Help
Options
Didn't know it?
click below
click below
Knew it?
click below
click below
Don't Know
Remaining cards (0)
Know
retry
shuffle
restart
0:00
Embed Code - If you would like this activity on your web page, copy the script below and paste it into your web page.
Normal Size Small Size show me how
Normal Size Small Size show me how
-diuretics
UVa med pharmacology block 3
| Question | Answer |
|---|---|
| Amiloride/Triamterene | K-sparing diuretics - tx mineralcort excess, prevent K loss - block Na influx via ENaC @ CCT->reduces apical NA influx + lumen neg voltage - bind to plasma prots, reach site by tubular secretion - triam extensively metab'd->shorter T1/2~4.2h vs Amil 21h |
| Spironolactone/Eplerenone | K-sparing diuretics - tx mineralcort excess, prevent K loss, in combo tx- compet inhib of aldosterone binding to MR->reduced expre of ENaC & Na-K-ATPase->reduces capacity of CCT to reabsorb - Spir has slow onset/offset of axn = protein turnover(24-72hrs) |
| What is the excretion pattern of K-sparing diuretics? | Na increased ~2% Cl incereased H secretion reduced though acidosis is rare HCO3 increased - alkylated urine K decreased |
| What are the toxicities of K-sparing diuretics? | Hyperkalemia - exacer'd in renal dx w/reduced GFR, drugs that reduce ang2 axn (ACEI/ARB) or renin secretion (beta blockers, NSAIDS) - never give w/K supps Gyneco/dysmeno (spir - not clean) Kidney stones (triam) Hyperchloremic metabolic acidosis (rare) |
| Hydrochlorothiazide/metalozone | Thiazide diuretics - tx HTN, DI, edema, hypercalcuria, in comb w/ACEI or vasodilators - anionic compete w/Cl @ NaCl cotrans->red's PVR - delivered to lumen via secretion/filtration - intermed T1/2~2.5hrs - potencies H=1, M=10 |
| Chlorthalidone/Indapamide | Thiazide diuretics - tx HTN, DI, edema, hypercalcuria, in comb w/ACEI or vasodilators - anionic compete w/Cl @ NaCl cotrans->red's PVR - gets to lumen via secretion/filtration, C inhibs CA - long T1/2 - C~47h, I~14h - potency C=1, I=20 |
| What is the urinary excretion pattern of thiazide diuretics? | Na increased 8% Cl increased Ca decreased K increased HCO3 decreased |
| What are the toxicities of thiazide diuretics? | Hypokalemia->arrhythmias, metabolic alkalosis, hyperglycemia Hyponatremia Hyperlipidemia Hyperuricemia Hypercalcemia |
| What parts of the tubules in the kidney are not permeable to water? | Thick Ascending Limb and Descending Loop are impermeable to water. |
| What part of the tubules do Osmotic Diuretics act on? | Proximal Tubule and Descending Limb |
| What part of the tubules do Thiazide Diuretics act on? | The proximal part of the Distal Tubule |
| What part of the tubule do K+ Sparing Diuretics work on? | The distal part of the Distal Tubule |
| What part of the tubules do the Loop Diuretics work on? | Thick Ascending Limb |
| The response to a diuretic is determined by its site of action. What are the responses from the following sites: Proximal Tubule Thick Ascending Limb Distal Tubule | Proximal Tubule: Increase in HCO3 excretion TAL: Increase in K and Cl excretion DT: Decrease in Ca excretion |
| What is the mechanism of K-sparing diuretics? | - Block entry of Na in ENaC channels (Amiloride or Triamterene) - Competitive Antagonism of Aldosterone Receptor --> Reduce expression of ENaC and Na-K-ATPase (Spironolactone, Eplerenone) |
| Which of the K-sparing diuretics has a slow onset/offset of action? Quick half-life/extensively metabolized? | Spironolactone has slow onset/offset of action (24-72hrs) Triamterene has a 4.2hr half-life. |
| How does blocking ENaC cause diuresis and spare potassium? | It reduces apical Sodium entry, thus leaving sodium in the lumen and keeping water there. Because the sodium is staying in the lumen, it decreases the lumen negativity that normally draws K+ out of Principal Cells. |
| How is Cl, H, and HCO3 excretion affected by K-sparing Diuretics? | - Cl excretion is increased (normally the negativity of lumen forces transcellular reabsorption of Cl) - H secretion is reduced (less lumen electronegativity) - HCO3 excretion is increased --> Alkalinization of urine. |
| What is the main concern with K-sparing diuretics and toxicity? | - Hyperkalemia - Retain more K due to "sparing" mechanism * Never give with K Supplements. |
| What can exacerbate Diuretic-induced Hyperkalemia? | - Renal disease with reduced GFR - ACE inhibitors - Angiotensin II Receptor Blockers - B-Blockers and NSAIDs that reduce Renin |
| What are some therapeutic uses for K-sparing Diuretics? | - Primary Hyperaldosteronism (Conn's Syndrome) - Secondary Hyperaldosterone - Diminished ECV (HF, Hepatic Cirrhosis, Nephrotic Syndrome) - To prevent K loss during chronic therapy w/ other diuretics. - In comb with other diuretics for greater natriure |
| Spironolactone can cause what type of side effect? | Has affinity for progesterone receptor, and can cause Gynecomastia/Dysmenorrhea. |
| Triamterene can cause what kind of side effect? | Kidney Stones. It is poorly soluble and can precipitate. |
| What are the relative potencies of the Thiazide diuretics Hydrochlorothiazide, Metalozone, Chlorthalidone, and Indapamide? | H & C = 1, M = 10, I = 20 |
| What is the mechanism of Thiazide diuretics? | - Compete with Cl for site on NaCl cotransporter - Reduce PVR with long term use (renal prostaglandin production) |
| What do Thiazide diuretics do to the Urinary Excretion of: Na, Cl, Ca? | Na is increased by 8% Cl increased Ca decreased (low IC Cl --> Hyperpolarizes membrane --> increased Ca reabsorption) |
| What happens to K excretion when using Thiazides? | Due to increased Na delivery, K secretion at Cortical Collecting Tubule is increased. |
| What are therapeutic uses of Thiazides? | - Hypertension - Hypercalcuria (with stone formation). - Nephrogenic Diabetes Insipidus (Promote salt loss enhances proximal Na reabsorption --> enhance water reabsorption) - Resistant Edema (not advised when kidney failure) |
| What are some ionic/metabolic imbalances that can be caused by Thiazides? | Hypokalemia (most kaliuretic agent) Hyponatremia (contracted ECV --> ADH secretion) Hyperlipidemia (Increased LDL/Cholesterol) Hyperuricemia (Competition with Urate for secretion in PT) Hypercalcemia (Prolonged therapy) |
| What are mechanisms for Loop diuretics? | - Inhibit Na-K-2CL transporter (Furosemide, Bumetanide, Torsemide, Ethacrynic Acid) - Inhibit Basolateral K-Cl transporter (Ethacrynic Acid) |
| What happens to medullary interstitium and urinary volume when using Loop Diuretics? | Large increase in urine volume due to reduced tonicity of medullary interstitium. * The water channels rely on Osmotic driving force of the medullary interstitium to reabsorb water. If this driving force is lower, less water is reabsorbed. |
| What are some therapeutic uses of Loop Diuretics? | - Edematous States - refractory edema, use with Thiazides or K-sparing - Renal insufficiency w/ salt retention, drug is delivered via secretion. - Life-threatening Hyponatremia (Promotes water loss > Na Loss) - Mild Hyperkalemia - Hypercalcemia |
| What are some cautious against using Loop Diuretics? | - Diminishing arterial blood volume too much - Reducing Vital Organ Perfusion - Initiating compensatory mechanisms for restoration of intravascular volume (Renin-Ang II) |
| What are some toxicities of Loop Diuretic use? | - Hypokalemic Metabolic Acidosis - Ototoxicity (Enhances toxicity of Aminoglycosides) - Hyperuricemia (Gout attacks) by promoting Urate absorption - Hypomagnesia (chronic use) -Dehydration - Hyperglycemia (reduced plasma K) - Hypokalemia (Chronic us |
| What is the mechanism of Carbonic Anhydrase Inhibitors? | - Inhibits H secretion in early PT, TAL, and CCT - Inhibits HCO3 Reabsorption |
| What are the main therapeutic uses for Carbonic Anhydrase inhibitors? | - Rarely used as diuretic - Glaucoma (Reduces aqueous humor production) - Urinary Alkalinization (enhance excretion of weak acids like uric, cystine) - Metabolic Alkalosis (restores acid-base balance in edematous patients with alkalosis) |
| What are some toxicities to consider when using Carbonic Anhydrase Inhibitors? | - Hyperchloremic Metabolis Acidosis - Renal Stones (Reduced Ca reabsorption) - Potassium Wasting |
| How do Osmotic Diuretics work? | - Raise osmolality of plasma and tubular fluid - Extract water from cells, expand ECV, removal of Na/Urea from medullary interstitium --> Decreased water reabsorption - Increased RBF, Increased GFR |
| How are osmotic diuretics administered? | Parenterally. If given orally they cause diarrhea. |
| Furosemide/bumetanide | Loop diuretics - Edematous states, mild hyperkalemia, hypercalcemia, hyponatremia - Inhibit Na-K-2CL symporter->increase venous capacitance->reduces ventircular filling pressure - protein bound, secretion only - t1/2 .8-1.5hrs - B 40x more potent than F |
| Torsemide | Inhibit Na-K-2CL symporter->increase venous capacitance->reduces ventircular filling pressure - protein bound, secretion only - t1/2 t1/2 ~3.5hrs - oral availability |
| Ethacrynic acid | Inhibit Na-K-2CL symporter & basolateral K-Cl transporter->increase venous capacitance->reduces ventircular filling pressure - protein bound, secretion only - t1/2 ~1hr |
| What is excretion pattern of Loop diuretics? | Na increased 25% Cl, K (<thiazides), Mg, Ca increased HC03 decreased (reabsorbed at CCT) Large urine volume increase Alkalosis 2ndary to increase in Ang2 |
| What are the toxicities of loop diuretics? | Hypokalemic metabolic alkalosis Ototoxicity Hyperuricemia Hypomagnesemia Severe dehydration - hypovolemia, hypotension hyperglycemia <thiazides hypokalmeia |
| Acetazolamide | Carbonic Anhydrase inhibitor - tx glaucoma, urinary alkalin, metabolic alkalosis - inhibs CA activity - stops H secretion in early PT, TAL, & CCT, inhibs HC03 reabsorption - t1/2 6-9hrs, 100% oral availability |
| What is the urinary excretion pattern of CA inhibitors? | Na increased 5% HC03 increased (45% inhibition of reabsorption) Cl decreased K increased |
| What are the toxicities of CA inhibitors? | Hyperchloremic metabolic acidosis Renal stones - due to reduced Ca rabsorption in PT Potassium wasting |
| Mannitol/Isorbide | osmotic diuretics - extract H20 from cells expands ECV, increase medullary BF, remove NA/urea from interstitium, decr H20 reab in thin DL, CCT, PT, incr RBF/GFR - give paranterally, not metab'd, reab'd nor secreted - increase in urine flow reduces Na reab |
Created by:
sam.mrosenfeld
Popular Pharmacology sets