Term
|
Definition
chlorothiazide
hydrochlorothiazide
chlorthalidone
indapamide
metalozone |
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Term
| potassium sparing diuretics |
|
Definition
spironolactone
eplenerone
amiloride
triamterene |
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Term
|
Definition
furosemide
bumetanide
torsemide
ethacrynic acid |
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Term
|
Definition
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|
Term
| carbonic anhydrase inhibitor |
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Definition
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|
Term
Alter reabsorption of Na+ @ different sites of nephron
(water and chloride follow into tubule) |
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Definition
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|
Term
Osmotic diuretics
In general diuretics: |
|
Definition
increase urine volume
often change the pH
change the ionic composition in the urine |
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Term
| Clinical uses of diuretics |
|
Definition
managing disorders involving abnormal fluid retention (edema)
treating hypertension |
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Term
| How do diuretics treat hypertension? |
|
Definition
decrease blood volume
decrease in blood pressure |
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Term
| The kidney regulates urine production @ five functional zones along the nephron |
|
Definition
proximal convoluted tubule
descending loop of henle
ascending loop of henle
distal convoluted tubule
collecting duct |
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|
Term
| Located in the renal cortex |
|
Definition
| proximal convoluted tubule |
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|
Term
| Almost all of the glucose, bicarbonate, amino acids, and other metabolites are reasbored here |
|
Definition
| proximal convoluted tubule |
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|
Term
| 2/3 of the Na+ is also reabsorbed here |
|
Definition
| proximal convoluted tubule |
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|
Term
| Chloride & water followed passively to maintain electrical & osmolar equality |
|
Definition
| proximal convoluted tubule |
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|
Term
| Site of the organic acid & base secretory system |
|
Definition
| proximal convoluted tubule |
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|
Term
The organic acid secretory systems secrete a variety of organic acids (uric acid, some antibiotics, diuretics) from |
|
Definition
| the blood stream into the proximal tubule’s lumen. |
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Term
| Most diuretic drugs are delivered to the tubular fluid via ?? |
|
Definition
| organic acid secretory system |
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Term
| ______ is saturable, & diuretic drugs in the bloodstream compete for transfer with endogenous organic acids (uric acid) |
|
Definition
organic acid secretory system
which explains why certain drugs cause hyperuricemia |
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|
Term
| The remaining filtrate, which is isotonic, enters.. |
|
Definition
| the descending loop of Henle & passes into the renal medulla |
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|
Term
| Does osmolality decrease/increase along the descending portion of the loop of henle? why? |
|
Definition
| it increaes because of water loss due to the countercurrent mechanism |
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|
Term
| The cells of the ascending tubular epithelium are unique in being.. |
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Definition
|
|
Term
| active reabsorption of Na+, K+, and Cl- is mediated by a Na+/K+/2Cl= cotransporter here |
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Definition
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|
Term
| 25-30% Na+ reabsorbed here |
|
Definition
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Term
| ____ enter the interstial fluid via the paracellular pathway in the ascending loop of henle |
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Definition
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|
Term
| What part is a major site for salt reabsorption? |
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Definition
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Term
| Drugs affecting this site, are the most efficacious of all the diuretic classes |
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Definition
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|
Term
| the cells of the ___ are also impermeable to water |
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Definition
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Term
| Up to ___ of the filtered NaCl is reabsorbed via a Na+/Cl- transporter, which is sensitive to thiazide diuretics |
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Definition
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|
Term
| Ca++ excretion is regulated by the parathyroid hormone in which portion of the tubule? |
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Definition
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|
Term
| the principal and intercalated cells of the ____ are responsible for Na+/K+ reabsorption, respectively |
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Definition
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Term
| Stimulation of aldosterone receptors in the principal cells of the collecting tubule results in... |
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Definition
| Na+ reabsorption & K+ secretion |
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|
Term
| _______ receptors promote the reabsorption of water from the collecting tubules & ducts which is mediated by cAMP |
|
Definition
| antidiuretic hormone (ADH, vasopression) |
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Term
| In many diseases he amount of sodium chloride reabsorbed by the kidney tubules is.. |
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Definition
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|
Term
| If the NaCl is abnormally high this leads to.... |
|
Definition
retention of water
an increase in blood volume
expansion of the extravascular fluid compartment
resulting in edema of the tissues |
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|
Term
|
Definition
decrease cardiac output
decrease renal blood flow & perfusion (increase RAAS)
increase salt & water reabsorption
increase blood volume
increase blood returned to heart |
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|
Term
| Unfortunately the heart cannot handle the increase blood volume and ..... |
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Definition
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|
Term
| Cirrhosis of the liver often results in.. |
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Definition
| accumulation of fluid in the abdominal cavity (ascites) |
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|
Term
| Cirrhosis often results in... |
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Definition
| portal blood flow obstruction = increase portal BP |
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|
Term
| In hepatic ascites, diseased liver has.. |
|
Definition
| impaired plasma protein synthesis = decreased blood colloidal osmotic pressure |
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|
Term
| In hepatic ascites, the diseased liver has impaired metabolism of what? |
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Definition
| aldosterone = increase levels of circulating aldosterone promotes fluid retention |
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|
Term
| Nephrotic syndrome - in damaged kidneys, the glomerular membranes |
|
Definition
| allow plasma proteins to enter the glomerular ultrafiltrate |
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|
Term
| Nephrotic syndrome - edema results from |
|
Definition
| lowered colloidal pressure caused by the loss of protein from plasma |
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|
Term
| Nephrotic syndrome- aldosterone secretion via |
|
Definition
| the RAAS is stimulated by low plasma volume |
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Term
| Premenstrual edema - swelling associated w/ menses is the result of imbalances in hormones such as |
|
Definition
estrogen excess
estrogen facilitates the loss of fluid into the ECS |
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Term
| Most widely used of the diuretics |
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Definition
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Term
| Prototype thiazide diuretic |
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Definition
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Term
|
Definition
distal tubule
decrease the reabsorption of Na+ by inhibition of a Na+/Cl- cotransporter on the luminal membrane |
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|
Term
| Chlorothiazide requires secretion into the |
|
Definition
tubular lumen to be effective
not as efficacious in pts w/ renal disorders |
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|
Term
| Actions of chlorothiazide |
|
Definition
decrease TPR
decrease urinary Ca++ excretion
hyperosmolar urine
acid-base status is not changed |
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|
Term
| Initial decrease in BP results from a decrease in blood volume & decrease CO |
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Definition
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|
Term
| Secondary - decrease peripheral vascular resistance from loss of Na+/Ca++ |
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Definition
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|
Term
| Therapeutic uses of chlorothiazide |
|
Definition
hypertension & CHF
renal impairement
hypercalciuria
nephrogenic diabetes insipidus |
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|
Term
Promotes the reabsorption of Ca+
(in contrast to the loops) |
|
Definition
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|
Term
| cheap, convenient to administer and well tolerated |
|
Definition
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|
Term
| Why does chlorothiazide decrease systolic and diastolic BP? |
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Definition
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|
Term
| If someone has renal impairement and the thiazides aren't working as well then what two drugs can be added? |
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Definition
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|
Term
| Why is chlorothiazide used for hypercalciuria? |
|
Definition
| because it decreases urinary Ca++ excretion & decreases calcium oxalate stones |
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|
Term
| How does chlorothiazide help nephrogenic diabetes insipidus? |
|
Definition
| decreases polyuria and polydipsia |
|
|
Term
| What is nephrogenic diabetes insipidus? |
|
Definition
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|
Term
| Pharmacokinetics of Chlorothiazide |
|
Definition
effective PO
biological half-life (40 hours)
secreted by the organic acid secretory system of kidney |
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|
Term
| AE: K+ depletion (dysrhythmias), volume depletion, hyperuricemia, hypercalcemia, hyperglycemia, hypersensitivity |
|
Definition
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|
Term
| Why do you have K+ depletion with chlorothiazide? |
|
Definition
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|
Term
| Chlorothiazide - volume depletion may cause |
|
Definition
| orthostatic hypotension or light-headedness |
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|
Term
| Since thiazides inhibit Ca++ secretion, it may lead to increase Ca++ in the blood which would cause |
|
Definition
hypercalcemia
good for kidney stones |
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|
Term
| Why does chlorothiazide have hypersensitivity? |
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Definition
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|
Term
| Bone marrow suppression, dermatitis, necrotizing vacuities & interstial nephritis are rare (Steven-Johnsons) |
|
Definition
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|
Term
Thiazide derivative that has proven to be more popular
more potent, same efficacy |
|
Definition
| hydrochlorothiazide (HCTZ) |
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|
Term
thiazide derivative that behaves like HCTZ
long duration & used once daily for HTN |
|
Definition
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|
Term
More potent than the thiazides
Unlike thiazides, because Na+ excretion in advanced renal failure |
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Definition
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|
Term
|
Definition
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|
Term
lipid soluble
nonthiazide diuretic w/ long duration of action |
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Definition
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|
Term
| direct arterial vasodilatation |
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Definition
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|
Term
| metabolized by the GI tract & kidneys so it is less likely to accumulate in renal failure |
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Definition
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|
Term
| used in advanced renal failure to induce further diuresis in addition to the loops |
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Definition
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|
Term
| may be used in low doses in hypertension |
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Definition
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|
Term
| highest efficacy in mobilizing Na+ and Cl- from the body |
|
Definition
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|
Term
| decreased reabsorption of 25-30% of filtered NaCl |
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Definition
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|
Term
| downstream sites are not able to reabsorb Na+ load |
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Definition
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|
Term
|
Definition
| inhibit Na+/K+/Cl- cotransport of the luminal membrane in the ascending limb of the loop of Henle |
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|
Term
|
Definition
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|
Term
| DOC for reducing acute pulmonary edema of CHF |
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Definition
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|
Term
| Also useful for hyperclacemia because they stimulate tubular Ca++ secretion |
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Definition
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|
Term
|
Definition
can be given PO, IM, or IV
duration of action is 1-4 hours (don't give @ bedtime) |
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|
Term
| Ototoxicity, hyperuricemia, acute hypovolemia, K+ depletion, cardiac arrhythmias, hypokalemic alkalosis |
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Definition
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|
Term
| Ototoxicity is seen with loop diuretics, especially when used with.. |
|
Definition
| aminoglycoside antibiotic |
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|
Term
| Cardiac arrhythmias seen in loop diuretics are secondary to the loss of |
|
Definition
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|
Term
| Act in the collecting tubule to inhibit Na+ reasbsorption, K+ secretion, & H+ secretion |
|
Definition
| potassium- sparing diuretics |
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|
Term
| used primarily when aldosterone is present in excess |
|
Definition
| potassium- sparing diuretics |
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|
Term
| Major use of potassium-sparing diuretics? |
|
Definition
| hypertension and may be used in combo w/ thiazides |
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|
Term
| When using potassium-sparing diuretics you should watch what levels? |
|
Definition
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|
Term
| Patient should NOT take K+ supplements while taking these drugs |
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Definition
| potassium-sparing diuretics |
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|
Term
Synthetic aldosterone antagonist that competes with aldosterone for intracellular cytoplasmic receptor sites |
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Definition
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|
Term
| decreased mediator proteins prevents Na+ reabsorption & K+ & H+ secretion |
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Definition
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|
Term
| Antagonizes the hormone activity (ADH) which results in K+ retention and Na+ excretion |
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Definition
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|
Term
| In most edematous states, aldosterone levels are high in the blood which leads to the retention of Na+ |
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Definition
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|
Term
If there is no circulating aldosterone, no diuretic effect will occur with this drug
(addison's dx or primary adrenal insufficiency) |
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Definition
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|
Term
| Spironolactone therapeutic uses |
|
Definition
diuretic
secondary hyperaldosteronism |
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|
Term
| How is spironolactone used as a diuretic? |
|
Definition
causes retention of K+ although it has low efficacy inmobilizing (wasting) Na+
ofen used w/ loops or thiazides |
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|
Term
| How is spironolactone used for secondary hyperaldosteronism? |
|
Definition
| because spironolactone competes with aldosterone |
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|
Term
| Completely absorbed PO & is strongly bound to proteins (induces hepati cytochrome P-450) |
|
Definition
|
|
Term
| Spironolactone is rapidly converted to an.. |
|
Definition
active metabolite, canrenon
(which has mineralcorticoid-blocking activity)
(pro-drug) |
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|
Term
| Should not be given in high doses on a chronic basis |
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Definition
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|
Term
| most effect when given for mild edema for a few days at a time |
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Definition
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|
Term
| AE: resembles some of the sex steroids it may induce gynecomastia in male & menstrual irregularities in females and hyperkalemia |
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Definition
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|
Term
| What are the AE of spironolactone associated wth hyperkalemia? |
|
Definition
dysrhythmias
nausea
lethargy & mental confusion can occur |
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|
Term
|
Definition
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|
Term
| What is the advanage of eplerenone? |
|
Definition
| less estrogenic/steroid adverse effects than spironolactone |
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|
Term
| Block Na+ transport channels resulting in a decrease in Na+/K+ exchange |
|
Definition
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|
Term
| Has K+ spraring actions similar to spironolactone |
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Definition
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|
Term
| Triamterene & Amiloride doesn't depend on... |
|
Definition
| aldosterone so it has diuretic activity even w/ addison's disease |
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|
Term
Not the most efficacious diuretics
frequently used in combination w/ other diuretics |
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Definition
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|
Term
less effective than loop diuretics or thiazides
not used commonly for the diuretic effect |
|
Definition
| carbonic anhydrase inhibitors |
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|
Term
MOA:inhibits carbonic anhydrase of prox. tublar epithelium
decrease ability to exchange Na+ for H+
(puts extra sodium in the mix) |
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Definition
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|
Term
| several days of therapy will result in the loss of HCO3 which leads to a hyperchloremis metabolic acidosis & decrease diuretic efficacy |
|
Definition
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|
Term
|
Definition
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|
Term
| AE: Metabolic acidosis, K+ depletion, renal stone formation, drowsiness, paresthesis |
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Definition
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|
Term
| Prototype drug of carbonic anhydrase |
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Definition
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|
Term
| Therapeutic uses of acetazolmide |
|
Definition
open-angle glaucoma
mountain sickness |
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|
Term
| How does acetazolmide treat open-angle glaucoma? |
|
Definition
decrease aqueous humor production
decrease IOP
|
|
|
Term
| Useful for chronic therapy but not in acute attacks of open angle glaucoma |
|
Definition
Acetazolamide
would use trusopt or azopt for acute |
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|
Term
| How does acetazolmide treat mountain sickness? |
|
Definition
Prophylaxis of acute mountain sickness in healthy, physically active people who rapidly ascend above 10,000’
Must be given nightly for 5 days prior to the ascent to prevent the weakness, breathlessness, dizziness, nausea, & cerebral & pulmonary edema |
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|
Term
| filtered through the glomerulus |
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Definition
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|
Term
| cause increase water excretion rather than Na+ excretion, they are not helpful with Na+ retention conditions |
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Definition
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|
Term
| used to maintain urine flow following acute toxic ingestion of substances capable of producing acute renal failure |
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Definition
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|
Term
| mainstay of tx for increased ICP |
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Definition
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|
Term
| Acute renal failure due to shock, drug toxicities and trauma |
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Definition
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|
Term
| maintaingin urine flow preserves long-term kidney function & may prevent need of dialysis |
|
Definition
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|
Term
| Which osmotic diuretic must be given IV? |
|
Definition
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