DIURETICS - Benvenuto · 2016-11-29 · DIURETICS POTASSIUM SPARING DIURETICS OSMOTIC DIURETICS ....
Transcript of DIURETICS - Benvenuto · 2016-11-29 · DIURETICS POTASSIUM SPARING DIURETICS OSMOTIC DIURETICS ....
DIURETICS
A diuretic is any substance that promotes diuresis, that is, the increased production of urine. This includes forced diuresis. There are several categories of diuretics. All diuretics increase the excretion of water from bodies, although each class does so in a distinct way.
CARBONIC ANHYDRASE INHIBITORS
THIAZIDE THIAZIDE-LIKE
LOOP DIURETICS
POTASSIUM SPARING DIURETICS
OSMOTIC DIURETICS
OSMOTIC DIURETICS
Substances that increase osmolality but have limited tubular epithelial cell permeability. They work primarily by expanding extracellular fluid and plasma volume, therefore increasing blood flow to the kidney, particularly the peritubular capillaries. This reduces medullary osmolality and thus impairs the concentration of urine in the loop of Henle. Furthermore, the limited tubular epithelial cell permeability increases osmolality and thus water retention in the filtrate
DRUG ADMIN ASBORBANCE PP
BINDING PLASMATIC HALF-LIFE
METAB. ELIMIN.
MANNITOLO (Isotol®),
Soluz 5%/fl
I.V.
VERY LOW
Oral availability: 20%
--- 1,5 h Liver
10% RENAL
MEDICAL USE
Mannitol is used for diuresis in treatment and prevention of reduced urine production in acute kidney failure, for reducing intracranial pressure and brain mass in people with swelling in the brain (cerebral edema), for reducing intraocular pressure, and irrigation of the urinary bladder to promote urinary excretion of toxic materials.
ADVERSE EFFECTS Pulmonary congestion, fluid and electrolyte imbalance, dry mouth, thirst, headache, blurred vision, dizziness, nausea, and chest pain.
The carbonic anhydrases are a family of enzymes that catalyze the rapid interconversion of carbon dioxide and water (CO2 + H2O) to bicarbonate and protons (HCO3- e H+ ) or vice versa, a reversible reaction that occurs relatively slowly in the absence of a catalyst.
Carbonic anhydrases participate in a variety of biological processes, including • respiration, • calcification, • acid-base balance, • bone reabsorption, • formation of aqueous humor, • cerebrospinal fluid, • saliva, • and gastric acid.
CARBONIC ANHYDRASE INHIBITORS Carbonic anhydrase inhibitors cause increased excretion of bicarbonate with accompanying sodium, potassium and water, resulting in an increased flow of alkaline urine. They inhibit transport of bicarbonate into the interstitium from the proximal convoluted tubule. Therefore less sodium is reabsorbed, causing greater sodium, bicarbonate and water loss in the urine.
CARBONIC ANHYDRASE INHIBITORS
ACETAZOLAMIDE
METHAZOLAMIDE
DORZOLAMIDE
BRINZOLAMIDE
SYSTEMIC USE: ORAL OR IV ADMINISTRATION
LOCAL USE: EYE INSTILLATION
Thiazide-type diuretics act on the distal convoluted tubule and inhibit the sodium-chloride symporter leading to a retention of water in the urine, as water normally follows penetrating solutes.
THIAZIDES and THIAZIDE-LIKE DIURETICS
• Frequent urination is due to the increased loss of water that has not been retained from the body as a result of a concomitant relationship with sodium loss from the convoluted tubule.
• The short-term anti-hypertensive action is based on the fact that thiazides decrease preload, decreasing blood pressure.
• On the other hand, the long-term effect is due to an unknown vasodilator effect that decreases blood pressure by decreasing resistance.
THIAZIDES and THIAZIDE-LIKE
HYDROCHOROTHIAZIDE
CHLORTHALIDONE
INDAPAMIDE
These drugs inhibit the Na-K-2Cl symporter in the medullary thick ascending limb. High ceiling diuretics may cause a substantial diuresis – up to 20% of the filtered load of NaCl and water. This is large in comparison to normal renal sodium reabsorption which leaves only about 0.4% of filtered sodium in the urine. Loop diuretics inhibit the body's ability to reabsorb sodium at the ascending loop in the nephron, which leads to an excretion of water in the urine, whereas water normally follows sodium back into the extracellular fluid.
LOOP DIURETICS
LOOP DIURETICS
FUROSEMIDE
DRUG ADMIN ABSOR PP BINDING
PLASMA HALF-LIFE
METAB ELIMIN
FUROSEMIDE 25 mg/cpr; 50, 250, 500 mg/f
OS: 20-80 mg IM, IV: 20-40 mg
60-70%
91-99% 30-120 m Liver 10%
glicuron
Kidney 60-90%
Bile duct %
ETHACRINIC Acid 50 mg/cpr;50 mg/f
OS: 25-50mgx2 EV: 50-100 mg
Bio orale: 100%
90% 1-4 h Liver Kidney 70%
LOOP DIURETICS – DIURETIC RESISTANCE
POTASSIUM SPARING DIURETICS
The term "potassium-sparing" refers to an effect rather than a mechanism or location; nonetheless, the term almost always refers to two specific classes that have their effect at similar locations:
2. ALDOSTERONE ANTAGONISTS
1. EPITHELIAL SODIUM CHANNEL BLOCKERS:
FARMACO SOMM ASSORBIM LEGAME
PROTEICO EMIVITA PLASM
METAB ELIMIN
IDROCLOROTIAZIDE +
AMILORIDE (Moduretic®)
50mg + 5 mg/cps;
OS: 5 mg/die
Biodispon
50%
scarso
6-9 h
-----
Renale 50%
Fecale: 40-50%
FUROSEMIDE +
TRIAMTERENE (Fluss40®)
OS: 50-100 mgx2
Biodispon
30-70%
55-65%
1,5-2,5 h
Epatico
Renale 50%
FARMACO SOMM ASSORBIM LEGAME
PROTEICO EMIVITA PLASM
METAB ELIMIN
SPIRONOLATTONE (Aldactone®)
25 mg/cps; 100 mg/conf
OS: 25-100 mgx2
Biodispon 73%
90% 1,4 h
16,5 h
Epatico
Metabolita attivo
canrenone
Renale 57%
Fecale: 41%
POTASSIUM SPARING DIURETICS
DIURETICS - SUMMARY