DIURETICS 1

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ssilvis
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195987
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DIURETICS 1
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2013-01-28 12:47:08
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Diuretics
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  1. Renal Physiology-
    • *Maintains fluid volume within narrow limits
    • *Maintains acid-base balance and electrolyte blanace in the body.
    • *Removes body of nitrogen wastes
  2. NEPHRON-
    • *Blood vessels
    • *Glomerulus
    • *Afferent and efferent arterioles
    • *Pertibular capillaries
    • *Coiled renal tubule- Proximal, Loop of Henle, and distal.
  3. THE PROCESS OF HOW KIDNEYS CARRY OUT THEIR FUNCTION-
    • 1.  Glomular filtration-
    • High BP in glomerulus forces out water, ions, small molecules.  Absorbed by cells of Bowman's capsule.
    • 2.  Tubular reabsorption-
    • Substances pass from tubule back into blood, involves active and passive processes.
    • 3.  Tubular secretion- substances pass from blood into tubule, involves mainly active processes.
  4. RESORPTION OCCURS:
    • *Ascending loop of Henle
    • *Early distal tubule
    • *Collecting tubules and ducts
  5. PROXIMAL TUBULE-
    • Reasorbs 60-70% of tubular fluid- water and sodium into renal tubule cell, then water and sodium then travel from cell back into BV's.
    • -Sodium with sugars, amino acids, ions
    • -Sodium with potassium and chloride
    • -Carbonic anhyrase system- sodium is exchanged for hydrogen.
  6. FILTRATION SYSTEM-
    • 1. Ascending limb of the loop of Henle-
    • Na, k, and cl cotransport system-absorbed back into blood.
    • 2.  Early distal tubule-
    • active transport of cl, na, and water follow -all absorbed back into the blood
    • 3.  Late distal tubule-
    • Aldosterone dependent na, k, exchange system-na is reabsorbed back into the blood and k is secreted into the renal tubule and excreted.
  7. RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM-
    • *BP detected by juxtaglomerular cells
    • *renin releases
    • *renin stimulates production of angiotensin 1
    • *angiotensin 1 is converted by ACE to angiotensin 2
    • *effects of angiotensin 2- direct vasoconstriction, stimulates thirst, affects CNS tostimulate sympathetic activity.
  8. ADH-
    • *Vasopressin (ADH) on the renal tubules
    • *Increases reabsoprtion  of water from the collecting duct:conserves body water and concentrates urine.
    • *Stimuli for release of ADH
    • 1.  Increasing plasma osmolarity monitored by osmorecptors in  hypothalmus
    • 2.  Volume depletion
    • 3. Stress, exercise
    • 4. ADH causes luminal cell membranes to become permeable to water
    • Diabetes insipidus- inability to make a concentrated urine.
  9. DIURETIC DRUGS
    THERAPUETIC USES:
    • *HTN
    • *Edema due to heart failure
    • *Nephrotic syndrome
    • *Ascities
  10. DIURETIC DRUG PHARMACOKINETICS-
    • *aLL  AFFECT ELECTROLYTES
    • *lIVER IS PRIMARY SITE OF METABOLISM
    • *cAUTION  WITH USING IN RENAL IMPAIRED
    • *CAUTION W ITH HEPATIC DYSFUNCTION
    • *METALAZONE AND BUMETANIDE AND SPIRANOLACTONE HAVE SOME EXCRETION  IN FECES AND BILE
    • (PLASMA HALF LIVES RANGE FROM 30-60 MIN FOR LASIX TO 30-50 HOURS FOR CHLORTHALADONE
  11. TYPES OF DIURETICS
    • 1.  Loop
    • 2. Thiazides
    • 3.  Osmotic
    • 4.  Carbonic anhydrase inhibitors
    • 5.  Postassium-sparing
    • *Aldosterone antagonists
    • *Nonaldosterone antagonists
  12. LOOP DIURETICS-
    • *Lasix, Edecrin, Bumetanide (Bumex)
    • *MOA- blocks 1 na, 1 k, and 2 cl-cotransport system in thick ascending limb of loop  of Henle
    • *Most powerful of all diuretics!!!!!
    • *Effects on diuresis- 25% of filtrate excreted, increased excretion of water, na, k, cl, ca, decreased excretion of uric acid
    • *Effect on Hemodynamics- vasodilation in kidney increases renal blood flow.
    • *SE- decreased blood volume- dehydration,shock, circulatory collapse, thrombi, and emboli.
    • -Electrolyte changes (lead to alkolosis and arrythmias)
    • -Ototoxicity- HIGH with Edecrin
    • -RARE se- nausea, allergic reaction d/t sulfa component, deafness.
    • *PO effect- 1 hour
    • *IV effect- 30 min
    • *Drug interactions- aminoglycosides, warfarin, clofibrate, cephaloridine
    • *Indications-
    • -HTN
    • -Edema d/t HF
    • -Nephrotic syndrome
    • -Ascities
    • -Pulmonary probems- edema
    • -Hypercalcemic crisis
    • -Renal failure
  13. THIAZIDE DIURETICS-
    • *HCTZ, chlorthalidone (Hygroton)
    • *MOA- decreases na and cl reabsoprtion at early distal tubule
    • *effects on  diuresis- 5-8%of filtrate excreted, increased excretion of water, decreased uric acid excretion, decreased excretion of CA!, extrarenal effects- hyperflycemia, vasodilation.
    • *Drug interaction increase effect of BP medications!
    • *po effect in 4-6 ours
    • *S/E-
    • 1.  Fluid and ELECTROLYTE IMBALNACES- decreased k, increased uric acid, hyperglycemia, increased calcium absorption, alkalosis.
    • 2.  Hyperlipidemia
    • 3.  Extrarenal s/e
    • 4.  Male impotence
    • 5.  Hypersensitivity reactions- skin rashes, blood dyscrasia, pancreatitis, acute pulmonary edema.
    • *Indications-
    • 1.  HTN
    • 2.  Edema d/t HF
    • 3.  nephrotic syndrome
    • 4. ascities
    • 5.  diabetes insipidous
    • 5.  Hypocalcemia
    • 6.  Osteoporosis
  14. POTASSIUM-SPARING DIURETICS-
    • *Spironalaction, triamterene, amiloride
    • *MOA- inhibition of na, k, exchange systemsi nt he distal tubule and collecting duct (only spironolactone is competitive antagonist of aldosterone)
    • *effects on diuresis 2-3% of filtered load excreted, increased water and na excretion, decreased k and h excretion.
    • *S/E- electroly imbalances, increased k
    • *Indications- adjunct use with other diuretics to: decrease k loss in HTN, edema, hyperaldosteronism.
  15. CARBONIC ANHYDRASE INHIBITORS-
    • *Acetazolamide (Diamox)
    • *MOA- inhibition of carbonic anhydrase in the  proximal tubule, so that na is excreted and h  is saved in the body
    • *Effect on diuresis- na, k and hco3 are excreted, less cl is excreted, urine becomes alkaline.
    • *S/E- k loss, acidosis, drowsiness, paresthesias, hypersensitivity, teratogenicity
    • *Indications- adjunct use with other diuretics- esp when alkalosis is present, grand mal epilepsy, glaucoma, mountain sickness.
  16. OSMOTIC DIURETICS-
    • *Mannitol (osmitrol)
    • *MOA- works throughout renal tubule, provides nonabsorbable particles that exert osmotic pressure in side renal tubuel
    • *Effect on diuresis- greatly increases water and solute excretion, incrreases excretion of na, k , cl, hco3, ca, mag
    • *Hemodynmaic effect- increases osmolality of plasma
    • *S/E- h/a, n/v, acidosis, increased edema- contraindicated in CHF
    • *used to prevent renal shutdown in burn and trauma pts and brain,eye and CV surgery.

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