SET 1,2 -24041501- 510 (24041501)

Quantities of light petroleum (boiling range 40º to 60º), ethanol (95%) and water after 20, 40 and 50 actuations of the valve. Remove the pressurised container and dry the membrane filter. Examine its entire filtering surface microscopically using a magnification of not less than X40. Record the number and size of all individual particles(not agglomerates) more than 10 µm in length measured along the longest axis. The number of particles longer than 20 gm does not exceed 50 and no particle exceeds 100 µm in length. Number of deliveries per container: Take the pressurised container used in the test for Particle size and discharge the remaining contents to waste, actuating the valve at intervals of not less than 5 seconds. Record the number of deliveries discharged. The total number of deliveries so discharged in the test for Particle size is not less than the number stated on the label Pressure test Select not less than 5 pressurised containers, remove the caps and covers, and immerse in a constant –temperature bath until the internal pressure is constant at a temperature of 25º ± 1º. Remove the containers from the bath, shake well, and remove the actuator and water, if any, from the valve system. Keep’ each containers in an upright position and place on the valve stem a pre-pressurised gauge of a calibration approximating the expected pressure and fitted with and adapter appropriate for the valve stem dimensions. Read the pressure directly from the gauge. Leak test: Select 12 pressurised containers at random, and record the date and time to the nearest half-hour. Weigh each container to the nearest mg, and record the weight, in mg, of each as W. Allow the container to a stand in an upright position at room temperature for not less than 3 days, and again weigh each container, recording the weight, in mg, of each as W2 and recording the date and time to the nearest half-hour. Determine the time, T, in hours during which the container where under test Calculate the leakage rate, in mg per year, of each container from the expression 365 x 24/T x (W,-W2). Empty the contents of each container tested by chilling the reduce internal pressure, removing the valve and pouring. Remove any residual contents by rinsing with suitable solvents, then rinse with a few portions of methanol. Retain as a unit the container, the valve, and all associated parts, and heat them at 100º for 5 minutes. Cool, weigh and record the weight as W3, and determine the net fill weight (W1,-W3) for each container tested. The requirements are met if the average leakage rate of the 12 containers is not more than 3.5 % of the net fill weight per year and none of the containers leaks more than 5.0% of the net fill weight per year. If one container leaks more than 5.0% per year, and if none of the containers leaks more than7.0% per year, determine the leakage rate of an additional 24 containers as direct herein. Not more than 2 of the 36 container leak more than 7.0% of the net fill weight per year. Where the net fill weight is less than 15 g the requirements are met if the average leakage rate of the 12 containers is not more than 525 mg per year and none of the container leaks more than 750 mg per year. If 1 container leaks more than 750 mg per year but not more than 1.1 g per year, determine the leakage rate of an additional 24 containers as directed herein. Not more than 2 of the 36 containers leak more than 750 mg per year and none of the 36 container leaks more than 1.1 g per year. ALBENDAZOLECategory: Anthelmintic Dose: Nematodal infestation, 400 mg as a single dose, cestodal infestation, 400 mg daily for three consecutive days, stronglyoidasis, 400 mg daily for three consecutive days. Description: White to pale buff-coloured powder. Solubility: Freely soluble in formic acid and in dimethylformide, sparingly soluble in methanol and in chloroform. It is soluble in dilute acids and in solutions of alkalis. Storage: Store in well-closed

containers. STANDARDSAlbendazole contains not less than 98.0 per cent and not more than 102.0 per cent of C12H15N3O2S calculated with reference to the dried substance. Identification Test A may be omitted if tests B, C and D are, carried out. Tests B and C may be omitted if tests A and D are carried out. A the infra-red absorption spectrum, Appendix 5.4, is concordant with the reference spectrum of albendazole or with the spectrum obtained from albendazole RS.B. The light absorption in the range 230 to 360 nm of a 0.001% w/v. Solution in 0.1 M sodium hydroxide exhibits a maximum at about 309 nm; absorbance at about 309 nm, about 0.74. Appendix 5.5.C: In the test for Related substances, the principal spot in the chromatogram obtained with solution (2) corresponds to that in the chromatogram obtained with solution (4).D: Melts between 208º and 210º, Appendix 8.8 pH: Between 5.0 and 7.0, determine in a 2% w/v suspension in carbon dioxide free water, Appendix 8.11. Related substances: and water for solution B. Calculate the percentage content of C16H19N3O4S from the difference between the absorbances of solution A and solution B. from the difference obtained by repeating the operation using 0.17 g of ampicillin trihydate RS in place of the substance being examined and from the content of C16H19N3O4S in ampicillin trihydrate RS. AMPICLLIN TRIHYDRATE C16H19N3O4S,3H2O trihydate. Ctegory: Antibacterial: Dose: The equivalent of 2 to 6 g of ampicillin daily, in divided doses. Description: White, crystalline powder. Solubility. Slightly soluble in water, practically insoluble in ethanol (95%), in chloroform, in ether and in fixed oils. It is soluble in dilute solution of acids and of alkali hydroxides. Storage: store in well-closed containers in a cool place.STANDARASAmpicillin Trihydrate contains not less than 96.0 per cent and not more than 100.5 per cent of C6H19N3O4S, calculated with reference to the anhydrous substance. Identification Test A may be omitted if tests B and C are contained out. Tests B and C may be omitted if tests A is carried out A: The infra-red absorption spectrum. Appendix 5.4, is concordant with the reference spectrum of ampicillin trhydrate or with the spectrum obtained from ampicillin trihydrate RS.B: Complies with test B described under ampicillin sodium. C: Complies with test C described under Ampicillin pH; Clarity of solution; Specific optical rotation; N,N-Dimethylaniline; Heavy metals: Sulphated ash: Complies with the test described under Ampicillin sodium. C: Complies with test C described under Ampicillin, pH; Clarity of solution: Specific optical rotation: N,N-Dimethylaniline: Heavy metals: Sulphated ash: Complies with the tests described under Ampicillin. Water. Between 12.0% and 15.0% w/w, determine on 0.1 g, Appendix 3.24 Assay: Clarity out the Assay described under Ampicillin AMPICILLIN DISPERSIBLE TABLETS Dispersible Ampicillin TabletsAmpicillin Dispersible Tablets contain Ampicillin or Ampicillin Trihydrate in a suitable dispersible base. Usual strengths: The equivalent of 125 mg and 250 mg of ampicillin Storage: Store in tightly-closed containers in a cool, dry place Labeling: The label states (1) the strength in terms of the equipment amount of ampicillin (when Ampicillin Trihydrate is used); (2) that the tablets should be dispersed in water immediately before use. STANDRDAmpicillin Dispersible Tablets contain Ampicillin or Ampicillin Trihydrate equipment to not less than 90.0 per cent and not more than 120.0 per cent of the statedamount of ampicillin. C16H19N3O4S. Identification: A: Comply with test B described under Ampicillin, using as solution (1) a solution prepared by dissolving sufficient of the powdered tablets in a 4.2% w/v solution of sodium bicarbonate so that it contains 0.25% w/v of ampicillin B: Shake a quantity of the powdered tablets equipment to 0.5 g of Ampicillin with 5 ml water for 5 minutes, filter, wash the residue first with ethanol and then with ether and dry for 1 hour at a pressure not exceeding 2.7 kPa. The residue gives reaction B

of penicillins and cephalosporins, Appendixx 3.1. Uniformity of dispersion: Comply with the test described under Tablets. Other requirements: Comply with the requirements of tests stated under Tablets Assay. Weigh and powder 20 tablets. Weigh accurately a quantity of the powder equipment to 0.15 g of ampicillin, add sufficient water to produce 500.0 ml, shake for 30 minutes, filter, and complete the Assay described under Ampicillin Capsules beginning at the –words “To 10.0 ml of the resulting solution…” ALPHA AMYLASE DiastaseAlpha Amylase is an amylolytic enzyme or a mixture of enzymes obtained from fungi such as Aspergillus oryzae or from a non-pathogenic variant of bacteria such as Bacillus subtilis and with the specific activity for converting starch into dextrin and maltose. It may contain suitable harmless diluents such as Lactose or D=,-asic calcium Phosphate. Category: Digestive enzyme. Dose: 200 to 500 mg. Description: Cream to light brown –coloured powder, almost odourless or with faint characteristic odour; hygroscopic. Splubility: Sparingly soluble in water (except when admixed with an insoluble diluent); insoluble in ethanol (95%) and in ether. Storage: store, in tightly-closed containers in a cool, dry place. Labelling: The label states (1) the nature of the enzyme – “fungal” or “bacteria”; (2) the name of the organism from which the enzyme is derived ; (3) the amylase activity in terms of units or the weight in grams of starch digested by one gram of the enzyme; (4) the name of any added diluent STANDARDSALpha Amylase has amylase activity of not less than 800 Units which represents the number of grams of for dry, soluble maize or corn starch digested by 1.0 of Alpha Amylase under the conditions or the Assay. Loss on drying: Not more than 5.0%, determined on 1 g by drying in an oven at 105º for 1 hour, Appendin 8.6 ASSay: Weigh accurately a quantity equivalent to 100 Units or amylase activity and triturate with 200ml of buffer solution pH 6.0(for bacterial amylase) or of acetale buffer pH 5.0 (for fungal amylase) and add surricient buffer for sterility. Appendix 9.5 BARIUM SULPHATE Mol. Wt. 233.39 Category: Diagnostic aid (radio-opaque medium for gastrointestinal tract). Description: Fine, heavy, white powder, free from gritty particles; odourless solubility: Practically insoluble in water, in organic solvents and in dilute solutions of acids and of alkalis. Storage: Store in well-closed containers. STANDARDSBarium sulbhate contains not less than 97.5 per cent and not less than 100.5 per cent of BaSO4 Identification: A: Boil 0.2 g with 5 ml of a 50% w/v solution of sodium carbonate for 5 minutes, add 10 ml of water and filter. Reserve the residue for test B. Acidify the filtrate with dilute hydrochloric acid; the solution gives the reactions of sulphates, Appendix 3.1 B: wash the residue obtained in test A three times with successive small quantities of water. To the residue add 5 ml of dilute hydrochloric acid, filter and add to the filterate 0.3 ml of dilute sulphuric acid; a white precipitate is formed which is insoluble in dilute sodium hydroxide solution. Acidity or alkalinity: Heat 5 g with 20 ml of carbon dioxide free water on a water-bath for 5 minutes and filter. To 10 ml of the filtrate add 1 drop of bromothymol blue solution. Not more than 0.5 ml of 0.01 M hydrochloric acid or 0.01 M sodium hydroxide is require to changr the colour of the solution. Arsenic: Disperse 5 g in 50 ml of water and add 10 ml of stannated hydrochloric acid. Theresulting solution compiles with the limit test for arsenic, Appendix 3.9 (2 ppm). Heavy metals: Not more than 10 ppm, determine by Method A on a solution prepared in the following manner. Boil 4.0 g with a mixture of 2 ml of glacial acetic acid and 48 ml of water for 10 minutes. Add water to make upto 50 ml, filter, rejected the first 5 ml of the filtrate and use 25 ml the filtrate for the test, Appendix 3.12. Phosphate: Boil 1 g with a mixture of 3 ml of nitric acid 5 ml of water for 5 minutes and add water to restore the original volume. Filter through a filter paper previously washed with dilute nitric acid. Add to the

warm filtrate an equal volume of ammonium molybdate solution; no yellow precipitate is formed. Sulphide: Boil 10 g with a mixture of 10 ml of dilute hydrochloric acid and 90 ml of water for 10 minutes. Expose a lead acetate paper to the vapours; the paper does not darken. Acid-soluble substances: Cool the mixture obtained in the test for Sulphide, add water to restore the original volume and filter through a filter paper previously washed with a mixture of 10 ml of dilute hydrochloric acid and 90 ml of water, returning the first portions, if necessary, to obtain a clear filtrate. Evaporate 50 ml of the filtrate to dryness on a water-bath and add 2 drops of hydrochloric acid 10 ml of water. Filter again through acid- washed paper, prepared as directed above, wash the filter paper with 10 ml of hot ‘water and evaporate the combined filtrate and washings. Dry the residue at 105º, cool and weigh (0.3%). Soluble barium salts: Digest the residue obtained in the test for Acid-soluble substance with 10* ml of water and filter through a filter paper previously washed with a mixture of 10 ml of dilute hydrochloric acid and 90 ml of water. Add 0.5 ml of dilute sulphuric acid to the clear filtrate and set aside for 30 minutes, no turbidity is produced. Bulkiness: Place 5.0 g in a glass-stoppered 50-m1 graduated cylinder having the 50-m1 graduation mark 14 cm from the base. Add water to 50 ml, shake the mixture for 5 minutes and allow to stand for IS minutes; it does not settle below the 15-ml mark. Assay: Weigh accurately about 0.60 g in a platinum crucible, add 5 g for sodium carbonate and 5 g of potassium carbonate and mix. Heat to 1000 degree and maintain at this temperature for 15 minutes. Allow to cool and suspend the residue in 150 ml of water. Wash the crucible with 2 ml of acetic acid and add to the suspension. Cool and ice and filter by decantation, transferring as little of the solid matter as possible to the filter. Wash the residue with successive quantities of a 2% w/v solution of sodium carbonate until the washings are free from sulphate and discard the washings. Add 5 ml of dilute hydrochloric acid to the filter and wash through into the vessel containing the bulk of the solid matter with water. Add 5 ml of hydrochloric acid and dilute to 100 ml with water. Add 10 ml of a 40 % w/v solution of ammonium acetate.25 ml of the 10% w/v solution of potassium dichromate and 10 q of urea. M sulphuric acid and 50 ml of water, add 2 ml of dischloromethane and 5 ml of a freshly prepared 2% w/v solution of chloramine T and shake; a brownish yellow colour is produced in the lower layer. D: A solution prepared by dissolving about 1 mg in 3 ml of 0.1 M hydrochloric acid gives the reaction for primary aromatic amines, Appendix 3.1.E: Dissolve about 20 mg in 1 ml of methanol and add 1 ml of water. The solution gives reaction A of chlorides, Appendix 3.1 Related substances: Carry out the method for thin-layer chromatography, Appendix 4.6, using silica gel GF254 as the mobile phase. Apply separately to the plate in small quantities a total of 20 micro litre of each offive solutions in methanol. Solutions (1) to (4) are solutions of the substance being examined containing (1) 2.0% w/v, (2) 0.20% w/v, (3) 0.005% w/v and (4) 0.00375% w/v respectively. Solution (5) is a 0.20% w/v solution of bromhexine hydrochloride RS. After removal of the plate, allow it to dry in air and examine under ultra-violet light (254 nm). Any secondary spot in the chromatogram obtained with solution (1) is not more intense than the spot in the chromatogram obtained with solution (4). Solphated ash: Not more than 0.1%, Appendix 3.22. Loss on drying: Not more than 1.0%, determined on 1 g by drying in an oven at 105º degree, Appendix 8.6.Assay: Weigh accurately about 0.3 g, dissolve in 70 ml of ethanol (95%), add 1 ml of 0 M hydrochloric acid and titrate with 0.1 M sodium hydroxide, determining the eand-point potentiometrically. Record the volume added between the two inflections. Each ml of 0.1 Msodium hydroxide is equivalent to 0.04126 g of C14H20Br2N2,HCL.BROIVIHEXINE HYDROCHLORIDE

TABLETSBromhexine. TabletsUsual strengths: 4 mg; 8 mg. Stroge: store in well-closed, light-resistant containers. STANDARDSBromhexine Hydrochloride Tablets not less than 92.5 per cent and not more than 107.5 per cent of the stated amount of bromhexine hydrochloride, C14H20Br2N2,HCL. Identification: A: The light absorption in the range 230 to 360 nm of the solution obtained in the Assay exhibits a maximum only at about 317 nm, Appendix 5.5.B: Suspected a quantity of the powdered tablets equivalent to 0.1 g of Bromhexine Hydrochloride in 5 ml of dilute ammonia solution and extract with two quantities, each of 20 ml, of chloroform. Wash the combined extracts with 5 ml of water, filter through anhydrous sodium sulphate and evaporate the filtrate to dryness using a rotary evaporator. If necessary, scratch the inside of the flask with a glass rod to induce crystallisation. Mix the residue with 1 g of sodium carbonate, heat at a dull red heat for 10 minutes, allow to cool, extract with water and filter. The filtrate, after acidification with 2M nitric acid, yields reaction A of bromodes, Appendix 3.1.c: Shake a quantity of the powdered tablets equivalent to 20 mg of Bromhexine Hydrochloride with 10 ml methanol and filter. The filtrate yields reaction A of chorides, Appendix 3.1. Related substances: Carry out the method for thin-layer chromatography, Appendix 4.6, using silica gel G as the coating substance and 90 volumes of heptane and 10 volumes of ethanol as the mobile phase. Apply separately to the plate 20 micro litre of each of the following solutions. For solution (1) shake a quantity of the powdered tablets equivalent to 0.10 g of Bromhexine Hydrochloride with 10 ml of methanol for 5 minutes, centrifuge and mix 9 volumes of the supernatant liquid with 1 volume of strong ammonia solution: For solution (2) dilute 1 volume of solution (1) to 400 volumes with the same solvent mixture. After removal of the plate, dry it in a current of warm air, place in tank containing a freshly prepared 10% w/v solution of sodium nitrite in 5M hydrochloric acid and allow to stand for 1 minute. Remove the plate and immediately spray with a 0.5% w/v solution of N-(1-napthyl)ethylenediamine dihydrochloride in methanol. Any secondary spot in the chromatogram obtained with solution (1) is not more intense than spot in the chromatogram obtained with solution (2). Uniformity of content: Comply with the requirements stated under Tablets using the following method of analysis. Powder one tablet, add 50 ml of oJ M methanolic hydrochloric acid, shake for 30 minutes and add sufficient 0.1M methanolic hydrochloric acid to produce 100.0 ml and filter. Dilute suitably, if required, with the same acid solution to produce a solution containing 40 to 80 ug of Bromhexine Hydrochloride per ml. Measure the absorbance of the resulting solution at the maximum at about 317 nm, Appendix 5.5 Calculate the content of C14H20Br2N2,HCL taking 87 as the value of A(1% 1 cm) at the maximum at about 317 nm. Other requirements: Comply with the requirements of tests stated under Tablets. Assay: Weigh and powder 20 tablets. Weigh accurately a quantity of the powder equivalent to 8 mg of Bromhexine Hydrochloride, shake with 50 ml of o.1M methanolic hydrochloric acid for 30 minutes, add sufficient 0.1M methanolic hydrochloric acid to produce 100.0 ml and filter. Measure the absorbance of the filtrate at the maximum at about 317 nm, Appendix 5.5 Calculate the content of C14H20Br2N2, Hc1 taking 87 as the value of A (1 %, 1 cm) at the maximum at about 317 run. BROMOCRIPTINE adjusting the pH to 7.5 ± 0.1 with 0.67 M disodium dihydrogen phosphate and diluting with water to 1000 ml. The chromatographic procedure may be carried out using (a) a stainless steel column (30 cm x 4 mm) packed with stationary phase LCI, (b) as the mobile phase with a flow rate of 1 to2 ml per minute a mixture of 15 ml of a 25% w/v solution of terabutylammonium hydroxide, 825 ml of water and 125 ml of acetonitrile, previously adjusted to pH 7.5 ± 0.1 with 0.67 M sodium dihydrogen phosphate, diluted with water to 1000 ml and

filtered and (c) a detection wavelength of about 254 run. The relative retention times for folinic acid and folic acid are 1.0 and about 1.6 respectively. The test is not valid unless the relative standard deviation for replicated injection is not more than 3.6 Calculate the content of C20H21aN7O7 from the declared content of C20H21CaN7O7 in calcium folinate RS. CALCUIM FOLINATE INJECTION Leucovorin Calcuim Injection Calcium Folinate Injection is a sterile solution of Calcium Folinate in water for Water for Injection. Usual strength: The equivalent of 3 mg of folinic acid per ml. (3.25 mg of calcium folinate is approximately equivalent to 3 mg of folinic acid). Description: Clear, yellowish solution. Storage: Store in single dose, light-resistant containers, preferably of type I glass. Labelling: The label states the strength in terms of the equivalent amount of folinic acid. STANDARDSCalcium Folinate Injection contains not less than 90.0 per cent and not more than 120.0 per cent of the stated amount of folinic acid, C20H23N7O7. Identification: Transfer a volume equivalent to about 6 mg of folinic acid to glass-stoppered, 50-m 1 centrifuge tube, add about 40 ml of acetone, mix, centrifuge for a few minutes and decant the liquid phase. Repeat the washing with the test described under Calcium Folinate. pH: Between 6.5 and 8.5, Appendix 8.11. Other requirements: Complies with the requirements of tests stated under Injectable Preoarations (Injections). Assay: Carry out the Assay described under calcium Folinate using as solution (1) a solution prepared in the following manner. Transfer an accurately measured volume of the Injection equivalent to about 9 mg of folinic acid to a 50-m1 volumetric flask, dilute to methanol to 900 ml of water, adjusting the pH to 7.5 ± 0.1 with 0.67M sodium dihydrogen phosphate and diluting with water to 1000 ml. Transfer 25.0 ml of this solution into a 60-m1 separator, add 25 ml of dichloromethane , shake the mixture, allow the layers to separate and discard the dichloromethane extract. Filter the aqueous layer, discarding the first 5 ml of the fitrate, and collect the remaining filtrate in a glass-stoppered conical flask. Calculate the content of C20H23N7O7 in each ml from the declared content of C20H23N7O7 in calcium folinate RS. (Each mg calcium folinate is approximately equivalent to 0.93 g of folinic acid). CALCIUM GLUCONATE C12H22CaO14,H2O Mol. Wt. 448.41 Calcium Gluconate is calcium D-gluconate monohydrate. Category: Calcium replenisher. Dose: Orally, upto 15 g daily, in divided doses. By inframuscular or slow intravenous injection, 1 to 2 g. (500 mg of calcium gluconate is approximately equivalent to 2.3 mol of Ca++). Description: White, crystalline powder or granules. Solubility: Sparingly soluble in water but freely soluble in bonding water; insoluble in ethanol (95%). Storage: Store in well-closed containers. STANDARDSCalcium Gluconate contains not less than 98.5 per cent and not more than 102.0 per cent of C12H22CaO14,a,H2O. Identification: A: Carry out the method for thin-layer chromatography, Appendix 4.6, using silica gel G as the coating substance and a mixture of acetate as the mobile phase. Apply separately to the plate 5 micro litre of each of two solutions in water containing (1) 2.0% w/v of the substance being examined and (2) 2.0% w/v calcium gluconate RS. Heating in each case, if necessary, to 60 degree in a water-bath to effect solution. After removal of the plate, dry it at 100 degree for 20 minutes, cool and spray with a 5% w/v solution of potassium dichromate in a 40% w/w solution acid. After 5 minutes the principal spot in the chromatogram obtained with solution add 0.05 ml of ferric chloride test solution; a yellow colour is produced. C:A.2% w/v solution gives reactions A and B of calcium salts, Appendix 3.1. Acidity and alkanity: Dissolve 0.5 g in 20 ml of water, add 0.1 M hydrochloric acid and 0.1 ml of phenolphthalein solution; no colour is produced. Add 0.3 ml of 0.001M sodium hydroxide; a pink colour is produced. Clarity and colour of solution: A 2.0% w/v solution at 60º degree is not more

intensely coloured than reference solution YS6, Appendix 6.2. On cooling to room temperature the solution is not more opalescent than opalescence standard OS2, Appendix 6.1. Arsenic: Dissolve 5 g in 50 ml of water and 12 ml of stannated hydrochloric acid. The resulting solution complies with the limit test for arsenic.

Produced Methimazole: Comply with the test described under Carbimazole, using as solution (1) a solution prepared by shaking a quantity of the powdered tablets equivalent to 10 mg of Carbimazole with 2 ml of chloroform for 5 minutes and filtering. Uniformly of content (For tablets containing 10 mg or less): Comply with the requirements stated under Tablets using the following method of analysis. Powder one tablet, add sufficient water warmed to a temperature not exceeding 35º degree, shakes for a few minutes and complete the Assay beginning at the words “Measure the absorbance…”.Other requirements: Comply with the requirements of tests stated under Tablets Assay: Weigh and powder 20 tablets. Weigh accurately a quantity of the powder equivalent to 40 mg of carbimazole, add 300 ml of water warmed to a temperature not exceeding 35 degree, shake for a few minutes and add sufficient water to produce 500.0 ml. Mix well and filter, dilute 50.0 ml of the filtrate to 500.0 ml with water and mix well. Measured theabsorbance of the resulting solution at the maximum at about 191 nm, Appendix 5.5. Calculate the content of C7H10N202S aking 557 as the value of A(1%, 1 cm) at about 291 nm. CARNAUBA WAXCanauba Wax is obtained from the leaves of Copemicia cerifera Mart. (Farm palmae) after purification to remove foreign matter. Category: Pharmaceutical aid (tablet coating agent). Description: Pale yellow to light brown coarse powder, lakes or lumps of hard brittle wax; odour, characteristic and free from rancidity. Solubility: Soluble on warming in chloroform, in ethl acetate and in xylene; practically insoluble in water and in ethanol (95%). Storage: Store in tightly-closed, light-resistant containers. STANDARDSIdentification: Carry out the method for thin-layer chromatography. Appendix 4.6, using silica gel G as the coating substance and a mixture of 98 volumes of chromatography, and 2 volumes of ethyl acetate as the mobile phase. Apply separately to the plate, as bands 20 mm x 3 mm, 30 micro litre of solution (1) and 10 micro litre of solution (2). For solution (1) dissolve 0.10 g of the substance being examined, with warming, in 5 ml of chloroform and use the warm solution. For solution (2) dissolve 5 mg of (+)-menthol, 5 micro litre of methyl acetate and 5 mg of thymol in 10 ml of toluene. After removal of the plate, allow it to dry in air and spray with a freshly prepared 20% w/v solution of phosphomolybdic acid in ethanol (95%) and heat at 105 degree for 15 minutes. The chromatogram obtained with solution (1) shows in the lower part a dark blue band due to methanol, a reddish band above it due to thymol and a dark blue band due to triacontanol (melissyl, alcohol) at an Rf value between those of the bands due to menthol and thymol in the chromatogram obtained with solution (1) and blue bands at Rf values between those of the bands due to methyl acetate and thymol in the chromatogram obtained with solution (1). In addition, the chromatogram obtained with solution (2) shows further bands at higher Rf values than menthyl acetate, that with highest Rf value being very pronounced, and a number of faint bands below that due to triacontanol; a band the line of excess of bromine with a few drops of stannous chloride solution AsT; the resulting solution complies with the limit test for arsenic, Appendix 3.9 (5 ppm). Heavy metals: Not more than 40 ppm, determine by Method A, Appendix 3.12, on 25 ml of the solution prepared in the following manner: Warm 1.0 g with 4 ml of dilute hydrochloric acid, add sufficient water to produce 50 ml and filter. Iron: Dissolve 0.2 g in a mixture of 5 ml of water and 0.5 ml of iron free hydrochloric acid with the addition of 1 g of citric

acid. Dilute the solution to 40 ml with water; the solution complies with the limit test for iron, Appendix 3.13 (200 ppm). Carbonate: Suspend 1 g in 10 ml of water and add 2 ml of hydrochloric acid, no effectivescence is produced Chloride: Dissolve 0.5 g in 25 ml of water by the addition of 1 ml of nitric acid the solution complies with the limit test for chlorides, Appendix 3.10 (500 ppm). Sulphate: Dissolve 100 mg in water with the aid of 3 ml of IM hydrochloric acid and dilute to 60 ml with water. 15 ml of the resulting solution complies with the limit test for sulphates, Appendix 3.15 (0.6%). Proteinous impurties: Heat 0.5 g gently in a dry test-tube; no change in colour is observed and no unpleasant odour is emitted. Loss on ignition: Not more than 8.0%, determined on 1g, Appendix 3.24. Assay: Weigh accurately about 1 g and dissolve in 10 ml of hydrochloric acid by heating on a water-bath, add 50 ml of water, cool and dilute to 250.0 ml with water. To 25.0 ml of the resulting solution add 30.0 ml of 0.05 M disodium edentate is equivalent to 0.00517 g of Ca3(PO4)2. CAPSULESCapsules are solid dosage forms in which the drug or a mixture of drugs is enclosed in Hard Gelatin Capsule Shells, in soft, soluble shells of gelatin, or in hard or soft shells of any other suitable material, of various shapes and capacities. They usually contain a single dose of active ingredient(s) and are intended for oral administration. The consistency of soft shells may be adjusted by the addition of substances such as Glycerin and Sorbitol. Exciplents such as opaque filters, anti-microbial preservatives, sweetening agents, flavouring agentsand one or more colouring agents permitted under the drugs and Cosmetic Rules, 1945 may be added Capsules may bear surface markings. The contents of capsules may be of solid, liquid or paste-like consistency. They consist of the medicament(s) with or without excipients such as vehicles, solvents, diluents, lubricants, filters, wetting agents and disintegrating agents. The contents of capsules other than Modified-release (Sustained-release) Capsules do not contain any added colouring agent. Hard capsules: hard capsules contain the drugs can be put as a form. Where two mutually incompatible drugs are present in the mixture, one of the drugs can be put as a tablet or pellet or in small capsules and then enclosed with the other drug in a large capsule. Soft Capsules: Soft capsules shells are usually formed, filled with medicament and sealed in a combined operation on machines. In some cases, shells for extemporaneous use may be performed. The shells which are thicker than those of hard capsules are formed to capsules which are spherical, oval or kPa, dissolve in 10 ml of dimethylformamide and carry out Method B for non-aqueous titration, Appendix 3.45, using 0.1 M terabutylammonium hydroxide as titrant and blue solution as indicator. Perform a blank determination and make any necessary correction. Each ml of 0.1 M tetrabutylammonlum hydroxide is equivalent to 0.03073 g of C34H48Na207. CARBENOXOLONE SODIUM TABLETSCarbenoxolone Tablets Usual strength: 50 mg. Storage: Store in well-closed containers. STANDARDSCarbenoxolone Sodium Tablets contain not less than 95.0 per cent and more than 105.0 per cent of the stated amount of carbonoxolone Sodium, Carbenoxolone Sodium, C34H48Na20,. Identification: A: Shake a quantity of the powdered tablets residue complies with tests B and C described under Carbenoxolone Sodium B: A5% w/v solution of the residue obtained in test A gives the reactions of sodium salts, Appendix 3.1. Related substances: Comply with the test described under Carbenoxolone Sodium, applying to he plate 5 micro litre of each of the followingsolutions. For solution (1) triturate a quantity of the powdered tablets equivalent to 0.10 g of Carbenoxolone Sodium with 20 ml of methanol, filter, evaporate the filtrate to low volume and add sufficient methanol to produce 10 ml. For solution (2) dilute 3 volumes of solution (1) to 100 volumes with methanol Other

requirements: Comply with the requirements of tests stated under Tablets Assay: Weigh and powder 20 tablets. Triturate a quantity of the powdered tablets equivalent to 75 mg of Carbenoxolone Sodium with a small volume of methanol, filter and add sufficient methanol to produce 250.0 ml. To 10.0 mladd 10 ml of 0.02M sodium carbonate and sufficient of a mixture of equal volumes of methanol and 0.02M sodium carbonate to produce 100.0 ml and measure the absorbance of the resulting solution at the maximum at about 256 nm, Appendix 5.5. Calculate the content of C34H48Na207 taking 199 as the value of A(1%, 1 cm) at the maximum at about 256 run. CARBIDOPAC 10H14N204, H2O Mol. Wt. 244.25 Carbidopa is (5)-2-(3,4-dihydroxybenzyl)-2-hydrazinopropionic acid monohydrate. Category: Antioarkinsonian with Leavodopa. Dose: 10 to 25 mg in combination with Leavodpa. Description: White to creamy white powder, odourless or practically odourless. Solubility: Slightly soluble in water, very slightly soluble in ethanol (95%) and in methanol; practically insoluble in acetone, in chloroform, in dichloromethane and in either. It is soluble in dilute solutions of mineral acids. Storage: Store in well-closed, light-resistant containers: STANDARDSCarbidopa contains not less than 98.5 per cent and not more than 101.0 per cent of C10H14N2O4, calculated with reference to the dried substance. Identification Tests A and C may be omitted if tests B, D and E are carried out. Tests B, D and E may be omitted if tests A and C are carried out A: The infra-red absorption spectrum of a mineral oil dispersion, Appendix 5.4, is concordant with the reference spectrum of carbidopa or with spectrum obtained from carbidopa RS.B: The light absorption in the range 230 to 360 nm of a 0.004% w/v solution in a 1% v/v solution of hydrochloric acid in methanol exhibits a maximum only at about 282 nm; absorbance at about 282 nm, about 0.52, Appendix 5.5.C: Complies with the test for Specific optical rotation. D: Shake vigorously about better demonstrated by MRI. Angiography may be required to make a definite diagnosis. Treatment – (a) Antibiotics – if sinus thrombosis is in origin. IV low molecular weight dextran. (b) Anticoagulants - the risks out weigh any theoretical benefits since many of these patients have hemorrhagic Infracts already. Subarachnoid Haemorrhage (SAH) Causes: I. Intracranial aneurysm – Rupture of congenital berry aneurysm or angioma. In order of frequency the aneurysms arise from anterior cerebral arteries, internal carotid intracerebrally, middle cerebral and from the basilar system. Rarely rupture of a mycotic aneurysm. 2. Arterio- venous malformation. 3. Cerebral or cerebellar haemorrhage leading into the ventricles or subarachnoid space. 4. Trauma. 5. No obvious cause. Spontaneous subarachnoid haemorrhage Clinical features: 1. B BEFORE RUPTURE – in some cases of aneurysm Migraine, focal symotoms like transitory attacks of blindness, monoplegia, cranial nerve palasies, or trigeminal anaesthesia 2. AFTER RUPTURE – (a) Symptoms due to rapidly increasing of hemorrhage. Loss of consciousness with generalised flaccidity occurs when leakage is considerable. In less severe. Cases the patient may remain semi-stuporose with severe headache and signs ofmeningal irritation, - headache, photophobia, neck stiffness and Kernig’s sign. Fever – Moderate pyrexia common. If severe and fluctuating, it may be suggest ischemic hypothalamic damage. Fundus – Unilateral or bilateral hemorrhage. In some cases, may be accompanied by subhyaloid and vitreous hemorrhages. (b) Focal symptoms – due to compression of neighbouring cranial nerves by blood clot, or to Invasion of the cerebral hemisphere by the hemrrhage – (i) Visual field defect from compression of optic nerve, chiasma or tracts. (ii) 3rd, 4th and 6th nerve involvement if aneurysm near cavernous sinus. (iii) Mental impairment, hemiparesis, and if on left side expressive aphasia from Skull radiograph – Shift of pineal gland (if calcified) when there is a large hematoma. CT scan – (a) Confirms diagnosis of SAH.

(b) Identifies other associated lesions such as hydrocephalus, intracerebral hematoma, A-V malformation. (c) Helps identification of site of aneurysm rupture. Digital subtraction angiography – has the advantage of giving computer-enhanced images and amount of contrast material required is small. 3. AFTER RECOVERY – Metabolic changes due to release of catecholamines produce ischemia of hypothalamus, kidneys and heart. Hence glycosuria, High blood pressure. ECG changes Vascular spasm may produce drowsiness, confusion, hemiplegia and aphasia. Prognosis: About one-third die in first attack; of survivors about half have recurrence within 2-4 weeks. Tendency for interval between successive hemornhages to become shorter. Prognosis better with angloma than with aneurysm. Management: 1. MEDICAL – (a) General – Bed rest with head slightly elevated if an aneurysm has been demonstrated and patient is not suitable for surgery, a minimum of 4 weeks of complete rest in bed will probably reduce risk of recurrent hemorrhage. (b) Reduction of B.P. – towards normal unless there is evidence of progressive neurologic deficit due to ischemia. (c) Nimodipine – a calcium channel bloker reduces the incidence of cerebral ischemia. Dose 60 mg every 4 hours should be started as soon as possible and continued for 21 days after the SAH. (d) Reduction of increased intracranial pressure as indicated by 1. of skull – to demonstrate any fracture, to slow condition of sella – erosin would suggest increased intracranial pressure; to slow infection in sinuses, mastoids or petrous bones which may suggest intracranial infection; to demonstrate pineal shift which suggest a mass lesion. 2. Of chest – may reveal carcinoma (cerebral tumour), bronchiectasis; abscess or empyma (cerebral abscess), tuberculosis (meningitis) or mitral stenosis (cerebral embolism). 3. CT scan or MRI – (a) Coma with focal signs or evidence of head injury, whether the focal sings indicate a brainstem or supratentorial lesion. A normal scan may be seen in patients with hypoglycaemia or hepatic coma. (b) Coma without focal sings but with meningeal irritation – Brain imaging is the ideal investigation to identify the presence of subarachnoid blood in SAH and to exclude the possibility of focal collections in case of bleeding or infection. Depending on thee results of the scan a lumbar puncture can be undertaken. 4. Cerebral angiography – Useful aid in brain tumor and subdural haematoma. E.EEG – (a) In comatose patients, where clinical examination has failed to localize the lesion and EEG may localize it to one hemisphere, of particular value in cerebral abscess. (b) May provide evidence of subclinical epilepsy. (c) An entirely normal EEG will make a supratentorial lesion unlikely. (d) It may give evidence of a specific cause such as hepatic encephalopathy or herpes simplex encephalitis, or minor epileptic status. F. Therapeutic test – IV 50% glucose can be given as a therapeutic test in any case unexplained coma or hemiparesis where hypoglycaemia is suspected Differential Diagnosis of Coma: Vascular causes: 1. Cerebral haemorrhage, thrombosis or embolism – (see table on p. 424). 2. Subarachnoid haemorrhage – (i) Sudden intense headache. (ii) Meningeal sings and neck rigidity usually promonet. (iii) Focal meurological sings frequently absent but can occur and are usually due to intracerebral clot or infraction in the region of the involved territory. (iv) Subhyaloid haemorrhage may be noted on fudus examination. (v) CSF – presence of blood 3. Hypertensive encephalopathy – (i) Common in patients with acute hypertension as in eclampsia, pheochromocytoma or acute nephritis. (ii) Convulsions, either focal or generalized. (iii) Transient cerebral symptoms like blindness, aphasia or hemiplegia. (iv) Papilloedema. (v) Lumbar puncture – CSF gushes out in a stream. 4. Cerebral venous thrombosis – Superior longitudinal sinus thrombosis occurs in relation to extra and intracranial sepsis, debilitating diseases, dehydration, pregnancy, pots-partum period, polycythemia, or in women taking contraceptive pills. Common clinical features include focal seizures,

loss of sensation and movement in the legs (crural dominance), and features of raised intracranial pressure – headache, vomiting and papilloedema. 5. Adams-Strokes syndrome – (i) History of myocardial infraction. (ii) Giddiness, faintness and convulsions precede coma. (iii) Heart rate very slow. 6. Shock – due to injury or loss of blood. (i) Evidence of cause. (ii) Low blood pressure. (iii) Feeble pulse. (iv) Cold and clammy skin Metabolic disorders: - Relative preservation of brain stem reflexes Seizures. Symmetrical sings. 1. Diabetic coma (Hyperglycemic ketoacidosis) – History of diabetes. Dehydration and hyperventilation (Kussmaul respiration). Breath smells of acetone. Often hypotension, tachycardia, warm skin. 2. chronic renal failure (uremia) – History of renal sisease. Variable rate of progress. Anaemia, hypertension. Ammoniacal odour of breath. Raised blood urea and creatinine. 3. Hepatic

Trauma, cord tumour or multiple sclerosis. (b) Autonomous bladder in cauda equina lesions. (c) Sensory bladder in subacute combined degeneration and multiple sclerosis. 7. TROPH IC CHANGES - Syringomyelia. a GAIT - (a) Ataxic in subacute combined degeneration and disseminated sclerosis.(b) Scissor gait in cerebral diplegia. (c) In lathyrism patient walks with staff, legs bent at knees and advancing lint strongly abducted and dragged forward with the toes reaching the ground first. 9. SPINE - Deformity, tenderness and rigidity in TB. spine. Kyphoscoliosis in syringomyelia and hereditary ataxias. Percussion tenderness in radicular spinal syndrome, and syringomyelia syndrome. 10. OTHER FINDINGS - (i) Other signs of syphilitic infection in spinal syphilis. 00 Anaemia and tenderness of calf muscles in subacute combined degeneration. Op Constitutional symptoms or evidence of tuberculosis elsewhere in the body in Potts disease. (iv) Painful, stiff neck with pain in arras with spastic weakness of legs in elderly persons should suggest cervical spondylotic myelopathy. (v) Symptoms due to primary disease, e.g. leukaemia (secondary deposits). (vi) Symptoms of increased intracranial tension in intracranial tumour. (vii) Short neck with a low hair line and limitation of rotation of neck in chronic progressive rnyelopathy complicating cranio-vertebral anomaly. (viii) Lhermitte's sign - may be positive in multiple sclerosis, craniovertebral anomaly, cervical spondylosis or cervical cord injuries, and subacute combined degeneration. The patient complains of sudden, transient, electric shock feeling spreading down the body when he flexes the head forward. (ix) Pes cavus in Frieclreich's ataxia and familial spastic paraplegia. (x) Mottling of teeth in fluorosis. III. Investigations - 1. CSF - Routine, serological tests for diagnosis of spinal syphilis. Froin's syndrome - In spinal tumour - (a) Xanthochromic fluid. (b) Increase in proteins as a result of which the fluid may coagulate spontaneously. (c) Slight or no increase of cells. 2. IMAGING - (a) Plain X-ray of vertebral column - Changes of T.B. spine, herniated intervertebral disc, secondary deposits, fracture dislocation. In spinal tumour increase of distance between pedicles or erosion of vertebra. X-rays of cervical spine for sponcylosis and for dislocation of atlanto-axial joints. Osteosclerosis in fluorosis. (b) MRI - is investigation of choice for cord compression. It gives information about site of compression and volume of the tumour in other areas of the spine. If tv1R1 is not available, rnyelography with CT scan. (c) CT scan - is useful when the lesion can be localized to a particular area e.g. lumbar disc disease. (d) IsAyelography - to confirm spinal block preferably via cisternal puncture if lumbar epidural space is the suspected site. (e) X-ray skull - Diagnosis of intracranial tumour and hydrocephalus. (f) CXR- Lung carcinoma is a common primary causing matastatic spinal disease. (g)Cerebral angiography - if suspicion of expanding mass or vascular abnormality. a BLOOD - (i) Megaloblastic anaemia in subacute combined degeneration. VORL positive in spinal

syphilis. Op Protein electrophoresis for multiple rnyeloma. (iv) Prostatic specific antigen for prostatic malignancy if indicated. 4. GASTRIC ANALYSIS — Pentagastrin - fast achlorhydria in subacute combined degeneration. 5. FUNDUS - Papilloedema in intracranial tumour. Temporal pallor in multiple sclerosis. 6. URINE - for fluorine estimation in endemic fluorosis. 7. THERAPEUTIC TEST - If suspected cervical disc degeneration, restriction of neck movements by rest or by wearing a collar for few weeks will often produce marked improvement in walking.

THE NERVOUS SYSTEM Vitamin B1 (Aneurin or thiamine) deficiency 1. NUTRITIONAL POLYNEUROPATHY (Neuritic beriberi). 2. WEAN ICKE-KORSAKOFF SYNDROME- WernickeS encephalopathy - Triad of: 1. Ophthalmoplegia - Eye signs consist of nystagrnus, Vlth and 111th nerve palsies, gaze palsies and occasionally ptosis. 2. Ataxia. a Confusion - in early stages followed by disorientation, drowsiness and terminal coma. Neuropathological lesions - Petechial hemorrhages in grey matter around 3rd and 4th ventricles and aqeduct of Sylvius, including the mammillary bodies. Korsakoffs psychosis - is the permanent sequel to Wernickes encephalopathy and is characterised by severe, irreversible loss of short-term memory, with relative sparing of other aspects of cognitive function. Some patients may confabulate. Neuropathological features are neuronal loss and gliosis, and hernosicierin-containing macrophages in the same distribution as lesions in Wernickes encephalopathy. Nicotinic acid deficiency - Mental confusion, sometimes fits, peripheral neuritic or spinal cord lesions occasional. Pyridoxine deficiency - 1. Chronic convulsions - in infancy may be due to lack of pyridoxine. 2. Polyneuropathy - as a complication of isoniazid treatment of tuberculosis arises from blocking of pyridoxine by the drug. Pantothenic acid deficiency - Burning feet syndrome - Intense discord oil in feet in absence of objective sensory alteration or of motor, or tendon reflex signs. There are two lines of evidence for this - (i) Its reproduction in human volunteers by giving them omega-methyl-pantothenic acid, an analogue of the vitamin which ads as an antagonist. 00 Nitro' urazone, a drug used in treating trypanosomiasis, causes an acute burning feet syndrome which responds promptly to parenternal calcium pantothenate. Vitamin B12 (Cyanocobalamin) deficiency — Types of disorders - (a) Cerebral type - Symptoms cover a wide range and consist of mild disorders of mood, mental *slowness, memory defect which may be severe, confusion which may be persistent or relapsing delusions and paranoid behaviour and sometimes violent mania, visual and auditory hallucinations. Faecal and urinary incontinence in the absence of overt spinal lesions. Epilepsy and ctysphasia may occur. These cerebral symptoms depend on ciernyelinating lesion of the white matter in the brain of the same nature as occur in the posterolateral column of the spinal cord and peripheral nerves. Optic atrophy or its precursor retrobulbar neuritis is not uncommon and may be the first manifestation, occurring predominantly in males. (b) Peripheral neuritis (See Polyneuritis). (c) Subacute combined degeneration. ETIOLOGY - (i) Age - 40-60. 00 Both sexes. Op Familial incidence known. (iv) Associated conditions - usually pernicious anaemia. Rarely as a result of carcinoma stomach, gastrectomy and gastro-enterostorny, steatorrhoea or malnutrition from protein deficiency. CLINICAL FEATURES - Onset - usually gradual, sometimes rapid. 1. Subjective sensory disturbances - Paraesthesia - Tingling and numbness in toes, later tips of fingers, rarely simultaneously in both upper and lower extremities. Sometimes burning or stabbing pains or even lightning pains like tabes. Paraesthesiae begin at periphery and tend to spread upwards. 2. Objective sensory loss - Sense of

vibration, posture and passive movement vibration, first in lower, later in upper limbs. Glove and stocking type of superficial sensory loss. Tenderness of calf muscles. a Motor symptoms - weakness and ataxia develop at variable interval after onset of sensory disturbances. 4. Reflexes –and reduced reflexes. Death before 3 years of age. (b) Type II SMA presents at about 6 months, and has, a more protracted course. Death from respiratory failure before age of 10. (c) Type III SfsilA (Kugelberg-Welander disease) presents at about 10 years with life expectancy of about 35 years. Progression tends to be slower that lower motor neurone forms of MND. Differential Diagnosis of MND DISORDER/SYNDROME MAIN DIAGNOSTIC TEST Cerebral and brain stem disorders Infiltrating tumors Cranial MRI Vascular disorders Cranial MRI, CSF, (e.g. multifocal ESR infarction, vasculitis, C-reactive protein, AN malformations) autoantibodies Syringobulbia Cranial MRI Cranial neuropathies EMG, nerve neuropathy conduction studies Spinocerebellar Degenerations 1, FRIEDREICHS ATAXIA - Progressive familial disorder with atrophy of posterior columns, posterior root ganglia, pyramidal and spinocerebellar tracts. Presents in early teenage years with ataxia, peripheral sensory loss, areflexia, loss of postural tone, kyphoscoliosis, pes cavus and cardiac conduction defects. Mental changes develop in a few An underlying defect of membrane transport and lipoamicle dehydrogenase has been demonstrated. 2. FAMILIAL SPASTIC PARAPLEGIA Family history of pure motor paraparesis in siblings or parents. Usually patient presents in the first decade. Pes cavus is often present. a ABETALIPOPROTEINEMIA - If untreated may produce similar neurological picture. 4. Due To UNKNOWN BIOCHEMICAL ABNORMALITY - Hereditary spastic ataxia (Marie), hereditary areflexic dystasia (Roussy-Levy), and olivopontocerebellar atrophy. 21. CEREBELLUM AND ITS DISORDERS Anatomy - The cerebellum, situated in the posterior fossa beneath the tentorium, and attached to the brain stern by the superior, middle and inferior peduncles, comprises two lateral hemispheres and the vermis which contain afferent and efferent nerve fibres. AFFERENT CONNECTIONS: Functionally, the cerebellar cortex is divided into three parts: 1. Vestibulocerebellum (lower vermis), which receives afferents from the vestibular system. 2. Spinocerebellum (upper vermis and anterior parts of the hemisphere), which receives afferents from the spinal cord a Neocerebellum - (cerebellar hemispheres), which receive, afferents from the cerebral cortex. EFFERENT CONNECTIONS: Efferent fibres originate from the Purkinje cells and pass to either the vestibular nuclei or deep cerebellar nuclei, which gives rise to a variety of ascending and descending projections. Each cerebellar subdivision sends elf erents principally to that part of the nervous system from which it receives its afferents. Cerebellor cortex Afferent connections Dysfunction .Vestibulocerebellum Vestibular system Truncal ataxia (lower vermis) Spinocerebellum From spinal cord Unsteadiness of gait and stance (positive Rombergism) Neocerebellum intention tremor) Causes: of cerebellar dysfunction - I. Acute - 1. Trauma - causing small capillary bleeding. 2. Infection - Encephalitis, abscess, Guillain Barre variant. a Vascular - Syndrome of posterior inferior cerebellar artery, anterior inferior cerebellar artery or superior cerebellar artery. Vertebro-basilar insufficiency. 4. Dernyelinating - Multiple sclerosis. 5. Drugs - Phenytoin, barbiturates, alcohol, streptomycin, gentarnycin, kenamycin, piperazine citrate. 6. Hyperpyrexia.l. Chronic - 1. Developmental - Agenesis, cranio-vertebral anomaly, Dandy Walker syndrome, von Hippel Linclau disease. 2. Familial - e.g., Refsurn's disease, lipidoses, leucodystrophies. a Degenerative - Holmes primary cerebellar degeneration,

(f) Anxiety and depression. (g) Emotional lability. Management of stroke and TIA: Hospitalization - for patients with suspected stroke Haemorrhage - Surgical evacuation of an intracranial hematoma beneficial in selected cases: (1) Hemorrhage into cerebellum. This is characterised by relative retention of power and sensation (in contradistinction to pontine or capsular lesions), with small pupils, gaze palsy, cerebellar ataxia and peripheral facial palsy. (2) Surgically accessible clot in a patient with good level of consciousness but a persistent neurological deficit after a trial of medical management for a period of one week. (3) When progressive cerebral oedema and coning necessitates surgical decompression. Thrombosis and Embolism — A. Supportive therapy - 1. Position in bed - Patient should be nursed with the head in a flat position. Disturbance of autoregulation in patients with stroke results in decrease in cerebral blood flow (CBF) if the head is elevated. Semiprone position in order to avoid falling back of the tongue. Frequent change of position to prevent lung congestion and bedsores. 2. Maintenance of air/gay - if patient is unconscious. The tongue must be kept forward, if necessary by use of an airway and the mouth clear of pillows so that when the patient vomits obstruction is less likely to occur. a Maintenance of hydration and nutrition - In the unconscious patient by passing a nasogastric tube. In first 24 hours 5% glucose solution (2000 ml) is adequate. This can be replaced after 24 hours, when the danger of vomiting or active regurgitation is passed, by milk, sugar, eggs, salt and vitarnins. Feeds are given 2-hourly preferably just after the patient's position is changed. 4. Care of the skin - Areas of reddening of the skin over heels, ankles, buttocks, shoulders and elbows are an indication of irnpencfing pressure necrosis. and indicate that the patient is not being turned frequently enough. Care of the bladder and bowel - Incontinent patients may require sterile indwelling catheters and bowel care since dampness and infection predispose to the formation of decubitus ulcers. Appropriate antibiotics should be given at the first sign of pyuria. 6. Care of the eyes - Antibiotic drops to prevent exposure keratitis. 7. Passive movements - to be commenced from the first day to prevent contracture (especially at the shoulder) and also to decrease risk of leg vein thrombosis. B. Treatment of associated conditions - 1. Cardiac condition - Treatment of arrhythrnias or of left ventricular failure. 2. Diabetes - Care should be taken to avoid hypoglycemia. a Hypertension - In acute stage mild to moderate elevation in BP requires no treatment. When associated with hypertensive encephalopathy or diastolic BP maintained at above 120 mm Hy. BP should be lowered cautiously using oral agents. 4. Hypotension - should be corrected by raising the foot of the bed and by fluid replacernent. 5. Infection - Appropriate antibiotics for pulmonary or urinary infection. Paracetamol to lower temperature since with rise of body temperature there is an increase in metabolic demands and cerebral oxygen consumption. C. Specific measures - I. Measures to reduce cerebral oedema - (a) fvlannitol- 350 ml of 20% aqueous solution IV. over 60-90 minutes. (b) Glycerol - 1.5 glkg of body weight every 24 hours in 3-4 cfivided doses mixed with fruit juice to mask the unpleasant taste or IV as 500 ml of 10% glycerol in 5% glucose or normal saline over a period of 34 hours daily for

mental confusion and headache precede coma. (ii) Shallow respiration. (Hi) Temperature subnormal. (iv) Fall of blood pressure. (v) Pupils fixed and usually small, may dilate terminally. Carbon dioxide narcosis - (i) Usually occurs in patients having a background of chronic pulmonary disease such as emphysema and

precipitated by pulmonary infection, congestive failure or some drugs, etc. (i) Associated manifestations such as tremor, rnyoclonic contractions, hyporeflexia, flaccid paralysis, convulsions and increased CSF pressure. Low shallow breathing and cyanosis. Diminished 02 saturation and pH of blood. Finding of frog eyes consisting of oedema, suffusion and injected conjunctiva valuable clue. Carbon- monoxide - (i) History of exposure to poisoning with the gas. (i) Headache, vertigo, muscular weakness, nausea, vomiting, drowsiness and coma. (iii) Intermittent convulsions. (iv) Cherry red colour. (v) Identification of carboxy haemoglobin. Organophosphorous poisoning - Dim vision, fixed rniosis, diziness, severe headache, rapid difficult breathing, vomiting and increasing cyanosis. Severe poisoning is indicated by sphincter incontinence, muscular twitching, tot convulsions, respiratory failure and pulmonary oedema. Pungent odour of breath. Intracranial infections and tumours: 1. Meningitis - (i) Gradual onset. (i) Signs of rneningeal irritation. (Hi) Fever, (iv) CSF changes. 2. Brain tumour - (i) Headache and vomiting. (i) Visual disturbances. (Hi) Neurological signs according to site of tumour. (iv) Progressive course. (v) Papilloeclerna. a Cerebral abscess - (i) Course usually more rapid than intracranial tumour. (i) Evidence of infection like sinusitis, otitis media, lung abscess, etc. (Hi) Fever. (iv) Leucocytosis. (v) CSF - increased cells. 4. Cerebral malaria - (i) History of fever with rigors. (i) Spleen may be enlarged. (Hi) Fever common; may be hyperpyrexia. 5. Encephalitis - (i) Acute onset. (i) Headache, (Hi) Insomnia or drowsiness. (iv) Pupillary and ocular changes. (v) Involuntary movements. (vi) CSF - Normal sugar suggestive. Post-epileptic coma: Diagnostic features - (a) History of characteristic seizures. (b) Scars on head from previous falls. (c) Tongue may be bitten. (d) Respiration slow (e) Pupils fixed during convulsion. (f) Evidence of involuntary defaecation or rnicturition. (g) Recovery usually within an hour without paralytic sequelae, but status epilepticus may be followed by prolonged coma. Coma of endocrine origin: 1. Hypopituitarisrn - Sudden onset if precipitated by infection. Usually female with changes of hypopituitarism. Low B.P. and low blood sugar. 2. fvlyxoederna - Characteristic appearance with slow pulse and subnormal temperature. a Suprarenal cortical failure - May occur suddenly as a result or stress e.g. operation in a patient known to be suffering from cortical deficiency. Low B.P. and electrolyte disturbances. Physical agents: 1. Heat hyperpyrexia and Sun stroke - (i) Prolonged exposure to high temperature or to heat of sun. (i) Suffused conjunctivae with contracted pupils. (Hi) Hyperpyrexia. (iv) Absence of sweating and dry skin. (v) Circulatory collapse. (vi) Convulsions. 2. Electric shock - (i) History of being exposed to electric current. 00 Evidence of skin burns. a Severe fevers - e.g. typhoid, typhus - (i) Insidious onset. (i) Fever of a few days duration. (iii) Other features or typhoid state. Psychogenic: Suggested by - (i) History of psychological disturbance

occurring at level of lesion. 5. REFLEXES - (a) Absent knee and ankle jerks with extensor plantar - (i) Subacute combined degeneration. OD Taboparesis. Friedreich's ataxia. (iv) Multiple sclerosis. (v) State of spinal shock. (vi) fvleningeal carcinomatosis. (vii) Coexisting lumbar and cervical sponcylosis. (viii) Motor neurone disease. (ix) Diabetic arnyotrophy. (x) Conus medullaris lesion. (b) Inversion of the radial reflex - long-standing cervical disc protrusion. 6. SPHINCTERS - (a) Spinal bladder from damage to spinal cord by trauma, cord tumour or multiple sclerosis. (b) Autonomous bladder in caucla equina lesions. (c) Sensory bladder in subacute combined degeneration and multiple sclerosis. 7. TROPH IC CHANGES - Syringomyelia. a GAIT - (a) Ataxic in subacute combined degeneration and disseminated sclerosis.(b) Scissor gait in cerebral diplegia. (c) In lathyrism patient

walks with staff, legs bent at knees and actvancing limb strongly abducted and dragged forward with the toes reaching the ground first. 9. SPINE - Deformity, tenderness and rigidity in T.B. spine. Kyphoscoliosis in syringomyelia and hereditary ataxias. Percussion tenderness in radicular spinal syndrome, and syringomyelia syndrome. 10. OTHER FINDINGS - (i) Other signs of syphilitic infection in spinal syphilis. 00 Anaemia and tenderness of calf muscles in subacute combined degeneration. Op Constitutional symptorrs or evidence of tuberculosis elsewhere in the body in Potts disease. (iv) Painful, stiff neck with pain in arms with spastic weakness of legs in elderly persons should suggest cervical sponcylotic myelopathy. (v) Symptoms due to primary disease, e.g. leukaemia (secondary deposits). (vi) Symptoms of increased intracranial tension in intracranial tumour. (vii) Short neck with a low hair line and limitation of rotation of neck in chronic progressive rnyelopathy complicating cranio-vertebral anomaly. (viii) Lhermitte's sign - may be positive in multiple sclerosis, craniovertebral anomaly, cervical sponctylosis or cervical cord injuries, and subacute combined degeneration. The patient complains of sudden, transient, electric shock feeling spreading down the body when he flexes the head forward. (ix) Pes cavus in Friecireich's ataxia and familial spastic paraplegia. (x) Mottling of teeth in fluorosis. III. Investigations - 1. CSF - Routine, serological tests for diagnosis of spinal syphilis. Froin's syndrome - In spinal tumour - (a) Xanthochromic fluid. (b) Increase in proteins as a result of which the fluid may coagulate spontaneously. (c) Slight or no increase of cells. 2. IMAGING - (a) Plain X-ray of vertebral column - Changes of T.B. spine, herniated intervertebral disc, secondary deposits, fracture dislocation. In spinal tumour increase of distance between pedicles or erosion of vertebra. X-rays of cervical spine for sponcylosis and for dislocation of atlanto-axial joints. Osteosclerosis in fluorosis. (b) MRI - is investigation of choice for cord compression. It gives information about site of compression and volume of the tumour in other areas of the spine. If fv1RI is not available, myelography with CT scan. (c) CT scan - is useful when the lesion can be localized to a particular area e.g. lumbar disc disease. (d) fvlyelography - to confirm spinal block preferably via cistemal puncture if lumbar epidural space is the suspected site. (e) X-ray skull - Diagnosis of intracranial tumour and hydrocephalus. (f) CXR- Lung carcinoma is a common primary causing matastatic spinal disease. (g) add 2 ml of 3M hydrochloric acid, boil for about 10 minutes and cool. Add 5 ml of sodium carbonate solution allow to stand for 5 minutes, dilute with water to 20 ml and filter. Add 5 ml of the clear filtrate to about 2 ml of potassium cupri-tartrate solution and boil for 1 minute; no red precipitate is formed immediately.Loss on drying: Between 10.5% and 12.0%, determined on 0.59 by drying in an oven at 60° at a pressure not exceeding 0.7 kPa for 5 hours, Appendix 8.6._Assay: Weigh accurately about 0.2 g, dissolve in 50 ml of water and complete the Assay described under Calcium Gluconate beginning at the words "add 5.0 ml of 0.051v1 magnesium sulphate....". Each ml of the remainder of 0.0tvl disodium edetate is equivalent to 0.01351 g of C14H14Ca06.CALCIUM LEVULINATE INJECTION Calcium Levulinate Injection is a sterile solution of Calcium Levulinate in Water for Injection.Usual strength: 100 mg per ml. Storage: Store in single dose containers. STANDARDSCalcium Levulinate Injection contains not less than 95.0 per cent and not more than 105.0 per cent of the stated amount of calcium levulinate, C10H14Ca06,2H20.1dentifIcation: Complies with tests A, B and C described under Calcium Levulinate.pH: Between 7.0 and 8.5. Appendix 8.11.Pyrogens: Complies with the test for pyrogens. Appendix 2.6, using a volume equivalent to 0.2 g of Calcium Levulinate per kg of the rabbit's weight.Other requirements: Complies with the requirements of tests stated under

Injectable Preparations (Injections). Assay: To a volume equivalent to 0.2 g of Calcium Levulinate add 50 ml of water and complete the Assay described under Calcium Gluconate beginning at the words "add 5.0 ml of 0.05M magnesium sulphate " Each ml of the remainder of 0.05M disodium edetate is equivalent to 0.01532 g of C10H14Ca06,2H20.CALCIUM PANTOTHENATEC18H32CaN2010 Mol, Wt, 476.S4 Calcium Pantothenate is the calcium salt of the dextrorotatory isomer of (R)-3-(2,4-dihydroxy-3,3-dimethyl-butyramido)propionic acid. Category: B-group vitamin (enzyme co-factor). Dose: 10 to 100. mg daily, in divided doses. Description: White powder; slightly hygroscopic. Solubility: Freely soluble in water, soluble in glycerin; slightly soluble in ethanol (95%), practically insoluble in ether. Storage: Store in tightly-closed containers.STANDARDSCalcium Pantothenate contains not less than 98.0 per cent and not more than 101.0 per cent of C18H32CaN2010, calculated with reference to the dried substanceldentification: A: In the test for p-Alanine, the principal spot in the chromatogram obtained with solution (2) corresponds to that in the chromatogram obtained with solution (3).B: Boil 50 mg in 5 ml of 1M sodium hydroxide for 1 minute, cool, and add 5 ml of 1 M hydrochloric acid and 2 drops of ferric chloride test solution; a strong yellow colour is produced.C: To 50 mg in 2 ml of 1M sodium hydroxide add 0.1 ml of copper sulphate solution; a blue colour is produced.D: Gives reaction A of calcium salts, Appendix 3.1.pH: Between 6.8 and 8.0, determined in a 5.0% w/v solution, Appendix 8.11.Clarity and colour of solution: A 5.0% w/v solution in carbon dioxide free water i s clear, Appendix 6.1, and colourless, Appendix 6.2.Specific optical rotation: Between +25.0° and +27.5°, determined at 20° in a 5% w/v solution, Appendix 8.9. p-Alanine: Carry out the method for thin-layer chromatography Appendix 4.6, using silica gel G as the coating substance and a mixture of 65 volumes of ethanol and 35 volumes of water as the mobile phase but allowing the solvent front to ascend 12 cm above the line of application. Apply separately to the plate 5 pl of each of four solutions in water containing (1) 4.0% w/v of the substance being examined, (2) 0.4% w/v of the substance being examined, (3) 0.4% w/v of calcium pantothenate RS and (4) 0.02% w/v of P-alanine. After removal of the plate, dry it in a current of air, spray with ethanolic ninhydrin solution and heat at 110° for 10 minutes. Any spot corresponding to P-alanine in the chromatogram obtained with solution (1) is not more intense than the spot in the chromatogram obtained with solution (4). Heavy metals: Not more than 20 ppm, determined by Method A on 1.0 g dissolved in 25 Store in well-closed containers. STANDARDSCarbenoxolone Sodium Tablets contain not less than 95.0 per cent and not more than 105.0 per cent of the stated amount of carbenoxolone Sodium, C34H48Na2Orldentification: A: Shake a quantity of the powdered tablets equivalent to 0.2 g of Carbenoxolone Sodium with 10 ml of methanol, filter and evaporate to dryness. The residue complies with tests B and C described under Carbenoxolone Sodium.B: A 5% w/v solution of the residue obtained in test A gives the reactions of sodium salts, Appendix 3.1.Related substances: Comply with the test described under Carbenoxolone Sodium, applying to the plate 5 pl of each of the following solutions. For solution (1) triturate a quantity of the powdered tablets equivalent to 0.10 g of Carbenoxolone Sodium with 20 ml of methanol, filter, evaporate the filtrate to low volume and add sufficient methanol to produce 10 ml. For solution (2) dilute 3 volumes of solution (1) to 100 volumes with methanoLOther requirements: Comply with the requirements of tests stated under Tablets.Assay: Weigh and powder 20 tablets. Triturate a quantity of the powdered tablets equivalent to 75 mg of Carbenoxolone Sodium with a small volume of methanol, filter and add sufficient methanol to produce 250.0 ml. To 10.0 ml add 10 ml of 0.02tvl sodium

carbonate and sufficient of a mixture of equal volumes of methanol and 0.02M sodium carbonate to produce 100.0 ml and measure the absorbance of the resulting solution at the maximum at about 256 nm, Appendix 5.5. Calculate the content of C34H48Na207 taking 199 as the value of A(1%, 1 cm) at the maximum at about 256 run. CARBIDOPAC10H14N204,H20 Wt, 244.25 Carbidopa is (5)-2-(3,4-dihydroxybenzyI)-2-hydrazinopropionic acid monohydrate.Category: Antiparkinsonian with Levodopa. Dose: 10 to 25 mg in combination with Levodopa. Description: White to creamy white powder; odourless or practically odourless.Solubility: Slightly soluble in water; very slightly soluble in ethanol (95%) and in methanol; practically insoluble in acetone, in chloroform, in dichloromethane and in ether. It is soluble in dilute solutions of mineral acids.Storage: Store in well-closed, light-resistant containers. STANDARDSCarbidopa contains not less than 98.5 per cent and not more than 101.0 per cent of C10H14N204, calculated with reference to the dried substance, Identification Tests A and C may be omitted if tests B, D and E are carried out. Tests B, D and E may be omitted if tests A and C are carried out.A: The infra-red absorption spectrum of a mineral oil dispersion, Appendix 5.4, is concordant with the reference spectrum of carbidopa or with the spectrum obtained from carbidopa RS.B: The light absorption in the range 230 to 360 nm of a 0.004% w/v solution in a 1 % v/v solution of hydrochloric acid in methanol exhibits a maximum only at about 282 nrn: absorbance at about 282 nm, about 0.52, Appendix 5.5.C: Complies with the test for Specific optical rotation.D: Shake vigorously about 5 mg with 10 ml of water for 1 minute and add 0.3 ml of ferric chloride solution; an intense green colour is produced, which quickly becomes reddish brown.E: Suspend 20 mg in 5 ml of water and add 5 ml of cupri-tartaric solution and heat; the colour of the solution changes to dark brown and a red precipitate is produced. Clarity and colour of solution: Dissolve 0.25 g in 25 ml of IM hydrochloric acid. The solution is clear, Appendix 6.1, and not more intensely coloured than reference solution BYS6 or BS6, Appendix 6.2.Specific optical rotation: Between -22.5° and -26.5°, determined in a solution prepared by dissolving 0.25 g in 25 ml of aluminium chloride solution, Appendix 8.9.Heavy metals: Not more than 20 ppm, determined on 1.0 g by Method B. Appendix 3.12.Hydrazine: Carry out the method for thin-layer chromatography, Appendix 4.6, using silanised silica gel G as the coating substance and a mixture of 2 volumes of methanol and 1 volume of water as the mobile phase. Apply separately to the plate 10 pl of each of the following solutions. For solution (1) place 25 g of strongly basic anion exchange resin into each of two stoppered conical flasks, add 150 ml of carbon dioxide -free water to each flask

electrodes are inserted within the muscles with an aim to record the total electrical activity of the motor nerve and the muscle uncier study. The machine that records the electrical activity is called electrornyograph and the record, the electrornyogram. In resting muscle, motor units display no electrical activity; when a motor nerve is stimulated, not only the nerve develops the AP, but also muscle fibers cievelop AP. !n a whole muscle, when many motor units are concomitantly stimulated, (as during a strong voluntary contraction), the resulting electrical activity may be considerable and in the resultant complex (as obtained by the machine), the individual APs are buried (i.e. the individual APs cannot be outlined). This is the normal pattern. In diseases of the motor nerve and the muscles, this normal pattern is altered. For example, in diseases of the lower motor neurones, (where some or majority of the motor axons have been ciead), in attempted contraction of the muscle, only a few motor units are

activated, resulting in a condition where the APs may remain discrete in the graph. Efv1G has greatly improved the diagnosis/ prognosis of lower motor neurone disease, rnusculopathies, peripheral neuritis and other diseases. ENERGY EXPENDITURE DURING CONTRACTION 1. When the muscles contract, the ready supply of energy comes from the break ciDv•in of ATP. ATP is broken ciDwn to ADP + Pi (Pi = inorganic phosphate). The different roles, played by ATP have been discussed earlier (chap. 1. sec. IX). 2, The ADP thus formed, is immediately resynthesized to ATP. However, for the resynthesis. Pi cannot recombine with the ADP; instead, a high energy phosphate radical has to combine with the ADP. The high energy phosphate is provided by creatine phosphate (CP). CP is plentifully available in the resting muscle. The equation : ADP + CP ATP + C (creatine) is called Lohrnann reaction, and is catalyzed by the enzyme, creatine phosphotransferase. As a result, the concentrations of ATP does not fall even after repeated contractions of the muscle (provicied the Lohrnann's reaction is not blocked artificially). The breakciDwn and resynthesis of ATP ciDes not require oxygen. The advantage from the teleological point of view is obvious; the animal/man, ciDes not have to wait for the oxygen for repeated contraction of the muscle. In fact, severe muscular activity, (e.g. running for life when chased by an enemy) although for a short time, is possible even without the supply of oxygen. 3. However, the creatine thus formed (from the Lohrnann reaction) must be resynthesized into creatine phosphate again. Like ADP, creatine also can take only high energy phosphate. 4. The low energy phosphate (Pi), can be converted into high energy phosphate, if the low energy phosphate gets an opportunity to trap the required amount of energy'. The high energy phosphate thus formed, Will now combine with creatine to form CP. 5. For providing the required amount of energy, catabosrn of carbohydrate, within the muscle, has to occur. The starting molecule may be glycogen or glucose. Resting muscles have an aciequate store of glycogen (assuming the man/ animal, is well fed). 6.The initial steps of glucose metabolism is, classically, the Ernbden fvleyerhof Pathway' (BAP). The end product of Elv1P is 'pyruvic acid', CH3C0 COOH. The details of steps have been discussed in chap.6, sec. VII, the operation of Elv1P produces some energy so that some (but not many) molecules of ATP can be resynthesized. If oxygen supply to the muscle is absent (anaerobic state), the pyruvic acid is converted into lactic acid, CH3 CHOH COOH. 7.The lactic acid, in the intact body, is recycled through the Cods' cycle (fig. 7.62) in which the lactic acid goes to the liver and converted into glucose and this glucose returns back to the same working muscles where the glucose unciergoes the Etv1P cycle of metabolism, once again. However, if oxygen is available, the pyruvic acid enters the Krebs tricarboxylic acid cycle (fig. 7.62) and is broken ciDwn to H20 and CO2. The operation of this cycle causes a much greater amount of energy or ATP formation (for details, see Krebs cycle, chap. 8, sec. VII, fig. 7.6.3). Alternate to the SWF, another

to the fact that it is dangerously addiction producing) thus can remove this warning system in our body and pave the way for injuries. Effects of training, Training improves the physical working capacity (PWC) of an individual. The word trainings here means, doing hard physical exercise regularly. With training the following effects are seen: (i) increase in cardio respiratory efficiency. (as determined by Voo2 max): stated simply. This means a rise. In Vo02 max, i.e. an increase in ability of the individual to utilize more oxygen per minute during exercise develops. As a result. 02debt (for the same intensity and duration of exercise) falls. (ii) Rise of blood lactate becomes less. where the intensity and duration of exercise remain same. Further.

Tolerance of lactic acid increases with Wining. As an example. an individual used to give up exercise at a juncture when his blood lactate concentration would reach. say, 75 mg/100 ml. After training the breaking point of exercise would coincide, with. say 110 mgi100 ml of blood lactate. (iii) The muscles which work regularly. become hypertrophied. (iv) Persons undergoing long term training develop bradycardia at rest. The resting pulse rates in some top class sportsmen "athletes (for example. Zatopek. Borg) are quite low. This bradycardia is believed to be due to excessive tone of the vagi. On the other hand. exercise of same intensity, will cause less rise of pluse rate after training. (v) Vety hard work carried routinely (i.e. day after day) for long time may produce cardiomegaly (cardiac enlargement). Long after the smtsman gives up his hard works. the only permanent change remaining. may be this catdiomegaly: The term 'hypertrophy' mentioned alx>ve should be dearly understood. The hypertrophy belongs to the class of 'work hypertrophy'. In hypeitrophy. there is no increase in the number of the muscle cells: only the individual cells (fibers) become more voluminous. In fact. in the post natal life, growth of skeletal muscles cc curs only by hypettrophy and not by hypeiplasia (increase in number of cells). Isometric versus isotonic exeirise An isometric exercise is one where the muscle is contracting but not shottening (as in attempting to move a heavily loaded stationaty car by pushing). In isotonic exercise, the muscle shottens as it contracts. Isometric exercises put a greater load on the heatt and thus should be avoided by elderly men. Therapeutic values of exercise Some diseases are known to improve with regular, controlled and moderate exercises. Included in the list of such diseases are. diabetes mellitus chronic coronaty ccclusive heart disease and benign essential hypertension. Some chronic disease of the joint (e.g. osteoalthritis) tend to cause crippling: regular exercise causes an improvement in the outicok. Moderate regular exercise has prophylactic values also. indeed most of the above mentioned diseases occur more commonly in sedentaty persons. Some special exercises (e.g. extension of the spine in persons suffering from prolapse of the intetvettebral disc) are part of the physiotherapy. Professional and prize fighting spottsmen however stiffer from various maladies: backache. knee troubles are commoner in pace bowlers of cricket. chronic injuty of the [main leading to permanent brain damage is apt to develop in 1>oxers. For treatment of severe obesity physical exercise is not of much help (see also chap. 15. sec. VI), although obese patients must do regular physical exercise. Indeed in all advanced countries, most of the population do regular jogging. There is. however no reason to believe that prize fighting professional spottsmen have a greater longevity. SUMMARY 8 HIGHLIGHTS Exercises are classified according to the (i) energy expenditure (02 consumption: direct measurement of energy expenditure is impracticable and 02 consumption correlates with energy expenditure: 02 consumption measurement is easy). (ii) Wattage and (.1i) pulse rate. In hot and humid climate (Calcutta vs Punjab) exercising is more difficult because both exercise and heat act as cardio vascular loads. Changes during exercise (are mostly aimed towards (i) meeting the demands of the over working muscles and (H) maintenance of homeostasis as far as possible) are many and include. (1) Cardiovascular CVS). (2) Respiratory (3) Metabolic (4) Thermoregulatory and so on. CVS changes are the most emphasized. because they. ultimately, decide the efficiency. the fitness of the individual and the breaking point of exercise. The CVS changes have been tabulated in T 9.3.1 and need not be repeated here except to emphasize the newly discovered phenomenon called. psychic vasodilatation and role of ACh (cholinergic sympathetic) in it. Respiratoty changes include, rise in VE exact cause of which is not dear. Of the metabolic changes. 02 debt and changes in RO have received greater attention. There are two contributors of

02 debt. (i) alactic acid. and (i) lactic acid debt. During the actual exercise RO rises but falls during recovery. In strenuous exercise. the fuel of the muscle is solely glucose but the same is fat in mild exercise. Tiaining improves the physical working capacity (PWC). A ttained spottsman has a resting bradycatdia and a greater Vco2 max. Severe exercise. routinely done over months together can lead to cardiomegaly (an undesirable effect) which persists. may be even life long. Introduction. 2. Functional anatomy. 3. Types of smcoth muscles. 4. Nemo effector Junction and neuromuscular transmission in smooth muscles. 5. Mechanism of contraction. 6. Pace maker.