Download Free Medical DIURETIC AGENTS PowerPoint Presentation

DIURETIC AGENTS PowerPoint Presentation

DOWNLOAD MEDICAL POWERPOINT PRESENTATION

About This Presentation

Description : Drugs that block specific transport functions of the renal tubules are valuable clinical tools in the treatment of these disorders. Technically, a “diuretic” is an agent that increases urine volume, whereas a “natriuretic” causes an increase in renal sodium excretion, and an “aquaretic” increases excretion of solute-free water.

Tags : DIURETIC AGENTS,DIURETIC

Published on : Nov 06, 2020 | Views : 4316 | Downloads : 14

Shareable Url :

Embed Code :

Comment

Transcript

Slide 1-

DIURETIC AGENTS Dr. Mohammed Samir Hussein BCs of Pharmaceutical Science MDs of Clinical Pharmacology
Slide 2-

OVERVIEW Drugs that block specific transport functions of the renal tubules are valuable clinical tools in the treatment of these disorders. Technically, a “diuretic” is an agent that increases urine volume, whereas a “natriuretic” causes an increase in renal sodium excretion and an “aquaretic” increases excretion of solute-free water.
Slide 3-

RENAL TUBULAR TRANSPORT MECHANISMS
Slide 4-

NEPHRON PARTS AND THEIR FUNCTIONS
Slide 5-

NEPHRON PARTS AND THEIR FUNCTIONS
Slide 6-

MAIN CLINICAL USES OF DIURETICS
Slide 7-

DIURETIC CLASSIFICATIONS
Slide 8-

Limited uses as diuretics Acetazolamide: prototype carbonic anhydrase inhibitor and it is developed from sulfanilamide (caused metabolic acidosis and alkaline urine). Mechanism of Action Inhibits carbonic anhydrase in renal proximal tubule cells. Carbonic anhydrase catalyzes formation of HCO3- and H+ from H2O and CO2. Inhibition of carbonic anhydrase decreases [H+] in tubule lumen. By blocking carbonic anhydrase, inhibitors blunt NaHCO3 reabsorption and cause diuresis. CARBONIC ANHYDRASE INHIBITORS
Slide 9-

Used to treat chronic open-angle glaucoma. For prevention and treatment of acute mountain sickness. For metabolic alkalosis (as it produces metabolic acidosis by excreting large amount of bicarbonates) Sometimes epilepsy Mostly used in combination with other diuretics in resistant patients Clinical uses CARBONIC ANHYDRASE INHIBITORS These drugs are well absorbed after oral administration. An increase in urine pH from the HCO3− diuresis is apparent within 30 minutes, is maximal at 2 hours, and persists for 12 hours after a single dose. Excretion of the drug is by secretion in the proximal tubule. Therefore, dosing must be reduced in renal insufficiency. Pharmacokinetics
Slide 10-

CARBONIC ANHYDRASE INHIBITORS Rapid tolerance. Increased HCO3- excretion causes metabolic acidosis. Drowsiness. Fatigue. CNS depression. Paresthesia (pins and needles under skin). Nephrolithiasis (renal stones). K+ wasting. Side effects
Slide 11-

Do not interact with receptors or directly block renal transport Activity dependent on development of osmotic pressure. Examples: Mannitol (prototype) – Urea – Glycerol – Isosorbide Mechanism of Action Osmotic diuretics are not reabsorbed. Increases osmotic pressure specifically in the proximal tubule and loop of Henle. Prevents passive reabsorption of H2O. Increased H2O excretion. OSMOTIC DIURETICS
Slide 12-

Drug of choice: non-toxic, freely filtered, non-reabsorbable and non-metabolized Administered prophylactically for acute renal failure secondary to trauma, CVS disease, surgery or nephrotoxic drugs. Short-term treatment of acute glaucoma. Infused to lower intracranial pressure. Urea, glycerol and isosorbide are less efficient. Clinical uses (mannitol) Mannitol is poorly absorbed by the GI tract, and when administered orally, it causes osmotic diarrhea rather than diuresis. For systemic effect, mannitol must be given IV Mannitol is not metabolized and is excreted by glomerular filtration within 30–60 minutes, without any important tubular reabsorption or secretion. Pharmacokinetics OSMOTIC DIURETICS
Slide 13-

Increased extracellular fluid volume. Cardiac failure. Pulmonary edema. Hypernatremia. Hyperkalemia (K) secondary to diabetes or impaired renal function. Headache, nausea, vomiting. Side effects OSMOTIC DIURETICS
Slide 14-

THIAZIDE DIURETICS Active in distal convoluted tubule. Chlorothiazide (prototype) – Hydrochlorothiazide – Chlorthalidone – Metolazone. Mechanism of Action Inhibit Na+ and Cl- transporter in distal convoluted tubules Increased Na+ and Cl- excretion Weak inhibitors of carbonic anhydrase, increased HCO3- excretion Increased K+/mg2+ excretion Decrease Ca2+ excretion
Slide 15-

Clinical uses Orally administered with poor absorption. Onset of action in ~ 1 hour. Wide range of T1/2 amongst different thiazides, longer than loop diuretics. Free drug enters tubules by filtration and by organic acid secretion. Pharmacokinetics Hypertension. Congestive heart failure. Hypercalciuria (prevent excess Ca2+ excretion to form stones in ducts) Osteoporosis. Nephrogenic diabetes insipidus. Treatment of Li+ toxicity (can induce nephrogenic diabetic insipidus). THIAZIDE DIURETICS
Slide 16-

Hypokalemia. Increased Na+ exchange in CCD. Volume-contraction induced aldosterone release. Hyponatremia. Hyperglycemia. Diminished insulin secretion. Elevated plasma lipids. Hyperuricemia. Hypercalcemia. Side effects THIAZIDE DIURETICS
Slide 17-

Loop Diuretics Active in loop of Henle. Furosemide (prototype) – Bumetanide – Torsemide - Ethacrynic acid. Mechanism of Action Enter proximal tubule via organic acid transporter Inhibits apical Na-K-2Cl transporter in thick ascending loop of Henle Competes with Cl- binding site. Enhances passive Mg2+ and Ca2+ excretion Increased K+ and H+ excretion in CCD Inhibits reabsorption of ~25% of glomerular filtrate
Slide 18-

Clinical uses Orally administered, rapid absorption. Rapid onset of action. Bound to plasma proteins: displaced by warfarin, clofibrate. Increase toxicity of cephalosporin antibiotics and lithium. Additive toxicity with other ototoxic drugs. Inhibitors of organic acid ion transport decrease potency (i.e. Probenecid, NSAID’s). Pharmacokinetics Edema: cardiac, pulmonary or renal Chronic renal failure or nephrosis Hypertension Hypercalcemia Acute and chronic hyperkalemia Loop Diuretics
Slide 19-

Hypokalemia. Hyperuricemia. Metabolic alkalosis. Hyponatremia. Ototoxicity. Mg2+ depletion. Side effects Loop Diuretics
Slide 20-

POTASSIUM SPARING DIURETICS Steroid aldosterone antagonists. Spironolactone, Eplerenone – Pteridines – Triamterene – Pyrazinoylguanidines – Amiloride. Mechanism of Action Potassium-sparing diuretics prevent K+ secretion by antagonizing the effects of aldosterone in collecting tubules. Inhibition may occur by direct pharmacologic antagonism of mineralocorticoid receptors (Spironolactone, eplerenone) or by inhibition of Na+influx through ion channels in the luminal membrane (amiloride, Triamterene). This latter property appears to be shared by adenosine antagonists, which primarily blunt Na+ reabsorption in the PCT, but also blunt Na+ reabsorption and K+ secretion in collecting tubules.
Slide 21-

Clinical uses Spironolactone Orally administered - Aldactazide: spironolactone/thiazide combo Amiloride Oral administration, 50% effective, not metabolized, not bound to plasma proteins Triamterine Oral administration, 50% effective, 60% bound to plasma proteins Liver metabolism, active metabolites Pharmacokinetics Primary hyperaldosteronism (adrenal adenoma, bilateral adrenal hyperplasia) Congestive heart failure Cirrhosis Nephrotic syndrome In conjunction with K+ wasting diuretics POTASSIUM SPARING DIURETICS
Slide 22-

Hyperkalemia: monitor plasma [K+]. Spironolactone: gynecomastia. Triamterene: megaloblastic anemia in cirrhosis patients Amiloride: increase in blood urea nitrogen, glucose intolerance in diabetes mellitus. Side effects POTASSIUM SPARING DIURETICS
Slide 23-

DRUGS ACTING ON RENAL CIRCULATION Cardiac Glycosides (Digitalis) GFR is raised by agents which increase renal blood flow (RBF), Cardiac Output or Blood Volume. Increase Cardiac Output during Heart failure. Digoxin often combined with conventional diuretics.
Slide 24-

DRUGS ACTING ON RENAL CIRCULATION Colloidal Substances If blood vol. falls (blood or protein loss) - GFR falls = renin-angiotensin cascade = edema. Colloidal substances may be given IV. to restore GFR. Xanthine 1. Inhibit Na+ & Cl- resorption. 2. Raise filtration pressure -dilate afferent > efferent arterioles to glomeruli. 3. Stimulate cardiac output. Exemple: . Caffeine - Theophylline (most potent) – Theobromine.
Slide 25-

PHARMACOLOGICAL OF DIURETICS
Slide 26-

CLINICAL PHARMACOLOGY OF DIURETICs HEART FAILURE In heart failure: reduction in cardiac output → changes in blood pressure and blood flow to the kidney → lead to renal retention of salt and water. Inspite of plasma expansion if cardiac output does not improve----interstitial or pulmonary eodema take place. Diuretics reduce the accumulation of edema, particularly in the lungs. Reduction of pulmonary vascular congestion with diuretics may actually improve oxygenation and thereby improve myocardial function. Reduction of preload can reduce the size of the heart, allowing it to work at a more efficient fiber length. Generally managed with loop diuretics. If salt and water retention may become so severe that a combination of thiazides and loop diuretics is necessary.
Slide 27-

KIDNEY DISEASE AND RENAL FAILURE Renal disorders cause retention of salt and water. If renal failure is severe (GFR < 5 mL/min), diuretic agents are of little benefit Many patient with renal disorders and dialysis patients with milder degrees of renal insufficiency (GFR of 5–15 mL/min), can be treated with diuretics when they retain excessive volumes of fluid between dialysis treatments. CLINICAL PHARMACOLOGY OF DIURETICs
Slide 28-

HEPATIC CIRRHOSIS Liver disease is often associated with oedema and ascites in conjunction with elevated portal hydrostatic pressures When ascites and oedema become severe, diuretic therapy can be very useful. The combination of loop diuretics and an aldosterone receptor antagonist may be useful in some patients Hepatorenal syndrome and hepatic encephalopathy are the unfortunate consequences of excessive diuretic use in the cirrhotic patient. CLINICAL PHARMACOLOGY OF DIURETICs
Slide 29-

HYPERTENSION The diuretic and mild vasodilator actions of the thiazides are useful in treating virtually all patients with essential hypertension Hydrochlorothiazide is the most widely used diuretic for hypertension, chlorthalidone may be more effective because of its much longer half-life. Loop diuretics are usually reserved for patients with mild renal insufficiency (GFR < 30–40 mL/min) or heart failure Often successful as monotherapy Diuretics enhance the efficacy of many agents, particularly ACE inhibitors. CLINICAL PHARMACOLOGY OF DIURETICs
Slide 30-

NEPHROLITHIASIS Approximately two thirds of kidney stones contain Ca2+ phosphate or Ca2+ oxalate. Treated with thiazide diuretics, which enhance Ca2+ reabsorption in the DCT and thus reduce the urinary Ca2+ concentration Fluid intake should be increased, but salt intake must be reduced Dietary Ca2+ should not be restricted, as this can lead to negative total body Ca2+ balance CLINICAL PHARMACOLOGY OF DIURETICs
Slide 31-

HYPERCALCEMIA Hypercalcemia can be a medical emergency Because loop diuretics reduce Ca2+ reabsorption significantly, they can be quite effective in promoting Ca2+ diuresis along with saline Potassium chloride may be added to the saline infusion as needed CLINICAL PHARMACOLOGY OF DIURETICs
Slide 32-

THANK YOU FOR YOUR ATTENTION