ALDOMET*

(methyldopa MSD Std) Indications: Sustained moderate through severe hypertension. Dosage Summary: Start usually with 250 mg two or three times daily during the first 48 hours; thereafter adjustat intervals ot not less than two days according to the patients response. Maximal daily dosage is 3.0 g of methyldopa. In the presence ot impaired renal function smaller doses may be needed. Syncope in older patients has been related to an increased sensitivity in tho.e patients with advanced arteriosclerotic vascular disease and may be avoided by reducing the dose. Tolerance may occur occasionally between the second and third month after initiating therapy. Eftectiveness can frequently be restored by increasing the dose or adding a thiazide. Contraindlcations: Active hepatic disease such as acute hepatitis and active cirrhosis; known sensitivity to methyldopa; unsuitable in mild or labile hypertension responsive to mild sedation or thiazides alone; pheochromocytoma; pregnancy. Use cautiously if there is a history of liver disease or dysfunction. Precautions: Acquired hemolytic anemia has occurred rarely. Hemoglobin and/or hematocrit determinations should be performed when anemia is suspected. If anemia is present, determine if hemolysis is present. Discontinue methyldopa on evidence of hemolytic anemia. Prompt remission usually results on discontinuation alone or the inibation of adrenocortical steroids. Rarely, however, fatalities have occurred. A positive direct Coombatest has been reported in some patients on continued therapy with methyldopa, the exact mechanism and significance of which is not established. Incidence has varied from 10 to 20%. If a positive test is to develop it usually does within 12 months following start of therapy. Reversal of positive test occurs within weeks to months after discontinuation of the drug. Prior knowledge of this reaction will aid in cross matching blood for transfusion. This may result in incompatible minorcross match. If the indirect Coombs test is negative, transfusion with otherwise compatible blood may be carried out. If positive, advisability of transfusion should be determined by a hematologist or expert in transfusion problems. Reversible leukopenia with primary eftect on granulocytes has been seen rarely. Rare cases of clinical agranulocytosis have been reported. Granulocyte and leukocyte counts returned promptly to normal on discontinuance of drug. Occasionally fever has occurred within the hrst three weeks of therapy, sometimes associated with eosinophilia or abnormalities in one or more liver function tests. Jaundice, with or without fever, may occur also, with onset usually within first 2 or 3 months of therapy. Rare cases of fatal hepatic necrosis have been reported. Liver biopsies in several patients with liver dysfunction showed a microscopic focal necrosis compatible with drug hypersensitivity. Determine liver function, leukocyte and differential blood counts at intervals during the first sis to twelve weeks of therapy orwhenever unesplained fever may occur. Discontinue if fever, abnormalities in liver function tests, or jaundice occur. Methyldopa may potentiate action of other antihypertensive drugs. Follow patients carefully to detect side reactions or unusual manifestations of drug idiosyncrasy. Patients may require reduced doses of anesthetics when on ALDOMEP. If hypotension does occur during anesthesia, it usually can be controlled byvasopressors. The adrenergic receptors remain sensitive during treatment with methyldopa. Hypertension occasionally noted after dialysis in patients treated with ALDOMEP may occur because the drug is removed by this procedure. Rarely involuntary choreoathetotic movements have been observed during therapy with methyldopa in patients with severe bilateral cerebrovascular disease. Should these movements occur, discontinue therapy. Fluorescence in urine samples at same wave lengths as catecholamines may be reported as urinary catecholamines. This will interfere with the diagnosis of pheochromocytoma. Methyldopa will not serve as a diagnostic test for pheochromocytoma. Usage in Pregnancy: Because clinical esperience and follow-up studies in pregnancy have been limited, the use of methyldopa when pregnancy is present or suspected requires that the benefits of the drug be weighed against the possible hazards to the fetus. Adverse Reactions: Cardiovascular: Angina pectoris may be aggravated; reduce dosage if symptoms of orthostatic hypotension occur; bradycardia occurs occasionally. Neurological: Symptoms associated with eftective lowering of blood pressure occasionally seen include dizziness, lightheadedness, and symptoms of cerebrovascular insufticiency. Sedation, usually transient, seen during initial therapy or when dose is increased. Similarly, headache, asthenia, or weakness may be noted as early, but transient symptoms. Rarely reported; paresthesias, parkinsonism, psychic disturbances including nightmares, reversible mild psychoses or depression, and a single case of bilateral Bells palsy. Gastrointestinal; Occasional reactions generally relieved by decrease in dosage: mild dryness of the mouth and astrointestinalsmtoms including distention, constipation, f Is?usandiarres; d.hYP rarely,test, nausea and hemolytic vomiting. Hematological: Positive direct Coomba acquired anemia, leukopenis and rare cases of thrombocytopenia. Toxic and Allergic: Occasional drug related fever and abnormal liver function studies with jaundice and hepatocellular damage, (see PRECAUTIONS) and a rise in BUN. Rarely, skin rash, sore tongue or black tongue', pancreatitis and inflammation of the salivary glands. Endocrine and Metabolic; Rarely, breast enlargement, lactation, impotence, decreased libido; weight gain and edema which may be relieved by administering a thiazide diuretic. If edema progresses or signs of pulmonary congestion appear, discontinue drug. Miscellaneous; Occasionally nasal stuftiness, mild arthralgia and myalgia: rarely, darkening of urine after voiding. Detailed information available on request, How Supplied: Tablets ALDOMET are yellow, film-coated, biconves shaped tablets, supplied as follows: Cs 8737 - each tablet containing 125mg of methyldopa, marked MSD 135 on one side, supplied in bottles of 100 and 500. Ca 3290 - each tablet containing 250mg of methyldopa, marked MSD 401 on one side, supplied in bottles of 50 and 500. Ca 8733 - each tablet containing 500 mg of methyldopa, marked MSD 518 on one side, supplied in bonles of 50 and 250. Also available: Cs 3293 Injection ALDOMET Ester hydrochloride, a clear colourless solution containing 250 mg methyldopate hydrochloride per 5 ml, supplied in 5 ml ampoules. (MC.94g)

MERCK SHARP

PM

I & DOHME CANADA LlMlTED/LlMtT.E

A Leader In Cardiovascular Medicine

Carbohydrates and brain metabolism To the editor: Dr. Muilner's letter (Can Med Assoc 1 111: 752, 1974) reveals an ignorance about carbohydrates that is unexpected and unexplained. He equates whole-grain cereals and starchy vegetables with sucrose, which is exactly what I am decrying. Highly refined carbohydrate is the bane of man's existence. This includes flour, starch and sugar and the things made from them. Unrefined grains, vegetables and fruits are not so quickly absorbed from the gut because they must first be broken down into a form that the body can use. The teachings of doctors and home economists tend to disregard this very significant fact. Persons dealing with allergy know that the more rapidly food is absorbed, the more quickly the individual becomes sensitized and reacts to subsequent exposures. One of the prime rules of food sensitization is that any food, if eaten frequently and in large amounts, will eventually act as an allergen. This is why corn, wheat, milk, coffee, potatoes, citrus fruits, etc. are the most common offenders. It is also why so many of us as we grow older lose our ability to compensate. Our innate ability to tolerate repeated insults is finally exhausted and we react to that food. The symptoms are those of withdrawal, as in addiction - first the "high", then the depression, fatigue, malaise, lack of concentration, etc. The symptoms are relieved, often for many years, by eating that food, but time runs out sooner or later, depending to a large extent on our intake of coffee, sugar, cigarettes and liquor, all of which overtax the body in one way or another. The intake of sugar in Canada has now reached 50 kg per person per year. It was only 100 years ago that 5 kg was the intake. Our metabolic processes have not kept up with the increased intake. If we had to chew 1 kg of sugar-beet to obtain 100 g of sugar the rate of food sensitivity would be very low indeed. Recent figures suggest that nearly 80% of the population is or will be sensitized to some degree. Our intake of refined carbohydrate is the main culprit. Dr. Mullner quotes some interesting observations that are still just hypotheses. I am not discussing brain metabolism but the ability of specific foods to produce symptoms attributable to the brain. These cover the full spectrum of psychiatric symptomatology, from minor fears and fatigue to phobias and hallucinations. I am not saying how they are produced but that they do occur. My observations are based on what the patient tells me is happening to him.

Has Dr. Muilner ever asked a patient if his face changes shape when he looks in the mirror, or if words or the ground move? If he has, has he given a few grams of niacinamide intravenously to relieve these symptoms? I can usually control most patients with severe delirium tremens in 24 hours using only vitamins B3, C, B1 to B6 and B12. I use chlorpromazine if they are unmanageable. I venture to suggest that symptoms of subclinical pellagra, a central nervous system allergic reaction, are present in those parts of the world where highly refined carbohydrates are used as staples in the diet. If one does not recognize the difference between a handful of wheat and a handful of white flour then all arguments are useless. R. GLa1.r GREEN, MD, CM

301 Medical Bldg. Prince Albert, Sask.

Verbum sapientibus To the editor: Mea culpa aussi (Can Med Assoc 1 111: 1054, 1974). I have heard from several Latin scholars and, paraphrasing Helaire Belloc, I would like to say, though my sins are as scarlet my pieces are read. At least you did not have to publish Dr. F. A. Perera's letter to expose me in public and, since you have frequently corrected my errors at the manuscript stage, verbum sapiendibus should not have escaped your scrutiny. My only comfort is that you have not yet published an Erratum notice. I'll admit that it is more than 50 years since I passed my Grade XIII Latin with flying colours, and cerebral arteriosclerosis is taking its toll. My recent experience suggests that the classics are taught better in the United Kingdom, since I have received no protest from a native-born Latinist. Sapientibus it is. With hindsight I should have abbreviated it to verb, sap., thus avoiding the complications of the (pro)vocative case. Modern languages are not alone the victims of mutilation. A. D. KELLY, MB

5 Edmund Gate Toronto, Ont.

Increased risk of breast cancer To the editor: It now seems to be well established that medicine must accept responsibility for another iatrogenic disease. Cancer of the breast occurs more frequently in women who had the misfortune to develop pulmonary tuberculosis in the preantibiotic years and who were treated by artificial pneumothorax. Fluoroscopic examinations were usually made before or after air "refills", and these were required every

CMA JOURNAL/JANUARY 25, 1975/VOL. 112 141

Letter: Carbohydrate and brain metabolism.

ALDOMET* (methyldopa MSD Std) Indications: Sustained moderate through severe hypertension. Dosage Summary: Start usually with 250 mg two or three tim...
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