Exam 1: Pulgar-Diuretics

Describe the structure of the kidneys/nephrons

Kidneys made up of cortex and medulla; cortex contains the glomeruli and the medulla contain the loops of Henle; afferent arterioles lead to glomeruli and efferent lean away; the Bowman's capsule surrounds glomeruli

Describe the normal functioning of the kidney/nephron.

Nephrons are highly vascularized and the pressure in the nephrons determines how much they filter; the filtrate goes through the PCT-->Loop of Henle-->DCT-->collecting duct; absorption of ions and water happen in different areas of the nephron

Describe the amounts of ions reabsorbed and from where in the nephron.

in glomerulus: bicarbonate, glucose, water and 65% of Na reabsorbed and some in PCT;

in loop of Henle: 25% Na, some K, Mg, Ca, Cl and most of water reabsorbed so urine is concentrated here;

in DCT: 5% of Na is reabsorbed and Ca under influence of PTH

in collecting duct: Na and Cl reabsorption under the influence of ADH(vasopressin)

The OAT controls excretion of:

organic acids like uric acid, toxins, common drugs

Carbonic anhydrase inhibitors work in the ____ and their MOA is ____

PCT; inhibit CA and the breakdown of bicarbonate and then Na us excreted and takes water with it

Thiazides work in the ____________ and their MOA is_________.

DCT (note: they are excreted by OAT in the PCT but act in the DCT); inhibit the Na/Cl symporter so more Na is excreted in lumen and water also

What is an important AE of thiazides and why?

allergy to the S in the structure

Names of Thiazide diuretics

Chlorthalidone (Hygroton)

Hydrochlorothiazide (HydroDiuril)

Indapamide (Lozol)

Metolazone (Zaroxolyn)

Methylclothiazide (Enduron)

Polythiazide (Renese)

What are other AE of thiazides? and why?

hypokalemia due to downward stream of Na reabsorption in DCT;

hypotension due to incr Na/H2O exretion and lowered BP;

hypercalcemia due to incr Na in the lumen causes the Na/Ca antitransporter to send Na from blood to DCT so Ca goes back to blood;

hyperuricemia due to drug competition to with OAT

What are the impt. DDI of thiazides?

decr effect of anticoagulants, and sulfonylurease, insulin, NSAIDs, etc

Name the uses for thiazides

hypertension

edema due to CHF

diabetes insipidus (but method unclear)

Which loop diuretic is best for pt. with sulfur allergy?

Ethacrynic acid (Edecrin)

Loop diuretics work in the ____ and the MOA is?

ascending loop of Henle; inhibit the NKCC symporter; this leads to loss of elec. pot. across mem. and thus Ca and Mg is not reabsorbed

What are some AE of loop diuretics?

hypomagnesemia and hypocalcemia;

What the uses of loop diuretics?

for rapid and large diuresis

acute pulmonary edema

Heart failure

hypercalcemia

hyperkalemia

acute renal failure

Loops stimulate aldosterone why?

due to low Na and low BP with result in low volume and the RAAS will kick in to stimulate aldosterone and this will stim expression of Na/K ATPase pumps bc aldosterone receptor is intracellular and alters gene expression

What are AE of loop diruetics?

ototoxicity

hyperuricemia

allergic reactions due to S (except for Ethacryni acid - Edecrin)

dehydration

Name the Loop Diuretics

Furosemide (Lasix)

Bumetanide (Bumex)

Ethacrynic Acid (Edecrin)

Torsemide (Demedex)

Potassium sparing diuretics work in the ____ and the MOA is ___?

collecting ducts;

by direct inhibition of the ENaC pump for the epithelial Na channel blockers so there is a decr in Na reabsorption;

AND indirect inhibition of Na/K ATPase pumps by blocking of the mineralocorticoid receptor using antagonist thereby inhibiting the the pumps aciton

Names of Potassium Sparing Diuretics

Epithelial Na channel blockers:

Amiloride (Midamor)

Triamterene (Dyrenium, Dyazide):

Mineralocorticoid receptor antagonists:

Spironolactone (Aldactone)

Eplerenone (Inspra)

What are some DDI for potassium sparing diuretics?

NSAIDs, ACE inh, ARBs, BBlockers due to additive effects of their actions on K

What are some uses for potassium sparing diuretics?

hypertension, hypokalmeia

What are the uses of the potassium sparing diuretics?

for ENaC inhibitors: Liddle syndrome, Cysitc fibrosis, Li induced diabetes inspidus

for Na/K ATPase pumps: HF, cardiac enlargement

What are AE of potassium sparing diuretics?

hyperkalemia, hyperchloremia,

with the ENaC -acute renal failure and kidney stones

What is a benefit of Eplerenone?

less SE bc its more specific for the receptor

How does ADH (vasopression) work?

acts on the V1 and V2 receptors in collecting tubule cells and stim. insertion of water channels (aquaporins) in kidney tubules; our thirst MOA sends signal to pituitary to act on collecting duts

What drug inihibits the aquaporin channel expression?

Conivaptan (Vaprisol)