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50 Cards in this Set
- Front
- Back
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List the principles of diuretic action
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They increase the rate of sodium excretion : this prevents sodium overload which leads to fluid build-up and edema
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List the classes of diuretic drugs and an example of each
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• Inhibitors of Na+-K+-2CL- Symport (Loop diuretics) Furosemide, Bumetanide, etc. • Inhibitors of Na+-CL- -Symport (Thiazide and Thiazide-like Diuretics); Chlorothalidone etc • Inhibitors of Renal Epithelial Na+ Channels (K+-sparing diuretics); Amiloride, Tramterene • Antagonists of mineralocorticoid receptors; Spironolactone, Canrenone, etc. • Inhibitors of Carbonic Anhydrase; Acetazolamide, Dichlorphenamide, Methazolamide • Osmotic Diuretics; Manitol, Urea, Isosorbide, and Glycerin |
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Explain where Carbonic Anhydrase is found
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• proximal tubule epithelial cells, the luminal and basolateral membranes and the cytoplasm
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What effect do CA inhibitors have on urinary excretion
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• Na+ excretion increased (by about 5%) • K+ excretion increased (by approx.70%) • Urine pH is increased to about 8 |
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What effect do CA inhibitors have on renal hemolytics
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• Reduced renal blood flow and decreased glomerular filtration (Tubuloglomerular Feedback) • Increased Na+ detection by the MACULA DENSA results in increased RENIN release and increased tone of the AFFERENT ARTERIOLE |
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Name the 3 CA inhibitor drugs
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• Acetazolamide • Dichlorphenamide • Methazolamide |
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What is the effect of CA inhibitor toxicity
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• Bone marrow depression • Allergic reactions • skin toxicity • renal lesions |
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What are contraindications for CA inhibitor use
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• Hepatic encephalopathy(due to increase NH4+ in systemic circulation) • liver cirrhosis • metabolic or respiratory acidosis • severe COPD |
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To which patients will we give CA inhibitors
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• Patients resistant to diuretic monotherapy • Glaucoma patients • Epilepsy sufferers • familial periodic paralysis sufferers • patients with metabolic alkalosis |
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Where do osmotic diuretics work and how
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• Proximal tubule and loop of Henle • Expand ECF volume, decrease blood viscosity, and inhibit renin release • Improve renal blood flow: removes NaCl and ureas reduced medullary tonicity reduced water removal |
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What effects do osmotic diuretics have on urinary excretion and its components
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• Increase the urinary excretion of Na+, K+, Ca2+, Mag2+, Cl-, HC03- and Phosphate
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What effects do osmotic diuretics have on renal hemolytics
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• They increase renal blood flow by: Dilating the afferent arteriole -> increasing glomerular capillary pressure Diluting the plasma -> decreasing the mean colloid osmotic pressure in the glomerular capillaries |
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When do we use Mannitol and how does it work
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• When there is rapid decrease in GFR it is used to prevent ischemic insult or offending nephrotoxin • How it works: Removal of obstructive tubular casts Dilution of nephrotoxic substances in the tubular fluid Reduction of swelling of tubular elements via osmotic extraction of water |
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List the 4 osmotic diuretics
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• Glycerin • Isosorbide • Mannitol • Urea |
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What are the adverse effects of osmotic diuretics?
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• Frank pulmonary edema in patients with heart failure or pulmonary congestion • Headache, nausea and vomiting secondary to hyponatremia • Hypernatremia secondary to loss of more water than electrolytes |
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What are the contraindications of osmotic diuretics
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• urea is avoided in patients with liver failure • avoid urea and mannitol in patients with active cranial bleeding • avoid glycerin in patients with impaired glucose tolerance or DM (when glycerin is metabolized it can cause hyperglycemia) |
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In which patients will we use osmotic diuretics
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• Acute renal failure and glaucoma patients • Jaundiced patients undergoing surgery (mannitol) • Acute Tubular Necrosis (Mannitol) • dialysis disequilibrium syndrome • prophylaxis against cerebral edema (mannitol and urea) |
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Where do loop diuretics work and how
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• Thick ascending limb • loop diuretics bind to the symporter of Na+-K+-2Cl at the Cl- binding site, and inhibit the symporter’s function, preventing electrolyte reabsorption • LD increase the excretion of uric acid acutely, but eventually they reduce uric acid excretion. • LD block the creation of the hypertonic medullary interstitium, inhibiting the kidney’s ability to concentrate urine during hydropenia. |
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What effects do loop diuretics have on urine and its contents
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Increase the excretion of Na+ and Cl- profoundly; Ca2+ and Mg+; HCO3- and phosphate; K+ and H+
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What effects do loop diuretics have on renal hemodynamics
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• Increase renal blood flow • Inhibit tubular glomerular feedback (very important) • Stimulate renin release via volume depletion • Frusemide increases systemic venous capacitance |
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List 4 important loop diuretic drugs
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• Furosemide (Secretion of Furosemide is competitively inhibited by probenecid) • Bumetanide (Metabolized by the liver) • Ethacrynic acid • Torsemide (Good bioavailability, recommended for patients with heart failure. Has longest half-life) |
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What are the adverse effects to loop diuretics
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• Hyponatremia • Reduced GFR • Circulatory collapse • Thromboembolic episodes • Hyperuricemia leading to gout |
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List some drug interactions with loop diuretics
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• Aminoglycosides + LD cause ototoxicity • LD + Digoxin can lead to cardiac arrest • Probenecid decreases effects of loop diuretics |
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What therapeutic uses are loop diuretics used for
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• Hypercalcemia • Hyponatremia • NOT used for hypertension!!! |
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How do thiazide and thiazide-like diuretics work
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• Have an unsubstituted sulphonamide group • Inhibit the luminal Na+Cl- transporter • Enhance Calcium reabsorption – Thiazide stop Na reabsorption, decreasing intracellular Na levels so Ca fills the gap. |
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What effects to Thiazide diuretics have on renal hemodynamics
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• The do not affect RBF • They act passed macula densa so they do not affect TGF |
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Name some Thiazide diuretics
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• Hydrochlorothiazide (Only thiazide given parenteraly) • Bendroflumethiazide • Chlorothiazide • Methyclothiazide • Polythiazide • Chlorthalidone • Metolazone |
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List some conditions caused by Thiazide diuretic toxicity
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• Extracellular fluid depletion, electrolyte imbalance, Hyperlipidemia • Hemolytic anemia and thrombocytopenia • Erectile dysfunction • Glucose intolerance or hyperglycemia in patients that are overtly diabetic |
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What drug interactions can occur with Thiazide diuretics
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• Reduce therapeutic effects of anticoagulants, uricosuric agents (treat gout), sulfonylureas, and insulin • Increase effects of anesthetics, diazoxide, digitalis glycosides, lithium, loop diuretics, and vitamin-D • NSAIDs inhibit the effects of thiazide diuretics |
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When will we use Thiazide diuretics
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• Hypertension • Heart failure • Nephrolithiasis-hypercalciuria • Nephrogenic diabetes insipidus |
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What contraindication is there for Thiazide diuretics
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• Hypersensitive to sulphonamides
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Name the 2 groups of K+ sparing diuretics and the drugs in each group
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• Inhibitors of sodium channels: Amiloride, Triamterene • Antagonists of mineralocorticoid receptors: Spiironolactione, Eplerenone |
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How do K+ sparing diuretics work
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Inhibit the function of the Na+ channels, reduce depolarization and thus reduce the secretion of K+ from the cell
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What effects do K+ sparing diuretics and aldosterone antagonists have on renal hemodynamics
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None
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Describe metabolism, excretion and toxicity of Triamterene
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• Metabolized into 4-hydroxytriamterene sulfate.• The metabolite is excreted renally • In cases of liver and kidney disease toxicity of Triamterene is increased |
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When do we use K+ sparing diuretics
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• To augment diuretic and antihypertensive response to thiazide and loop-diuretics • In cases of hypertension • To prevent kaliuresis • Cystic fibrosis |
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What are contraindications for using K+ sparing diuretics and Aldosterone antagonists
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• Patients with hyperkalemia or increased risk of hyperkalemia • Patients taking ACE inhibitors • Patients taking K+ supplements |
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What drugs can interact with K+ sparing diuretics
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• ACE inhibitors • NSAIDS |
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What are possible side effects of using K+ sparing diuretics
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• Triamterene -> Glucose intolerance, photosensitivity, Nephritis, renal stones, nausea, vomiting, leg cramps, dizziness (It’s a folic acid antagonist)• Tramterene -> megaloblastosis • Amiloride -> Nausea, vomiting , diarrhea, and headache • Hyperkalemia |
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How does Aldosterone effect the mineralocorticoid receptors in the nephron
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• Aldosterone binds to the mineralocorticoid receptors, forming an MR-Aldosterone complex • The complex is transported to the nucleus where it binds to the DNA • Starts the synthesis of Aldosterone Induced Proteins (Na+ channels and Na+ pumps) • Hyperpolarization of the lumen facilitates the secretion of potassium into the lumen |
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When do we use Aldosterone antagonists
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•Edma • hypertension • Primary hyperaldosteronism • hepatic Cirrhosis (spironolactone) • ventricular arrhythmias • myocardial Infarction |
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What adverse effects can be caused by Aldosterone Antagonists
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• Hyperkalemia • Spironolactone: gynecomastia • Impotence • Decreased libido • Hirsutism • menstrual irregularities • Diarrhea, gastritis, gastric bleeding, peptic ulcers • Skin rashes • Breast Cancer |
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What drugs can cause interactions with Aldosterone Antagonists
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• Salicylates • Digitalis glycosides • Strong inhibitors of CYP3A4 may increase eplerenone and vice-versa. |
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Why should we take caution when using diuretics
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Excessive use can reduce blood volume and thus compromise blood supply to vital organs/tissues.
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When should we consider using diuretics
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• Heart failure -> Reduced BP and reduced blood supply to kidneys -> Na+ and H2O retention = Use diuretics • Renal failure if GFR is less than 5-15mL/min = Use diuretics • In nephrotic syndromes associated with Na+ and H2O retention = Use diuretics • Do not use diuretics in cases of renal failure where GFR is more than 5mL/min or in cases of ascites |
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What should be used in cases of hepatic cirrhosis with ascites and edema
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• Best choice is Aldosterone antagonists • Loop diuretics should NOT be used |
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When can Thiazide diuretics be used
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• Hypertension: causes vasodilation • Nephrolithiasis • Mild Pulmonary edema in patients with Chronic Heart failure |
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When can loop diuretics be used
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• Hypercalcemia: Administer with NaCl to avoid volume depletion • Massive Pulmonary edema in patients with ACUTE left sided heart failure • Mild Pulmonary edema in patients with Chronic Heart failure |
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What can cause resistance to Loop diuretics (cause them to fail)
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• NSAIDs • COX-2 inhibitors • Chronic Heart Failure • Nephrotic Syndrome • Liver Cirrhosis, HF, and Nephritic syndrome |
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What should be done in cases of resistance to Loop diuretics
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• Bed rest and reduced salt intake • Increase dose of loop diuretics • IV administration or small but frequent doses • Combine with other diuretics • Take shortly before meals |
