RBF, hypoperfusion activatoin of RAS/SNS
Loop diuretic adverse effects
hypokalemic metabolic alkalosis (increase K/H secretion) Ototoxicity Hyperuricemia/hyperglycemia Hypomagnesemia Hypotension (overdose)
Hypokalemia predisposes pt to ___?
ectopic pacemakers/arrhythmias
Loop diuretics includes?
Furosemide (most common)
Bumetanide, torsemide (higher F and longer t1/2)
DCT is _____ to H2O
impermeable
Na is reabsorpted in DCT via ___?
NCC (NaCl co transporter)
Ca reabsorption occurs via ___?
Na/Ca exchanger
NCX in DCT is regulated by
PTH (Parathyroid hormone)
Thiazides inhibits ___
NCC (increase NaCl excretion)
Thiazides _______ Ca
increase reabsorption of Ca
low Na intracellular, activates NCX, decrease Ca intracell, Ca reasborbed from urine
Thiazides drugs include ___?
hydrochlorothiazide (prototype 2x/day)
chlorthalidone/metolazone - longer duration
Thiazide adverse efects
Hypokalemia hyperaldosteronism (volume decrease) hyperglycemia/glycosuria Hyperuricemia (precipitate gout attack) hyperlipidemia (HTN risks) Allergic - sulfonamide
Thiazide acts in ___
DCT
Aldosterone acts on __
collecting tubules
K excretion is ____ to Na ______ in CT
coupled,
Na reabsorption
Aldosterone acts on CT by ____?
gene transcription - increase number/activity of Na/K-atpase
Trimaterne, amiloride diuretics acts by ___ at __
direct Na Channel block
CT
(less Na reabsorb = less K excreted
Apironolactone/eplerenone act by ____ at __
competitive antagonist at aldosterone receptor
CT
- decrease Na reabsorption, decrease K excretion
Uses of potassium sparing diuretics
CHF - aldosterone antag (also at heart)
Hyperaldosteronism
PCOS Hirustism - block androgens
HTN
Aldosterone antagonists important actions ____?
anti-remoding (less hypertrophy/fibrosis)
Increase K serum = less arrhythmias
Potassium sparing diuretics include?
spironolactone/eplerenone (aldosterone receptor)
Triamterene/amiloride (diuretcs Na)
Potassium sparing diuretics include?
Hyperkalemia EKG changes (Avoid NSAID) Endocrine abn (spiro - gynescomastia)
ACEI includes
lisinopril, captopril, enalapril, moexipril, benazepril
ACEI mechanism of action
block ATII induced vasoconstriction (decrease pre/afterload) block ATII myocardial hypertrophy/remodeling (aldosterone) Increase BK (block inactivatio - vasodilates) Increase endothelial function - NO Reduce SNS
ACEI uses
HTN
CHF
Delay progression of diabetic enphropathy
ACEI are ___ (except) converted to ____ by ___
prodrugs (lisinopril, captopril)
Active metabolite
by de-esterification in liver
ACEI Eliminated by:
renal (except Moexi + Fosino)
ACEI Adverse effect
dry cough, hyperkalemia HTN/acute renal failure (RA stenosis), angioedema Neurtropenia/proteinuria NOT FOR PREGNANCY
Angiotensin II receptor antagonists acts on
AT1 receptor
ARB are ACEI without ____
cough and less angioedema