By S S D BHAVANI RAJA - PowerPoint Presentation

1. By S S D BHAVANI RAJAASSISTANT PROFESSOR DEPARTMENT OF PHARMACEUTICAL CHEMISTRYDepartment of Pharmaceutical Chemistry

2. Electrolyte is a substance that ionizes when dissolved in a suitable ionising solvent such as water.This includes most soluble acids, bases & gases.An electrolyte may be defined as concentrated if it has high concentration of ions or dilute if it has low concentration of ions.The electrolyte concentration is maintained constant in the body fluids.If a person undergoes surgery or remain ill or under undesirable condition for a long time, the body cannot maintain the electrolyte balance, then it is done by external administration which is termed as Replacement therapy.Electrolytes are used for the correction of acid-base balance in various body fluids.MAJOR INTRA & EXTRACELLULAR ELECTROLYTES

3. The electrolyte concentration of body fluids have been different in various body fluid compartments. They are1. Intracellular fluid:- The fluid which is present inside the cell. Ex- CytoplasmIt constitutes 40-50% of body weight & its volume is 30 litres.2. Interstitial fluid:- The fluid which is present between the cells. It constitutes 12-15% of body weight & its volume is 10 litres.3. Plasma (Vascular fluid):- The fluid which is present within the blood vascular system.This constitutes 4-5% of body weight & its volume is 3-5 litres.The fluids present in the interstitial & vascular compartments are referred to collectively as Extracellular fluid (ECF).MAJOR INTRA & EXTRACELLULAR ELECTROLYTES

4. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTES

5. Sodium & chloride are the main ions of ECF while potassium & phosphate are the major ions of ICF.The three fluid compartments are demarcated from each other by membranes which are permeable to water & certain inorganic & organic components present in the body fluids.These membranes do not permit the transfer of certain molecules like proteins.For certain ions like Na, K, Mg the membrane shows selective permeability. Thus the composition & concentration of various solutes in body fluids have been definite but different from one another.The body fluids are having various inorganic ions which are either anionic or cationic.Anionic electrolytes- HCO₃⁻, Cl⁻, SO₄²⁻, HPO₄²⁻Cationic electrolytes- Na⁺, K⁺, Ca²⁺, Mg²⁺MAJOR INTRA & EXTRACELLULAR ELECTROLYTES

6. MAJOR INTRA & EXTRACELLULAR ELECTROLYTESElectrolyteExtracellular (mEq/L)Intracellular (mEq/L)Plasma range (mEq/L)Cations:-Na⁺14210135-145K⁺41404.5-5.5Ca²⁺2.40.00012.1-2.6Mg²⁺1.2581.5-3.0Anions:-Cl⁻103498-105*SO₄²⁻120.3-1.5HCO₃⁻281025-31* HPO₄²⁻4751.2-3.0*Concentration of important Electrolytes* - Adults

7. MAJOR INTRA & EXTRACELLULAR ELECTROLYTESThe fluid in each compartment is ionically balanced. Body has the capacity to adjust slight variations in electrolytic concentration of the fluid compartments. If concentration of electrolytes changes – water will migrate across the cell membrane to re-establish Osmotic equilibrium.

8. MAJOR INTRA & EXTRACELLULAR ELECTROLYTES

9. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTES

10. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTES

11. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTESRole of Major Physiological Ions

12. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTESSODIUM – Location- extracellular compartment as a salt (90%).Normal plasma level- 136-142 mEq/L Normal intake of NaCl per day- 5-20gDaily requirement – 3-5gExcess quantity of salt consumed gets excreted in the urine.The sodium level in the blood is controlled by aldosterone & ADH.Food sources- table salt, milk, baking powder, meat & some vegetables. Functions- Regulates acid-base equilibrium.Along with chloride maintain osmotic balance of various fluids.Plays an important role in permeability of cellTransmission of nerve impulse.

13. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTES

14. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTESPOTASSIUM –Normal intake of KCl-5-7g/dayDaily requirement – 1.5-4.5gSources- milk, certain vegetables, meat & whole grains.It is rapidly absorbed from diet & rapidly excreted through kidneys. Maintains electrolyte composition of various body fluids.Influences acid-base balance & water retention.

15. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTESConditionHyperkalaemiaHypokalaemiaElevated K⁺ levelsLow K⁺ levelsReasonRenal failure, Dehydration or shock, Addison’s diseaseProlonged diuretic therapy, Inadequate intake, Severe diaphoresis, Use of laxative, vomiting, Excess insulin, Excess stress, Hepatic disease, Acute alcoholismSymptomsApathy, Confusion, Numbness/ paraesthesia of extremities, Abdominal cramps, Nausea, Flaccid muscles, Diarrhoea, Oliguria, Bradycardia, Cardiac arrestAnorexia, Nausea, vomiting, Drowsiness, lethargy, confusion, Leg cramps, Muscle weakness, Hyperreflexia (overactive or overresponsive reflexes)., Hypotension, Cardiac dysrhythmias, Polyuria

16. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTESCALCIUM –The total calcium content in body is about 22g/kg body weight Daily requirement – 0.8g99% of calcium is found in bones and 1% in ECFSources- milk, cheese, green vegetables, eggs, some fish.It can be absorbed from all parts of small intestine by an active transport mechanism.Greater amounts of calcium are needed in children and during pregnancy, lactationThe normal range for total plasma calcium – 2.2 to 2.6m mol/litre About half of this is bound to plasma proteins, a small fraction gets complexed with citrate and phosphate and remaining amount circulates in blood as ionised calciumIonised calcium plays a vital role in the functioning of nerves, blood clotting and muscle contractionThe level of calcium ions in plasma is regulated by parathyroid hormone and calcitonin

17. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTESFUNCTIONS –Normal functioning of ANS and voluntary systemFor cardiac functionImportant factor in coagulation of blood For the formation of bonesMuscle contraction and maintenance of muscle toneTransmission of nerve impulses across synapseRelease of certain neurotransmitters(Ach)

18. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTESConditionHypercalcemiaHypocalcaemiaElevated Ca⁺² levelsLow Ca⁺² levelsReasonHyperparathyroidism, Excess vit D intakeDecreased calcium absorption, Hypoparathyroidism, vit D deficiency, Cushing’s syndrome, Osteoblastic metastasisSymptomsFatigue, muscle weakness, constipation, Anorexia, Cardiac irregularitiesTitanic spasms, convulsions

19. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTESMagnesium –Second most abundant cation in the ICF The adult human body having 25gms of Mg about 54% is present in the bones along with P, Ca, about 45% is in ICF and about 1% is in ECFDaily requirement – 350mgSource – nuts, soyabeans, whole grains, sea foodsFunctions – (a). Activates enzymes which are involved carbohydrates and protein metabolism (b). Important in neural transmission, myocardial function, neuromuscular activity (c). Needed for the operation of Na⁺- K⁺- ATPase pump system (d). It is a cofactor for phosphate transferring enzymes (e). Constituent of teeth and bones

20. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTESConditionHypomagnesemiaHypermagnesemiaLow levels of MagnesiumElevated levels of MagnesiumReasonMalnutrition, Diarrhoea, Chronic alcoholism, Excessive loss of Dietary Mg, GI diseasesRenal failure, Decreased excretion Mg due hypothyroidism, increased intake of antacids, cathartics, enemas, Addison’s disease, dehydration, bone carcinoma, acute diabetic acidosisSymptomsWeakness, Hyper irritability, Muscular Tremor, Confusion, Delirium, Convulsions, Anorexia, Nausea, Cardiac arrhythmias, HypertensionSlurred speech, drowsiness, impaired muscular coordination, Hypotension, Cardiac arrest

21. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTESChloride –Major extracellular anionTotal chloride ion present in the body – 50mEq/kg body wt.Daily requirement – 5 to 10gSource – common table saltIt readily gets absorbed throughout GIT.Mainly excreted through urine & through skin during sweating.Functions – Chloride ion along with sodium ion maintain osmotic balance between different body fluids.Maintains charge balance between the body fluids i.e. ICF & ECF both as they can pass through all membranes.Maintains acid-base balance & also take part in the formation of gastric HCl.Maintains proper hydration.

22. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTESChloride Imbalance –Hypochloremia- due to metabolic acidosis diabetic mellitus & excessive vomiting.Hyperchloremia- due to dehydration Excess chloride intake CHF Severe renal failure

23. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTESBicarbonate –Second largest anion in the ECF.Along with carbonic acid, it acts as one of the important buffer system in the maintenance of acid-base balance.A lack of bicarbonate causes metabolic acidosis while an excess of bicarbonate causes metabolic alkalosis.

24. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTESPhosphate –The phosphate ions such as H₂PO₄⁻, HPO₄⁻², PO₄⁻³ are the major anions of ICF. Among these HPO₄⁻² is most important for maintaining pH at 7.4.Normal plasma phosphate concentration is 1.7 to 2.6 mEq/litre.Almost 4/5 of the total body phosphate is present in teeth & bones along with calcium.Rest of the phosphate ion is covalently bound with lipids, proteins, carbohydrates, nucleic acids, ATP.Functions-Plays a vital role in maintaining pH of body fluids.HPO₄⁻²/ H₂PO₄⁻ is an important biochemical buffer.Essential for normal bone & tooth development & proper calcium metabolism.Serum inorganic phosphate plays an important role in regulating erythrocyte glucose metabolism.Under normal conditions, deficiency of phosphate ions does not occur. However since the serum phosphate levels are usually correlated with serum calcium levels, any change in the normal serum calcium levels may result in change in normal serum phosphate levels

25. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTESHypophosphatemia –Seen in vit D deficiency (Rickets), hyperparathyroidism & lack of phosphate reabsorption by kidney tubule due to infections, cancer in patients consuming a large amount of antacids specifically Al(OH)₃Hyperphosphatemia-Occur due to inappropriate excretion as a result of renal failure, increase in absorption due to hypervitaminosis D & hypoparathyroidism.Hyperphosphatemia leads to formation of phosphatic urinary calculi ( a form of kidney stone).

26. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTES

27. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTES

28. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTESMETHOD OF PREPARATION :-Sodium Chloride (NaCl) can be obtained from natural source as well as it can also be prepared in laboratory. Naturally It can be obtained from Rock salt strata & Sea water. But from these sources it can be obtained in impure form. The pure form of salt can be obtained by the filtration process & finally the dried form can be collected by evaporation process. It can also be prepared in laboratory in small scale by the acid- base reaction. In which strong acid (HCl) reacts with strong base (NaOH) & finally it gives Sodium Chloride.On commercial scale it is prepared by evaporation of sea water in shallow pans. It contains impurities of sodium carbonate, sodium sulphate, magnesium chloride, magnesium sulphate, calcium chloride etc. these impurities are removed by dissolving the salt in water in a cemented tank; some alum and lime are added. The suspended impurities are allowed to settle down. The clear solution is decanted into iron pans and concentrated. The crystals of sodium chloride settle down which are then collected and dried.

29. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTES

30. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTES

31. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTESAssay: The assay of sodium chloride is dependent on the modified Volhard’s method in which indirect volumetric precipitation titration is involved. An acidified solution of sodium chloride with nitric acid is treated with a measured excess amount of standard solution of silver nitrate in the presence of nitrobenzene.Some of the silver nitrate is consumed in the reaction with sodium chloride. The remaining unreacted AgNO3 is determined by titration with standard solution of ammonium thiocyanate using ferric alum (ferric ammonium sulphate) as indicator.Nitrobenzene prevents interaction of AgCl with ferric thiocyanate. The end point is obtained as a permanent brick red color due to formation of ferric thiocyanate. Procedure: Accurately weigh the substance (0.1 gm) and dissolve in 50 ml water. Add 50 ml of 0.1N AgNO3 , 3 ml HNO 3 , 5 ml nitro benzene, 2 ml ferric ammonium sulphate and mix thoroughly. The solution is titrated with ammonium thiocyanate until the color becomes brick red.1ml of 0.1N AgNO3 ≡ 0.005844 gm NaCl

32. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTESUses: Used as fluid and electrolyte replenisher, manufacture of isotonic solution, flavour enhancer. Used in homeopathic medicine.Isotonic solutions are used in 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 solution/injection are used when there is loss of sodium in excess.Hypertonic solution is used as an emetic & thus can be used incase of poisoning as first aid.NaCl solution may be used as an eyedrop, nasal drop ( to relieve nasal congestion) & as a mouth wash (to remove debris).It is a constituent of Ringer’s solution.

33. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTES

34. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTESPreparation: It is prepared by fusing carnallite whereby liquefied magnesium chloride hexahydrate is separated from the solid potassium chloride. The crushed carnallite is dissolved by boiling with liquor leaving other impurities undissolved. These are filtered off and the filtrate is crystallizes to get cubic crystals of potassium chloride. It is also prepared in laboratory by reacting HCl with potassium carbonate or bicarbonate K₂CO₃ + 2HCl KCl + H₂O + CO₂ KHCO₃ + HCl KCl + H₂O +CO₂

35. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTES

36. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTESUSES:-It is used as electrolytes replenisher. pH buffers Preparation of fertilizers, explosives, potassium metal and potassium hydroxide. In treatment of hypokalaemia (potassium deficiency disorder) Used as an antidote in treatment of digitalis poisoning Used in treatment of myasthenia gravisIt is a constituent of Ringer’s solution.Constituent of ORSSometimes used as diuretic

37. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTESCALCIUM GLUCONATEM.F- C₁₂H₂₂O₁₄Ca. H₂OPreparation:-It is prepared by boiling a solution of gluconic acid with excess of calcium carbonate, filtering & crystallising the product from the filtrate.

38. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTESPhysical properties:-White crystalline powderOdourlessTastelessFreely soluble in boiling water, sparingly soluble in water.Insoluble in alcohol, ether, chloroformChemical properties:-When treated with dil. HCl it is decomposed into gluconic acid & calcium chloride.

39. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTESASSAY:-

40. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTESUSES:-Calcium replenisherIn the treatment of hypocalcaemia deficiency

41. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTESOral Rehydration Salts (ORS):-ORS contains anhydrous glucose, NaCl, KCl & either NaHCO₃ or Sodium citrate.These dry powder preparations are to be mixed in specific amounts of water along with certain flavouring agent and a suitable agent for free flow of the powder.These are used for oral rehydration therapy.In ancient times, homemade ORS is used which constitutes of 1 tablespoonful of salt, 2 tablespoonful of sugar in 1 litre of water.The following 3 formulations are usually prepared.When glucose is used, NaHCO₃ is packed separately.The quantities given below are for preparing 1 litre solution.

42. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTESIngredientsFormula IFormula IIFormula IIINaCl1g3.5g3.5gKCl1.5g1.5g1.5gNaHCO₃1.5g2.5g-Sodium citrate--2.9gAnhydrous glucose36.4g20g20gOr Glucose40g22g-The formula II & III are recommended by WHO & UNICEF for control in diarrhoeal diseases.

43. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTESPhysiological acid base balance:-The number of hydrogen ions present in the solution is a measure of the acidity of the solution. But pH is negative logarithm of [H⁺]. Thus pH may be considered as a measure of acidity of the solution. Electrolytes also play an important role in regulating body’s acid-base balance. Body fluids contain balanced quantities of acids & bases. These qualities are regulated by intricate mechanisms. The maintenance of normal pH range within the body fluids is essential since the biochemical reactions taking place in the living systems are very sensitive to even small changes in acidity or alkalinity.Ex:- 1. the low pH value in the stomach provides the environment best suited to the functioning of the enzyme pepsin that helps in digestion of dietary protein.2. Saliva-pH range is 5.4-7.4 which is necessary for optimum functioning of ptyalin, an enzyme present in saliva which digests the carbohydrates.

44. Department of Pharmaceutical ChemistryMAJOR INTRA & EXTRACELLULAR ELECTROLYTESThe pH values of certain body fluids are:- Urine4.5 to 8.0Blood7.4 to 7.5Gastric juice1.5 to 3.5Saliva5.4 to 7.5Bile6.0 to 8.5Semen7.2 to 7.6The pH of blood of a healthy person remains constant around 7.35If the pH of blood becomes low (high H⁺ concentration) acidosis results.If the pH of blood becomes high (low H⁺ concentration) alkalosis results.The range of pH of the blood compatible with life is 7-7.8.Since the kidneys help to remove excess acid from the body, urine can be quite acidic.