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Diuretic drugs

Diuretic drugs


    I-Overview

    They are drugs inducing a state of increased urine flow
    They are ion transport inhibitors that decrease the reabsorbtion of Na at different sites in the nephron

    As a result,Na and other ions such as cl enter the urine in greater amounts than normal along with water which is carried passively to maintain osmotic equilibrium

    II-Kidney function in disease
    in many diseases,the amount of Nacl reabsorbed by the kidney tubules is abnormally high

    this leads to the retention of water,an increase in blood volume,and expansion of the extravascular fluid compartment resulting in edema of the tissues

    Several commonly encounterd causes of edema include

    a- Congestive heart failure

    the decreased ability of the failing heart to sustain adequate cardiac output,causes the kidney to respond as if there were a decrease in blood volume
    The kidney as a part of normal compensatory mechanism retains more salt and water as a means of raising blood volume and increasing the amount of blood that it is returned to the heart
    However,the diseased heart can not ingrease its cardiac output,and the increased vascular volume results in edema

    b-Hepatic ascitis

    Ascitis: the accumulation of fluid in abdominal cavity,is a common complication of cirrhosis of the liver
    that is due to
    The increased portal blood pressure
    the secondary hyperaldosteronism

    c-Nephrotic syndrome
    d-Premenstural edema
    is a result of imbalances in hormones such as estrogen exess which facilitates the loss of fluid into the extracellular space

    A-Carbonic anhydrase inhibitors
    e.g acetazolamide

    Therapeutic uses

    Treatment of glaucoma :by decreasing the production of aquous humor ,probably by blocking the carbonic anhydrase in the cilliary body of the eye
    it is useful in the chronic treatment of glaucoma but should not be used for an acute attack

    N.B. Pilocarpine is preferred in acute attack because of its immediate action

    Epilepsy : it reduces the severity and magnitude of the seizures
    often it is used chronically in conjunction with antiepileptic medication to enhance the action of these other drugs
    Mountain sickness:less commonly it can be used in the prophylaxis of acute mountain sickness among healthy physically active individuals who rapidly ascend above 10000 feet

    B-Loop diuretics
    e.g bumetanide-furosemide

    These drugs have the highest efficacy in mobilizing Na & cl from the body
    Furosemide shows the greater side effects than those seen with the other loop diuretics
    Bumetanide is much more potent and its use is increasing

    Therapeutic uses
    Drugs of choice for reducing the acute pulmonary edema of C.H.F because of their rapid onset of action
    Useful in treatment hypercalcemia

    Adverse effects

    a-Ototoxicity :particullary when used in conjunction with aminoglucosides antibiotics

    N.B. Permanent damage may result with continued treatment

    b- hyperuricemia :especially furosemide causing or exacerbating gouty attacks

    c- Acute hypovolemia:with possibility of hypotension,shock and cardiac arrythmias

    d- Potassium depletion : which can be averted by use of potassium sparing diuretic or dietary supplementation with K

    C-Thiazides and related agents
    e.g: chlorthiazide - hydroghlorothiazide-indapamide

    The most widely used of diuretic drugs
    Chlorthiazide

    Therapeutic uses

    Hypertension =discussed
    C.H.F = discussed
    Renal impairment :if loop diuretics alone fail in treatment
    Idiopathic hypercalciuria
    Diabetes inspidus

    Adverse effects
    as loop diuretics plus
    In hyperglycemia :patients with diabetes mellitus who are taking thiazides for hypertension may become hyperglycemic and have difficulty in maintaining appropiate blood sugar levels

    Hydrochlorothiazide

    is a thiazide derivative has proven to be more popular than the parent drug as it is more potent so less dose is required to provide the same efficacy of the parent drug

    Indapamide = thiazide analoge
    at low doses it

    Shows significant antihypertensive action with minimal diuretic effects
    Often used in advanced renal failure to stimulate additional diuresis on top of that achieved by loop diuretics

    Less likely to accumulate in patients with renal failure and may be useful in their treatment

    D-Potassium-sparing diuretics
    e.g spironolactone

    act in the collecting tubule to inhibit Na reabsorbtion,K secretion and H secretion

    The major use of it is in the treatment of hypertension most often in combination with a thiazide

    it is often used in conjunction with a thiazide or loop diuretic to prevent potassium excretion that would otherwise occur with these drugs

    Adverse effects

    as it is chemically resembles some of the *** steroids, it does have minimal hormonal activity and may induce gynecomastia in males and menstural irregularities in females

    E-Osmotic diuretics
    e.g:mannitol

    They are used to maintain renal flow following acute toxic ingestion of substances capable of producing acute renal failure

    A mainstay of treatment for patients with

    a- increased intracranial pressure
    b-drug toxicity
    c- trauma

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