 Paired kidneys  A ureter for each kidney  Urinary bladder  Urethra 2

 Kidneys filter blood to keep it pure ◦ Toxins ◦ Metabolic wastes ◦ Excess water ◦ Excess ions  Dispose of nitrogenous wastes from blood ◦ Urea ◦ Uric acid ◦ Creatinine  Regulate the balance of water and electrolytes, acids and bases 3

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Filtration a. Fluid is squeezed out of the glomerular capillary bed Resorption b. Most nutrients, water ad essential ions are returned to the blood of the peritubular capillaries Secretion c. Moves additional undesirable molecules into tubule from blood of peritubular capillaries 7

 Diuretics are used to treat anuria, hypertension, and edema.  There are six classes of diuretics: ◦ Osmotic agents ◦ Carbonic anhydrase inhibitors ◦ Thiazide and thiazide-like compounds ◦ Organic acids[loop diuretics] ◦ Potassium-sparing diuretics ◦ ADH antagonists 25 -8

 The kidneys are responsible for urine production.  The working units of the kidney are known as nephrons.  The nephron is composed of several segments.  Urine is produced through filtration, reabsorption, and secretion

 Renal disease and cardiovascular dysfunction alter the functioning of the kidney, leading to: ◦ Decreased urine flow ◦ Decreased urine volume (oliguria) ◦ No urine production (anuria) ◦ Uremia ◦ Edema ◦ Hypotension

 Metabolic acidosis due to excess ACID IN THE BODY NOT ELIMINATED, itself usually causes rapid breathing. Confusion or lethargy may also occur. Severe metabolic acidosis can lead to shock or death. In some situations, metabolic acidosis can be a mild, chronic (ongoing) condition

 Metabolic alkalosis is caused by too much bicarbonate in the blood.  Hypokalemic alkalosis is caused by the kidneys' response to an extreme lack or loss of potassium, which can occur when people take certain diuretic medications

 Confusion (can progress to stupor or coma) Confusion  Hand tremor  Lightheadedness  Muscle twitching  Nausea, vomiting  Numbness or tingling in the face or extremities  Prolonged muscle spasms (tetany)muscle spasms  Arrhythmia  Seizures 1- 13

 Filtered by glomerulus but not reabsorbed by renal tubules, creating osmotic gradient.  Stimulate urine flow, producing mild diuresis with no electrolyte imbalance.  USES: Treatment for anuria and oligouria  Adverse effects include nausea, dizziness, headache, and chills. Mannitol is contraindicated in patients with edema from cardiovascular insufficiency, pulmonary edema, or intracranial bleeding

 Common Drugs: ◦ 1-Glycerin (oral) ◦ 2-Isosorbide (oral) ◦ 3-Mannitol (Osmitrol) IV USED IN:  Acute renal failure or cardiovascular surgeries  Cerebral edema and glaucoma  Increase flow to help excrete toxic substance  4-UREA I.V.

 Increase sodium and water excretion by inhibiting carbonic anhydrase: ◦ No hydrogen ions to exchange for sodium ions ◦ Decreased sodium reabsorption ◦ Sodium ions and increased water excreted in urine ◦ Increased loss of potassium in urine ◦ Decreased bicarbonate in blood (acidosis)

 Used in :  1- treatment of CHF or drug- induced edema  2-Reduce pressure with glaucoma (stop production of aqueous humor)  3-Useful in the treatment of epilepsy (acidosis)  Adverse effects: ◦ Drowsiness ◦ Headache ◦ GI distress ◦ Acidosis

 Inhibit sodium transport in the distal portion of the nephron, causing substantial loss of sodium and water  Produce intense diuresis  Can eliminate edema of any cause  Useful in treatment of mild to moderate hypertension

 Mobilization of sodium causes potassium excretion as well (hypokalemia).  Side effects include: ◦ Hyponatremia ◦ Orthostatic hypotension ◦ Hyperglycemia ◦ Muscle spasms or cramps ◦ GI distress ◦ Headache

 Thiazide: ◦ Chlorothiazide (Diuril) ◦ Hydrochlorothiazide (Ezide, HydroDIURIL, Hydro- par) ◦ Methyclothiazide (Enduron, Aquatensen)  Thiazide-like Diuretics: ◦ Chlorthalidone (Hygroton, Thalitone) ◦ Indapamide (Lozol) ◦ Metolazone (Zaroxolyn) 1- 20

 Inhibit sodium and chloride ion transport in the LOOP OF HENLE  Highly bound to plasma proteins  Used: 1- for treatment of edema in patients who have become thiazide resistant  2-Useful in severe peripheral & pulmonary edema in CHF, liver dz, & renal dz

 Side effects are similar to thiazide diuretics: ◦ Nausea ◦ Hypotension ◦ Hypokalemia ◦ Hyperuricemia ◦ Hyperglycemia  Additional side effects include:-Ototoxicity (esp. when combined with aminoglycoside antibiotics)

 Bumetanide (Bumex)  Ethacrynic acid (Edcrin)  Furisemide (Lasix)  Torsemide (Demadex) 1- 23

 Inhibit potassium secretion in DCT  Produce mild diuresis without electrolyte or acid-base disturbances  Side effects: ◦ Nausea ◦ Diarrhea ◦ Hyperkalemia ◦ Gynecomastia

 Amiloride (Midamor) ◦ Caution with hyperkalemia  Spironolactone (Aldactone) ◦ Adjunct therapy for hypertension ◦ Potential issue with tumor development over long term use  Triamterene (Dyrenium) ◦ Adjunct therapy for hypertension 1- 25

 Most diuretics cause electrolyte and acid-base imbalance: ◦ Potassium loss is most common. ◦ Patients should supplement potassium.  Blood pressure may be altered.  Blood glucose levels may be altered

 ADH regulates water balance in the body. (monitored in the hypothalamus Na+, excreted by the posterior pituitary gland)  ADH antagonists block the ADH receptors in the kidneys.  Inhibition of ADH receptors causes excretion of free water without electrolyte loss. (aquaresis)

 Conivaptan  Lixivaptan  Tolvaptan 1- 28

 Xanthine derivatives are naturally occurring drugs that produce mild diuretic responses. (caffeine, theobromine, theophylline)  They stimulate urine flow by increasing blood flow to kidneys.  Side effects include CNS stimulation, hypotension, and headache

 Diuretics are involved in a number of drug interactions due to their MOA: ◦ Bind to plasma proteins ◦ Alter acid-base balance ◦ Stimulate renal excretion  Diuretics when mixed in IVs with other solutions can cause precipitate formation

ADH Antagonists Euvolemic and hypervolemic hyponatremia Carbonic Anhydrase Inhibitors Glaucoma, edema with alkalosis and mountain sickness Loop Diuretics Pulmonary and peripheral edema, hypertension and acute renal failure Thiazides Hypertension, mild heart failure, and nephrolithiasis Osmotic Diuretics Improve renal failure, reduce intracranial pressure, glaucoma Potassium-sparing Diuretics Hypokalemia due to other diuretics and post MI

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