0
....rgesic:nui.esic Therapeutic Classification: NORGESIC is a non-narcotic analgesic effective in the relief of pain of mild to moderate intensity. Formula: Each white tablet contains: orphenadrine citrate (2-dimethylaminoethyl 2-methylbenzhydryl ether citrate) 25 mg. acetylsalicylic acid.300 mg. caffeine.30mg. Actions: Orphenadrine citrate is a centrally-acting (brain stem) compound which in animals selectively blocks facilitatory functions of the reticular formation. Orphenadrine does not produce myoneural block, nor does it affect crossed extensor reflexes. Orphenadrine prevents nicotine-induced convulsions but not those produced by strychnine. Combinations of acetylsalicylic acid and caffeine have been extensively used, and their pharmacology and toxicity profiles are well known. The addition of orphenadrine citrate does not alter the toxicity of aspirin and caffeine. Indications and ClinIcal Uses: Symptomatic relief of acute pain of mild to moderate intensity associated with musculo-skeletal disorders. Clinical evaluations of NORGESIC have revealed an overall satisfactory response of approximately 80% in patients with a wide variety of painful disorders involving musculoskeletal disorders. Contraindications: Because of the mild anticholinergic effect of orphenadrine, NORGESIC should not be used in patients with glaucoma, pyloric or duodenal obstruction, achalasia, prostatic hypertrophy or obstructions at the bladder neck. NORGESIC is also contraindicated in patients with myasthenia gravis, in patients known to be sensitive to aspirin or caffeine, and in patients with peptic ulcer or history of peptic ulcer. WARNING: Not to be administered to children under six years of age except on the advice of a physician. Adverse Reactions: Side effects of NORGESIC are those seen with aspirin and caffeine or those usually associated with mild anticholinergic agents. These may include tachycardia, palpitation, urinary hesitancy or retention, dry mouth, blurred vision, dilatation of the pupil, increased intra-ocular tension, weakness, nausea, vomiting, indigestion, headache, dizziness, constipation, drowsiness, and rarely, urticaria and other dermatoses. Infrequently, an elderly patient may experience some degree of confusion. Mild central excitation and occasional hallucinations may be observed. These mild side effects can usually be eliminated by reduction in dosage. Dosage and Administration: Adults: One or two tablets t.i.d. Children (acute use only): 6 to 12 years of age, one tablet t.i.d. Not to be administered to children under six years of age except on the advice of a physician. Availability: Tablets, bottles of 100 and 500. Caution: May be injurious if taken in large doses or for a long time. Do not exceed recommended dose without consulting a physician. Keep out of reach of children.
Rikur Pharmacuutlcal Ca. Ltd. 3214 WHARTON WAY* MISSISSAUGA ONTARIO
mality, the subjects being divided into arteriographic classes and clinical groups according to the presence of typical angina pectoris. Inspection of this graph from the standpoint of the clinical diagnosis shows that with 3 exceptions the 37 subjects with typical angina had severely diseased coronary arteries, and with 7 exceptions they had 1.0 mm or more of ischemic ST-segment shift. From the arteriographic standpoint, subjects with severe disease commonly had ischemic ST-segment depression with exercise but those with normal arteries rarely did. From the electrocardiographic standpoint the presence of ST-segment depression of 1.0 mm or more was, with four exceptions, indicative of a severe degree of coronary artery disease as shown by arteriography. These comparisons give firm objective support to the clinician's strong reliance on the ominous importance of typical angina pectoris. The failure of three subjects with a clinical diagnosis of angina pectoris to show either ischemic change in the electrocardiogram or arteriographic abnormality may shed doubt on the clinical diagnosis, or it may indicate that pain can develop from an ischemic area too small to be seen arteriographically or electrocardiographically. The positive exercise tests in four subjects with arteriographically normal vessels (classes 0 and I) may have a similar explanation. In classes II, III and IV are 11 subjects who failed to demonstrate a positive electrocardiographic stress test. Five of these did not have angina pectoris; this is best explained by the fact that arteriographically severe lesions need not produce myocardial ischemia if the collateral circulation is adequate. This three-way comparison thus helps to delineate the usefulness and accuracy of each of the three variables considered. Three different manifestations of the underlying disease are measured and, therefore, perfect agreement among the three would not be expected. Fig. I also shows that there are seven subjects with typical angina pectoris whose tests are just barely positive, with 1.0-mm ischemic ST-segment shift. The use of 0.75 mm as the criterion for positivity would more clearly separate the angina patients but such a criterion would result in the inclusion of three more false-positives. If the value of 2.0 mm (used by Dr. Cumming) were accepted, many more false-negatives would appear. It appears, therefore, that 1.0 mm is the best criterion for a positive test.
tiple-lead exercise electrocardiography: experience in 107 normal subjects and 67 patients with angina pectoris, and comparison with coronary cinearteriography in 84 patients. Circulation 36: 517, 1967 2. MASON RE, LIKAR I: A new system of multiple-lead exercise electrocardiography. Am Heart J 71: 196, 1966 3. Ross RS, FRIESINGER GC: Coronary arterlography. Am Heart / 72: 437, 1966
To the editor: Originally we had 11 references correlating results of coronary angiography and exercise tests to cover the statement that exercise tests may be negative "in up to 75% of symptomatic patients with narrowing of only one major coronary artery, and in up to 50% of subjects with previous infarctions". Knowing editors' penchant for brevity, we used the earliest of these references (that of Dr. Likar and his colleagues) and this was an error. Review of the references14 below will show that our statement is supported by the literature. To obtain the criteria used for classifying electrocardiograms as normal or abnormal, Dr. Likar would have had to read the original paper on our population.6 He would have found that we used 0.1-mV STsegment depression, not the 0.2 mV (2.0 mm) that he suggests. GORDON R. CUMMING, MD Head Section of cardiology Health Sciences Children's Centre Winnipeg, Man.
References 1. BARTEL AG, BEHAR VS, PamR RH, et al: Graded exercise stress tests in angiographically documented coronary artery disease.
Circulation 49: 348, 1974 2. KAPLAN MA, HARRIS CN, ARONOW WS, et al: Inability of the submaximal stress test to predict the location of coronary disease. Circulation 47: 250. 1973 3. MARTIN CM, MCCONAHAY DR: Maximal treadmill exercise electrocardiography: correlations with coronary angiography and cardiac hemodynamics. Circulation 46: 956, 1972 4. REDWOOD DR, EPSTEIN SE: Uses and limitations of stress testing in the evaluation of ischemic heart disease. Ibid, p 1115 5. WEEDA HWH: ECG changes during and after maximal exercise test in patients with myocardial infarction. Mal Cardiovasc 10: 61, 1969 6. CUMMING GR, BORYSYK W, DUFRESNE C: The maximal exercise ECG in asymptomatic men. Can Med Assoc 1 106: 649, 1972
Drugs in pregnancy
2045 Dufferin St. Toronto, Ont.
To the editor: I am very grateful to Dr. Buck (Can Med ASSOC 1 112:1285, 1975) for bringing to my attention her comprehensive and critical prospective investigation of perinatal causes of brain damage. The results of her study, insofar as the 70 infants who received meperidine (via the mother) are concerned, provide some answers to the question I posed. I would agree with Dr. Buck's conclusion that the meperidine in this group of term infants did not have any harmful effects on their psychological and physical development.
I.. MASON RE, LIKAR I, BIERN RO, Ct al: Mul-
Department of pediatrics State University of New York at Buffalo Buffalo, NY
I. LIKAR, MB, BS, FRCP[C]
SUMNER J. YAPPE, MD
References
CMA JOURNAL/JUNE 21, 1975/VOL. 112 1391
....rgesic:nui.esic Therapeutic Classification: NORGESIC is a non-narcotic analgesic effective in the relief of pain of mild to moderate intensity. Formula: Each white tablet contains: orphenadrine citrate (2-dimethylaminoethyl 2-methylbenzhydryl ether citrate) 25 mg. acetylsalicylic acid.300 mg. caffeine.30mg. Actions: Orphenadrine citrate is a centrally-acting (brain stem) compound which in animals selectively blocks facilitatory functions of the reticular formation. Orphenadrine does not produce myoneural block, nor does it affect crossed extensor reflexes. Orphenadrine prevents nicotine-induced convulsions but not those produced by strychnine. Combinations of acetylsalicylic acid and caffeine have been extensively used, and their pharmacology and toxicity profiles are well known. The addition of orphenadrine citrate does not alter the toxicity of aspirin and caffeine. Indications and ClinIcal Uses: Symptomatic relief of acute pain of mild to moderate intensity associated with musculo-skeletal disorders. Clinical evaluations of NORGESIC have revealed an overall satisfactory response of approximately 80% in patients with a wide variety of painful disorders involving musculoskeletal disorders. Contraindications: Because of the mild anticholinergic effect of orphenadrine, NORGESIC should not be used in patients with glaucoma, pyloric or duodenal obstruction, achalasia, prostatic hypertrophy or obstructions at the bladder neck. NORGESIC is also contraindicated in patients with myasthenia gravis, in patients known to be sensitive to aspirin or caffeine, and in patients with peptic ulcer or history of peptic ulcer. WARNING: Not to be administered to children under six years of age except on the advice of a physician. Adverse Reactions: Side effects of NORGESIC are those seen with aspirin and caffeine or those usually associated with mild anticholinergic agents. These may include tachycardia, palpitation, urinary hesitancy or retention, dry mouth, blurred vision, dilatation of the pupil, increased intra-ocular tension, weakness, nausea, vomiting, indigestion, headache, dizziness, constipation, drowsiness, and rarely, urticaria and other dermatoses. Infrequently, an elderly patient may experience some degree of confusion. Mild central excitation and occasional hallucinations may be observed. These mild side effects can usually be eliminated by reduction in dosage. Dosage and Administration: Adults: One or two tablets t.i.d. Children (acute use only): 6 to 12 years of age, one tablet t.i.d. Not to be administered to children under six years of age except on the advice of a physician. Availability: Tablets, bottles of 100 and 500. Caution: May be injurious if taken in large doses or for a long time. Do not exceed recommended dose without consulting a physician. Keep out of reach of children.
Rikur Pharmacuutlcal Ca. Ltd. 3214 WHARTON WAY* MISSISSAUGA ONTARIO
mality, the subjects being divided into arteriographic classes and clinical groups according to the presence of typical angina pectoris. Inspection of this graph from the standpoint of the clinical diagnosis shows that with 3 exceptions the 37 subjects with typical angina had severely diseased coronary arteries, and with 7 exceptions they had 1.0 mm or more of ischemic ST-segment shift. From the arteriographic standpoint, subjects with severe disease commonly had ischemic ST-segment depression with exercise but those with normal arteries rarely did. From the electrocardiographic standpoint the presence of ST-segment depression of 1.0 mm or more was, with four exceptions, indicative of a severe degree of coronary artery disease as shown by arteriography. These comparisons give firm objective support to the clinician's strong reliance on the ominous importance of typical angina pectoris. The failure of three subjects with a clinical diagnosis of angina pectoris to show either ischemic change in the electrocardiogram or arteriographic abnormality may shed doubt on the clinical diagnosis, or it may indicate that pain can develop from an ischemic area too small to be seen arteriographically or electrocardiographically. The positive exercise tests in four subjects with arteriographically normal vessels (classes 0 and I) may have a similar explanation. In classes II, III and IV are 11 subjects who failed to demonstrate a positive electrocardiographic stress test. Five of these did not have angina pectoris; this is best explained by the fact that arteriographically severe lesions need not produce myocardial ischemia if the collateral circulation is adequate. This three-way comparison thus helps to delineate the usefulness and accuracy of each of the three variables considered. Three different manifestations of the underlying disease are measured and, therefore, perfect agreement among the three would not be expected. Fig. I also shows that there are seven subjects with typical angina pectoris whose tests are just barely positive, with 1.0-mm ischemic ST-segment shift. The use of 0.75 mm as the criterion for positivity would more clearly separate the angina patients but such a criterion would result in the inclusion of three more false-positives. If the value of 2.0 mm (used by Dr. Cumming) were accepted, many more false-negatives would appear. It appears, therefore, that 1.0 mm is the best criterion for a positive test.
tiple-lead exercise electrocardiography: experience in 107 normal subjects and 67 patients with angina pectoris, and comparison with coronary cinearteriography in 84 patients. Circulation 36: 517, 1967 2. MASON RE, LIKAR I: A new system of multiple-lead exercise electrocardiography. Am Heart J 71: 196, 1966 3. Ross RS, FRIESINGER GC: Coronary arterlography. Am Heart / 72: 437, 1966
To the editor: Originally we had 11 references correlating results of coronary angiography and exercise tests to cover the statement that exercise tests may be negative "in up to 75% of symptomatic patients with narrowing of only one major coronary artery, and in up to 50% of subjects with previous infarctions". Knowing editors' penchant for brevity, we used the earliest of these references (that of Dr. Likar and his colleagues) and this was an error. Review of the references14 below will show that our statement is supported by the literature. To obtain the criteria used for classifying electrocardiograms as normal or abnormal, Dr. Likar would have had to read the original paper on our population.6 He would have found that we used 0.1-mV STsegment depression, not the 0.2 mV (2.0 mm) that he suggests. GORDON R. CUMMING, MD Head Section of cardiology Health Sciences Children's Centre Winnipeg, Man.
References 1. BARTEL AG, BEHAR VS, PamR RH, et al: Graded exercise stress tests in angiographically documented coronary artery disease.
Circulation 49: 348, 1974 2. KAPLAN MA, HARRIS CN, ARONOW WS, et al: Inability of the submaximal stress test to predict the location of coronary disease. Circulation 47: 250. 1973 3. MARTIN CM, MCCONAHAY DR: Maximal treadmill exercise electrocardiography: correlations with coronary angiography and cardiac hemodynamics. Circulation 46: 956, 1972 4. REDWOOD DR, EPSTEIN SE: Uses and limitations of stress testing in the evaluation of ischemic heart disease. Ibid, p 1115 5. WEEDA HWH: ECG changes during and after maximal exercise test in patients with myocardial infarction. Mal Cardiovasc 10: 61, 1969 6. CUMMING GR, BORYSYK W, DUFRESNE C: The maximal exercise ECG in asymptomatic men. Can Med Assoc 1 106: 649, 1972
Drugs in pregnancy
2045 Dufferin St. Toronto, Ont.
To the editor: I am very grateful to Dr. Buck (Can Med ASSOC 1 112:1285, 1975) for bringing to my attention her comprehensive and critical prospective investigation of perinatal causes of brain damage. The results of her study, insofar as the 70 infants who received meperidine (via the mother) are concerned, provide some answers to the question I posed. I would agree with Dr. Buck's conclusion that the meperidine in this group of term infants did not have any harmful effects on their psychological and physical development.
I.. MASON RE, LIKAR I, BIERN RO, Ct al: Mul-
Department of pediatrics State University of New York at Buffalo Buffalo, NY
I. LIKAR, MB, BS, FRCP[C]
SUMNER J. YAPPE, MD
References
CMA JOURNAL/JUNE 21, 1975/VOL. 112 1391
