Lecture 16: Diuretics

Question 1

Where is renin released?

Answer 1

Juxtaglomerular cells

turns angiotensinogen to angiotensin 1

Question 2

Angiotensin II

Answer 2

potent and direct vasoconstrictor

enhance sympathetic nervous system & release

increase aldosterone secretion

increase Na reabsorption at Proximal tubule

remodelling of cardiovascular

Question 3

Captopril, Enalapril

Answer 3

ACE-inhibitor

decrease TPR, no change in cardiac output or heart rate

inhibits ACE, prevent conversion of angiotensin I to II

Enalapril is a PRODRUG

Question 4

Losartan, Candesartan

Answer 4

Angiotensin receptor blocker (ARB)

decrease TPR by blocking vasoconstriction and decrease aldosterone release

selective antagonist for angiotensin 1 receptor in vascular periphery

Question 5

Aldosterone

Answer 5

release mediated by angiotensin II

release via K+ increase, increase aldosterone

release from adrenal cortex, synthesize more Na K ATPase

increase Na reabsorption and K secretion and excretion

Question 6

Vasopressin (anti diuretic hormone ADH)

Answer 6

release from posterior pituitary

acts on collecting duct to increase water permeability and reabsorption

increase blood volume

Question 7

Atrial Natriuretic peptide (NP) (ANP/ANF)

Answer 7

release in response to atrial stretch due to increase BP and blood volume

increase GFR

increase Na and H2O excretion

decrease aldosterone and renin

decrease in Na concentration, blood pressure and blood volume

Question 8

Where is the most water reabsorption in kidney?

Answer 8

Proximal tubule 60-70%

Question 9

Loop diuretics (Furosemide)

Answer 9

inhibit NKCC2 (Na-K-Cl cotransporter)

at thick ascending limb (loop of henle)

increase K+ (H+) secretion

block Na/Cl reabsorption at H2O impermeable segments

indirectly inhibit Ca2+ and Mg2+ reabsorption and increase their excretion

leads to decrease in CALCIUM level

TREAT HYPERCALCEMIA

Question 10

Adverse effect for loop diuretics

Answer 10

decrease blood volume

hypokalemia (metabolic acidosis)

hyperuricemia (gout)

hyperglycemia (increase LDL decrease HDL)

NSAIDS can reduce sodium excretion and blunt the effect of loop diuretics

Question 11

Thiazide Diuretics (chlorothiazide)

Answer 11

inhibit Na reabsorption from DCT by blocking Na/Cl cotransporter (NCC)

increases K secretion

DECREASE Ca EXCRETION by stimulating Ca reabsorption in DCT (maintain bone mineral density)

FIRST LINE TREATMENT of hypertension

even effective in elderly and african american descent

Question 12

Adverse effect of thiazide diuretics

Answer 12

decrease of blood volume

hypokalemia

hyperuricemia (gout)

hyperglycemia, glucose intolerance, increase LDL, TG

NSAIDS blunt effect by inhibiting Na excretion

Hyponatremia (lose Na)

HYPERCALCEMIA (due to retain of Ca, but in rare cases only)

GI intolerance

QUINIDINE interaction (long Q-T syndrome, hypokalemia)

Question 13

Carbonic Anhydrase inhibitor (Acetazolamide)

Answer 13

weak block of Na reabsorption

indirect and direct inhibition of Na reabsorption via Na-H exchanger at proximal tubule (NaHCO3 symporter)

inhibit CA, increase H+, decrease HCO3, decrease Na reabsorption

Question 14

Potassium Sparing Diuretics (Spironolactone)

Answer 14

Aldosterone antagonist

inhibit Na reabsorption by aldosterone

block K secretion

Question 15

Adverse effect of spironolactone

Answer 15

hyperkalemia leads to renal failure

nausea and vomiting

peppermint taste

steroid structure effects

Question 16

Trimeterene, Amiloride

Answer 16

potassium sparing diuretics

sodium channel blockers

competitive antagonist at Na channel

at cortical collecting duct

inhibit Na reuptake leads to decrease in K+ loss

Question 17

Osmotic diuretics (plasma expanders)

Answer 17

Mannitol, urea

large molecules which drag water wherever they go

administered IV because too large

can be rapidly filtered (rapid GPR)

prevent/reduce BRAIN EDEMA (pull fluid in circulatory system)

adverse effect: hypokalemia, hyponatremia, pulmonary edema, dehydration