Term
| What are the seven classes of diuretics? |
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Definition
1. Osmotic diuretics
2. Carbonic anhydrase inhibitors
3. Thiazide diuretics
4. Thiazide-like diuretics
5. Loop/high ceiling diuretics
6. Potassium-sparing diuretics
7. Mineralocorticoid antagonists |
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Term
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Definition
A.Cortical and Medulary Collecting Tubule
B. Thin Descending Limb (loop of henle)
C. Thin Ascending Limb
D. to renal vein
E. Glomerular Capsule
F. Glomerulus
G. Artery (afferent(in) and efferent (out))
H. Proximal Tubule
I. Distal Convoluted Tubule (location of macula densa)
J. Peritubular Capillary |
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Term
| Name two Osmotic Diuretics |
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Definition
Isosorbide and Mannitol
...also urea and glycerin (gycerol) |
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Term
| Name a Carbonic Anhydrase Inhibitor |
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Definition
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Term
| Name eight Thiazide Diuretics |
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Definition
Chlorthiazide
Benzthiazide
HCTZ
Trichloromethiazide
Methylclothiazide
Polythiazide
Hydroflumethiazide
Bendroflumethiazide |
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Term
| Name four Thiazide-like Diuretics |
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Definition
Metolazone
Quinethazone
Chlothalidone
Indapamide |
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Term
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Definition
Furosemide
Ethacrynic Acid
Bumetadine
Torsemide |
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Term
| Name two Potassium-Sparing Diuretics |
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Definition
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Term
| Name three Aldosterone Antagonists (Mineralcorticoid Receptor Antagonists) |
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Definition
Spironolactone
Canrenone
Eplerenone |
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Term
| Where is the site of action of osmotic diuretics? |
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Definition
| Proximal tubule and the loop of henle and the collecting tubule |
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Term
| Where is the site of action of carbonic anhydrase inhibitors? |
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Definition
| proximal convoluted tubule |
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Term
| What is the site of action of the thiazides and thiazide-like diuretics? |
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Definition
| cortical portion of the thick ascending limb of the loop of henle and distal tubule. |
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Term
| What is the site of action of the loop (or high ceiling) diuretics? |
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Definition
| thick ascending limb of the loop of henle |
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Term
| What is the site of action of the potassium-sparing diuretics? |
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Definition
| distal tubule and collecting duct |
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Term
| What is the mechanism of action of osmotics? |
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Definition
| (limits water reabsorption) osmotic effects decrease Na and water reabsorption. Increases medullary blood flow to decrease medullary hypertonicity and reduce Na and water reabsorption. Na and water reabsorption decreases because of reduced medullary hypertonicity and elevated urinary flow rate. |
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Term
| What is the mechanism of action of CA inhibitors? |
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Definition
| Inhibitiion of renal carbonic anhydrase decreases Na-HCO3 reabsorption. |
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Term
| What is the mechanism of action of thiazides and thiazide-like diuretics? |
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Definition
| inhibition of Na-Cl symporter |
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Term
| What is the mechanism of action of loop or high ceiling diuretics? |
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Definition
| inhibition of the luminal Na/K/2Cl transport system |
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Term
| What is the mechanism of action of loop or high ceiling diuretics? |
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Definition
| inhibition of the luminal Na/K/2Cl transport system |
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Term
| What is the mechanism of action of potassium-sparing diuretics? |
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Definition
inhibition of Na and water reabsorption by:
Competitive inhibition of aldosterone (spironolactone).
Blockade of Na channel at the luminal membrane (triamterene and amiloride) |
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Term
| Why are osmotic diuretics not frequently used? |
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Definition
| it takes a lot to cause diuretic action |
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Term
| What is isosorbide primarily used in? |
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Definition
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Term
| Absorption is a balancing act between ___________ and _________________________________________. |
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Definition
| absorption is a balancing act between solubility and the ability to cross a membrane. |
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Term
| The logP method of estimating polarity... |
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Definition
| sums the hydrophobic/hydrophillic values of functional groups on a molecule (the pi values) |
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Term
| what does a large logP value mean? |
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Definition
| low solubility (USP defines water solubility as >3.3% or approx logP<=0.5) |
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Term
| How does a diuretic help to cross the BBB? |
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Definition
| its integrity can be breeched by using an osmotic agent to shrivel up the cells, because it sucks water out of them. |
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Term
| Mannitol is administered via IV because... |
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Definition
| The molecule is polar, but it had bad absorption. |
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Term
| If you toss something into a beaker of water and oil...if it stays in the oil portion, what is the logP? |
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Definition
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Term
| If you toss something into a beaker of water and oil...if it stays in the water portion, what is the logP? |
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Definition
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Term
| If you have a low logP, it will_______, but not____________________. |
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Definition
| Low logP: goes into soln well, but doesn’t get across membranes. |
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Term
| What does the methyl group on methazolamide do? |
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Definition
| The methyl group on methazolamide increases penetration into the ocular fluid. |
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Term
| CA Inhibitors limit the number of protons needed for... |
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Definition
| proton coupled Na readsorption in the proximal tubule. |
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Term
| What drug is a weak diuretic AND an antibiotic? |
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Definition
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Term
| The sulfonamide group is an iosostere of carbonic acid. This allows the compound to bind to carbonic anhydrase and inhibit the enzyme. What does isostere mean? |
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Definition
| biologically replaceable. |
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Term
| What are the two early classes of diuretics and give examples. |
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Definition
Heterocyclic Sulfonamides and meta-disulfamoylbenzene. Sulfa group!
Acetazolamide and methazolamide are made from heterocyclic sulfonamides. |
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Term
| In terms of substitutions and halogens, what do meta-disulfamoylbenzenes need? |
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Definition
| they require the meta position to be an unsubstituted sulfamoyl moiety and they need a halogen at the top corner. (ie: dichlorphenamide and chloraminophenamide.) |
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Term
| Meta-disulfamoylbenzene derivatives are clinically available __________ and are all _____________ from the gut, have ______ metabolism and are excreted primarily by the _________. |
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Definition
| meta-disulfamoylbenzene derivatives are clinically available CA inhibitors and are all well absorbed from the gut, have little metabolism and are excreted primarily by the kidney. |
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Term
| What are the toxicities associated with meta-disulfamoylbenzene derivatives? |
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Definition
| metabolic acidosis (because there are a bunch of protons), hypokalemia (because it's a diuretic), reduction in the GFR, and sulfonamide hypersensitivity (because its related to a sulfonamide) |
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Term
| Chloraminophenamide can be made into_____________ by acylating agents which form a __________. |
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Definition
| Chloraminophenamide can be made into thiazides by acylating agents which forma a double bond |
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Term
| Chloraminophenamide can be made into_____________ with aldehydes (or ketones) which form __________. |
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Definition
| chloraminophenamide can be made into hydrothiazides with aldehydes (or ketones) which form hydrothiazides. |
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Term
| Upon ring closure, chloraminophenamide lost much of its ____________ activity, but still retained its diuretic activity leading to the _____________and _____________ diuretics. |
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Definition
| Upon ring closure, chloraminophenamide lost much of its CA activity, but still retained its diuretic activity leading to the thiazide and hydrothiazide diuretics. |
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Term
In order to be made for infusion, the salts should be:
a. weakly basic
b. weakly acidic
c. strongly basic
d. strongly acidic |
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Definition
| salts are weakly acidic so they can be made for IV infusion. |
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Term
| What is the standard treatment for hypertension? |
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Definition
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Term
| In terms of thiazides and hydrothiazides, what is essential in the structure for activity? |
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Definition
| substitution with an electron withdrawing group - Cl, F, CF3 - is essential for activity. |
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Term
| T/F In hydrothiazide diuretics, the H2NO2S on the seven position can be substituted. |
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Definition
| FALSE. In hydrothiazide diuretics, the H2NO2S on the seven position CAN'T be substituted. |
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Term
| T/F In the proximal convoluted tubule, reabsorption occurs and weak acids are preferentially secreted. |
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Definition
| True. In the proximal convoluted tubule, reabsorption occurs and weak acids are preferentially secreted. |
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Term
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Definition
| Take a disulfabenzene ring in the meta position, add a Cl at the 6th potision, reduce the double bond and you get HCTZ. |
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Term
| In Thiazide and Hydrothiazide diuretics, What position changes the PK/ADME properties? |
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Definition
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Term
| T/F The thiazide-like diuretics have different efficacy, ADRs, electrolyte patterns, but the same site of action so they are included with the thiazides. |
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Definition
| FALSE. The thiazide-like diuretics have similar efficacy, ADRs, electrolyte patterns, site of action and are included with the thiazides. |
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Term
| Which group has been associated with hypersensitivity in the diuretics, and what reactions can it cause? |
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Definition
| The sulfamoyl group has been associated with hypersensitivity. It can lead to uticaria, drug induced fever, blood dyscrasias, interstitial nephritis - an individual hypersensitivity to one will probably be hypersensitive to all. |
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Term
| In Loop diuretics (or high ceiling diuretics) what leads to extensive secretion into the proximal tubule? |
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Definition
| weak acids lead to extensive secretion into the proximal tubule in loop/high ceiling diuretics. |
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Term
| Which diuretic has a very rapid onset, and therefore should not be taken right before bed? |
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Definition
| Lasix (furosemide) has rapid onset with LOTS of urine. It's a very quick diuretic. It is a loop diuretic because it works at the loop of henle. You lose lots of Na, Cl, and H2O. |
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Term
| Where do loop diuretics work, and how? |
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Definition
| loop diuretics work at the loop of henle. They cause excretion of lots of Na, Cl, and H2O. |
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Term
| What ion do you worry about for loop diuretics? |
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Definition
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Term
| _________ blocks the Na/K/Cl co-transport system. |
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Definition
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Term
| __________ blocks sulfhydryl enzymes involved in readsorbtion |
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Definition
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Term
| Name four new high ceiling diuretics |
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Definition
muzolimine
azosemide
piretanide
tripamide |
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Term
| What is the primary mineral corticoid in humans, and how does it work? |
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Definition
| Aldosterone is the primary mineral corticoid in humans, and it works by promoting Na and water retention and K and H excretion, particularly at site 4. |
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Term
| What completely inhibits the action of aldosterone? |
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Definition
| Spironolactone completely inhibits the action of aldosterone |
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Term
| Why does the body absorb potassium sparing diuretics so well? |
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Definition
| They look like steroids, so the body absorbs them well. |
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