Pharma

• Diuretics


  • Thiazide and thiazide-like
  • Loop
  • Potassium-sparing
  • Osmotic
  • Carbonic-anhydrase inhibitors
• Thiazide and thiazide-like diuretics


  Sulfonamide derivatives that promote the excretion of water and electrolytes by the kidneys
• Thiazide diuretics


  • bendroflumethiazide
  • benzthiazide
  • chlorothiazide
  • hydrochlorothiazide
  • hydroflumethiazide
  • methyclothiazide
  • polythiazide
  • trichlormethiazide
• Thiazide-like diuretics


  • chlorthalidone
  • indapamide
• Thiazide diuretics


  • Absorbed rapidly but incompletely from the GIT after oral administration
  • Cross placenta and secreted in the breastmilk
  • Differ in how well they are metabolized
• Thiazide-like diuretics


  • Absorbed from GIT
  • Excreted primarily in the urine
• Pharmacodynamics of thiazide and thiazide-like diuretics

  • Work by preventing sodium from being reabsorbed in the kidney
  • Increase the excretion of chloride, potassium and bicarbonate which can result in electrolyte imbalance
• Loop diuretics


  High ceiling diuretics that act on the thick ascending loop of Henle to inhibit chloride transport of Na into the circulation
• Loop diuretics


  • bumetanide
  • ethacrynate sodium
  • ethacrynic acid
  • torsemide
  • furosemide
• Loop diuretics


  • Absorbed well and distributed rapidly
  • Highly protein bound
  • Undergo partial or complete metabolism in the liver except for furosemide, which is excreted primarily unchanged
  • Excreted by the kidneys
• Pharmacodynamics of loop diuretics


  • Most potent drugs available
  • High potential for causing severe adverse reactions
  • Act primarily on the thick ascending loop of Henle to increase the secretion of sodium, chloride and water; may also inhibit the reabsorption of these substances
• Potassium-sparing diuretics


  Have weaker diuretic and antihypertensive effects than other diuretics but have the advantage of conserving potassium
• Potassium-sparing diuretics


  • amiloride
  • spironolactone
  • triamterene
• Potassium-sparing diuretics


  • Available orally and absorbed in the GIT
  • Metabolized in the liver except for amiloride
  • Excreted primarily in the urine and bile
• Pharmacodynamics of potassium-sparing diuretics

  • Urinary excretion of sodium and water increases as does the excretion of chloride and calcium ions
  • Excretion of potassium and hydrogen ion decreases
  • Spironolactone is structurally similar to aldosterone and acts as aldosterone antagonist
• Osmotic diuretics


  Pull water into the renal tubule without sodium loss
• Osmotic diuretics


  • mannitol
• Osmotic diuretics


  • Effects are not limited to kidneys because the injected substance pulls fluid into the vascular system from extravascular spaces, including the aqueous humor
  • Mannitol is only available for IV use
  • Freely filtered at the renal glomerulus, poorly reabsorbed by the renal tubule and resistant to metabolism
• Carbonic anhydrase inhibitors


  Mild diuretics that block the effects of carbonic anhydrase thereby slowing down the movement of hydrogen ions; as a result, more sodium and bicarbonate are lost in the urine
• Carbonic anhydrase inhibitors


  • acetazolamide
  • methazolamide
• Carbonic anhydrase inhibitors


  • Rapidly absorbed and widely distributed
  • Can be orally or IV
  • Drugs peak in 2-4 hours, 15 minutes if given IV; duration is 6-12 hours
  • Excreted in the urine
  • Have been associated with fetal abnormalities and should not be used during pregnancy
• Electrolyte


  A compound or element that carries an electrical charge when dissolved in water
• Normal amount of potassium: 3.5-5.5 mEq/L
• Dietary requirement for potassium: 40-60 mEq
• Potassium supplements


  • Absorbed readily from GIT
• Interactions


  There may be an increased excretion of salicylates and lithium if they are combined with these drugs
• Drugs for Fluid & Electrolyte Balance

  • Illness can easily disturb the homeostatic mechanisms that help maintain fluid and electrolyte balance
  • Loss of appetite, medication administration, vomiting, surgery, and diagnostic tests can also alter the balance
• Electrolyte replacement drugs


  Mineral salts that increase depleted or deficient electrolyte levels
• Potassium


  • Major cation in ICF (intracellular fluid)
  • Adequate amounts must be ingested daily
  • Potassium supplement can be accomplished orally or IV with potassium salts, such as potassium bicarbonate, potassium chloride, potassium gluconate, potassium sulfate
  • Normal amount: 3.5-5.5 mEq/L
  • Dietary requirement: 40-60 mEq
• Potassium


  • Absorbed readily from GIT
  • After absorption into the ECF (enterocutaneous fistula), almost all potassium passes into the ICF
  • Normal serum levels of potassium are maintained by the kidneys, which excrete most of the excessive potassium intake; the rest is excreted in the feces and sweat
• Potassium


  • Moves quickly into the ICF to restore depleted potassium levels and re-establish balance
  • Essential element in determining cell membrane potential and excitability
  • Necessary for proper functioning of all nerve and muscle cells for nerve impulse transmission
  • Essential for tissue growth and repair and for maintenance of acid-base balance
  • Needed for enzyme action used to change carbohydrates to energy and amino acids to proteins
• Calcium


  • Almost all calcium in the body is stored in the bone, where it can be mobilized if necessary
  • Chronic insufficient calcium intake can result in bone demineralization
  • Promotes normal nerve and muscle activity and increases the contraction of the heart's muscle
  • Replaced orally or IV with calcium salts, such as calcium carbonate, calcium chloride, calcium citrate, calcium gluconate, calcium glubionate, calcium lactate
  • Normal amount: 4.5 to 5.5 mEq/L or 8.5 to 10.5 mg/dl
  • Daily requirement: 1,300 mg (14-18); 1,000 mg (19-50 yo); 1,200 mg (above 50 yo)
• Calcium


  • Absorbed readily from the duodenum and proximal jejunum
  • pH of 5 to 7, parathyroid hormone and vitamin D all aid calcium absorption
  • Distributed primarily in the bone
  • Calcium salts are eliminated primarily in the feces; the rest is excreted in the urine
• Calcium


  • Extracellular ionized calcium plays an essential role in normal nerve and muscle excitability
  • Calcium is integral to normal functioning of the heart, kidneys and lungs and it affects the blood coagulation rate as well as cell membrane and capillary permeability
  • Calcium is a factor in neurotransmitter and hormone activity, amino acid metabolism, vitamin B12 absorption and gastrin secretion
  • Plays a major role in normal bone and tooth formation
• Magnesium


  • Most abundant cation in ICF after potassium
  • Essential in transmitting nerve impulses to muscle and activating enzymes necessary for carbohydrate and protein metabolism
  • Stimulates parathyroid hormone secretion thus regulating ICF calcium levels
  • Aids in cell metabolism and the movement of sodium and potassium across cell membranes
  • Typically replaced in the form of magnesium sulfate
  • Normal value: 1.5-2.5 mEq/L
  • Daily requirement: 19-30 years, 400 mg (men) and 310 mg (women); 31 years up, 420 mg (men) and 320 mg (women)
• Magnesium


  • Distributed widely throughout the body; IV magnesium sulfate acts immediately, whereas after IM administration, it acts within 30 minutes
  • Not metabolized and is excreted unchanged in the urine; some are excreted in the breast milk
• Magnesium


  Replenishes and prevents magnesium deficiencies; also prevents seizures by blocking neuromuscular transmission
• Sodium


  • Major cation in ECF
  • Maintains the osmotic pressure and concentration of ECF, acid-base balance and water balance
  • Contributes to nerve conduction and, neuromuscular function
  • Replacement is necessary for conditions that deplete it such as excessive GI fluid loss and excessive perspiration
  • Normal value: 135-145 mEq/L
  • Daily dietary requirement: 2 g
• Sodium


  • Oral and parenteral preparations are quickly absorbed and distributed widely throughout the body
  • Not significantly metabolized, primarily eliminated in the urine
• Sodium


  Replaces deficiencies of the sodium and chloride ions in the blood plasma