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IMMUNOGLOBULIN TO PREVENT HEPATITIS B
1086 its role. Descriptions of such developments can be read in the American Journal of Hospital Pharmacy and in Drug Intelligence and Clinical Pharmacy. Book reviews should be written on the basis of literary content rather than the author’s profession: it is the patient who would suffer most from any alienation of medicine and pharmacy.
von Muhlendahl and colleagues (Jan. 26, p. 209) refer four cases of "paralytic ileus" but in neither of the original reports is there any evidence of ileus. What was described was, apparently, constipation: where reported, bowel sounds were present and the removal of impacted faeces or the use of enemas resolved all four cases. Had any of these been cases of paralytic ileus, which is doubtful, then hypokalaemia from acute diarrhoea would have been a more likely explanation than loperamide. The doses used were a single normal dose of 0.045 mg/kg, an overdose (3-fbld in their original paper, appearing as 17 t-fold in their letter), or a dose of unspecified frequency and duration. How could a single normal dose of any anti-diarrhoeal drug transform acute gastroenteritis with diarrhoea into constipation with impacted faeces? With overdosage, constipation is to be expected, and the manufacturer’s" literature warns about this. But constipation is not paralytic ileus. On the question of safety in general, loperamide, unlike other opioid anti-diarrhoeal agents, does not reach the brain, unless the blood brain barrier is defective or immature. The appropriateness of loperamide in children with severe or life-threatening secretory diarrhoea is supported by evidence of its ability to inhibit induced small bowel secretion and salt loss.I.2 In chronic diarrhoea after bowel resection and in "toddler diarrhoea", the drug in suitable doses can restore normal frequency of bowel action. As Dr Sandhu and colleagues pointed out (March 1, p. 483), the efficacy and safety of loperamide in acute infective diarrhoea has not been proved; however, clinical trials are in hand.
expand
Dr
to
Janssen Pharmaceutical Ltd, Marlow, Bucks SL7 1ET
School of Pharmacy, Pharmacy, Southern California, University of Southern Los Angeles, California, U.S.A.
IMMUNOGLOBULIN TO PREVENT HEPATITIS B
JOHN HEAP ALEXANDER MACNAIR
DRUG EMERGENCIES AND THE PHARMACIST open your review of D’Arcy and Griffin’s Druginduced Emergencies (April 19, p. 853) by insinuating that a
SIR,-You
of pharmacy would have no credentials for writing book on emergencies caused by drugs. A physician’s qualifications for writing on pharmacology are seldom questioned, so why question a pharmacist’s ability to write on emergency medicine? Your view may have been based on medical pharmacy practices in Britain: however, The Lancet is an international journal. In the United States almost all pharmacy programmes are now clinically oriented (especially the PHARM.D. programmes). Our curriculum heavily stresses subjects of clinical importance
professor a
(pathology, histology, microbiology, physiology, pharmacokinetics, clinical therapeutics, and
so on) to prepare students take an active role in treating, monitoring, and educating the patient. The last year is totally devoted to the variety clinical hospital rotations (e.g., psychiatry, internal medicine, cardiology, antimicrobial therapy) that a student might be expected to complete. After graduation many take up residency posts. Outside the university, clinical pharmacists have increased their role to many areas, such as skilled nursing facilities, group family practices, total parenteral nutrition programmes, drug information services, clinical pharmacokinetic services, primary ambulatory care, nuclear medicine, poison prevention and treatment3-and emergency medicine.45 The profession of pharmacy is about to create specialties which would further
to
1. Sandhu B, Tripp JH, Candy DCA, Harries JT. Loperamide inhibits cholera toxin-induced small intestine secretion. Lancet 1979; ii: 689-90. 2. Tytgat GN, Huibregtse K. Loperamide and ileostomy output: Placebo-controlled double-blind crossover study. Br Med J 1975; ii: 667. 3. Roberts RW, Russell WL. A pharmacist-based toxicology service. Drug Intell Clin Pharm 1978; 12: 665-70. 4. Elenbaas, RM, Waeckerle, JF, McNabney WK. The clinical pharmacist in emergency medicine. Am J Hosp Pharm 1977; 34: 843-46. 5. Edwards GA, Samuels TM. The role of the hospital pharmacist in emergency situations. Am J Hosp Pharm 1968; 25: 128-33.
PEL TER MITCHELL PELTER McGHAN WILLIAM MCGHAN
’
SiR,—The confusion that has long reigned over the efficacy of immunoglobulin in preventing hepatitis B after potentially infectious percutaneous or mucous membrane exposures is not clarified by the combined M.R.C./P.H.L.S. report (Jan. 5, p. 6). The report states that two U.S. studies’were comparable, both randomly giving "normal immunoglobulin" and immunoglobulin with high titres of anti-HBs. The report then correctly states that one study demonstrated a difference between the efficacy of the two immunoglobulins and the other did not. In fact the two studies are not comparable. The normal immunoglobulin given in the study by Seeff et al. contained no detectable anti-HBs and could, therefore, be considered a placebo. That study demonstrated a significant difference in the subsequent manifestation of clinical hepatitis B in the two groups (1.4% in the high titre recipients versus 5.9% in the placebo globulin recipients). Grady et al .2 compared globulins with low, intermediate, and high titres of anti-HBs and, therefore, could only evaluate relative efficacy between globulins with varying levels of anti-HBs. They concluded that there was no difference in hepatitis B incidence between any of the groups. The only difference, as stated in the combined report, was a prolongation of incubation period of those in the very high titre globulin group. Taken together the two U.S. studies (which are the only two large post-exposure studies in hospital personnel which have been undertaken) lead to two conclusions: (1) that post-exposure immunoprophylaxis in this setting appears to be moderately efficacious and (2) that there seems to be no difference in efficacy for low, intermediate, or high titre immunoglobulin
preparations. What role then does the expensive hepatitis B immune have in this setting? The National Advisory Committee on Immunisation in Canada has recently recommended that either normal human immunoglobulin or hyperimmune globulin could be used for post-exposure prophylaxis.’ The current recommendations in the United States favour HBIG over ISG in post-exposure settings.4 This recommendation was based mainly upon a study by Krugman et al.5 in which globulin with high anti-HBs titre was shown to be superior to lower titre preparations when given soon after experimental human infection. The applicability of this latter study to prophylaxis in the general population is now being re-evaluated.
globulin
Hepatitis Laboratories Division, Bureau of Epidemiology, Center for Disease Control, Phoenix, Arizona 85014, U.S.A.
DONALD P. FRANCIS JAMES E. MAYNARD
1. Seeff LB, Wright EC, Zimmerman HJ, et al. Type B hepatitis after needlestick exposure: Prevention with hepatitis B immune globulin: Final report of the Veterans Administration Cooperative Study. Ann Intern Med 1978; 88: 285-93. 2. Grady GF, Lee VA, Prince AM, et al. Hepatitis B immune globulin for accidental exposures among medical personnel: Final report of a multicenter controlled trial. J Infect Dis 1978; 138: 625-38. 3. Canada Dis Wkly Rep 1980; 6 (4): 13-14. 4. Recommendations of the Public Health Service Advisory Committee on Immunization Practices. Immune globulins for protection against viral hepatitis. December, 1977. 5. Krugman S, Giles JP, Hammond J. Viral hepatitis type B (MS-2 strain) prevention with specific hepatitis immune globulin. JAMA 1971; 218: 1665-70.
von Muhlendahl and colleagues (Jan. 26, p. 209) refer four cases of "paralytic ileus" but in neither of the original reports is there any evidence of ileus. What was described was, apparently, constipation: where reported, bowel sounds were present and the removal of impacted faeces or the use of enemas resolved all four cases. Had any of these been cases of paralytic ileus, which is doubtful, then hypokalaemia from acute diarrhoea would have been a more likely explanation than loperamide. The doses used were a single normal dose of 0.045 mg/kg, an overdose (3-fbld in their original paper, appearing as 17 t-fold in their letter), or a dose of unspecified frequency and duration. How could a single normal dose of any anti-diarrhoeal drug transform acute gastroenteritis with diarrhoea into constipation with impacted faeces? With overdosage, constipation is to be expected, and the manufacturer’s" literature warns about this. But constipation is not paralytic ileus. On the question of safety in general, loperamide, unlike other opioid anti-diarrhoeal agents, does not reach the brain, unless the blood brain barrier is defective or immature. The appropriateness of loperamide in children with severe or life-threatening secretory diarrhoea is supported by evidence of its ability to inhibit induced small bowel secretion and salt loss.I.2 In chronic diarrhoea after bowel resection and in "toddler diarrhoea", the drug in suitable doses can restore normal frequency of bowel action. As Dr Sandhu and colleagues pointed out (March 1, p. 483), the efficacy and safety of loperamide in acute infective diarrhoea has not been proved; however, clinical trials are in hand.
expand
Dr
to
Janssen Pharmaceutical Ltd, Marlow, Bucks SL7 1ET
School of Pharmacy, Pharmacy, Southern California, University of Southern Los Angeles, California, U.S.A.
IMMUNOGLOBULIN TO PREVENT HEPATITIS B
JOHN HEAP ALEXANDER MACNAIR
DRUG EMERGENCIES AND THE PHARMACIST open your review of D’Arcy and Griffin’s Druginduced Emergencies (April 19, p. 853) by insinuating that a
SIR,-You
of pharmacy would have no credentials for writing book on emergencies caused by drugs. A physician’s qualifications for writing on pharmacology are seldom questioned, so why question a pharmacist’s ability to write on emergency medicine? Your view may have been based on medical pharmacy practices in Britain: however, The Lancet is an international journal. In the United States almost all pharmacy programmes are now clinically oriented (especially the PHARM.D. programmes). Our curriculum heavily stresses subjects of clinical importance
professor a
(pathology, histology, microbiology, physiology, pharmacokinetics, clinical therapeutics, and
so on) to prepare students take an active role in treating, monitoring, and educating the patient. The last year is totally devoted to the variety clinical hospital rotations (e.g., psychiatry, internal medicine, cardiology, antimicrobial therapy) that a student might be expected to complete. After graduation many take up residency posts. Outside the university, clinical pharmacists have increased their role to many areas, such as skilled nursing facilities, group family practices, total parenteral nutrition programmes, drug information services, clinical pharmacokinetic services, primary ambulatory care, nuclear medicine, poison prevention and treatment3-and emergency medicine.45 The profession of pharmacy is about to create specialties which would further
to
1. Sandhu B, Tripp JH, Candy DCA, Harries JT. Loperamide inhibits cholera toxin-induced small intestine secretion. Lancet 1979; ii: 689-90. 2. Tytgat GN, Huibregtse K. Loperamide and ileostomy output: Placebo-controlled double-blind crossover study. Br Med J 1975; ii: 667. 3. Roberts RW, Russell WL. A pharmacist-based toxicology service. Drug Intell Clin Pharm 1978; 12: 665-70. 4. Elenbaas, RM, Waeckerle, JF, McNabney WK. The clinical pharmacist in emergency medicine. Am J Hosp Pharm 1977; 34: 843-46. 5. Edwards GA, Samuels TM. The role of the hospital pharmacist in emergency situations. Am J Hosp Pharm 1968; 25: 128-33.
PEL TER MITCHELL PELTER McGHAN WILLIAM MCGHAN
’
SiR,—The confusion that has long reigned over the efficacy of immunoglobulin in preventing hepatitis B after potentially infectious percutaneous or mucous membrane exposures is not clarified by the combined M.R.C./P.H.L.S. report (Jan. 5, p. 6). The report states that two U.S. studies’were comparable, both randomly giving "normal immunoglobulin" and immunoglobulin with high titres of anti-HBs. The report then correctly states that one study demonstrated a difference between the efficacy of the two immunoglobulins and the other did not. In fact the two studies are not comparable. The normal immunoglobulin given in the study by Seeff et al. contained no detectable anti-HBs and could, therefore, be considered a placebo. That study demonstrated a significant difference in the subsequent manifestation of clinical hepatitis B in the two groups (1.4% in the high titre recipients versus 5.9% in the placebo globulin recipients). Grady et al .2 compared globulins with low, intermediate, and high titres of anti-HBs and, therefore, could only evaluate relative efficacy between globulins with varying levels of anti-HBs. They concluded that there was no difference in hepatitis B incidence between any of the groups. The only difference, as stated in the combined report, was a prolongation of incubation period of those in the very high titre globulin group. Taken together the two U.S. studies (which are the only two large post-exposure studies in hospital personnel which have been undertaken) lead to two conclusions: (1) that post-exposure immunoprophylaxis in this setting appears to be moderately efficacious and (2) that there seems to be no difference in efficacy for low, intermediate, or high titre immunoglobulin
preparations. What role then does the expensive hepatitis B immune have in this setting? The National Advisory Committee on Immunisation in Canada has recently recommended that either normal human immunoglobulin or hyperimmune globulin could be used for post-exposure prophylaxis.’ The current recommendations in the United States favour HBIG over ISG in post-exposure settings.4 This recommendation was based mainly upon a study by Krugman et al.5 in which globulin with high anti-HBs titre was shown to be superior to lower titre preparations when given soon after experimental human infection. The applicability of this latter study to prophylaxis in the general population is now being re-evaluated.
globulin
Hepatitis Laboratories Division, Bureau of Epidemiology, Center for Disease Control, Phoenix, Arizona 85014, U.S.A.
DONALD P. FRANCIS JAMES E. MAYNARD
1. Seeff LB, Wright EC, Zimmerman HJ, et al. Type B hepatitis after needlestick exposure: Prevention with hepatitis B immune globulin: Final report of the Veterans Administration Cooperative Study. Ann Intern Med 1978; 88: 285-93. 2. Grady GF, Lee VA, Prince AM, et al. Hepatitis B immune globulin for accidental exposures among medical personnel: Final report of a multicenter controlled trial. J Infect Dis 1978; 138: 625-38. 3. Canada Dis Wkly Rep 1980; 6 (4): 13-14. 4. Recommendations of the Public Health Service Advisory Committee on Immunization Practices. Immune globulins for protection against viral hepatitis. December, 1977. 5. Krugman S, Giles JP, Hammond J. Viral hepatitis type B (MS-2 strain) prevention with specific hepatitis immune globulin. JAMA 1971; 218: 1665-70.