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Diuretics Lilley Reading & Workbook, Chap 25 Drugs that accelerate the rate of urine formation In the nephron, where sodium goes, water follows ◦ 20% to 25% of all sodium is reabsorbed into the bloodstream in the ascending loop of Henle ◦ 5% to 10% in the distal convoluted tubules ◦ 3% in collecting ducts If water is not absorbed, it is excreted as urine Result: removal of sodium and water Carbonic anhydrase inhibitors Loop diuretics Osmotic diuretics Potassium-sparing diuretics Thiazide and thiazide-like diuretics The enzyme carbonic anhydrase helps to make H+ ions available for exchange with sodium and water in the proximal tubules CAIs ◦ block the action of carbonic anhydrase, ◦ thus preventing the exchange of H+ ions with sodium and water ◦ reduces H+ ion concentration in renal tubules Result: ◦ increased excretion of bicarbonate, sodium, water, & K+ ◦ Resorption of water is decreased and urine volume is increased acetazolamide (Diamox) methazolamide dichlorphenamide Adjunct drugs in the long-term management of open-angle glaucoma* Used with miotics to lower intraocular pressure before ocular surgery in certain cases Also useful in the treatment of: ◦ Edema* ◦ Epilepsy ◦ High-altitude sickness Acetazolamide (Diamox) is used in the management of edema secondary to HF when other diuretics are not effective* CAIs are less potent diuretics than loop diuretics or thiazides—the metabolic acidosis they induce reduces their diuretic effect in 2-4 days Metabolic acidosis Anorexia Hematuria Photosensitivity Melena Hypokalemia Drowsiness Paresthesias Urticaria Act directly on the ascending limb of the loop of Henle to inhibit chloride and sodium resorption Increase renal prostaglandins, resulting in the dilation of blood vessels and reduced peripheral vascular resistance bumetanide (Bumex) ethacrynic acid (Edecrin) furosemide (Lasix) Potent diuresis and subsequent loss of fluid Decreased fluid volume causes: ◦ Reduced BP ◦ Reduced pulmonary vascular resistance ◦ Reduced systemic vascular resistance ◦ Reduced central venous pressure ◦ Reduced left ventricular end-diastolic pressure Potassium and sodium depletion Edema associated with HF or hepatic or renal disease Control of hypertension Increase renal excretion of calcium in patients with hypercalcemia Certain cases of HF resulting from diastolic dysfunction Body System Adverse Effects CNS Dizziness, headache, tinnitus, blurred vision GI Nausea, vomiting, diarrhea Agranulocytosis, neutropenia, thrombocytopenia Hematologic Metabolic Hypokalemia, hyperglycemia, hyperuric Work mostly in the proximal tubule Nonabsorbable, producing an osmotic effect Pull water into renal tubules from the surrounding tissues Inhibits tubular resorption of water and solutes Increases glomerular filtration and renal plasma Reduces excessive intraocular pressure Used in the treatment of patients in the early, oliguric phase of ARF To promote the excretion of toxic substances Reduction of intracranial pressure Treatment of cerebral edema NOT indicated for peripheral edema Convulsions Thrombophlebitis Pulmonary congestion Also headaches, chest pains, tachycardia, blurred vision, chills, and fever mannitol (Osmitrol) Intravenous infusion only May crystallize when exposed to low temperatures—use of a filter is required Interfere with sodium-potassium exchange in collecting ducts and convoluted tubules Competitively bind to aldosterone receptors ◦ Block the resorption of sodium and water Prevent potassium from being pumped into the tubule, thus preventing its secretion Competitively block the aldosterone receptors and inhibit its action Sodium and water are excreted amiloride (Midamor) spironolactone (Aldactone) triamterene (Dyrenium) Also known as aldosterone-inhibiting diuretics spironolactone and triamterene ◦ Hyperaldosteronism ◦ Hypertension ◦ Reversing the potassium loss caused by potassium-losing drugs ◦ Certain cases of heart failure ◦ Liver failure Amiloride ◦ Treatment of HF Body System Adverse Effects CNS Dizziness, headache GI Cramps, nausea, vomiting, diarrhea Other Urinary frequency, weakness **hyperkalemia** Spironolactone Gynecomastia Amenorrhea Irregular menses Postmenopausal bleeding Actions: Acts in the distal convoluted tubule ◦ Inhibit tubular resorption of sodium, chloride, and potassium ions ◦ Result: water, sodium, and chloride are excreted Potassium is also excreted to a lesser extent Dilate the arterioles by direct relaxation Results: ◦ Lowered peripheral vascular resistance ◦ Sodium, water, chloride and potassium are excreted Thiazide diuretics ◦ hydrochlorothiazide (Esidrix, HydroDIURIL) ◦ chlorothiazide (Diuril) ◦ trichlormethiazide (Metahydrin) Thiazide-like diuretics ◦ chlorthalidone (Hygroton) ◦ metolazone (Mykrox, Zaroxolyn) Thiazides should not be used if creatinine clearance is less than 30 to 50 mL/min (normal is 125 mL/min) Metolazone (Zaroloxyn) remains effective to a creatinine clearance of 10 mL/min Hypertension – first line drug for HTN Edematous states Idiopathic hypercalciuria Diabetes insipidus Heart failure due to diastolic dysfunction Adjunct drugs in treatment of edema related to HF, hepatic cirrhosis, corticosteroid therapy Body System Adverse Effects CNS Dizziness, headache, blurred vision, paresthesias, decreased libido GI Anorexia, nausea, vomiting, diarrhea GU Impotence Integumentary Urticaria, photosensitivity Metabolic Hypokalemia, glycosuria, hyperglycemia, hyperuricemia OTHER EFFECTS ALSO Thorough patient history and physical examination Assess baseline fluid volume status, intake and output, serum electrolyte values, weight, and vital signs— especially postural BPs/orthostatic BPs Assess for disorders that may contraindicate or necessitate cautious use of these drugs Monitor serum K+ levels during therapy ◦ K+ supplements are usually recommended to maintain K+ levels at approximately 4 mEq/L Instruct patients to take in the morning as much as possible to avoid interference with sleep patterns Teach patients to maintain proper nutritional and fluid volume status Teach patients to eat more potassium-rich foods when taking any but the potassium-sparing drugs Foods high in potassium include bananas, oranges, dates, raisins, plums, fresh vegetables, potatoes, meat, and fish, apricots, whole grain cereals, legumes Patients taking diuretics along with a digitalis preparation digoxin (Lanoxin) should be taught to monitor for digitalis toxicity Diabetic patients who are taking thiazide and/or loop diuretics should be told to monitor blood glucose and watch for elevated levels Change positions slowly, and to rise slowly after sitting or lying to prevent dizziness and possible fainting related to orthostatic hypotension Encourage patients to keep a log of their daily weight A weight gain of 2 or more pounds a day or 5 or more pounds a week should be reported immediately Encourage patients to return for follow-up visits and labwork Notify physician if you are ill with nausea, vomiting, and/or diarrhea because fluid loss may be dangerous Excessive consumption of licorice can lead to an additive hypokalemia in patients taking thiazides Signs and symptoms of hypokalemia include muscle weakness, constipation, irregular pulse rate, and overall feeling of lethargy Notify the physician immediately if rapid heart rate or syncope occurs (reflects hypotension or fluid loss) Diuretics are used for which of the following reasons? (Select all that apply.) 1. treat hypertension 2. treat edema with heart failure 3. increase urine fl ow 4. treat hyperuricemia (increased uric acid level) Potassium-sparing diuretics are administered in combination with other types of diuretics to do which of the following? (Select all that apply.) 1. treat hypertension 2. treat heart failure 3. prevent hypokalemia 4. prevent hyperkalemia The most potent class of diuretics currently available is: 1. thiazide-type. 2. potassium-sparing type. 3. loop-type. 4. carbonic anhydrase inhibitor. Patients with diabetes mellitus receiving a diuretic should be observed for: 1. hypoglycemia. 2. hyperglycemia. 3. hyperkalemia. 4. normonatremia.