Prescription Practice: Progress in Medicine

PRESCRIPTION PRACTICE

• PROGRESS In MEDICINE Chlorpromazine in Treatment of Porphyria Chlorpromazine, administered in dosage of 25 mg. three or four times daily, was followed promptly by disappearance of pain and nervous symptoms in nine cases of intermittent acute porphyria. It did not cure established paralysis. In three patients a single 100-mg. dose was first followed by complete clinical remission, but according to the report by Drs. J. C. Melby, J. P. Street, and C. J. Watson, J. Am. Med. Assoc., 162, 174(Sept. 15, 1956), the improvement was not correlated with any significant changes in excretion of porphyrin or porphobilinogen. Food Sterilization by Irradiation There is a basic difference between heat sterilization and sterilization by irradiation of food products. The first method requires high temperatures to kill the putrefactive organisms, while other toxin-producing organisms are killed immediately at moderately hot temperatures. All putrefactive and toxin-producing organisms are also killed by radiation sterilization. For an unknown reason, however, radiation does not kill the toxin producers immediately, but causes them to experience lingering death. According to L. L. Kempe, University of Michigan bacteriologist, the big question confronting safe sterilization by radiation is this: Does the lingering process that the toxin producing organisms probably go through leave behind a lethal toxin? Pasteurization by radiation has possibilities also but here, as with sterilization, there are unanswered questions. "In pasteurization, radiation selects certain organisms, kills them, and leaves the rest. We need to evaluate the effect of the remaining organisms-what they do to people, and what happens to them in storage." Gitalin in Geriatric Cardiac Cases Successful treatment of congestive heart failure in 77 patients with an average age of 78.4 years, by use of gitalin (Gitaligin), is reported by Drs. R. Harris and R. R. Del Giacco, Am. Heart J., 52, 300(Aug. 1956) . The initial gitalinizing dose in 155 trials ranged from 2.5 to 22.5 mg., averaging 7.0 mg. The daily maintenance dose was 0.5 to 2.5 mg. averaging 0.92 mg. Gitalin was generally well tolerated. Fifteen of 17 patients refractory to other glycosides were adequately controlled with gitalin. Nausea, anorexia, and occasional ventricular premature contractions were the 114

earliest indications of toxicity. No serious toxic effects were noted. No paroxysmal arrhythmias developed in this series despite doses intentionally calculated to produce toxicity. Gitalin is considered a very useful cardiac glycoside for the treatment of congestive heart failure in elderly patients because of its wide therapeutic range and efficacy. Glyceryl Triacetate as a Fungicide Glyceryl triacetate (triacetin) was found to possess fungicidal and/ or fungistatic action, according to a report by Drs. S. A. M. Johnson and J. L. Tuura, A.M.A. Arch. Dermatol., 74, 73(July 1956). The drug in different strengths was incorporated in an ointment base of Carbowax 4000 and PEG 400, and in a lotion vehicle of 50% isopropyl alcohol. In the treatment of 80 patients with various types of fungus and yeast infections, glyceryl triacetate ointment 25% was more efficacious than the 5% ointment and equal to the 50% ointment. Addition of 5% benzoic acid did not seem to enhance the action. No untoward reactions were observed. Infections due to Trichophyton mentagrophytes,

Microsporum lanosum, Epidermophyton /foccosum, M. furfur and Nocardia tenuis responded well to treatment. T. purpureum infections in several instances, except for nails, cleared after four months of therapy. Superficial infections of Candida albicans and cutaneous infections of Blastomycosis dermatitidis did not respond to glyceryl triacetate application. Nine cures in 19 cases of Microsporum audouini infection of the scalp were noted. The other 13 cases showed improvement and no spread of infection. Japanese B Encephalitis Virus Japanese B encephalitis is a disease in which there is inflammation of the brain. It is related to sleeping sickness and polio. The virus causing the disease has been isolated from the tissue of an American soldier just returned from Pusan, Korea, where earlier outbreaks of t he disease had occurred among American servicemen. The patient died four days after admission to the U.S. Army Hospital, Fort Lawton, ·Wash. The report of the case by H. E. Shuey and T. O. Berge, J. Am. Med. Assoc., 162, 564(Oct. 6, 1956) repeats earlier warnings about the possibility of introducing the virus into the U.S. where conditions could allow its spread.

JO URNAL OF THE AMERICAN PHARM ACEUTICAL ASSOCIATION

6-Methyl-delta-1-hydrocortisone (Medrol)-Clinical Trials as Antiarthritic Synthesized by a combination of chemical steps and microbiological oxygenation, 6-methyl-delta-1-hydrocortisone is now being tried clinically in rheumatoid arthritis, according to E. M . Glenn , who reported on the work of an Upjohn Company team to the December 1956 meeting of the American Rheumatism Association at t he National Institutes of Health. Animal experiments indicate that the new hormone exhibits 12 to 18 times the antiinflammatory action of cortisone and hydrocortisone. It did not cause sodium or water retention. Methyl Phenylpiperidylacetate in Narcolepsy Good results with methyl phenylpiperidylacetate (Ritalin) in the treatment of 36 patients with narcolepsy are reported by Drs. D. D. Daly and R . E. Voss in Proc. Staff Meetings Mayo Clinic, 31 , 620(Nov. 14, 1956). This preliminary report includes data on 25 patients who were adequately followed for 1 to 6 months. Twenty-one (84%) reported "good" to "excellent" relief of their abnormal sleepiness. The majority of the patients took one 20mg. tablet at a time but some required a 40-mg. dose, and the number of doses varied from 2 to 7 per day. It is noted that individualization, with regard to dosage and time of administration, is essential for optimal results. Side effects were frequent but were of a minor nature. The physicians conclude that methyl phenylpiperidylacetate appears at this time to be the drug of choice in the treatment of narcolepsy. 19-Nor Steroids-Effects on the Human Menstrual Cycle Administration to 50 women (22 to 39 years old) of (I) 17 a-ethinyl-19nortestosterone, (II) 17 a-ethinyl-5(10)estraeneolone, and (III) 17a-ethyl-19nortestosterone (Nilevar), in oral dosages of 5 to 50 mg. per day during days 5 through 25 of the menstrual cycle, gave results which indicate that the three compounds are effective ovulation-inhibitors in women. In dosages of 10 mg. per day and higher, compounds I and II, by their intrinsic action on the endometrium and/ or by their only partial suppression of ovarian secretion, can maintain the endometrium in such a state that a catamenia-like withdrawal bleeding occurs after cessation of therapy. Compound III at dosages

up to 50 mg. per day fails to exhibit such support in half the cases studied. None of the 50 women became pregnant during the months of medication. Within 5 months after the last treated cycle, 7 patients conceived, and 5 of these had been inexplicably barren for periods of 3 to 6 years. It appears that, in these 7 cases at least, the steroids did not damage the ovaries and might have been helpful in the relief of sterility. The studies are reported by J. Rock, G. Pincus, and C. R. Garcia, Science, 124, 891(Nov. 1956).

tion, especially in combination with atropine, in patients with cancer without addiction to narcotics. Even with prolonged dosage of 6 to 20 mg. to cancer patients addicted to other narcotics, idiosyncrasy was not noted in any age group. The addictive properties of N umorphan were not less than those of morphine or Dilaudid (dihydromorphinone).

tute Clinic of Surgery. The hearts of twenty of these dogs were treated with a series of novocain injections at the top of the left auricle under the heart's "skinlike" epicardium. Ventricular fibrillation did not develop in a single dog so treated, but 18 (90%) of the untreated dogs fibrillated. To date, more than 40 human patients at the National Heart Institute have undergone "ice bath" heart operations protected by novocain injections. HEW's release of October 23, 1956, cites the work of Dr. L. R. Radigan of the Heart Institute and Dr. A. Riberi of Indiana University.

Prednisolone and Hydrocortisone Ointments-Effectiveness In an attempt to determine the comparative effectiveness of prednisolone and hydrocortisone in dermatological therapy, 40 patients with various skin diseases were treated with 0.5% and 0.25% prednisolone ointment and a control ointment containing 1% hydrocortisone. The base was petrolatum in all preparations. Prednisolone ointment was less effective than hydrocortisone ointment in 23, equally effective in 13, and more effective in 4 cases. The method of simultaneous symmetrical paired comparison was used in the report by Dr. C. C. Smith, A.M.A. Arch. Derma/ol. 74, 414(Oct. 1956).

Novobiocin-Clinical Observations Clinical use of novobiocin by Dr. W. J. Martin, et al., Proc. Staff Meetings Mayo Clinic, 31, 416(July 11, 1956), indicates that oral dosage of 500 mg. every 6 hours is usually effective for infections of moderate severity caused by sensitive organisms, particularly Micrococcus pyogenes var. aureus that is resistant to other antibiotics. Dosage of 250 mg. every 6 to 8 hours is sufficient for minor infections, and, for very young children and infants, 100 mg. in capsule or syrup every 6 to 8 hours. Parenteral administration of novobiocin appeared to produce adequate concentrations in the serum. It does not appear likely that use of novobiocin will be complicated by micrococcal enterocolitis, because of its inability to eradicate Esch. coli, A. aerogenes, and Pseudomonas aeruginosa from the gastro'ntestinal tract. The report notes that 5 of the 34 cases treated with oral novobiocin developed allergic dermatitis, which the physicians believe may militate against its indiscriminate use.

Numorphan-Analgesic Properties A new synthetic narcotic 14-hydroxydihydromorphinone·HCI (Numorphan, Endo) was tested for analgesic activity on 200 patients with promising results, according to Drs. A. Coblentz and H. R. Bierman, New Engl. J. Med. 255 , 694(Oct. 11, 1956). Numorphan was promptly effective in doses of 1 to 5 mg. in patients with neoplastic diseases. It was an efficient preoperative medica-

Communicable Disease Summary

T

HE numbers of cases of the communicable diseases shown in the table below are based on reports by State Health Officers to the National Office of Vital Statistics of the Department of Health, Education, and Welfare, Washington, D.C. The numbers of cases of each disease occurring during each

Cases of Communicable Diseases

Novocain in "Cold" Heart Surgery In heart surgery with hypothermia (refrigeration) the anesthetized patien t is placed in an ice bath until his body temperature falls 20 degrees below normal and a state somewhat comparable to hibernation is reached. In the chill of hypothermia the normally urgent demands of body tissues for blood-borne oxygen are drastically reduced and the surgeon is provided with a period of 8 to 10 minutes in which he can interrupt the work of the heart and make repairs. At these unnaturally low body temperatures, however. the heart often loses its normal coordinated pattern of nerve impulses and muscle contractions. The individual heart muscle fihers may take up independent action. causing ventricular fibrillation, and the heart fail to provide effective pumping action. The effectiveness of the novocain technique in ice hath operations was demonstrated on the hearts of forty dogs at the Public Health Service's National Heart Insti-

of the last 4 weeks are reported and also for the corresponding weeks of one year ago. The second column headed "52 weeks 1956" gives the totals of the diseases for t he entire preceding year. In the table this month this second column replaces the usual weekly comparison for that date.

Commu nica ble Disease

~-------Cases

R eported for W eek

Ending---------~

Jan. 5 Jan. 7 Jan. 12 Jan. 14 Jan. 19 Jan. 21 1956 1956 1956 1957 1957 1956 1957 1 37 la 2 12

Dec. 29 52 wks.

1956 Anthrax Botulism Brucellosis (undulant fever) Diphtheria Encephalitis, infectious Hepatitis, infectious and serum Malaria Measles Meningococcal infections Meningitis, other Poliomyelitis Paralytic Nonparalytic Unspecified Psittacosis Rabies in man Typhoid fever Typhus fever, endemic

16 33

1,100 1,581

17 20

15 41

11 2.5

16 57

9 24

35

22

2,193

19

20

19

17

17

19

395

19,278 234 613,906

316 384 1 5 6,650 4,464

401 2 10,475

472 5 7,247

365 1 9,166

522 1 7,082

5~

84 23 117 62 37 18 5 3 27

4,510

41 32 29 17 7 5 2

59 22 120 66 35 19 2

23 47 26 13 8 3

87 22 114 67 24 23 2

53 29 56 32

12

2,696 1,624 15,400 6,708 5,878 2,814 508 9 1,759

19

20

20

23

15

2

105

1

43 26 102 58 30 14 5

6

8

16 3

11

3

a Reported in Massachusetts.

VOL. 18, NO .2, FEBRUARY, 1957/ PRACTICAL PHARMA CY EDITIO N

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