EPITOMES--GENERAL AND FAMILY PRACTICE (consultation), paramedic guide of triage and ex- Family physicians would be well advised to amination, office billing and aids to diagnosis. think of aspirin as a potential allergen in all Computer services were leased from a commercial asthmatic patients, not only those with the nasal supplier remote from the office at a cost of $1,200 polyp sinusitis triad. It is also pertinent to realize to $1,300 per month. Personnel savings, together that related analgesics, even though they have a with billings for patient histories, patient educa- very different chemical makeup, may produce the tion and paramedic routines, are projected to same asthmatic reaction. cover these costs. To date, cost savings, physician J. BLAIR PACE, MD satisfaction and patient acceptance have been REFERENCES adequately shown. Mathison DA, Stevenson DD, Tan EM, et al: Clinical profiles is needed to more of bronchial asthma. JAMA 224: 1134-1139, May 21, 1973 Although further experience Editorial comment. Br Med J 3:419-420, 1973 fully assess the real value of computers in various family practice settings, the state of the art is becoming more refined and there is promise that computer applications can be developed which Metaproterenol as a will improve the quality, efficiency and effective- ness of patient care in family practice. METAPROTERENOL used throughout Europe and in Australia for the past ten years under the name JOHN P. GEYMAN, MD of is now available in this country REFERENCE under the trade name Alupent®. It would appear Morrison CC, Bostwick GW, Belknap SL, et al: The computer improvement over pre- Med Assoc 64:226-230, Oct 1973 to represent a significant in family practice. J Maine viously available bronchodilator drugs. The action of metaprotherenol resembles that of isoproterenol, which has been widely used in this country. There are two distinctive advantages Analgesics and Asthma with metaproterenol. One of these is a 2- to 3- A SYMPTOM TRIAD of sinusitis, nasal polyps and hour longer effectiveness, and the second is the asthma in response to aspirin sensitivity was first availability and usefulness of metaproterenol as recognized more than 50 years ago. Aspirin and an orally administered . Metaprotere- other analgesics, including indomethacin and nol, like isoproterenol, is a beta adrenergic drug paracetamol, may likewise precipitate an asthma with a greater affinity for the beta 2 receptors. attack in aspirin-sensitive patients. Because of this, it does not produce pronounced This author has observed one aspirin-allergic cardiovascular effects. The usual effect is a slight, patient with asthma who had repeated problems but not clinically significant slowing of the heart because he failed to recognize aspirin or related rate, with a slight drop of the blood pressure. analgesics in various multi-drug mixtures. Each In comparison studies using metaproterenol time a severe attack would occur, we would find and isoproterenol given by inhalation effective- the medication he had taken and discover in the ness was quite comparable, with response to fine print there was acetylsalicylate of some kind. metaproterenol being somewhat slower than re- The patient eventually died of agranulocytosis as sponse to isoproterenol. After 30 days of use, a result of getting aspirin in a mixture which was metaproterenol retained effectiveness up to four not clearly labelled. hours whereas isoproterenol retained effective- The group at Scripps Clinic and Research ness only up to one hour. After 60 days of use as Foundation in La Jolla observed an 8 percent an inhalant, metaproterenol retained effectiveness incidence of allergy to aspirin in patients referred up to three hours with isoproterenol primarily to them. Many of the patients in this 8 percent effective only in the first five minutes. group did not have the classic triad of nasal Compared with given orally, meta- polyps and sinusitis. In this sense these persons proterenol given orally in 20 mg doses appears to were aspirin-sensitive but unrecognized as such. have a four-hour span of effectiveness without de- The group at Scripps suggest cautious aspirin velopment of resistance. Ephedrine tends to be challenge under close supervision. The British ex- effective no more than three days if used continu- press some misgivings about aspirin challenge, re- ously, after which the epinephrine stores are ex- porting that this has been known to prove fatal. hausted in the lung tissues and the ephredine

302 OCTOBER 1975 * 123 * 4 EPITOMES-GENERAL AND FAMILY PRACTICE becomes inactive. As a new drug in this country, pressed as a ratio with T4 similarly determined we have the security of knowing that metapro- in normal serum. terenol has stood the test of time in the rest of The ETR should not be confused with the FTI the world. (free-thyroxine index). The FTI is also an accu- J. BLAIR PACE, MD rate measurement of thyroid function and is calculated for each patient, T3 X T4 X 100. The REFERENCES Kerr A, Gebbie T: Comparison of orciprenaline, ephedrine, ETR is a competitive protein-binding assay and and methoxyphenamine as oral . N Engl J Med 492:320-322, May 1973 correlates well with the FTI and could replace the Hurst A: Metaproterenol, a potent and safe bronchodilator. more complicated FTI procedure in patients with Ann Allergy 31: 460-466, Oct 1973 known abnormalities of binding proteins and suspected thyroid disease. Several studies now show that the ETR iS the best single and practical test of thyroid function. Effective Thyroxine Ratio (ETR) The results, however, (normal range: 0.86 to THE MOST ACCURATE measurement of thyroid 1.13) should be carefully interpreted: In hypo- function can be obtained by measuring the thyroidism the decreased level may not correlate amount of free, unbound thyroxine (T), but an well with the degree of hypofunction. For in- inexpensive assay has not been perfected for stance, a 0.84 may represent a rather severe routine use. There is a precise correlation between hypothyroidism with myxedema. The other area serum T4 concentration and thyroid status, pro- of misinterpretation is in patients who have re- viding the concentration of serum thyroxine-bind- ceived 1311 or antithyroid drugs and are euthyroid. ing globulin (TBG) is normal. These patients tend to have low ETR scores. Changes in the concentration of serum TBG are WILFRED SNODGRASS, MD often associated with parallel changes in serum T4 REFERENCES concentration even though the thyroid function is Powers JS, Roach C, Berdon T, et al: The effective thyroxine ratio as a test of thyroid function. Obstet Gynecol 44:806-810, normal. Therefore a euthyroid woman in whom Dec 1974 there is an concentration of TBG due to Thorson SC, Mincey EK, McIntosh HW, et al: Evaluation of increased a new in-vitro blood test for determining thyroid status: the pregnancy or estogen ingestion often shows a T4 effective thyroxine ratio. Br Med J 2:67-71, Apr 8, 1972 concentration above normal. The effective-thy- roxine ratio (ETR) reflects serum T4 levels and automatically compensates to a large extent for variations in TBG. Combination Therapy of If TBG concentration showed no variation in Parkinson's Disease the normal population, then the value for the ETR BY COMBINING a decarboxylase inhibitor with would be determined entirely by the level of T4. L-dopa at a fixed ratio of one part inhibitor called For this reason there is a very high linear corre- carbidopa to ten parts of levodopa or L-dopa, lation between ETR and T4 when patients with three definite advantages have been achieved over TBG abnormalities are excluded. the use of the single drug levodopa. First, the Although estrogens and progestins are the combination causes less nausea and vomiting. most frequent causes of increased T4 serum Second, the combination brings about therapeutic concentration, sulfamethoxazole, chloramidinone, results more quickly. Third, additional improve- clofibrate, and residual radio- ment occurs in patients who have reached the activity also cause an increase. Decreases in maximum improvement or the maximum toler- T4 can be caused by at least 30 different drugs ance of the single drug. by either decreasing T4 synthesis, by increasing Major central nervous system side effects- T4 destruction, by decreasing the amount of TBG such as involuntary movements and mania and or by displacing T4 from binding sites. other psychiatric disturbances-occur as fre- Anything that increases TBG will increase the quently with the combination as they do with the measurable T4 or protein bound iodine, but will single drug. reduce the triiodothyronine (T3) proportionately. The effective dosage range with the combina- The ETR measures only that concentration of tion drug is very broad and varies from a low of T4 that determines thyroid function, and is ex- 30 mg carbidopa, plus 300 mg levodopa, to a

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