Diuretics: Uses and Types

Module 7: Diuretics

• Diuretics, commonly known as water pills, are drugs that increase urine production.

Disease Spotlight

• Edema is the accumulation of fluid in the interstitial spaces.
• Typically seen in patients with heart failure, cirrhosis, other liver diseases, and renal diseases
• Hypertension is persistently high blood pressure, often with no known cause (idiopathic).
• Diuretics manage hypertension by reducing blood volume and sodium.
• Glaucoma is an eye disease characterized by increased intraocular pressure (IOP).

5 Categories of Diuretics

Thiazide and Thiazide-Like Diuretics

• Used to treat hypertension and peripheral edema.
• Not effective for immediate diuresis.
• Primarily for patients with normal renal function.
• Cause loss of sodium, potassium, and magnesium, but promote calcium reabsorption.

Benzothiadiazides

• Commonly called thiazides, they have been a useful class of diuretics and antihypertensive agents since the 1960s.

Chlorothiazide

• The first thiazide, marketed in 1957.
• Hydrochlorothiazide followed a year later.

Loop or High-Ceiling Diuretics

• Act on the thick ascending loop of Henle.
• Inhibit chloride transport of sodium into the circulation.
• Inhibit passive reabsorption of sodium.
• Resulting in the loss of sodium and water, along with potassium, calcium, and magnesium.
• Ethacrynic Acid was the first marketed loop diuretic.
• Followed by furosemide and then bumetanide (more potent than furosemide).
• Their high diuretic potential earns them the name "high ceiling diuretics" or "potassium-wasting diuretics."
• Bumetanide, furosemide, and torsemide are used for edema from heart failure, liver cirrhosis, renal disease, and nephrotic syndrome.
• The primary outcome of sulfonamide loop diuretic therapy is diuresis.

Osmotic Diuretics

• Increase osmolality (concentration) and sodium reabsorption in the proximal tubule and loop of Henle.
• Used to prevent kidney failure, decrease intracranial pressure (ICP), and decrease intraocular pressure (IOP).

Mannitol

• Most frequently prescribed osmotic diuretic, followed by urea.
• Used with cisplatin and carboplatin in cancer chemotherapy to induce diuresis and decrease side effects.
• Mannitol is a sugar that is not well absorbed by the tubules and acts to increase urine production.

Carbonic Anhydrase Inhibitors

• Acetazolamide and methazolamide block carbonic anhydrase.
• Carbonic anhydrase is an enzyme needed to maintain the body's acid-base balance.

Acetazolamide

• A weak diuretic that inhibits carbonic anhydrase in the kidneys, brain, and eyes.

Potassium-Sparing Diuretics

• Weaker than thiazides and loop diuretics.
• Can be used in combination with hydrochlorothiazide or an antihypertensive drug.

Spironolactone

• Aldosterone antagonist discovered in 1958.
• It was the first potassium-sparing diuretic.

Aldosterone

• It is a mineralocorticoid hormone.
• Promotes sodium retention and potassium excretion.

Module 8: Hemostasis

• Hemostasis is the process that stops blood loss when an injury occurs and involves 3 steps.

Vascular Spasm

• Smooth muscle in blood vessel walls contracts immediately when injured, reducing blood loss.

Platelet Plug Formation

• Platelets that encounter damaged blood vessels form a "platelet plug" to close the gap.
• Key stages include platelet adhesion, platelet release reaction, and platelet aggregation.

Blood Clotting (Coagulation)

• Blood remains liquid inside vessels but thickens and coagulates (gel-like) when injury occurs.
• Anticoagulation slows down the blood clotting to prevent the formation of blood clots.
• Anticoagulant agents slow down or prevent formation of blood clots.

Anticoagulants

• Prevent blood clotting in patients with thrombophlebitis, pulmonary embolism, & embolism.
• Heparin & warfarin prevent thrombosis in the veins

Types of Heparin

• Regular or Unfractionated Heparin
• LMWHS (low molecular weight heparin)/fractionated

Antithrombin III

• Is a substance that inactivates thrombin.
• synthesized in the liver and circulates in plasma

Heparin Antagonist

• Suspends the effect of heparin.
• Protamine sulfate (10mg for 1000 unit of heparin)

Partial Thromboplastin Time -PTT/Activated Partial Thromboplastin Time - aPTT

• Laboratory tests detect deficiencies of certain clotting factors.
• Tests used to monitor heparin therapy.

Thrombocytopenia/Bleeding Complications

• Excessive bleeding managed by administering protamine sulfate to reverse heparin.

Warfarin (Coumadin)

• Warfarin is absorbed rapidly and almost completely when taken orally.
• Dicoumarol and Anisindone are also anticoagulants.

International Normalized Ratio (INR)

• Is the laboratory test frequently used to report PT results

Antidote for Warfarin

• Vitamin K or phytonadione
• Direct thrombin inhibitors are a new class of anticoagulants that bind directly to thrombin and block its interaction with its substrates.

Antiplatelet Drugs

• Used to prevent thrombosis in the arteries that suppresses platelet aggregation
• These drugs decrease the formation of the platelet plug by decreasing the responsiveness of the platelets

COX Inhibitors: Aspirin

• Inhibits cyclooxygenase, the enzyme platelets need to synthesize thromboxane.
• Has prolonged antiplatelet activity.

Adenosine Diphosphate (ADP) Antagonists

• Clopidogrel
• Dipyridamole

Thrombolytics

• Thrombolysis is a treatment with the goal of dissolving blood clots that cause obstruction.
• Thrombolytics are used to dissolve clots, improve blood flow, and prevent damage to tissues and organs.
• Thrombolytics activate the natural anti-clotting fibrinolytic mechanism to convert plasminogen to plasmin.
• Destroys and breaks down the fibrin threads in the blood clot (FIBRINOLYSIS)
• Thromboembolism is the occlusion of an artery or vein caused by thrombus or embolus, resulting in ischemia (deficient blood flow) that causes necrosis

Common Thrombolytics

• Tissue plasminogen activator (t-PA) or alteplase, Steptokinase, Urokinase, Anistreplase, Reteplase, and Tenecteplase

Alteplase

• Also known as tissue plasminogen activator (tPA) & tenecteplase (TNK tPA)

Streptokinase

• Obtained from B haemolytic streptococci group C
• Non-intrinsic enzyme activity