Loop diuretics Domina Petric, MD.

Slides:



Advertisements
Similar presentations
Chapter 51 Diuretic Agents
Advertisements

Diuretics Clinical Conditions Requiring Diuretic Therapy:
THIAZIDE DIURETICS Secreted into the tubular lumen by the organic acid transport mechanisms in the proximal tubule Act on the distal tubule to inhibit.
Chapter 41 Diuretics 1.
Diuretics and Dehydrants. §1 Diuretics Abnormalities in fluid volume and electrolyte composition are common and important clinical problems. Drugs that.
DIURETICS. Functions of the kidneys Volume Acid-base balance Osmotic pressure Electrolyte concentration Excretion of metabolites and toxic substances.
Diuretics. Why do we want to know about diuretics? What do kidneys do? What can go wrong? Interventions that can be used how do they work? Effects, side.
Excretion of Water and Electrolytes
BIMM118 Renal Pharmacology Diuretics: Carbonic Anhydrase Inhibitors Thiazides Loop Diuretics Potassium-sparing Diuretics.
DIURETICS Brogan Spencer and Laura Smitherman. What is a diuretic? Substance that promotes the formation (excretion) of urine.
Transport Of Potassium in Kidney Presented By HUMA INAYAT.
Role of Kidneys In Regulation Of Potassium Levels In ECF
Diuretics Chris Hague, PhD
DIURETICS By: Prof. A. Alhaider.
DPT IPMR KMU Dr. Rida Shabbir.  K+ extracellular 4.2 mEq/L  Increase in conc to 3-4 mEq/L causes cardiac arrhythmias causing cardiac arrest and fibrilation.
Diuretics. From Knauf & Mutschler Klin. Wochenschr : % 20% 5% 4.5% 0.5% Volume 1.5 L/day Urine Na 100 mEq/L Na Excretion 155 mEq/day.
Diuretic Agents in Hypertension and other disorders
Prof. Hanan Hagar Pharmacology Department
DIURETIC DRUGS.
Urinary System. Introduction Kidneys and lungs: two systems that both help and create homeostasis (balancing compositions of fluids and tissues within.
1-Overview 2-Classification 3-Indiviual drugs 1-Indications of Diuretics. 2-Adverse effects. 3-Mannitol and Carbonic Anhydrase inhibitors.
BYL Nair Ch. Hospital, Mumbai
Diuretics the role of different portions of the nephron in ion exchange; the sites of action and pharmacology of diuretics; the therapeutic applications.
CARBONIC ANHYDRASE INHIBITORS ACETAZOLAMIDE E It is a sulfonamide derivative. It is a sulfonamide derivative. noncompetitively but reversible inhibits.
DIURETICS Part 1 Prof. Hanan Hagar Pharmacology Unit.
CHAPTER © 2012 The McGraw-Hill Companies, Inc. All rights reserved. 25 Diuretics.
DIURETIC DRUGS (DR.Farooq Alam) DIURETIC DRUGS (DR.Farooq Alam)
DIURETICS Part 1 Prof. Hanan Hagar Pharmacology Department.
Prof. Hanan Hagar Pharmacology Department
Pharmacology Department
Gout Familial metabolic disease characterized by : Acute arthritis Uric acid stones in the kidneys Hyperuricemia.
DIURETICS Diuretics are drugs which increase the excretion of sodium and water from the body by an action on the kidney. Their primary effect is to decrease.
Fluids and Acid Base Physiology Dr. Meg-angela Christi Amores.
Diuretic Agents.
RENAL SYSTEM PHYSIOLOGY
DIURETICS How do they work? WHAT DO THEY DO? When do I use them? How do I use them?
Pharmacology – I [PHL 313] DiureticsDiuretics Dr. Hassan Madkhali Assistant Professor Department of Pharmacology E mail:
Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Chapter 21 Diuretic Agents.
DIURETICS By: Prof. A. Alhaider 1433 H. Anatomy and Physiology of Renal system ► Remember the nephron is the most important part of the kidney which regulates.
Excretion of Drugs By the end of this lecture, students should be able to Identify main and minor routes of Excretion including renal elimination and biliary.
Regulation of Potassium K+
DIURETICS By: Prof. A. Alhaider. Anatomy and Physiology of Renal system ► Remember the nephron is the most important part of the kidney that regulates.
What is high ceiling diuretic & Why?
Diuretics. A. INHIBITING NaCl REABSORPTION: THIAZIDES: 1. Bendroflumethiazides 2. Benzthiazides 3. Polythiazide 4. Chlorothiazide 5. Quinethazone 6. Chlorthalidone.
Diuretic Agents. Carbonic Anhydrase Inhibitors.
DRUGS AND THE KIDNEY DR.ALI A.ALLAWI ASSISTANT PROFESOR CONSULTANT NEPHROLOGIST.
Osmotic diuretics Osmotic diuretics are pharmacologically inert substances (e.g. mannitol ) that are filtered in the glomerulus but not reabsorbed by the.
Diuretics Abnormalities in fluid volume and electrolyte composition are common and important clinical disorders. Drugs that block specific transport functions.
Diuretics Blake Briggs, Class of 2017.
Objectives for Lecture on Diuretics
Diuretics.
Drugs Used for Diuresis
Renal mechanisms for control ECF
Drugs Effecting Body Fluids and Volume
Sodium Channel Inhibitors
(Furosemide, Ethacrynic acid, Bumetanide and Torsemide) DIURETICS: LOOP DIURETICS (Furosemide, Ethacrynic acid, Bumetanide and Torsemide)
Diuretics dr shabeel pn.
Kidney and Drugs.
Renal autacoids Domina Petric, MD.
Renal tubule transport mechanisms
Carbonic anhydrase inhibitors
Clinical pharmacology of diuretic agents
Potassium-sparing diuretics
Domina Petric, MD Aquaretics.
Thiazides Domina Petric, MD.
Diuretics By S.Bohlooli, PhD.
Diuretic Drugs.
REGULATION OF K,Ca, PHOSPHATE & MAGNISIUM
Ass. Prof. Dr. Naza M. Ali Lec G2 19 May 2019 G1 22 May 2019
Drugs Used for Diuresis
Presentation transcript:

Loop diuretics Domina Petric, MD

Introduction Loop diuretics selectively inhibit NaCl reabsorption in the thick ascending limb of Henle´s loop (TAL). TAL has large NaCl absorptive capacity. Diuretic action of loop diuretics is not limited by development of acidosis. These drugs are the most efficacious diuretic agents currently available.

Chemistry Furosemide, ethacrynic acid! Bumetanide and torsemide are sulfonamide loop diuretics. Ethacrynic acid is a phenoxyacetic acid derivative containing an adjecent ketone and methylene group. The methylene group forms an adduct with the free sulfhydryl group of cysteine. The cysteine adduct appears to be an active form of the drug. Organic mercurial diuretics also inhibit salt transport in the TAL, but are toxic.

Pharmacokinetics The loop diuretics are rapidly absorbed. They are eliminated by the kidney by glomerular filtration and tubular secretion. Absorption of oral torsemide is 1 hour and that of furosemide 2-3 hours. Oral absorption is nearly as complete as with intravenous administration. The duration of effect for furosemide is 2-3 hours and of torsemide 4-6 hours.

Pharmacokinetics Half-life depends on renal function. Loop agents act on the luminal side of the tubule. Their diuretic activity correlates with their secretion by the proximal tubule. NSAIDs and probenecid compete for weak acid secretion in the proximal tubule. Simultaneous administration of loop diuretics and NSAIDs result in reduction in the secretion of loop diuretics.

Pharmacodynamics Loop diuretics inhibit the luminal Na+/K+/2Cl- transporter (NKCC2) in the TAL of Henle´s loop. These agents reduce the reabsorption of NaCl and diminish the lumen-positive potential that comes from K+ recycling. Loop diuretics cause an increase in Mg2+ and Ca2+ excretion. Prolonged use can cause significant hypomagnesemia.

Pharmacodynamics Loop diuretics do not generally cause hypocalcemia because vitamin D-induced intestinal absorption and parathyroid hormone-induced renal reabsorption of Ca2+ can be increased. In disorders that cause hypercalcemia, Ca2+ excretion can be enhanced by treatment with loop diuretics combined with saline infusions. Loop diuretics induce expression of cyclooxygenase 2 (COX-2) which participates in the synthesis of prostaglandins from arachidonic acid.

Pharmacodynamics PGE2 inhibits salt transport in the TAL and participates in the renal actions of loop diuretics. NSAIDs can interfere with the actions of loop diuretics by reducing prostaglandin synthesis in the kidney. This interference is significant in patients with nephrotic syndrome or hepatic cirrhosis. Furosemide increases renal blood flow via prostaglandin actions on kidney vasculature. Furosemide and ethacrynic acid reduce pulmonary congestion and left ventricular filling pressures in heart failure.

Typical dosages of loop diuretics Drug Total daily oral dose Bumetanide 0,5-2 mg Ethacrynic acid 50-200 mg Furosemide 20-80 mg Torsemide 5-20 mg

Clinical indications The most important are ACUTE PULMONARY EDEMA, OTHER EDEMATOUS CONDITIONS AND ACUTE HYPERCALCEMIA. Other indications are hyperkalemia, acute renal failure and anion overdose.

Edematous states Reduction of peripheral or pulmonary edema that has accumulated as a result of cardiac, renal or vascular disease, that reduce blood flow to the kidney. This reduction is sensed as insufficient effective arterial blood volume, which leads to salt and water retention. Excessive diuretic therapy may compromise the effective arterial blood volume and reduce the perfusion of vital organs. The use of diuretics to mobilize edema requires careful monitoring of the patient´s hemodynamic status.

Hyperkalemia Loop diuretics can significantly enhance urinary excretion of potassium. This response is enhanced by simultaneous NaCl and water administration.

Acute renal failure Loop agents can increase the rate of urine flow and enhance potassium excretion in acute renal failure. They can not prevent or shorten the duration of renal failure. If a large pigment load has precipitated acute renal failure, loop agents may help to flush out intratubular casts and ameliorate intratubular obstruction. Loop agents can worsen cast formation in myeloma and light chain nephropathy: increased distal Cl- concentration enhances secretion of Tamm-Horsfall protein. This protein aggregates with myeloma Bence Jones proteins.

This is important to avoid extracellular fluid volume depletion. Anion overdose Loop diuretics are useful in treating toxic ingestions of bromide, fluoride and iodide, which are reabsorbed in the TAL. Saline solution must be administered to replace urinary losses of Na+ and to provide Cl-. This is important to avoid extracellular fluid volume depletion.

Toxicity Hypokalemic metabolic alkalosis Ototoxicity Hyperuricemia Hypomagnesemia Allergic and other reactions

Hypokalemic metabolic alkalosis By inhibiting salt reabsorption in the TAL, loop diuretics increase sodium delivery to the collecting duct. Increased delivery leads to increased secretion of potassium and hydrogen ions by the duct: hypokalemic metabolic alkalosis. This toxicity is a function of the magnitude of the diuresis and can be reversed by potassium replacement and correction of hypovolemia.

Dose-related hearing loss is usually reversible. Ototoxicity Dose-related hearing loss is usually reversible. It is most common in patients who have diminished renal function or who are receiving simultaneously other ototoxic agents (for example, aminoglycoside antibiotics).

Hyperuricemia Loop diuretics can cause hyperuricemia and precipitate attacks of gout. This is caused by hypovolemia-associated enhancement of uric acid reabsorption in the proximal tubule. It may be prevented by using lower doses to avoid development of hypovolemia.

Hypomagnesemia Magnesium depletion is a consequence of the chronic use of loop agents. It occurs most often in patients with dietary magnesium deficiency. It can be reversed by administration of oral magnesium preparations.

Allergic and other reactions All loop diuretics, except ethacrynic acid, are sulfonamides: skin rash eosinophilia interstitial nephritis This toxicity usually resolves rapidly after drug withdrawal. Allergic reactions are much less common with ethacrynic acid.

Allergic and other reactions Henle´s loop is indirectly responsible for water reabsorption by the downstream collecting duct. Loop diuretics can cause severe dehydration. Hyponatremia is less common than with the thiazides. Patients who increase water intake in response to hypovolemia-induced thirst can become severly hyponatremic. Loop agents can cause hypercalciuria, which can lead to mild hypocalcemia and secondary hyperparathyroidism.

Allergic and other reactions Loop agents can have the opposite effect, hypercalcemia, in volume-depleted patients who have another cause for hypercalcemia: metastatic breast or squamous cell lung carcinoma.

Contraindications Furosemide, bumetanide and torsemide may exhibit allergic cross-reactivity in patients sensitive to other sulfonamides, but it is very rare. Overzealous use of any diuretic is dangerous in hepatic cirrhosis, borderline renal failure and heart failure.

Katzung, Masters, Trevor. Basic and clinical pharmacology. Literature Katzung, Masters, Trevor. Basic and clinical pharmacology.