Inorganic Pharmaceutical Chemistry PDF

Inorganic Pharmaceutical Chemistry Replacement Therapy  Replacement Therapy  The basic objective of replacement therapy is to restore the volume and composition of the body fluids to normal one.  Volume contraction is a life threatening condition because: 1. It impairs the circu...

Inorganic Pharmaceutical Chemistry Replacement Therapy  Replacement Therapy  The basic objective of replacement therapy is to restore the volume and composition of the body fluids to normal one.  Volume contraction is a life threatening condition because: 1. It impairs the circulation. 2. Blood volume decreases. 3. Cardiac output falls and the integrity of microcirculation is compromised.  When volume depletion to sufficient magnitude that threaten life, a prompt infusion of isotonic sodium chloride solution is indicated.  In an extreme case, intravenous therapy at the rate of 100 mL per minute for the first 1000mL has been considered necessary for the successful treatment of cholera.  1) Sodium Replacement Sodium Chloride: (NaCl; MW 58.44))  It occurs as colorless cubic crystals or as white crystalline powder having a saline taste.  Itis freely soluble in water & more soluble in boiling water, soluble in glycerin and slightly soluble in alcohol.  Its uses range from replacement therapy and manufacture of isotonic solution to a flavor enhancer.  Isotonic solutions are used as wet dressings, for irrigating body cavities or tissues  Hypotonic solutions are administered for maintenance therapy when patients are unable to take fluids and nutrients orally for one to three days.  Hypertonic injections are used when there is loss of sodium in excess (should be given slowly in small volume200-400mL).  Official Preparations of Sodium Replacement Sodium Chloride Injection, solution & tablets. Bacteriostatic sodium chloride injection. Dextrose and sodium chloride injection & tablets. Mannitol and sodium chloride injection. Fructose and sodium chloride injection. Ringer’s injection. Lactate ringer’s injection.  Official preparations of Sodium chloride Sodium Chloride Injection a sterile isotonic solution of sodium chloride in water for injection. It contains not less than 0.85 % and not more than 0.95 % w/v of sodium chloride. It contains no antimicrobial agents. It is a clear, colorless solution with pH between 4.5-7.0.  Sodium Chloride Hypertonic Injection (Hypertonic saline) It is a sterile solution of sodium chloride in water for injection. It contains not less than 1.52 % and not more than 1.68 % w/v of sodium chloride. It contains no antimicrobial agents. It is a clear, colorless solution with pH between 5.0-7.5.  Compound Sodium Chloride Injection (Ringer injection) 1. not less than 0.82 % and not more than 0.9 % w/v of sodium chloride. 2. not less than 0.0285 %, not more than 0.0315 % w/v of potassium chloride. 3. not less than 0.03 % and not more than 0.036% w/v of calcium chloride in water for injection. It contains no antimicrobial agents. It is a clear, colorless solution with pH between 5-7.5.  Sodium Chloride and Dextrose Injection It is a sterile solution of sodium chloride and dextrose in water for injection. It is clear colorless or faintly straw colored solution with pH between 3.5-6.5. It contains 0.9% of sodium chloride and 5% dextrose.  2) Potassium Replacement  Potassium Chloride: (KCl; M.Wt. 74.56).  It occurs as colorless, elongated, prismatic, or cubical crystals, or as white, granular powder.  It is odorless, has a saline test, and is stable in air.  It is freely soluble in water and even more soluble in boiling water, giving solution that are neutral to litmus. It is insoluble in alcohol.  Used in:  Oral replacement of potassium (Irritating to GIT & solution must be well diluted).  Familial periodic paralysis (a recurring, rapidly progressive, flaccid paralysis).  Meniere’s syndrome ( disease of inner ear which includes dizziness and noise in the ear).  As antidote in digitalis intoxication (not a specific antidote and can potentiate some of the cardiac complication).  As an adjunct to drugs used in the treatment of myasthenia gravis (A progressive, sever muscle weakness).  Contraindication in patient with:  Impaired renal function with oliguria (diminished urine out put).  Acute dehydration.  Hyperpotassemic condition such as myotonia congenita (tonic muscle rigidity & spasm), adynamia episodica hereditaria (periodic weakness or paralysis of skeletal muscle).  Potassium-sparing drugs.  Official Preparations of Potassim Replacement:  Potassium Chloride injection & tablets.  Ringer’s injection.  Lactate Ringer’s injection.  Lactate potassium saline injection.  Potassium gluconate elixir & tablets.  3)Calcium Replacement  Calcium Chloride: (CaCl2.2H2O; M.Wt. 147.02).  It occurs as white, hard, odorless fragments or granules, it is freely soluble in water, alcohol and boiling alcohol and very soluble in boiling water.  It is irritating to the veins and should be injected slowly.  Used as: the calcium source in many commercially available electrolyte replacement and maintenance solutions.  Official Préparations of Calcium Replacement:  Calcium chloride include: Ringer's injection & Lactate ringer's injection.  Calcium gluconate injection & tablets.  Calcium lactate tablets.  Dibasic calcium phosphate.  Tribasic calcium phosphate  4) Parenteral Magnesium Administration:  Magnesium Sulfate: (MgSO4.7H2O; M.Wt. 246.47)  When injected has been used as central nervous system depressant in the treatment of eclampsia (convulsions and coma), and in magnesium deficient alcoholics.  Overtreatment can cause respiratory paralysis and cardiac depression.  I.V.injection of Ca salts is used to counteract Mg intoxication.  Should not be administered in patient with renal insufficiency.  Used as: Anticonvulsant; cathartic. Official Preparations of Magnesium:  Magnesium sulfate injection Physiological Acid Base Balance  Disturbances of the pH of body are frequently encounter and are of major clinical importance.  Acidemia and alkalemia refer respectively to an abnormal decrease or increase in the pH of the blood.  Acidosis and alkalosis refer respectively to clinical state that can lead to either acidemia or alkalemia.  However, in each condition the extent to which there is an actual change in pH depends in part on the degree of compensation which varies in most clinical disturbances.  Acids either carbonic from carbon dioxide or lactic from (anaerobic metabolism) are constantly being produced during metabolism.  Most metabolic reactions occur only within narrow pH range of 7.38-7.42, therefore the body utilizes several efficient buffer systems.  Two of the major buffer system in the body are bicarbonate/carbonic acid (HCO3–/H2CO3) found in the plasma & kidney and monohydrogen phosphate/dihydrogen phosphate (HPO42-/H2PO4-) found in the cells and kidneys.  RBC’s have hemoglobin buffer system which is the most effective single system for buffering the carbonic acid produced during metabolic process.  For each millimole of oxygen that dissociates from hemoglobin (Hb) 0.7 millimole of H+ are removed.  Carbon dioxide, the acid anhydride of carbonic acid is continuously produced in the cells.  It diffuses from the cell into the plasma where a small portion dissolved and another small portion reacts with water to form carbonic acid.  The increased carbonic acid is buffered by plasma proteins.  Most CO2 enters the erythrocytes where it either rapidly forms H2CO3 by the action of carbonic anhydrase or combines with Hb.  The tendency to lower the pH of the erythrocytes due to increased concentration of H2CO3 is compensated by Hb.  CO2 + H2O Carbonic anhydrase H2CO3  The bicarbonate anion then diffuses out of erythrocytes and chloride anion diffuses in.  This has been named as chloride shift.  The bicarbonate in plasma, along with the plasma carbonic acid now acts as efficient buffer system  The normal HCO3-/ H2CO3 ratio is 27/1.35 meq/l (20:1) corresponding to pH 7.4.  In lungs there is reversal of the above process due to the large amount of O2 present.  Oxygen combines with the protonated deoxy hemoglobin releasing proton.  These combine with HCO3- forming H2CO3 which then dissociates to CO2 and water.  The carbon dioxide is exhaled by the lungs.  Thus by regulating breathing it is possible for the body to exert a partial control on the HCO3-/H2CO3 ratio.  The phosphate buffer system is also effective in maintaining physiological PH.  At pH 7.4 the HPO4-2/H2PO4- ratio is approximately 4:1.  In kidney, the pH of urine can drop to 4.5-4.8 corresponding to HPO4-2/H2PO4- ratio of 1:99- 1:100.  The steps of acid excretion from kidney shown as following: 1. Sodium salt of mineral or organic acids are removed from the plasma by glomerular filtration. 2. Sodium is preferentially removed from the renal filtrate or tubular fluid and in the tubular cells reacts with carbonic acid formed by the carbonic anhydrase catalyzed reaction of carbon dioxide & water. This is sometimes called Na+- H+ exchange. 3. The NaHCO3 returns to the plasma (eventually being removed in the lungs as CO2) & the protons enter the tubular fluid, forming acids of the anions that originally were sodium salts (H2PO4-, lactate, etc).  Types and Causes of Acidosis: 1. Metabolic acidosis: primary bicarbonate ion deficit,(diabetic acidosis, renal failure and diarrhea).  Buffer System: HCO3-/H2CO3.  Compensatory mechanisms: Hyperventilation causing increased excretion of H2CO3 as CO2 (respiratory function), increased acid excretion by Na+-H+ exchange, increased NH3 formation and HCO3- reabsorption (renal function). 2. Respiratory Acidosis: primary carbonic acid excess (cardiac disease, lung damage, drowning).  Buffer system: hemoglobin and protein.  Compensatory mechanisms: increased CO2 excretion through the lungs (respiratory function), increased acid excretion by Na+-H+ exchange, increased NH3 formation and HCO3- reabsorption (renal function).  Types and Causes of Alkalosis: 1. Metabolic alkalosis: primary HCO3- excess (administration of excess alkali, vomiting, potassium ion).  Buffer System: HCO3-/H2CO3.  Compensatory mechanisms: CO2 retention causing increased H2CO3 concentration (respiratory function), decreased Na+-H+ exchange, decreased NH3 formation , and reabsorption of HCO3- (renal function). 2. Respiratory alkalosis: primary H2CO3 deficit, (fever, hysteria, anoxia, salicylate poisoning).  Buffer System: HCO3-/H2CO3.  Compensatory mechanisms: CO2 retention causing increased H2CO3 concentration (respiratory function), decreased Na+-H+ exchange, decreased NH3 formation, and reabsorption of HCO3- (renal function).  Electrolytes used in acid base balance  1)Sodium acetate  which is metabolized to carbon dioxide and then to bicarbonate, can be used as an effective buffer in metabolic acidosis.  It approaches sodium bicarbonate in its ability to restore blood pH and plasma bicarbonate in patient suffering from: 1. metabolic acidosis of acute cholera ( a disease involving sever diarrhea resulting in the loss of electrolytes). 2. Uremic acidosis (acidic urine) has been corrected by infusion of sodium acetate giving results comparable to equivalent amount of sodium bicarbonate infusion.  2)Potassium acetate  The alkalinity increases as the solution stand, are agitated or are heated. It is stored in well closed containers.  It is soluble in water and insoluble in alcohol. 3) Sodium bicarbonate  It categorized as an alkalizer.  Along with potassium citrate and bicarbonate, it is found in potassium triplex.  Sodium bicarbonate used to: 1. Combate gastric hyperacidity. 2. To combate systemic acidosis. 3. For miscellaneous uses. Found as sodium bicarbonate injection and tablets. 4) Potassium bicarbonate Occurs as colorless, transparent, monoclinic prisms or as a white granular powder which is odorless, and is stable in air.  It solution are neutral or alkaline. It is freely soluble in water and practically insoluble in alcohol. It is officially classified as an electrolyte replenisher and is a component of potassium triplex and oral effervescent potassium replacement solutions (K-Lyte). 5) Sodium biphosphate It is classified as urinary acidifier since the excess dihydrogen phosphate anion is excreted by the kidneys. 6) Sodium citrate 1. official for its use as an anticoagulant for whole blood, it chelates serum calcium, thereby removing one of the components of blood clotting. 2. Citrates are used for the chelation of other cations, e.g., Benedict's Solution and Ferrous Sulfate Syrup. 3. Citric acid and its salts are also used as buffering agents.  Because citrate, a component of the tricarboxylic acid or Krebs cycle, is rapidly metabolized to carbon dioxide and then to bicarbonate, sodium citrate is used in chronic acidosis to restore bicarbonate reserve. 4. It also has a diuretic effect due to increased body salt concentration. 7) Potassium Citrate  Potassium citrate occurs as transparent crystals or as a white granular powder. It is odorless, has a cooling saline taste, and is deliquescent when exposed to moist air.  It is freely soluble in water and almost insoluble in alcohol.  8)Ammonium Chloride  The ammonium cation falls into certain pharmacological categories: 1. Acid-base equilibrium of the body. 2. Diuretic effect. 3. Expectorant effect. Electrolyte Combination Therapy  Infusions: In short-term therapy, such as following surgery, infusion of standard glucose & saline solution may be adequate; however when deficits are severe or protracted, solution containing additional electrolyte are usually required. While combinations compounded according to need of each individual patient would be ideal, this usually is not feasible from the standpoint of cost and sterility. These combination products can be divided into two groups: fluid maintenance and electrolyte replacement.  Maintenance therapy with intravenous fluids is intended to supply normal requirements for water and electrolytes to patients who cannot take them orally. All maintenance solutions should contain at least 5% dextrose. This minimizes the buildup of those metabolites associated with starvation: urea, phosphate, and ketone bodies. In addition to dextrose, the general electrolyte composition of maintenance solutions is Na, K, Cl, HCO3 (or equivalent amounts of lactate or acetate), Mg, and P. Replacement therapy is needed as in: 1. Prolonged fever. 2. Severe vomiting. 3. Diarrhea. There are two types of solutions used in replacement therapy: 1. Solution for rapid initial replacement. 2. Solution for subsequent replacement. The electrolyte concentrations in solution for rapid initial replacement more or less resemble the electrolyte concentrations found in ECF.  Some may have larger amounts of potassium, the concentration of ions varies, these variations allows the clinician to select solution which best fits the electrolyte and acid-base needs of the patients. Official combination of electrolyte infusions: Ringer's injection It contains potassium Chloride, sodium chloride, and calcium chloride (as the dihydrate). This is equivalent to Na, K, Ca, and Cl. Lactated Ringer's Injection It contains sodium chloride, sodium lactate, potassium chloride and calcium chloride (as the dihydrate). These are equivalent to Na, K, Ca, Cl and lactate. It is usually available as injections. Oral Electrolyte Solutions Orally administered electrolyte solutions are available. Two (Lytren and Pedialyte) are used to supply water and electrolytes in amounts needed for maintenance as soon as intake of usual foods and liquids is discontinued and before serious fluid losses or deficits occur (diarrhea, etc.).