LETTERSTOTHE EDITORS
Br. J. clin. Pharmac. (1978), 6 V.K. KULSHRESTHA, M. THOMAS, JANE WADSWORTH & A. RICHENS Department of Clinical Pharmacology, St Bartholomew's Hospital, London, ECIA 7BE Received May 8, 1978 References
AMBRE, J.J. & FISCHER, LJ. (1973). Effect of coadministration of aluminium and magnesium hydroxide on absorption of anticoagulants in man. Clin. Pharmac. Ther., 14, 231-237. BOCHNER, F., HOOPER, W.D., TYRER, J.H. & EADIE, M.J.
(1972). Factors involved in an outbreak of phenytoin intoxication. J. Neurol. Scand., 16,481-487. BROWN, O.D. & JUHL, R.P. (1976). Decreased bioavailability of digoxin due to antacids and kaolin-pectin. New Eng. J. Med., 295, 1034-1037. CASPARY, W.F. (1972). Inhibition of intestinal calcium transport by diphenylhydantoin in rat duodenum. Naunym. Schmiedebergs Arch. exp. Path. Pharnak., 274, 146-153. FANN, W.E., DAVIES, J.M., JANOWSKI, D.S., SEKERKE,
HJ. & SCHMIDT, D. (1973). Chlorpromazine: effects of antacids on its gastrointestinal absorption. J. clin. Pharinac., 13, 388-390.
179
GLAZKO, AJ. & CHANG, T. (1972). Diphenylhydantoin: absorption, distribution and excretion. In Antiepileptic Drugs. Ed Woodbury, D.M., Penry, J.K. & Schmidt, R.P. pp. 127-136. New York: Raven Press. GREENBLATT, DJ., SHADER, R.I., HARMATZ, J.S.,
FRANKE, K. & KOCH-WESER, J. (1976). Influences of magnesium and aluminium hydroxide mixture on chlordiazepoxide absorption. Clin. Pharmac. Ther., 19, 234-239. HOUGHTON, G.W. & RICHENS, A. (1974). Inhibition of phenytoin metabolism by sulthiame in epileptic patients. Br. J. clin. Phannac., 1, 59-66. KUNIN, C.M. & FINLAND, M. (1961). Clinical pharmacology of the tetracycline antibiotics. Clin. Pharmac. Ther., 2, 51. KUTT, H. (1975). Interactions of antiepileptic drugs. Epilepsia (N.Y.), 16,393-402. REES, H. van & ROACH, E.L. (1973). The intestinal absorption of diphenylhydantoin from a suspension in rats. Arch. int. Pharmacodyn. Ther., 206, 76-83. RICHENS, A. (1977). Interactions with antiepileptic drugs. Drugs, 13,266-275. RICHENS, A. & DUNLOP, A. (1975). Serum phenytoin levels in the management of epilepsy. Lancet, Hi, 247-248. WAISBREN, B.A. & HUECKEL, J.S. (1950). Reduced absorption of aureomycin caused by aluminium hydroxide gel. Proc. Soc. exp. Biol. Med., 73, 73-74.
CLINICAL PHARMACOLOGY AND COMMUNICATION ON NEW DRUGS The study of the action of drugs on experimental animals or on the healthy volunteer human subject is 'pure' pharmacology. Though such studies may have implicit clinical applications they are not part of clinical pharmacology. Nontheless because of the probable clinical implications it is highly appropriate that they should be reported in a journal of clinical pharmacology. The main aim of clinical pharmacology however is the application of pharmacological knowledge to the treatment of the sick patient. Or to reduce the matter to the approach of the clinician in charge of the patient, the aim of the clinical pharmacologist ought to be to ensure that all the patients for whom he has any responsibility receive those drugs in appropriate dosage which will most rapidly lead to a reversal of the disease process and the most rapid possible recovery. The clinical pharmacologist however frequently does not have direct access to many patients, for the majority of drug treatment in a hospital or in general practice is carried through by others. The clinical pharmacologist's responsibility is then to ensure that other doctors have the necessary information which enables them to pick out the drug appropriate to the patient's condition and to give it in the proper dosage for the appropriate period. There is however one school of thought within the country which starts from
the premise that the vast majority of doctors do not possess adequate knowledge of clinical pharmacology and are therefore liable if not likely to prescribe inappropriate drugs in an inappropriate dosage. It is also tacitly assumed that drugs are being prescribed which are necessarily more expensive and that money is thus being wasted. There is also a suggestion that one reason why drugs are inappropriately used is that their virtues are all too often sung of loudly by representatives from commercial firms whose aim is of course primarily to sell the drugs and make profits for their employers. This argument has political overtones and many doctors will want to keep out of such a field. There is in fact plenty of evidence that more and more expensive drugs are being prescribed for patients but what is not available is evidence that expensive drugs are being inappropriately prescribed. Some come into use as a result of fashions in medicine. For example, ten years ago barbiturates were almost universally prescribed in hospital for night sedation for the patient who was unable to sleep simply because of his unfamiliar surroundings. Then there arose a cry that barbiturates were habit-forming, though this had been known for years. What was new was a realization that a very small minority of the population did themselves great harm by injecting themselves intravenously with barbiturate preparations not intended
180
LETTERSTO THE EDITORS
for such use. We were therefore told that the benzdiazepines should be substituted, a procedure which almost overnight doubled the cost of night sedation in hospital. And incidentally this storm also swept away in its track methaqualone and its proprietary version Mandrax which again was relatively cheap, but which was never shown to be seriously habit forming and left the patient clear and bright next morning. Of course the disappearance of these profound hypnotics from the market removed a weapon from the hands of the potential suicide who today is much more likely to take an overdose of antidepressant or indeed aspirin which in sufficient dose is perhaps more lethal than any of the drugs so far mentioned. Yet no measures for its control are suggested. The use of metoclopramide as an anti-emetic on the other hand is an example of a situation which has probably been the result of over-zealous promotion, where an expensive remedy has been put in the place of chlorpromazine or a similar drug which would be equally effective. Furthermore, phenothiazine drugs are effective in a wider range of situations, including some where metoclopromide is useless. It is true that chlorpromazine and like drugs occasionally cause jaundice, but the supposed freedom from side effects which is claimed for metoclopramide has in fact not been borne out by a wider clinical experience of the drug, for extrapyramidal responses are now proving to be common. In relation to new drugs in general the clinical pharmacologist has a special role to play as an intermediary between drug firms and the general prescribing medical population. Drug firms in fact use the British Journal of Clinical Pharmacology just in such a way, giving in its special numbers detailed information about new drugs to the profession. The
Br. J. clin. Pharrnac. (1978), 6
impact of the spoken word is however always greater than that of the written. It would therefore seem that it would be to the advantage of drug firms to bring together all the clinical pharmacologists who work in a field in which a new drug has been developed. (If there are no clinical pharmacologists as such then perhaps those medical practitioners with an interest in matters pharmacological would be interested.) To them thus assembled can be presented the facts about a new drug. If the material is well presented and the drug represents a genuine advance each will go out from the meeting convinced of the value of the new agent and determined to ensure that it will be given to as many patients as are likely to benefit from it with the minimum of delay. Thus the problem which besets the practice of medicine in this country would be solved, for it would no longer be necessary for drug firms to send representatives round to visit medical practitioners and present to them a one-sided view of the value of a new drug. By the same token it would not be necessary for the Department of Health and Social Security to cut back on the amount of money which it is prepared to recognize for tax purposes as appropriate to the promotion of new drugs. It is easy to see how too rigid an enforcement of minimal expenditure on publicity achieved by representatives could in the end result in patients being deprived of a new agent which would cure them simply because of inadequate facilities for spreading the knowledge of its action. A.R. HUNTER Department of Anaesthetics, The Royal Infirmary, Manchester M13 9WL Received April 25, 1978
THE ROLE OF THE CLINICAL PHARMACOLOGIST IN DISTRICT GENERAL HOSPITALS-A PHARMACEUTICAL VIEW We were interested to read the case made recently (British Journal of Clinical Pharmacology, 1978) for an extension of clinical pharmacology appointments to District General Hospitals. Underlying this proposal is the suggestion that the present state is unsatisfactory and needs to be improved. It would, indeed, be a myopic or partisan observer who could see no scope for improvement in the medical care of patients generally and in the quality of prescribing specifically. Is it now seriously suggested, however, that the quality of care will be improved by the addition of yet another specialist? The consultant physician, who usually has a specialized knowledge of the particular branch of medicine concerned, is already supported by laboratory services in respect of
medical microbiology and chemical pathology and is provided with information and expertise in regard to medicines by the hospital pharmacist. Careful appraisal is required of the impact made on care by clinical pharmacologists in those hospitals where such appointments have already been made, if their place in every District General Hospital is to be justified. Is there evidence, for example, that Drug and Therapeutics Committees are more effective in rationalizing prescribing where there is a clinical pharmacologist appointment? The solution might simply be a committee with some executive powers whose chairman, be he clinician or pharmacologist, has the respect of his medical colleagues. We suggest that there is little that a consultant clinical pharmacologist
Br. J. clin. Pharmac. (1978), 6 V.K. KULSHRESTHA, M. THOMAS, JANE WADSWORTH & A. RICHENS Department of Clinical Pharmacology, St Bartholomew's Hospital, London, ECIA 7BE Received May 8, 1978 References
AMBRE, J.J. & FISCHER, LJ. (1973). Effect of coadministration of aluminium and magnesium hydroxide on absorption of anticoagulants in man. Clin. Pharmac. Ther., 14, 231-237. BOCHNER, F., HOOPER, W.D., TYRER, J.H. & EADIE, M.J.
(1972). Factors involved in an outbreak of phenytoin intoxication. J. Neurol. Scand., 16,481-487. BROWN, O.D. & JUHL, R.P. (1976). Decreased bioavailability of digoxin due to antacids and kaolin-pectin. New Eng. J. Med., 295, 1034-1037. CASPARY, W.F. (1972). Inhibition of intestinal calcium transport by diphenylhydantoin in rat duodenum. Naunym. Schmiedebergs Arch. exp. Path. Pharnak., 274, 146-153. FANN, W.E., DAVIES, J.M., JANOWSKI, D.S., SEKERKE,
HJ. & SCHMIDT, D. (1973). Chlorpromazine: effects of antacids on its gastrointestinal absorption. J. clin. Pharinac., 13, 388-390.
179
GLAZKO, AJ. & CHANG, T. (1972). Diphenylhydantoin: absorption, distribution and excretion. In Antiepileptic Drugs. Ed Woodbury, D.M., Penry, J.K. & Schmidt, R.P. pp. 127-136. New York: Raven Press. GREENBLATT, DJ., SHADER, R.I., HARMATZ, J.S.,
FRANKE, K. & KOCH-WESER, J. (1976). Influences of magnesium and aluminium hydroxide mixture on chlordiazepoxide absorption. Clin. Pharmac. Ther., 19, 234-239. HOUGHTON, G.W. & RICHENS, A. (1974). Inhibition of phenytoin metabolism by sulthiame in epileptic patients. Br. J. clin. Phannac., 1, 59-66. KUNIN, C.M. & FINLAND, M. (1961). Clinical pharmacology of the tetracycline antibiotics. Clin. Pharmac. Ther., 2, 51. KUTT, H. (1975). Interactions of antiepileptic drugs. Epilepsia (N.Y.), 16,393-402. REES, H. van & ROACH, E.L. (1973). The intestinal absorption of diphenylhydantoin from a suspension in rats. Arch. int. Pharmacodyn. Ther., 206, 76-83. RICHENS, A. (1977). Interactions with antiepileptic drugs. Drugs, 13,266-275. RICHENS, A. & DUNLOP, A. (1975). Serum phenytoin levels in the management of epilepsy. Lancet, Hi, 247-248. WAISBREN, B.A. & HUECKEL, J.S. (1950). Reduced absorption of aureomycin caused by aluminium hydroxide gel. Proc. Soc. exp. Biol. Med., 73, 73-74.
CLINICAL PHARMACOLOGY AND COMMUNICATION ON NEW DRUGS The study of the action of drugs on experimental animals or on the healthy volunteer human subject is 'pure' pharmacology. Though such studies may have implicit clinical applications they are not part of clinical pharmacology. Nontheless because of the probable clinical implications it is highly appropriate that they should be reported in a journal of clinical pharmacology. The main aim of clinical pharmacology however is the application of pharmacological knowledge to the treatment of the sick patient. Or to reduce the matter to the approach of the clinician in charge of the patient, the aim of the clinical pharmacologist ought to be to ensure that all the patients for whom he has any responsibility receive those drugs in appropriate dosage which will most rapidly lead to a reversal of the disease process and the most rapid possible recovery. The clinical pharmacologist however frequently does not have direct access to many patients, for the majority of drug treatment in a hospital or in general practice is carried through by others. The clinical pharmacologist's responsibility is then to ensure that other doctors have the necessary information which enables them to pick out the drug appropriate to the patient's condition and to give it in the proper dosage for the appropriate period. There is however one school of thought within the country which starts from
the premise that the vast majority of doctors do not possess adequate knowledge of clinical pharmacology and are therefore liable if not likely to prescribe inappropriate drugs in an inappropriate dosage. It is also tacitly assumed that drugs are being prescribed which are necessarily more expensive and that money is thus being wasted. There is also a suggestion that one reason why drugs are inappropriately used is that their virtues are all too often sung of loudly by representatives from commercial firms whose aim is of course primarily to sell the drugs and make profits for their employers. This argument has political overtones and many doctors will want to keep out of such a field. There is in fact plenty of evidence that more and more expensive drugs are being prescribed for patients but what is not available is evidence that expensive drugs are being inappropriately prescribed. Some come into use as a result of fashions in medicine. For example, ten years ago barbiturates were almost universally prescribed in hospital for night sedation for the patient who was unable to sleep simply because of his unfamiliar surroundings. Then there arose a cry that barbiturates were habit-forming, though this had been known for years. What was new was a realization that a very small minority of the population did themselves great harm by injecting themselves intravenously with barbiturate preparations not intended
180
LETTERSTO THE EDITORS
for such use. We were therefore told that the benzdiazepines should be substituted, a procedure which almost overnight doubled the cost of night sedation in hospital. And incidentally this storm also swept away in its track methaqualone and its proprietary version Mandrax which again was relatively cheap, but which was never shown to be seriously habit forming and left the patient clear and bright next morning. Of course the disappearance of these profound hypnotics from the market removed a weapon from the hands of the potential suicide who today is much more likely to take an overdose of antidepressant or indeed aspirin which in sufficient dose is perhaps more lethal than any of the drugs so far mentioned. Yet no measures for its control are suggested. The use of metoclopramide as an anti-emetic on the other hand is an example of a situation which has probably been the result of over-zealous promotion, where an expensive remedy has been put in the place of chlorpromazine or a similar drug which would be equally effective. Furthermore, phenothiazine drugs are effective in a wider range of situations, including some where metoclopromide is useless. It is true that chlorpromazine and like drugs occasionally cause jaundice, but the supposed freedom from side effects which is claimed for metoclopramide has in fact not been borne out by a wider clinical experience of the drug, for extrapyramidal responses are now proving to be common. In relation to new drugs in general the clinical pharmacologist has a special role to play as an intermediary between drug firms and the general prescribing medical population. Drug firms in fact use the British Journal of Clinical Pharmacology just in such a way, giving in its special numbers detailed information about new drugs to the profession. The
Br. J. clin. Pharrnac. (1978), 6
impact of the spoken word is however always greater than that of the written. It would therefore seem that it would be to the advantage of drug firms to bring together all the clinical pharmacologists who work in a field in which a new drug has been developed. (If there are no clinical pharmacologists as such then perhaps those medical practitioners with an interest in matters pharmacological would be interested.) To them thus assembled can be presented the facts about a new drug. If the material is well presented and the drug represents a genuine advance each will go out from the meeting convinced of the value of the new agent and determined to ensure that it will be given to as many patients as are likely to benefit from it with the minimum of delay. Thus the problem which besets the practice of medicine in this country would be solved, for it would no longer be necessary for drug firms to send representatives round to visit medical practitioners and present to them a one-sided view of the value of a new drug. By the same token it would not be necessary for the Department of Health and Social Security to cut back on the amount of money which it is prepared to recognize for tax purposes as appropriate to the promotion of new drugs. It is easy to see how too rigid an enforcement of minimal expenditure on publicity achieved by representatives could in the end result in patients being deprived of a new agent which would cure them simply because of inadequate facilities for spreading the knowledge of its action. A.R. HUNTER Department of Anaesthetics, The Royal Infirmary, Manchester M13 9WL Received April 25, 1978
THE ROLE OF THE CLINICAL PHARMACOLOGIST IN DISTRICT GENERAL HOSPITALS-A PHARMACEUTICAL VIEW We were interested to read the case made recently (British Journal of Clinical Pharmacology, 1978) for an extension of clinical pharmacology appointments to District General Hospitals. Underlying this proposal is the suggestion that the present state is unsatisfactory and needs to be improved. It would, indeed, be a myopic or partisan observer who could see no scope for improvement in the medical care of patients generally and in the quality of prescribing specifically. Is it now seriously suggested, however, that the quality of care will be improved by the addition of yet another specialist? The consultant physician, who usually has a specialized knowledge of the particular branch of medicine concerned, is already supported by laboratory services in respect of
medical microbiology and chemical pathology and is provided with information and expertise in regard to medicines by the hospital pharmacist. Careful appraisal is required of the impact made on care by clinical pharmacologists in those hospitals where such appointments have already been made, if their place in every District General Hospital is to be justified. Is there evidence, for example, that Drug and Therapeutics Committees are more effective in rationalizing prescribing where there is a clinical pharmacologist appointment? The solution might simply be a committee with some executive powers whose chairman, be he clinician or pharmacologist, has the respect of his medical colleagues. We suggest that there is little that a consultant clinical pharmacologist
