Classes of Diuretics
Cardiovascular Diuretics
Physiological Diuretics
Osmotic Diuretics
Loop (High Ceiling) Diuretics
Thiazide Diuretics
Potassium Sparing Diuretics
Carbonic Anhydrase Inhibitors
Physiologic Diuretics
Not diuretic by definition, but have diuretic effect
Major effects of Alpha 1 adrenoceptors
Vasoconstriction
Increased peripheral resistance
Increased blood pressure
Mydrasis
Increased closure of internal sphincter of the bladder
Therapeutic uses of osmotic diuretics
Treatment of cerebral edema
Treatment of glaucoma
Treatment of acute renal failure
Mobilization of edema fluid
Used in patients with drug overdose
Examples of Carbonic Anhydrase Inhibitors
Acetazolamide
Methazolamide
Dorzolamide and Brinzolamide (Topical Ophthalmic)
Adverse effects of Thiazide diuretics
Electrolyte imbalances
Hyperglycemia
Hypersensitivity reactions
Hyperlipidema
Most effective diuretics are
Loop diuretics
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Inhibit the most reabsorption of Na acting on ALoH
Diuretic efficacy of Spironolactone depends on
Levels of endogenous aldosterone
Pharmacokinetics of Triamterine and Amiloride
Admistered orally
Amiloride is excreted by the kidneys
Triamterene is convered to an active metabolite in the liver whihc is actively secreted in the urine
What osmotic diuretic is not metabolized and is elimiated rapidly by the kidney
Mannitol
Pharmacokinetics of Thiazide Diuretics
Administered orally
Absorption is slow and incomplete
Bind extensively to plasma proteins
Excreted maily by the kidneys and are actively secreted in urine by the organic acid secretory machanism
Decreased renal blood flow decreases their effectiveness
Glycerin and isosorbide are administered
Orally
Pharmacokinetics of Spironolactone
Administered orally
Readily absorbed and is highly bound to plasma protein
Extensively metabolized by the liver and is converted to an active metabolite
Onset of action is slow (2-3 days) and duration of action is long
Diuretic
Medication that increases urine flow or urine volume
T/F: Diuretics are drugs that increase urination
False
Potency of diuretics depends on
Where it acts in the nephron
Examples of physiologic diuretics
Water
Sodium Chloride
Therapeutic uses of Thiazide Diuretics
Treatment of edema of CHF, liver cirrhosis, nephrotic syndrome and acute glomerular nephritis
Treatment of hypertension alone or combined with other antihypertensive drugs
Treatment of nephrogenic diabetes insipidus and useful in central diabetes insipidus
Treatment of calcium nephrolithiasis and may be useful for the treatment of osteoporosis
Treatment of udder edema in cows
Duretics ranked from most effect to least effective
Loop Diuretics > Thiazide Diuretics > Osmotic Diuretics > Potassium Sparing Diuretics
Adverse effects of carbonic anhydrase inhibitors
Mild systemic acidosis
Hypokalemia
Hyperglycemia
Mechanism of Action of Osmotic Diuretics
- Interfere with transport mechanisms in the thick ascending limb increasing the urinary excretion of Na, K, Ca, Mg, Cl, HCO3 and phosphate
- Osmotic effect in the tubule and reduce medullary tonicity
- Increase renal blood flow and renal medullary blood flow by several mechanisms
Mechanism of action of Loop or Ceiling Diuretics
- Inhibit Na-K-Cl Symporter in the loop of henle
- Inhibits the paracellular reabsorption of Na, Ca, Mg
- Increased Na delivery to late distal tubule and collecting duct increases depolarization of the luminal membrane creating a lumen -negative transmembrane potentail difference - facilitates K excretion
- Stimulate Renin-Angiotension- Aldosterone
- Increases total renal blood flow
- Increase systemic venous capacitance
Therapeutic uses of Triamterine and Amiloride
Treatment of hypokalemia and hypomagnesemia
Occassionally used in edematous disorders and hypertension - very weak diuretics
Mannitol and urea are administered
IV
Mechanism of action of Spironolactone
- Competitively blocks aldosterone binding to aldosterone receptor in the late distal tubule and collecting duct
- Excretion of NaCl and diuresis as well as retention of K and H
Major effects of Alpha 2 adrenoceptors
Inhibition of norepinephrine release
Inhibition of insulin release
Mechanism of Action of Thiazide Diuretics
- Inhibit the Na-Cl symporter in distal convoluted tubule - inhibition of tubular reabsorption of Na, Cl and diuresis
- Inhibit K and Mg reabsorption but increase reabsorption of Ca
- Cause hypokalemia and systemic alkalosis similarly to loop diuretics
Examples of Loop or Ceiling Diuretics
Therapeutic uses of Spironolactone
Diuretic
Treatment of primary and secondary hyperaldosteronism
Adverse effects of loop or ceiling diuretics
Ototoxicity
Hypokalemia
Hypomagnesemia
Acute hypovolemia
Hypotension
Cardiact arrhythmias
Hyperglycemia
Hyperuricemia
Systemic alkalosis
Hypersensitivity reactions
Pharmacokinetics of carbonic anhydrase inhibitors
Acetazolamide is administered orally
Onset of action is about 30 minutes and duration of action is 4-6 hours in small animals
Acetazolamide is eliminated maily by the kidneys and is actively secreted in urine by the organic acid secretory mechanism
Dorzolamide and Brinzolamide are administerd topically on the eye
Adverse effects of Spironolactone
Hyperkalemia
Systemic acidosis
Adverse effects on reproduction because it acts on progesterone and androgen receptors
Important Adrenoceptors
Alpha 1
Alpha 2
Beta 1
Beta 2
Adverse effects of Triamterine and Amiloride
Hyperkalemia
Systemic acidosis
Examples of Thiazide Diuretics
Hydrochlorothiazide
Chlorothiazide
Therapeutic use of cardiovascular diuretics
Treatment of edema associated with congestive heart failure
Mechanisms by which Loop or Ceiling Diuretics contribute to hypokalemia and systemic alkalosis
- K excretion through K channel in the luminal membrane of the principal cell and H secretion in type A intercalated cell into the lumen
- Stimulating the renin-angiotension-aldosterone
Examples of Potassium Sparing Diuretics
Spironolactone
Triamterene
Amiloride
General mechanism of action of all diuretics
Inhibit the reabsorption of Na
Examples of osmotic diuretics
Mannitol
Urea
Glycerin
Iso
Examples of cardiovascular diuretics
Digitalis
Phosphodiesterase inhibitors
Pharmacokinetics of Furosemide
Administered orally and IV
Onset of action is rapid and duration is short
Partially metabolized by conjunction and partially excreted unchanged in urine and actively secreted in urine by the organic acid secretory mechanism
Cardiovascular Diuretics
Not a diuretic by definition, but have diuretic effect
Any drug that cause increased contractility/ cardiac output of the heart to have a diuretic effect due to increased renal blood flow
Osmotic diuretics act on what portion of the nephron
Act both on the loop of henle (primary site) and proximal tubule (secondary site)
Mechanism of action of Triamterine and Amiloride
- Block epithelial Na channels in the luminal membrane of the principal cells in the late distal tubule and collecting duct
- Excretion of Na and diuresis as well as retention of K and H
Therapeutic uses of carbonic anhydrase inhibitors
Treatment of open-angle glaucoma
Acetazolamide has been used in udder edmea
Therapeutic uses of loop or ceiling diuretics
Treatment of pulmonary edema and pulmonary congestion
Treatment of generalized edema associated with CHF, chronic renal failure and liver cirrhosis
Combined with isotonic saline to treat hypercalcemia and prevent volume depletion
May be used in patients with acute renal failure
Treatment of increased intracranial pressure and udder edema
Etc.
Major effects of Beta 2 adrenoceptors
Vasodilation
Slightly decreased peripheral resistance
Bronchodilation
Increased muscle and liver glycogenolysis
Increased release of glucagon
Relaxed uterine smooth muscle
Mechanism of action of carbonic anhydrase inhibitors
- Reversible inhibition of carbonic anhydrase (CA) which inhibits the exchange of hydrogen for sodium in the proximal tubule which is the primary site
- Secondary site is the collecting duct
- Carbonic anhydrase inhibitors lower intraocular pressure by inhibition of carbonic anhydrase in the eye decreasing formation of aqueous humor
Major effects of Beta 1 adrenoceptors
Tachycardia
Increased lipolysis
Increased myocardial contractility