Second pain is also spoken of as pathological pain. Besides, the fast pain is better localized while the

that is why we seek removal of Ihe injurious agent by appropriate measures. For example in leprosy, the pain sensation in the affecled region may be lost, resulting in ignoring of small culs/ sores etc Ultimately, the unattended (untreated) wound may enlarge and lead lo much crippling deformities. In acute abdominal pain, where the exacl cause of pain is yet lo be diagnosed, powerful pain killers should not be given, because this produces only a false sense of well being (as the pain is now absent) withoul elimination of the disease, as a result of which Ihe disease may be masked. However, in some cases, the presence of pain may be counter productive to the mlerest of Ihe patient. The classical example is pain in incurable forms of cancers, where the presence of the pain only adds to Ihe misery of the patient. Receplors and the slimulus Receptors Bare nerve terminals serve as pain receptor. However, other cutaneous receplors, when stimulated excessively, may cause pain. Stimulus. As soon as an acute injury is received, a pain is produced. But long afler the injury is apparently over, the pain may be continued to be felt. [Thus a pain is felt as soon as a hard blow is received, but long after Ihe blow is over, the pain may be continued to be felt]. It is difficult to say whal exactly causes Ihe pain which is produced immediately but the leter pain is almost certainly due to release of some chemicals, liberated by Ihe damaged (damaged due to Ihe injury; blow in this example) lissues; question is, whal are these endogenous chemicals ? A short answer is given below. In Ihe damaged tissues, particularly in the skin, some algogenic (= pain producing) substances are released. These algogenic subslances (AS) come in contact with the pain receptors (bare nerve terminals) ---> pain is produced. Identity of these AS are still controversial. Possible candidates are - (i) a peptide, allied to bradykinin and called 'pain producing peptide', PPS, (ii) bradykmm itself (iii) serotonin (5 HT) (iv) K+ ions (vi) AMP (vi) acetyl cholme; all of them, experimentally, can produce pain. Proslaglandins (PGs) deserve special mention. By Ihemselves, PGs are not very algogenic but they (= the PGs) potentate Ihe algogenic power of serotonin and bradykinin Non opiod analgesics (= pain killers) like (i) NSAIDs as well as (ii) cortisol and related compounds, inhibit the synthesis of PGs and thus relieve pain, for which they are popular in such diseases like rheumatoid arthritis. [NB. 1. NSAID = non steroidal anliinflammatory agent. Example includes, aspirin, ibuprofen etc; chemically Ihey are not sleroids and pharmacologically they are antiin-flammatory, analgesics and anlipyretics. 2. Cortisol and relaled drugs are, on the other hand, steroids]. Characteristics (properties) of pain 1. Threshold and intensity If the intensity of the slimulus is below the threshold (subthreshold), pain is not felt. As the intensity increases more and more, pain is felt more and more according to the Weber-Fechner's law (chap XB1. 1) and the pain sensation spreads, i.e. it begins to be felt in the neighbouring regions also. However, if the mind is distracled, the threshold of pain increases (see chap XB1. 1). Severe excitemenl and emotion can altogether abolish even a severe pain (see, endogenous pain inhibiting system, later this chapter). 2. Adaptation Pain receptors show no adaptation and so the pain continues as long as the receplors continue to be stimulated A s stated already, this is usually beneficial to the subject. 3. Localisation of pain Pain sensation is somewhat poorly localized. However, superficial pain is comparalively betler localized than the deep pain. Visceral pain is usually referred (ie, felt al a place which is other than the area overlying the viscus). 4. Emotional accompaniment Pain sensations are commonly accompanied by emolions. These emotions, as a rule, are unpleasant (recall, touch and other sensations may or may not be accompanied by pleas-ant/unpleasant emotions). 5. Influence of the rate of damage on the intensity of pain If the rale of tissue injury (exlent of damage per unit. time) is high, intensity of pain is also high and vice versa. Therefore, a very slowly growing tissue damaging agent (eg, cancer at early stage), may not produce any pain at all. [Most cancers, in the beginning, are painless]. 6. First (fast) and second (slow) pain After receiving a nociceptive stimulus, two types of nerve fibers are stimulated, viz, and C type of nerve fibers (table 10A.3.1). The fibers are somewhat thick and finely myelinated with a faster rate of conduction, but, C fibers are very thin and non myelmated with a much slower rale of conduction. C type of fibers however outnumber the A fibers. When an injury is received both or any one of the groups of fibers [that is, either A or C may be stimulated (depending on the nalure of the stimulation)], but sensalion due to Ihe stimulation of A fibers are felt earlier whereas that due lo C fibers are felt after a longer interval (because of Ihe slowness of conducting of C fibers). They are called first or fast (due lo A fibers) and second or slow (due to C fibers) pain respectively. Usually, the pain due to C fiber stimulation, is particularly unpleasant and outlasts Ihe period of stimulation. Second pain is also spoken of as pathological pain. Besides, the fast pain is better localized while the slow pain is not. Reactions of pain (i) Behavioral Crying/moaning/whining (in animals). In long standing pain, frustration/ mental irritation /depression can develop. (ii) Muscular Spasm of the skeletal muscles in the affected region (eg. spasm of the muscles around a fraclured bone, abdominal muscular spasm in peritonitis, and so on). Usually speaking, this spasm is beneficial, as it causes immobilisation of the injured part and puts Ihe affected part lo forcible rest (which is essential for healing). However,

IMMUNE DISORDERS ASSOCIATED WITH MYASTHENIA GRAVIS

myopathies (malignant hyperthermia, acute alcoholic myopathies). 2. EMG and n. conduction studies -confirm the diagnosis of either a myopathy anchor neuropathy. Abundant single-fibre activity in inflammatory myopathy, can also occur in adult form of acid maltase deficiency. 3. Muscle biopsy -provides conclusive evidence whether a motor unit disease is of myopathic or neuropathic origin 4 Molecular genetic analysis - of blood cells, muscle tissue or cultured muscle cells can diagnose symptomatic and presymptomatic hereditary diseases. It can also detect carriers and be suitable for prenatal diagnosis. 5. Muscle imaging by CT or MRI - can establish the distribution and degree of involvement in individual ire This may be diagnostic ally helpful or indicate a suitable site for biopsy. In vivo 32P or proton-based magnetic resonance spectroscopy are particularly useful to differentiate some cases of metabolic myopathies from chronic fatigue syndrome and fibromyalgia. 6. Miscellaneous tests -Biochemical methods to analyse deficiency states (e.g. glycogenolytic enzyme defects, carnitine deficiency). Immunlogical and serological studies - for investigating inflammatory myopathies or retroviral diseases. Management 1. Treatment of cause where possible - e.g. cessation or reduction of corticosteroids together with high protein diet in steroid myopathy, correction of endocrinopathy. 2. Drug therapy - In DMD, muscle destruction can be slowed and clinical course stabilised by oral prednisolone or deflazacort 0.76 mg/kg/day. Mexiletine controls myotonia in myotonia congenita and paramyotonia congenita. Acetazolamide or spironolactone for preventing acute attacks of hypokalemic periodic paralysis. Dantrolene for prevention and treatment of malignant hyperthermia crisis. Some mitochondria! myopathies respond to graded m conditioning aided by oral dichloroacetate. 23. MYASTHENIA GRAVIS Definition: An acquired autoimmune disorder causing skeletal muscle fatigability and weakness which can present at any age. Under age of 40, the disease predominantly affects females, in older age group men predominate. It is associated with a serum IgG antibody that binds acetylcholine receptors (AChR) in the. postsynaptic membrane of the neuromuscular junction and causes receptor loss. Symptoms and Signs: MUSCULAR WEAKNESS - following repetitive contraction with a tendency to recovery of motor power after a period of inactivity. a) Ocular muscles - first to be involved causing double vision or ptosis Symptoms are asymmetrical. b) Limb weakness - may involve proximal or distal muscles. (c) Bulbar muscle weakness - leads to loss of facial expression, inability to whistle, difficulty with speech, chewing and swallowing. Weakness of neck muscles and jaw causes patient to use a hand to support his jaw. (d) Respiratory muscle involvement - can lead to shortness of breath and ventilator/ failure in severe cases Other precipitating factors - Emotional stress, pregnancy and infection apart from exercise can lead to exacerbation of symptoms IMMUNE DISORDERS ASSOCIATED WITH MYASTHENIA GRAVIS - Rheumatoid arthritis, hyperthyroidism, hypothyroidism, polymyositis, SLE, pernicious anaemia, Sjogren's syndrome, pemphigus. Clinical types _ 1. Neonatal myasthenia -Transient illness in babies born to myasthenic mothers. 2. Juvenile myasthenia - in younger age group. 3 Eaton-Lambert

cholecalciferol or ergocalclferol, in mg, from the difference between the absorbances at about

H44O in cholecalciferol RS or of C?SH440 in ergocalciferol RS, as appropriate. CALCIFEROL INJEC HONCalciferol Injection is a sterile solution of Cholecalciferol or Ergocalclferol in Ethyl Oleate. Usual strength: 7.5 mg of Cholecalciferol or Ergocalclferol per ml. [Cholecalciferol or Ergocalclferol contains 40,000 Units of antirachitic activity (vitamin D) in each mg]. Description: Pale yellow, oily liquid. Storage: Store in single dose, light-resistant containers in a cool place Labelling: The label states (1) that the preparation is for intramuscular use only; (2) the number of Units of antirachitic activity (vitamin D) per ml. STANDARDSCalciferol Injection contains not less than 90.0 per cent and not more than 110.0 per cent of the stated amount of cholecalciferol, C27H44O or ergocalclferol, C?gH440 Identification: To 1 ml of a 0.2% v/v solution of the injection in ethanol-free chloroform add 9 ml of antimony trichloride solution. The light absorption of the resulting solution exhibits a maximum at about 500 nm, Appendix 5.5. Other requirements: Complies with the requirements of tests stated under Injectable Prepations (Injections). Assay: Carry out the following procedure in subdued light. Weigh accurately about 0.1 g of the injection and dilute to 50.0 ml with dry 1,2-dichloroethane that has been purified by passing it through a column of silica gel. To 1.0 ml of this solution add rapidly 9 ml of antimony trichloride in 1,2-dichlomethane solution and measure the absorbance of the resulting solution at about 500 run and about 550 run, Appendix 5.5, 90 to 120 seconds after adding the reagent. Repeat the operation using 1.0 ml of a 0.002% w/v solution of cholecalciferol RS or ergocalclferol RS in dry, purified 1,2-dichloroethane beginning at the words "add rapidly 9 ml of....... ". Calculate the content of cholecalciferol or ergocalclferol, in mg, from the difference between the absorbances at about 500 nm and 550 rim and from the declared content of C28H44O in cholecalciferol RS or of C28H44O in ergocalclferol RS, as appropriate. Calculate the percentage w/v of cholecalciferol or ergocalclferol taking 0.87 g as the value of the weight per ml of the injection: CALCIFEROL ORAL SOLUTION Calciferol Oral Drops; Calciferol Solution Calciferol Oral Solution is a solution of Cholecalciferol or Ergocalclferol in a suitable vegetable oil and may be prepared by warming to 40° a 1 % w/v suspension of Cholecalciferol or Ergocalclferol in a suitable vegetable oil, such as Arachis Oil, carbon dioxide being bubbled through it to facilitate solution, and adding a sufficient quantity of the oil to produce a solution containing the stated amount of Cholecalciferol or Ergocalclferol. Usual strength: 75 µg of Cholecalciferol or Ergocalclferol per ml. [Cholecalciferol or Ergocalclferol contains 40,000 Units of antirachitic activity (vitamin D) in each mg]. Description: Pale yellow, oily liquid, odour, slight but not rancid. Storage: Store in well-filled, well-closed, light-resistant containers in a cool place Labelling: The label states the number of Units of antirachitic activity (vitamin D) per ml. STANDARDSCalciferol Oral Solution contains not less than 85.0 per cent and not more than 120.0 per cent of the stated amount of cholecalciferol, C27H44O. or ergocalclferol, C28H44O. Identification: To 1 ml of a 20% v/v solution in ethanol free chloroform add 9 ml of antimony trichloride solution. The light absorption of the resulting solution exhibits a maximum at about 500 run, Appendix 5.5. Other requirements: Complies with the requirements,of tests stated under Oral Liquids. Assay: Carry out the following procedure in subdued light. Weigh accurately about 1.5 g, add 0.1 g of hydroqumone and 25 ml of 0.5M ethanohc potassium hydroxide, boil under a reflux condenser for 20 minutes, cool and add 50 ml of water. Extract with three quantities, each of 30 ml, of ether, wash the combined ether. extracts with 20 ml of water, then with 20 ml of 0.5M potassium hydroxide and finally with successive quantities, each of 20 ml, of water until the washings are no longer alkaline to phenolphthalem solution Filter the ether solution through absorbent cotton, wash with two quantities, each of 10 ml, of ether and evaporate the combined extracts and washings to dryness under oxygen free nitrogen by immersion in a water-bath at 50° Dissolve the residue in about 10 ml of hexane, transfer to a column (20 cm x 10 mm) packed with deactivated alumina and elute continuously with a 15 to 20% v/v solution of ether in hexane, using a flow rate of 1 to 2 ml per minute and collecting the fraction that contains the calciferol (identified conveniently by testing ahquots of successive 10-m1 fractions with antimony trichloride solution). Evaporate the solvent under oxygen free nitrogen at a temperature not exceeding 50° and dissolve the residue in 5 0 ml of ethanol free chloroform. Using duplicate 1.0-m1 portions of this solution add rapidly 9 ml of antimony trichloride solution and measure the absorbance of each solution at about 500 nm and 550 nm, 90 to 120 seconds after adding the reagent, Appendix 5.5. Repeat the operation using duplicate 1.0-m1 portions of a solution containing a known amount of cholecalciferol RS or ergocalclferol RS in ethanol free chloroform and beginning at the words "add rapidly 9 ml of antimony trichloride solution..... ". Calculate the content of cholecalciferol or ergocalclferol, in mg, from the difference between the absorbances at about 500 nm and 550 nm and from the declared content of C27H44O in cholecalciferol RS or of

The reason is, as acidosis advances, most of the enzymes in our body become inefficient and eventually all chemical reactions

glucose molecules are subsequently absorbed by the portal blood. After being absorbed the glucose molecules may be catabolized into C02 and H20. During its catabolism large amount of energy is produced, but only a part of this energy appears as heat; rest of the energy is stored in the form of energy rich phosphate compounds like ATP (adenosine triphos-phate). ATP subsequently will supply energy for doing various works in the body (like, muscular contraction, chemical reactions etc. ). One of the aims of the catabolism, therefore, is to produce energy rich compounds. On the other hand glucose molecules may be broken down into simpler molecules, like pyruvic acid, CHS COCOOH; pyruvic acid may be aminated to form alanine. Alanine will subsequently be required for building polypeptides. The polypeptides in turn are required for production of the proteins ofthe body (e.g. , muscle), peptide hormones (e.g. , insulin) etc. The pyruvic acid may be further broken down to the two carbon structure, viz, acetic acid or rather 'active acetate' (acetyl coenzyme A, CH3 COSCoA) and required for synthesis of long chain fatty acids (e .g. palmitic acid) or cholesterol. Or, the glucose molecule may be requisitioned for the synthesis of glycogen. All these are examples of anabolism of glucose . ENZYMESDefinition. Special features of enzymic actions. Factors influencing enzymic activities. Mechanism of the actions of enzymes. Mechanism of inhibition of enzymic Classification Coenzyme, cofactor and prosthetic group. Isoenzymes. Regulatory enzymes. Applied physiology. Definition Enzymes are organic catalytic agents, protei in nature, produced by living cells but for whose actions presence of living cells are not necessary. Special features of enzymic (enzymatic) activity 1. Enzymes accomplish their action at body temperature, without harming the host cells Thus, oxidation, reduction or hydrolytic reactions, if done in the laboratory, will require great deal of heating, addition of corrosive quantities of acids or alkalis and yet long time. But within our body, the enzymes accomplish hydrolysis, oxidation, reduction etc, (i) at body temperature (38°C), (ii) without injuring the cells and (iii) speedily. Moreover, chemical reactions in the laboratory usually produce side products. Enzymic (enzymatic, ) catalysis does not produce side products. Thus, stated simply, enzymic catalysis is much more efficient process than man made catalysts. 2. Enzymes are highly specific. Thus, sucrase splits sucrose but not maltose, although sucrose and maltose molecules are closely similar. On the otherhand, maltase splits maltose but not sucrose. Some enzymes however can act on a group of chemically very closely related substrates (substrate = the chemical compound on which the enzyme acts. Thus sucrose is the substrate of the enzyme sucrase). Furthermore, the enzymes show optical specificity. Thus, the enzymes in our body which can act on L ammo acids, cannot act on D ammo acids. FACTORS INFLUENCING ENZYME ACTIVITIES I. Temperature Most of the enzymes in our body act best around our normal body temperature, say around 38°C. If the temperature of the reaction medium falls, the efficiency of the enzyme also falls. At around 0°C, the enzymes become remarkably inactive and become totally inactive at around - 20°C. But on thawing the activity reappears in the enzyme. If the medium in which the enzyme is acting, becomes too hot, the enzyme, being protein in nature, is denatured. On further rise of temperature, the enzyme coagulates (heat coagulation). Cooling the enzyme now will not bring the activity of the enzyme back and the enzyme is said to be killed (by the heat). Optimal temperature is that temperature at which the enzyme acts best. Most human body enzymes are denatured if the temperature goes above 45°C. Plant enzymes, however, usually can survive somewhat higher temperatures. Fig. 7.1.1. Interrelationship between the temperature and enzyme activity. 2. Ph Every enzyme has an optimal pH, that is, a pH in which it acts best. Thus the optimal pH for pepsin, trypsin and salivary amylase, three digestive tract enzymes, are 1.5, 8.0, and 6.8 respectively. For probable explanation so as to how the pH influences the enzymic action, see mechanism of enzyme action, later this chapter. Outside its optimal pH, the enzyme loses its efficiency. Thus, in the stomach (where the pH is very low), there is a lipase, but as this lipase can act only in much higher pH, gastric lipase is an useless enzyme within the stomach of man. Or it is well known that acidosis is dangerous and if not corrected, leads to death. The reason is, as acidosis advances, most of the enzymes in our body become inefficient and eventually all chemical reactions (including the vital ones in the brain and heart muscle) stop and death ensues. 3. Effects of ions Some enzyme actions cannot proceed at all unless ions like Mg ++, Zn++ or Mn++ ions are present in the reaction medium. Cl- ions enhance the action of salivary amylase. 4. Concentration of the substrate As the concentration of the substrate on which the enzyme is acting rises, the velocity of the reaction increases, until a maximal velocity is obtained (V in fig. 7.1.2). Further increase of the substrate (without increasing the amount of the enzyme) does not cause increase of the rate of reaction (fig. 7.1.2). See also mechanism of enzymic action for explanation. Fig. 7.1.2. Effect of concentration of substrate on the velocity of reaction. MECHANISM OF ENZYME ACTION The enzyme combines

thickened due to the resultant anoxia and pulmonary hypertension develops →this leads to right venlricular hypertrophy and finally failure.

the finer vessels become thickened due to the resultant anoxia and pulmonary hypertension develops →this leads to right venlricular hypertrophy and finally failure. As a resulf of pulmonary congestion, pulmonary capillary BP rises → pulmonary edema develops. Recall, normally, lung fields are dry primarily because of low (about 9 mm Hg) capillary BP in the pulmonary circulation. But in mitral stenosis this may become something like 20 or 25 mm Hg. Characteristic clinical finding of mitral sfenosis is mid diastolic murmur and where the heart is beating regularly with a sinus rhythm ( = pace maker remains the SAN), there is usually a presystolic accentuation. Atrial fibrillation often develops in cases of mitral stenosis and with the onset of atrial fibrillation, the presystolic accentuation disappears. Explanation of the murmur. Recall, in most situations, normally, flow of the blood is streamllie Streamline flows are silent but turbulent flows are noisy. Streamline flows can become turbulent (and, therefore, noisy), under some circumstances, like when the Reynold's number exceed 1000 (chap 7 sec V). For example, when the velocity of blood rises or the lumen of the vascular tube is very wide, the stream line flow becomes turbulent (and noisy) because it exceeds the critical Reynold's number of 1000. " British physiologist and clinician (a renowned cardiologist), Lewis made lasting contributions in many fields, like ECG, pain producing substance- substance P histamine, circus movement and was also guru of Pickering (the great exponent of hypertension). Sir Thomas worked mostly in the pre 2nd world war time. However, if the flowing blood meets an obstacle, the flowing blood rebounds the particles of blood collide with one another turbulence is produced. This type of turbulence will be produced, even when the Reynold's number is much below 1000. In mitral stenosis, there is narrowing of the mitral opening (from a normal value of 4 to 6 sq cm, the orifice may become now well below 2 sq. cm). This produces an obstruction to the flow murmur develops with a Reynold's number value well below 1000. Nevertheless, if the velocity be increased (eg. by exercising the patient) the murmur becomes louder. The presystolic accentuation is due to the last rapid filling phase which in turn is due to atrial contraction, causing increase in the velocity. In atrial fibrillation, where there is no atrial contraction, there is, therefore, no presystolic accentuation. II. Mitral incompetence Vast majority of mitral incompetence cases are chronic cases and most ol them are of rheumatic fever origin. Mitral valve prolapse, however, is another important cause, particularly in the west In mitral incompetence, the mitral valves cannot close completely during ventricular systole as a result, some blood from the left ventricle regurgitates into the left atrium during ventricular systole (mitral regurgitation) a the regurgitated blood may also enter the pulmonary veins. Characteristic finding in mitral incompetence is a systolic murmur (= murmur during ventricular systole). Recall, part of the 1st heart sound is due to turbulence created by rebounce of blood from the undersurface of the mitral valve during ventricular contraction. To this, another kind of turbulence is created due to leakage of blood into the atrium. Left atrium contains extra blood due to regurgitation. This extra blood can produce 3rd heart sound (protodiastohc gallop ) during 1st rapid filling phase. III. Aortic incompetence (regurgitation) Great majorities of aortic incompetence cases are chronic. Rheumatic fever is a very important cause, syphilis is another. Rheumatic fever can cause scarring of the aortic valve a condition is created when these valves cannot close properly therefore, blood from the aorta regurgitates into the left ventricle during ventricular diastole ventricle receives extra blood in its diastohc period (volume overload or preload, see chap 2 sec V) operation of Frank Starling's law rise in stroke volume sharp rise in systolic BP (SBP). Further, regurgitation causes too quick and too extensive draining of blood from the aorta reduction of diastohc BP (DBP), further, duration of diastole is also short. Major findings of aortic incompetence, are therefore, (i) a water hammer pulse, (ii) high SBP but low DBP (eg. 160/ 30 mm Hg) both the features are due to reasons stated above (see also 'water hammer pulse' in 'pulse' chap 9 sec V); and (mi) a diastohc murmur (which is due to turbulence of blood in the ascending arota and left ventricular cavity) heard in the clinical aortic area. As coronary arteries are filled mostly in the diastole, and as the DBP is very low in such cases, in aortic incompetence cases, coronary supply is often geopardised. HEART FAILURE Heart failure may be viewed as a condition, where there is insufficient contractility (inotropic state) of the heart which results in such a reduction of cardiac output despite adequate venous filling that it leads to insufficient perfusion of the tissues. In the beginning, there operate the compensatory mechanisms and in well compensated cases ('mild heart failure') patient may remain reasonably symptom free at rest. In advanced or severe heart failure, despite the operation of compensatory mechanisms, the patient worsens. [This definition of heart failure covers only the 'classical or systolic heart failure'. Other types, however, have been ignored to keep the discussion simple. ] The signs and symptoms of heart failure are to a large extent, due to the compensatory mechanisms. In dealing with the heart failure, traditionally, two terms are used : (1) Forward failure (introduced

ammonia to 20 ml of a 0.05% w/v solution of atropine sulphate RS and complete the procedure described

lemperature and spray with dilute polassium indobismuthate solution. Any secondary spot in the chromatogram obtained with solution (1) is not more intense than the spot in the chromatogram obtained with solution (2) and not more than one such spot is more intense than the spot in the chromatogram obtained with solution (3). Sulphated ash: Not more than 0.2% Appendix 3.22: Water: Not more lhan 4,0% w/w, determined on 0.5 g, Appendix 3.24. Assay: Weigh accurately about 0.5 g, dissolve m 30 ml of anhydrous glacial acetic acid and carry out Method A for non-aqueous titration, Appendix 3.45, determining the end-point potenti ometrically.. Perform a blank determination and make any necessary correction: Each mlof 0.1M perchloric acid is equivalent to 0.06768 g of (C17H23NO3)2,H2S04,ATROPINE SULPHATE EYE OINTMENTAtropme Eye OintmentAtropine Sulphate Eye Ointment is a sterile preparation of Atropine Sulphate in an eye ointment base. Usual strength: 1.0% w/w. STANDARDSAtropine Sulphate Eye Ointment contains not less than 92.5 per cent and not more than 107.5 per cent of the stated amount of atropine sulphate, (C17H23N03)2,H204,H20. Identification: Carry out the method for thin-layer chromatography, Appendix 4.6, using silica gel G as the coating substance and a mixture of 50 volumes of chloroform, 40 volumes of acetone and 10 volumes of diethylamine as the mobile phase. Apply separately to the plale 5 µl of each of the following solutions. For solution. (1) dissolve a quantity of the ointment equivalent to 10 mg of Atropine Sulphate as completely as possible in 10 ml of light petroleum (boiling range 40° to 60°) and extract with two quantities, each of 10 ml, of 0.05M sulphuric acid, washing each acid solution with the same 5 ml of light petroleum (boiling range 40° to 60°) Mix Ihe acid solutions, make alkaline with dilute ammonia solution, and extract with two quantities, each of 15 ml, of chloroform. Remove the chloroform and dissolve the residue in 2 ml of ethanol (95%). Solution (2) contains 0.5% w/v of atropine sulphate RS in ethanol (95%). After removal of the plate, dry it at 105° for 20 minutes, allow it to cool lo room temperature and spray with polassium iodobismuthate solution. The principal spot in the chromatogram obtained with solution (1) corresponds to that in the chromalogram obtained with solution (2). Other requirements: Complies with the requirements of tests stated under Eye Ointments. Assay: Carry out Ihe method for gas chromatography, Appendix 4.2, using the following solutions. For solution (1) dissolve a quantity of Ihe eye ointment equivalent to 10 mg of Atropine Sulphate in 15 ml of chloroform, add 2 ml of a 0.5% w/v solution of homatropine hydrobromide RS (internal standard) in methanol (solulion A) and extract with two quantities, each of 10 ml, of 0.1M hydrochloric acid. Wash the combined exlracts with 10 ml of chloroform, add 2 ml of 5M ammonia. Extract with Iwo quantities, each of 10 ml, of chloroform, shake the combined extracts with 2 g of anhydrous sodium sulphate, filter and evaporate Ihe filtrate to dryness. Dissolve the residue m 5 ml of dichloromethane. To 1 ml of this solulion add 0.2 ml of a mixture of 4 volumes of N,O-bis(trimethylsilyl)acetamide and 1 volume of trimelhylchlorosilane, mix and allow to stand for 30 minutes. Prepare solution (2) in the same manner as solution (1) but omittmg the addition of solution A. For solution (3) add 2 ml of solulion A and 2 ml of 5M ammonia to 20 ml of a 0.05% w/v solution of atropine sulphate RS and complete the procedure described under solution (1) beginning at the words "Extract with two quantities, each of 10 ml, of chloroform......, ".The chromatographic procedure may be carried out using a glass column (1.5 m x 4 mm) packed with acid washed, silanised dialomaceous support (80 to 100 mesh) coated with 3% w/w of phenyl methyl silicone fluid (50% phenyl) (OV-17 is suitable) and maintained at 220° Calculate the content of (C17H23NO3)2,H2S04,H20 from Ihe declared content of (C17H23NO3)2,H2S04,H20 in atropine sulphate RS.ATROPINE SULPHATE INJECTION Atropine InieclionAtropine Sulphate Iniection is a slerile solution of Atropine Sulphate in Water for Iniection. Usual strenqths:

The phase of apnea normal respiratory rhylhrn Therefore, afler a bout of severe" voluntary hypervenMahOn. apnea follows then comes slighl

ring twelfth PaCO2 aid P*C02 begin (0 snub and return in normal or ri«» above normal values a trsn&ionl hyperpnp* correction of blood gas abnormalities due lo The phase of apnea normal respiratory rhylhrn Therefore, afler a bout of severe" voluntary hypervenMahOn. apnea follows then comes slighl hyperpmc phase and then Ihe respiration 15 back 10 normal The appearance of apnea in conscious hyperventilating subjects, is. however, nol regularly seen Enplanafton of symptom it ology
1 During voluntary hyperbrtathmg stage, the PaC02, falU and PaO2 uses (A similar sort of ihings happen in high attitude; and lh& reader is referred to (h* 'alveolai equal ion1 in high altitude sickness earlier in this chapter) 2 In normal persons and in non-nal environment 02 has practically no influence on Ihe frequency and amplitude of respiration H is only the C02. amongst Ihe gases, which has a strong influence Therefore law PaC02 withdrawal of the stimufation from ihe C02 sensitive chemoreceptoTS (fig 4 36) of medulla epnea 3 During the voluntary tiyperpnea. ihe subject may feel a:zness and visual biat kouT. This 15 due to low PeC02 When PiCO2 of ctmbril anenes fall they undergo vasospism This may b* called, msre'ore. hypocapmc cerebral vasospasm 1 Aflprwar-H unne may become slrongly alkaline This is because tht hfpoeapnis produces atkalosis. called, respiratory alkalosis The kidneys now eicrete the e'cess alhah ions and th*" homaostasrs of pH is maintained BREATH HOLDING Healthy persons, at Iht and of respiration can hold up his breath for •bout 50 seconds or so After 50 seconds ihe subject (a els distressed and develops a strong desire to breathe A] [his point,, (called ihe breaking point") ha is forced to breathe once again ae the 'breaking point1. typicaHy the PaO2 and PaCQJ are both about 60 mm Kg [normal, about 95 arid 4Q mm Hg respectively) The breaking paint depends mainly on ihe PaC02 Thus r lithe PaCO2 of 50 mm Hg i* reached quickly, as in breath holding Following muacular exercise, Ihe durihDn of breath holding will be short On the other hand if one holds up breath after a voluntary hyperventilation. Ihe duration may b* substantially prolonged This is because Ihe hyperventjlalion causes, washing out of CO2 so that buridmg up of PaC02" requires more lima Professional divers in the rive/is, who hive to stay under wstsi for sometime, often mike seven voluntary hypefvenl rial ten before diving so thai undarwater slay can be lengthened Thiv however, is dangerous, bacaus* the attainment of Ihe value of 60 mm Hg tor PaC02 it delayed no doubi but by this time the Pa02 mighi become dangerously \o*t and the subject may become unconscious due to hyprj*ia under waisr AHhough PaC02 value is Ihe mosii important influencing laclor for deiermming tr>e breaking point, oiher factors are also important Such (actors are (0 the concomitant hypoiemia. (n) neural factors like the role of vagus and the glosSOpharyngeal nerves They however will nol be drccusied hvre OXYGEN THERAPY The daiiical indcaTions of oirygtn therapy arB such condrtions like hypouc hypoxil. CO poisoning flic ip Ihe typical hypoiic hypoma, *verylhmg is normal bul The availably of O2n poor Whereas in CO poisoning, 02, particularly wtien given underpressure, replaces CO from ihe Hb molecule by mass action (in) In imonai-. edema. 02 therapy oflen trnpcoves the picture sharply/. This is because, inlhis condilion, there is ditlicully. m diffusion through thealveolo capillary membrane Inhalation of 1CK% 02 increases lh« PI02 lesulting in elevation of PAO2 and so .the alveolo capillary gradiBril of 02 greatly increases and the diffusion ofO2 improves (recall ihe Pick's Law. p 1EW) On ihe other hand., m anemia. The amounl of Hb or PBC fc poor, but the PaO2 is nomial Inhalation of 100% 02 and the following rse o( PIO2 and Pa02 therefore can increase only the 02m physical solution (normally about 0 3 ml/ 100 ml) but not Ihe 02 bound with the Kb, as Hb is praclicilly saturated wilh the 02 Therefore m anemia, the improvement by O2 therapy is only marginal In advanced cases of chronic bronchitis and corpulmcinale O2 therapy must be given with caution In these conrttionsr there Js chrome hypona as well as hypercapma The medullary CO2 sensitive celfs (central chemoreceplors, fig4 38), owing to chronic eicposura to the excess CO?, lose their sensitivity lo CO?, and O2tack remains the only dnve lefl to the patient for [h* breaihing 02 therapy, therefore, might kill ihe patient by withdrawing the only drive laftia ihe patient In CO poisoning and, with surgenes on hearl or lung, grealfy hyperbaTC 02 (i e 02 under high pressure) therapy is done where Such fec*lles e^isl Us dangers are given beow 1 When the PLO2 is very high, Ihe PaO2 ai*o becomes high and the amount of dissolved
02 (m physical solution) may rise greatly [say to values like 4 or 5 ml/100 ml from a normal value ofO 3 ml/IX ml), when Ihn occurs, for onygenatron of the tissues, this dissoked 02 alone is sufficient tnd tht HbO2 is not called for so that il remains imact This maeans, that Ihe carbamino Hb compounds cannot be formed and CO2 accumulates in the tissues (Retati. tht carbamioo Hb compounds, as shown m p 172 play a very crucial parr in transfer of CQ2) Accumulation of CO? can lead to. rather paradoxically, exaggerated respiration (panting for air due in excess O2'i) 2 High PaU2 produces cerebral vavot0*im Tins is id tame e'leni btntficial »s ihe hi »in ii»«uet ara protaciid from ihe mjur