- Email: [email protected]
Digitalis
955
300-500 mg. Occasionally, however, there are method. The patient-usually this in difficulties obese woman-may have no visible or palpable veins suitable for giving the injection of 10 ml. or more that is needed. Again, the solution of saccharated iron is very dark and therefore not too easy to give since it is alkaline, if a little gets outside the vein into the tissues an unpleasant local reaction may result. So it is necessary to use well-fitting syringes, or of glass except for a metal preferablyandall-glass the injection must be given slowly. nozzle. Many busy general practitioners find that intravenous injections of iron take up too much time both In some in preparation and in administration.) be cannot iron natients given intravenously, because reactions.3 One of the comit causes unpleasant monest is pain over the kidneys in the back ; another is an allergic type of dyspnoea, and a few deaths But due to allergic reactions have been reported. on the whole intravenous iron has been very successful, and obstetricians in particular have found it useful in treating the iron-deficiency anaemia of pregnancy when time is short and iron by mouth is useless because of gastro-intestinal disturbances. It was clear that some of the difficulties of intravenous administration would be avoided if instead the iron could be given intramuscularly. The intravenous-iron solution was unsafe for intramuscular mjection, because of its alkalinity. But now a dextraniron solution has been prepared which, so far at least, seems safe and effective ; and in this issue Dr. BAIRD and Mr. PODMORE, of Sheffield, describe their experienees with it. This dextran-iron is isotonic with tissuefluids and has a pH of 60-7-0. It is more concentrated than the intravenous-iron solutions, containing 5% of iron. compared with 2%. This is just as well, since few people comfortably tolerate large intramuscular inyections, and the dose of intramuscular iron is larger than that of intravenous iron. BAIRD and PODMORE consider that an increase of 0-34 g. haemoalobin per 100 ml. blood can be expected for every 190 mg. of iron injected (i.e., every 2 ml.) ; in other wonls. 43 mg. iron is needed for every 1% hæmoAlobin (leficit (intravenous doses of iron are usually alculated on the basis of 25 mg. iron for every 1% hæmoglobin deficit, though sometimes up to 37 mg. ziven). The intramuscular injection must be given arefully; otherwise the skin will be seriously stained, Mel the patient will have notable discomfort at the tion site. Even when the injection is given with ’ in. needle inserted on a Z-shaped track the may be stained for several weeks, so the injection be made into the gluteal muscles. As might be ted, there is considerable individual variation the effectiveness of the intramuscular injection, judged by the serum-iron peak ; for example, Bugd and PODMORE gave 250 mg. of iron to two of about the same weight with a haemoglobin and the peak serum-iron levels reached were and 1000 µg. per 100 ml. Corresponding variawere found in the response of the haemoglobin and. as with intravenous iron. it was usually days after starting treatment before the haeinolevel rose notably. BAIRD and PODMORE doses of 5 ml., equivalent to 250 mg. of metallic an
3.
Nissim, J. A. Brit. med. J. 1954, i, 352.
as often as twice daily for but inpatients, outpatients twice weekly more in either case the requisite convenient : -. proved total dose of iron is soon given. The introduction of a satisfactory preparation of iron for intramuscular injection should make it possible for every iron-deficient patient to be effectively treated. But it would be unwise without clear cause to substitute intramuscular iron for intravenous iron ; and oral iron. where this will suffice, should be given in preference to either. Iron preparations for intramuscular injection are still about five times as expensive as those for intravenous injection, and their absorption may be less regular. Intramuscular iron is. at present, essentially a therapeutic weapon to be kept in reserve. All this work on iron preparations has led to improvements in the way oral iron is presented Plain ferrous sulphate, in tablets or capsules, is stil a.s efficient as any preparation. and it is very cheap The difficulty with it is that some patients-usually estimated at about a third—get gastro-intestina disturlamces which are severe enough to preven the proper dose. or any of the dose, being taken This difficulty is often avoided when the patien takes enteric-coated ferrous-sulphate tablets, pro and th vided the coating is done properly the Intravenou tablet disintegrates beyoncl pylorus. administration of ferric hydroxide has revived it use for oral preparations, and really effective tablet and liquid are now to be had. It is well tolerated an effectively absorbed-, ferric hydroxide yields abou 50"o of metallic iron, compared with 27.5% from ferrous sulphate. Some organic salts o iron are also on trial. Ferrous gluconate yield of metallic iron ; it is said to be bette only 11.5% the is not very convincing but evidence absorbed,4 Ferrous succinate is a similar salt, but there is sti no firm evidence of its efficieney and it is considerabl There are also preparations of iro more expensive. combined with vitamins, liver, folic acid, and man other substances that the devisers of these " blunder busses " believe to be useful. In dealing with poten remedies, however, there are not only disadvantages but positive dangers in the use of complex mixtures and the more a physician knowsof haematology th more likely he is to abjure methods which ar
iron ; this dose could be given
to
therapeutically imprecise. With ferrous sulphate or ferric hydroxide fo administration by mouth, and preparations for intra venous and intramuscular injection, every patien with primary iron-deficiency anapmia can now b successfully treated.
Digitalis
congestive heart-failure digitalis folia or i purified derivatives should still be the sheet-anoho of treatment : but preoccupation with reducin oedema by restriction of salt intake and administratio of diuretic agents has lately tended to obscure th fact that the primary disorder lies in the heart an that the renal disturbances are secondary. WITHERIN himself thought that the diuretic effect of digital was due to a direct action on the kidney, and rece studies5 suggest that digoxin may influence t 4. Haler, D. Ibid, 1952. ii, 1241. 5. Farber, S. E. D. Alexander, J. IN
J., Circulation, 1951, 4, 378.
D., Pellegrino,
D., Earle,
956
auricular fibrillation.14 When it fails to do either tubular reabsorption of sodium ; but there is convinthat it mainly acts directly on the quinidine is given, digitalis administered concurre cing evidence cardiovascular system. Early in their studies with diminishes the risk of an accelerated ventricular cardiac catheterisation MCHICHAEL and SHARPEYby impairing conduction in the A-V junctional ti Such are the indications for treatment with digit SHAFERwere impressed by the fall in venous pressure There i that followed administration of digoxin ; this led What preparations should be used ? them to believe that perhaps the main action of the evidence that the various digitalis compound,. drug was on the venous system, whereby a reduction qualitatively different in their action. Dinere in venous pressure (comparable to that which follows between them are due to differences in dosage phlebotomy or the application of tourniquets to the in the speed and duration of action. For prac thighs) was followed by a reduction in diastolic filling purposes the physician need be familiar with and lessening of the overload on the heart. Sub- two preparations : a long-acting one, such as dig and techfolia, and a more rapidly acting one, such as di others,7-10 using improved sequently they which is quickly absorbed when given by mouth found that or ouabain cause an niques, digoxin might can be given intravenously in an emergency. increase in cardiac output before, or without, any Thus reduction in venous filling pressure. it was dosage of either cannot be defined except in ge reaffirmed that the primary action of the drug was terms, because the requirements of each patien different and often vary considerably during the c on the heart itself. The dosage should be that of the disease. the has two effects on heart a Digitalis principal direct action on the heart-muscle, and slowing of produces the greatest benefit without toxic e MACKENZIE and LEWIS held that In patients with auricular fibrillation, the ventri the heart-rate. value is of only when failure is associated rate and the disappearance of the pulse defic digitalis valuable guides to dosage, but in patients with with rapid fibrillation; but there is now ample evidence that it also brings about great improvement rhythm assessment is more difficult and it is Moat of the necessary to persist until mild toxic effects are in in heart-failure with sinus rhythm. slowing is secondary to improvement in myocardial and then reduce the dose. The first toxic manifest function, which is evident from the increased force of is loss of appetite, which is followed by nause systolic contraction, better emptying of the ventricles, vomiting. Bradycardia, premature ventricular and ability of the heart to do as much or more work tractions, and coupling (pulsus bigeminus) ar Less common sig common signs of toxicity. with less oxygen consumption. It is still insufficiently and headache, in certain ( vertigo, electrocardiographic that, except arrhythmias, appreciated such as multifocal premature bea unless the abnormalities, is valueless In is heart digitalis failing. patients with cardiac enlargement but no failure ventricular or auricular tachyeardia.16 The co digitalis induces either no change or a fall in cardiac E.c.G. changes due to digitalis-namely, depress output.11 Even when failure is present, digitalis may the s-T segment and inversion of the first p the T wave-give no indication of whether th not provide benefit. It is chiefly effective in failure is being given in optimal dosage, and conv low with a cardiac output ; and in this group it severe digitalis poisoning may occur without is more effective in hypertensive and ischaemic heart disease (when the metabolism of heart-muscle changes. The introduction of purified glycosides may be disturbed) than in constrictive peri- can be given by mouth (when they are carditis or aortic stenosis (where mechanical factors absorbed) or intravenously has increased the in 17 This is due the outstanding handicap). Exactly how of toxicity in the U.S.A.16 may be influences causes : first the practice in that country of atte is metabolism digitalis myocardial being investigated 12 13; apparently its action, in common full digitalisation with a single large dose, and se the now well-established fact that the toxic with that of certain other steroids, is concerned with the movement of potassium ions across the cell of digitalis appear more readily in patients w membrane. By increasing vagal tone, prolonging the depleted of potassium.15 18 19 Heart-failure is refractory period, and decreasing conduction in the panied by shifts in the body electrolytes; th atrio-ventricular (A-V) junctional tissue, digitalis is of body-potassium is reduced, and intensive admin tion of ammonium chloride and mercurial d value in the treatment of paroxysmal auricular tachycardia and auricular flutter, with or without enhances the loss of potassium (as well as of s Serious digitalis intoxication cardiac failure. In paroxysmal auricular tachycardia in the urine. avoided it is the drug of choice if pressure. on the carotid by moderation, shunning the tempta sinus and other simple measures to increase vagal digitalise the patient unnecessarily rapidly. tone do not stop the attack. In auricular flutter rapid digitalisation is necessary digoxin is digitalis may convert as many as 50% of cases to to digitalis folia or digitoxin, which are less sinus rhvthm and another third to more manageable eliminated from the body and so have a long action if an overdose is given- LOWN and LE 6. McMichael, J., Sharpey-Schafer, E. P. Quar .J. Med. 1944, 13, 123. have called attention to an auricular tachycard 7. Ahmed, S., Bayliss, R. I. S., Briscoe, W. A., McMichael, J. Clin. Sci. 1950, 9, 1. A-v block which may be a manifestation of M. J.. H.
pre
8.
9. 10. 11.
12. 13.
Hyman, A. L.. Kelly, G., Bayliss, R. I. S., Etheridge, McMichael, J., Reid, E. A. S. Brit. Heart J. 1950, 12, 317. Harvey, R. M., Ferrer, M. I., Cathcart, R. T., Richards, D. W., Cournand, A. Amer. J. Med. 1949, 7, 439. McMichael, J. Pharmacology of the Failing Human Heart. Oxford, 1950. Harvey, R. M.. Ferrer, M. I., Cathcart, R. T., Alexander, J. K. Circulation, 1951, 4, 366. Szent-Gyorgyi, A. Bull. N. Y. Acad. Med. 1952, 28, 3. Szent-Gyorgyi, A. In Mechanisms of Inflammation. Edited by H. Selye. Montreal, 1953.
14. Luckey, H. Amer. J. Med. 1954, 17, 271. 15. Lown, B., Wyatt, N. F., Crocker, A. T., Goodale, W. T S. A. Amer. Heart J. 1953, 45, 589. 16. Master, A. M. J. Amer. med. Ass. 1948, 137, 531. 17. Burwell, W. B., Hendrix, J. P. Amer. J. Med. 1950, 18. Lown, B., Weller, J. M., Wyatt, N., Hoigne, R., Merr J. clin. Invest. 1952, 31, 648. 19. Lown, B., Levine, S. A. New Engl. J. Med. 1954,
819, 866.
957 is noteworthy for its implication that a overdosage; and they point out that the rapid heart- This statement receives official sanction unless it can be proved drug nte may prompt the physician to give more digitalis. that it has no value—which reflects an therapeutic with fatal results. They have found that 5 g. potassium attitude that is from one that ia voiced different radically chloride by mouth will often remove the symptoms in other quarters (and especially by some teachers in our of intoxication and stop digitalis-induced arrhythmedical school;-) that the onus of proof that a drug has miss.19 20 procainamide (05-1 g. by mouth four-hourly therapeutic value rests on those who make the claim. 22 Nevertheless some diserimination is exercised ; for if of six-hourly) may also control the arrhythmias.21 the book were simply a cumulative furmulary of all LOWN and LEVINE have sought to solve the problem have had too much or too official and non-official remedies, its publication would little whether of patients a in test which a tolerance italis by rapidly acting long ago have proved impracticable. The additions include nearly a hundred general and a effect with short-lived (acetyl strophancoside The potency of the new drugs is special thidin) is injected intravenously. The degree of another monographs. remarkable sign of the times—when the syndiritalisation is assessed by the amount of the drug thetic chemist is the keeper of the doctor’s required to produce E.C.G. evidence of digitalis arrnoury. These virtually drugs include dyflos (D.F.P.), hexa* moxication.19 This test may prove of particular methonium tartrate. phenylbutazone, procainamide in determining the digitalis requirements of sulpliate, suxamethonium chloride, and tolazoline hydropatients previously given digitalis who develop cardiac chloride. Among antiriera, vaccines, and related failure or an arrhythmia after operation on the heart. substances interesting additions are B.C.G. vaccien, diphtheria and immune human "
whooping-cough prophylactic, surgeon’s needs are well catered for : among the new dressing-; listed are delustred regenerated cellulose and animal wool for chiropody. About eighty new items appear in the formulary. but many of these refer to preparations which became ofncial in the B.P. 1953. Dead wood has been cut away mercilessly : upwards of two hundred and fifty monographs have been deleted
sera.
Annotations THE CODEX
THE British Pharmaceutical Codex is almost as old as the century in which we live. The sixth edition, 23 published the week, fulfils even more successfully than its predethe intention of the Pharmaceutical Society of Britain : to produce a book of reference for those in prescribing or dispensing medicines." A good deal of what appears in the Codex is necessarily predetermined by the contents of the Briti8h Pharmapaia. But for twenty years the Codex has published andards for many drugs not contained in the B.P. Comprehensiveness is desirable, but the Codex Revision fommittee is obliged to bar the way to inclusion when hut is less evident than fantasy. No doubt the commuttee’s sense of responsibility has increased with the palisation that the B.P.C. (and the National F’orrn2cltary) New rank with the B.P. itself in guiding the Joint Committee on Prescribing in its herculean task of classifying proprietary medicinal preparations. Another outstanding frature of the B.P.C., as compared with the B.P., is the mclusion of paragraphs on actions and uses ; thus, in effeet, the Codex incorporates a handbook of clinical pnarmacology. The new edition is notable for a more attitude towards the reputed therapeutic value of old and new alike. The moulding of policy and the of developments in particular directions may - seem to come within the committee’s terms of refer. Even so, such is the status and the scope of this that the work of the experts who revise it inevitably the outlook of teachers of pharmacy and of therato this extent the B.P.C. exercises an important on the shape of things to come. The revision ttee, however, is obliged to bear in mind that its to meet the needs of contemporary doctors and in their professional work. Thus grave about the value of a drug do not necessarily mention of it to be excluded. In the words of the uction:
gaged
instances many medical practitioners have drugs and preparations with confidence in their aithough convincing clinical evidence of their value is Such drugs and preparations have not been excluded there is acceptable evidence that they are ineffective in some
have fallen into virtual disuse."
berg, C. D., Simmons, H. G., Mintz, A. A. Amer. Heart J. 39, 713. K., Garlett, E. L., Bellet, S., Getter, W. I. Amer. J. 11, 431. ord, M. C., Taguchi, J. T. Circulation, 1951, 4, 387. Pharmaceutical Codex 1954. London: Pharmaceutical
1951,
Pp. 1340. 63s.
"
The
from the old volume, and no fewer than four hundred items have vanished from the formulary. As usual there are many appendices ; these have proved invaluable in hospitals and laboratories of many kinds. It is refreshing to find the main titles of drugs and preparations given in English at the top of each monograph. The Latin title in full and in its abbreviated form is retained but relegated to a lower place. This is an appropriate gesture from the revision committee, whose members have evidently felt the need for plain words and clear thinking ; and what language is more expressive than English ? CHEST PAIN THE diagnosis of ischaemic heart-disease often resta on the history alone ;but Morton et al.1 point out that the six classical features of cardiac pain (onset related to effort or emotion ; substernal position, commonly with radiation to the left arm ; short duration ; constricting in character ; rapidly relieved by nitroglycerin) are by no means pathognomonic. Harrison found that the pain was substernal in only half of his patients with angina pectoris. Parkinsonpointed out that pain radiating to the left arm may be a symptom of hiatus hernia, pleural disease, or spinal disease. Morton ot al. have investigated the chest pain of 100 patients with proven ischæmic heart-disease and 100 with " functional " heart-disease. They found that the two conditions could not be differentiated by the character or site of the pain alone ; tightness in the chest and dull aching pain occurred in functional In a quarter of the as well as in ischaemic heart-disease. functional cases the pain was substernal, and associated with effort ; and in 36% of those who took nitroglycerin repeatedly, this relieved the pain. Un the other hand, among the patients with ischæmic heart-disease, the pain was precordial or in the left chest in 30% ; it came on at rest in the same proportion ; and it was not relieved by nitroglycerin in 10—15%. Morton et al. point out that none of the six classical features should be relied on alone in differentiating between cardiac and noncardiac pain, but suggest that if three or more of these features are present, ischæmie heart-disease can be more or
less
definitely diagnosed.
Morton, A. M., Jaffe, H. L., Pordy, L. Ann. intern. Med. 1954, 41, 315. 2. Harrison, T. R. Amer. J. med. Sci. 1944, 207, 561. 3. Parkinson, J. Ann. intern. Med. 1951, 35, 499. 1.
300-500 mg. Occasionally, however, there are method. The patient-usually this in difficulties obese woman-may have no visible or palpable veins suitable for giving the injection of 10 ml. or more that is needed. Again, the solution of saccharated iron is very dark and therefore not too easy to give since it is alkaline, if a little gets outside the vein into the tissues an unpleasant local reaction may result. So it is necessary to use well-fitting syringes, or of glass except for a metal preferablyandall-glass the injection must be given slowly. nozzle. Many busy general practitioners find that intravenous injections of iron take up too much time both In some in preparation and in administration.) be cannot iron natients given intravenously, because reactions.3 One of the comit causes unpleasant monest is pain over the kidneys in the back ; another is an allergic type of dyspnoea, and a few deaths But due to allergic reactions have been reported. on the whole intravenous iron has been very successful, and obstetricians in particular have found it useful in treating the iron-deficiency anaemia of pregnancy when time is short and iron by mouth is useless because of gastro-intestinal disturbances. It was clear that some of the difficulties of intravenous administration would be avoided if instead the iron could be given intramuscularly. The intravenous-iron solution was unsafe for intramuscular mjection, because of its alkalinity. But now a dextraniron solution has been prepared which, so far at least, seems safe and effective ; and in this issue Dr. BAIRD and Mr. PODMORE, of Sheffield, describe their experienees with it. This dextran-iron is isotonic with tissuefluids and has a pH of 60-7-0. It is more concentrated than the intravenous-iron solutions, containing 5% of iron. compared with 2%. This is just as well, since few people comfortably tolerate large intramuscular inyections, and the dose of intramuscular iron is larger than that of intravenous iron. BAIRD and PODMORE consider that an increase of 0-34 g. haemoalobin per 100 ml. blood can be expected for every 190 mg. of iron injected (i.e., every 2 ml.) ; in other wonls. 43 mg. iron is needed for every 1% hæmoAlobin (leficit (intravenous doses of iron are usually alculated on the basis of 25 mg. iron for every 1% hæmoglobin deficit, though sometimes up to 37 mg. ziven). The intramuscular injection must be given arefully; otherwise the skin will be seriously stained, Mel the patient will have notable discomfort at the tion site. Even when the injection is given with ’ in. needle inserted on a Z-shaped track the may be stained for several weeks, so the injection be made into the gluteal muscles. As might be ted, there is considerable individual variation the effectiveness of the intramuscular injection, judged by the serum-iron peak ; for example, Bugd and PODMORE gave 250 mg. of iron to two of about the same weight with a haemoglobin and the peak serum-iron levels reached were and 1000 µg. per 100 ml. Corresponding variawere found in the response of the haemoglobin and. as with intravenous iron. it was usually days after starting treatment before the haeinolevel rose notably. BAIRD and PODMORE doses of 5 ml., equivalent to 250 mg. of metallic an
3.
Nissim, J. A. Brit. med. J. 1954, i, 352.
as often as twice daily for but inpatients, outpatients twice weekly more in either case the requisite convenient : -. proved total dose of iron is soon given. The introduction of a satisfactory preparation of iron for intramuscular injection should make it possible for every iron-deficient patient to be effectively treated. But it would be unwise without clear cause to substitute intramuscular iron for intravenous iron ; and oral iron. where this will suffice, should be given in preference to either. Iron preparations for intramuscular injection are still about five times as expensive as those for intravenous injection, and their absorption may be less regular. Intramuscular iron is. at present, essentially a therapeutic weapon to be kept in reserve. All this work on iron preparations has led to improvements in the way oral iron is presented Plain ferrous sulphate, in tablets or capsules, is stil a.s efficient as any preparation. and it is very cheap The difficulty with it is that some patients-usually estimated at about a third—get gastro-intestina disturlamces which are severe enough to preven the proper dose. or any of the dose, being taken This difficulty is often avoided when the patien takes enteric-coated ferrous-sulphate tablets, pro and th vided the coating is done properly the Intravenou tablet disintegrates beyoncl pylorus. administration of ferric hydroxide has revived it use for oral preparations, and really effective tablet and liquid are now to be had. It is well tolerated an effectively absorbed-, ferric hydroxide yields abou 50"o of metallic iron, compared with 27.5% from ferrous sulphate. Some organic salts o iron are also on trial. Ferrous gluconate yield of metallic iron ; it is said to be bette only 11.5% the is not very convincing but evidence absorbed,4 Ferrous succinate is a similar salt, but there is sti no firm evidence of its efficieney and it is considerabl There are also preparations of iro more expensive. combined with vitamins, liver, folic acid, and man other substances that the devisers of these " blunder busses " believe to be useful. In dealing with poten remedies, however, there are not only disadvantages but positive dangers in the use of complex mixtures and the more a physician knowsof haematology th more likely he is to abjure methods which ar
iron ; this dose could be given
to
therapeutically imprecise. With ferrous sulphate or ferric hydroxide fo administration by mouth, and preparations for intra venous and intramuscular injection, every patien with primary iron-deficiency anapmia can now b successfully treated.
Digitalis
congestive heart-failure digitalis folia or i purified derivatives should still be the sheet-anoho of treatment : but preoccupation with reducin oedema by restriction of salt intake and administratio of diuretic agents has lately tended to obscure th fact that the primary disorder lies in the heart an that the renal disturbances are secondary. WITHERIN himself thought that the diuretic effect of digital was due to a direct action on the kidney, and rece studies5 suggest that digoxin may influence t 4. Haler, D. Ibid, 1952. ii, 1241. 5. Farber, S. E. D. Alexander, J. IN
J., Circulation, 1951, 4, 378.
D., Pellegrino,
D., Earle,
956
auricular fibrillation.14 When it fails to do either tubular reabsorption of sodium ; but there is convinthat it mainly acts directly on the quinidine is given, digitalis administered concurre cing evidence cardiovascular system. Early in their studies with diminishes the risk of an accelerated ventricular cardiac catheterisation MCHICHAEL and SHARPEYby impairing conduction in the A-V junctional ti Such are the indications for treatment with digit SHAFERwere impressed by the fall in venous pressure There i that followed administration of digoxin ; this led What preparations should be used ? them to believe that perhaps the main action of the evidence that the various digitalis compound,. drug was on the venous system, whereby a reduction qualitatively different in their action. Dinere in venous pressure (comparable to that which follows between them are due to differences in dosage phlebotomy or the application of tourniquets to the in the speed and duration of action. For prac thighs) was followed by a reduction in diastolic filling purposes the physician need be familiar with and lessening of the overload on the heart. Sub- two preparations : a long-acting one, such as dig and techfolia, and a more rapidly acting one, such as di others,7-10 using improved sequently they which is quickly absorbed when given by mouth found that or ouabain cause an niques, digoxin might can be given intravenously in an emergency. increase in cardiac output before, or without, any Thus reduction in venous filling pressure. it was dosage of either cannot be defined except in ge reaffirmed that the primary action of the drug was terms, because the requirements of each patien different and often vary considerably during the c on the heart itself. The dosage should be that of the disease. the has two effects on heart a Digitalis principal direct action on the heart-muscle, and slowing of produces the greatest benefit without toxic e MACKENZIE and LEWIS held that In patients with auricular fibrillation, the ventri the heart-rate. value is of only when failure is associated rate and the disappearance of the pulse defic digitalis valuable guides to dosage, but in patients with with rapid fibrillation; but there is now ample evidence that it also brings about great improvement rhythm assessment is more difficult and it is Moat of the necessary to persist until mild toxic effects are in in heart-failure with sinus rhythm. slowing is secondary to improvement in myocardial and then reduce the dose. The first toxic manifest function, which is evident from the increased force of is loss of appetite, which is followed by nause systolic contraction, better emptying of the ventricles, vomiting. Bradycardia, premature ventricular and ability of the heart to do as much or more work tractions, and coupling (pulsus bigeminus) ar Less common sig common signs of toxicity. with less oxygen consumption. It is still insufficiently and headache, in certain ( vertigo, electrocardiographic that, except arrhythmias, appreciated such as multifocal premature bea unless the abnormalities, is valueless In is heart digitalis failing. patients with cardiac enlargement but no failure ventricular or auricular tachyeardia.16 The co digitalis induces either no change or a fall in cardiac E.c.G. changes due to digitalis-namely, depress output.11 Even when failure is present, digitalis may the s-T segment and inversion of the first p the T wave-give no indication of whether th not provide benefit. It is chiefly effective in failure is being given in optimal dosage, and conv low with a cardiac output ; and in this group it severe digitalis poisoning may occur without is more effective in hypertensive and ischaemic heart disease (when the metabolism of heart-muscle changes. The introduction of purified glycosides may be disturbed) than in constrictive peri- can be given by mouth (when they are carditis or aortic stenosis (where mechanical factors absorbed) or intravenously has increased the in 17 This is due the outstanding handicap). Exactly how of toxicity in the U.S.A.16 may be influences causes : first the practice in that country of atte is metabolism digitalis myocardial being investigated 12 13; apparently its action, in common full digitalisation with a single large dose, and se the now well-established fact that the toxic with that of certain other steroids, is concerned with the movement of potassium ions across the cell of digitalis appear more readily in patients w membrane. By increasing vagal tone, prolonging the depleted of potassium.15 18 19 Heart-failure is refractory period, and decreasing conduction in the panied by shifts in the body electrolytes; th atrio-ventricular (A-V) junctional tissue, digitalis is of body-potassium is reduced, and intensive admin tion of ammonium chloride and mercurial d value in the treatment of paroxysmal auricular tachycardia and auricular flutter, with or without enhances the loss of potassium (as well as of s Serious digitalis intoxication cardiac failure. In paroxysmal auricular tachycardia in the urine. avoided it is the drug of choice if pressure. on the carotid by moderation, shunning the tempta sinus and other simple measures to increase vagal digitalise the patient unnecessarily rapidly. tone do not stop the attack. In auricular flutter rapid digitalisation is necessary digoxin is digitalis may convert as many as 50% of cases to to digitalis folia or digitoxin, which are less sinus rhvthm and another third to more manageable eliminated from the body and so have a long action if an overdose is given- LOWN and LE 6. McMichael, J., Sharpey-Schafer, E. P. Quar .J. Med. 1944, 13, 123. have called attention to an auricular tachycard 7. Ahmed, S., Bayliss, R. I. S., Briscoe, W. A., McMichael, J. Clin. Sci. 1950, 9, 1. A-v block which may be a manifestation of M. J.. H.
pre
8.
9. 10. 11.
12. 13.
Hyman, A. L.. Kelly, G., Bayliss, R. I. S., Etheridge, McMichael, J., Reid, E. A. S. Brit. Heart J. 1950, 12, 317. Harvey, R. M., Ferrer, M. I., Cathcart, R. T., Richards, D. W., Cournand, A. Amer. J. Med. 1949, 7, 439. McMichael, J. Pharmacology of the Failing Human Heart. Oxford, 1950. Harvey, R. M.. Ferrer, M. I., Cathcart, R. T., Alexander, J. K. Circulation, 1951, 4, 366. Szent-Gyorgyi, A. Bull. N. Y. Acad. Med. 1952, 28, 3. Szent-Gyorgyi, A. In Mechanisms of Inflammation. Edited by H. Selye. Montreal, 1953.
14. Luckey, H. Amer. J. Med. 1954, 17, 271. 15. Lown, B., Wyatt, N. F., Crocker, A. T., Goodale, W. T S. A. Amer. Heart J. 1953, 45, 589. 16. Master, A. M. J. Amer. med. Ass. 1948, 137, 531. 17. Burwell, W. B., Hendrix, J. P. Amer. J. Med. 1950, 18. Lown, B., Weller, J. M., Wyatt, N., Hoigne, R., Merr J. clin. Invest. 1952, 31, 648. 19. Lown, B., Levine, S. A. New Engl. J. Med. 1954,
819, 866.
957 is noteworthy for its implication that a overdosage; and they point out that the rapid heart- This statement receives official sanction unless it can be proved drug nte may prompt the physician to give more digitalis. that it has no value—which reflects an therapeutic with fatal results. They have found that 5 g. potassium attitude that is from one that ia voiced different radically chloride by mouth will often remove the symptoms in other quarters (and especially by some teachers in our of intoxication and stop digitalis-induced arrhythmedical school;-) that the onus of proof that a drug has miss.19 20 procainamide (05-1 g. by mouth four-hourly therapeutic value rests on those who make the claim. 22 Nevertheless some diserimination is exercised ; for if of six-hourly) may also control the arrhythmias.21 the book were simply a cumulative furmulary of all LOWN and LEVINE have sought to solve the problem have had too much or too official and non-official remedies, its publication would little whether of patients a in test which a tolerance italis by rapidly acting long ago have proved impracticable. The additions include nearly a hundred general and a effect with short-lived (acetyl strophancoside The potency of the new drugs is special thidin) is injected intravenously. The degree of another monographs. remarkable sign of the times—when the syndiritalisation is assessed by the amount of the drug thetic chemist is the keeper of the doctor’s required to produce E.C.G. evidence of digitalis arrnoury. These virtually drugs include dyflos (D.F.P.), hexa* moxication.19 This test may prove of particular methonium tartrate. phenylbutazone, procainamide in determining the digitalis requirements of sulpliate, suxamethonium chloride, and tolazoline hydropatients previously given digitalis who develop cardiac chloride. Among antiriera, vaccines, and related failure or an arrhythmia after operation on the heart. substances interesting additions are B.C.G. vaccien, diphtheria and immune human "
whooping-cough prophylactic, surgeon’s needs are well catered for : among the new dressing-; listed are delustred regenerated cellulose and animal wool for chiropody. About eighty new items appear in the formulary. but many of these refer to preparations which became ofncial in the B.P. 1953. Dead wood has been cut away mercilessly : upwards of two hundred and fifty monographs have been deleted
sera.
Annotations THE CODEX
THE British Pharmaceutical Codex is almost as old as the century in which we live. The sixth edition, 23 published the week, fulfils even more successfully than its predethe intention of the Pharmaceutical Society of Britain : to produce a book of reference for those in prescribing or dispensing medicines." A good deal of what appears in the Codex is necessarily predetermined by the contents of the Briti8h Pharmapaia. But for twenty years the Codex has published andards for many drugs not contained in the B.P. Comprehensiveness is desirable, but the Codex Revision fommittee is obliged to bar the way to inclusion when hut is less evident than fantasy. No doubt the commuttee’s sense of responsibility has increased with the palisation that the B.P.C. (and the National F’orrn2cltary) New rank with the B.P. itself in guiding the Joint Committee on Prescribing in its herculean task of classifying proprietary medicinal preparations. Another outstanding frature of the B.P.C., as compared with the B.P., is the mclusion of paragraphs on actions and uses ; thus, in effeet, the Codex incorporates a handbook of clinical pnarmacology. The new edition is notable for a more attitude towards the reputed therapeutic value of old and new alike. The moulding of policy and the of developments in particular directions may - seem to come within the committee’s terms of refer. Even so, such is the status and the scope of this that the work of the experts who revise it inevitably the outlook of teachers of pharmacy and of therato this extent the B.P.C. exercises an important on the shape of things to come. The revision ttee, however, is obliged to bear in mind that its to meet the needs of contemporary doctors and in their professional work. Thus grave about the value of a drug do not necessarily mention of it to be excluded. In the words of the uction:
gaged
instances many medical practitioners have drugs and preparations with confidence in their aithough convincing clinical evidence of their value is Such drugs and preparations have not been excluded there is acceptable evidence that they are ineffective in some
have fallen into virtual disuse."
berg, C. D., Simmons, H. G., Mintz, A. A. Amer. Heart J. 39, 713. K., Garlett, E. L., Bellet, S., Getter, W. I. Amer. J. 11, 431. ord, M. C., Taguchi, J. T. Circulation, 1951, 4, 387. Pharmaceutical Codex 1954. London: Pharmaceutical
1951,
Pp. 1340. 63s.
"
The
from the old volume, and no fewer than four hundred items have vanished from the formulary. As usual there are many appendices ; these have proved invaluable in hospitals and laboratories of many kinds. It is refreshing to find the main titles of drugs and preparations given in English at the top of each monograph. The Latin title in full and in its abbreviated form is retained but relegated to a lower place. This is an appropriate gesture from the revision committee, whose members have evidently felt the need for plain words and clear thinking ; and what language is more expressive than English ? CHEST PAIN THE diagnosis of ischaemic heart-disease often resta on the history alone ;but Morton et al.1 point out that the six classical features of cardiac pain (onset related to effort or emotion ; substernal position, commonly with radiation to the left arm ; short duration ; constricting in character ; rapidly relieved by nitroglycerin) are by no means pathognomonic. Harrison found that the pain was substernal in only half of his patients with angina pectoris. Parkinsonpointed out that pain radiating to the left arm may be a symptom of hiatus hernia, pleural disease, or spinal disease. Morton ot al. have investigated the chest pain of 100 patients with proven ischæmic heart-disease and 100 with " functional " heart-disease. They found that the two conditions could not be differentiated by the character or site of the pain alone ; tightness in the chest and dull aching pain occurred in functional In a quarter of the as well as in ischaemic heart-disease. functional cases the pain was substernal, and associated with effort ; and in 36% of those who took nitroglycerin repeatedly, this relieved the pain. Un the other hand, among the patients with ischæmic heart-disease, the pain was precordial or in the left chest in 30% ; it came on at rest in the same proportion ; and it was not relieved by nitroglycerin in 10—15%. Morton et al. point out that none of the six classical features should be relied on alone in differentiating between cardiac and noncardiac pain, but suggest that if three or more of these features are present, ischæmie heart-disease can be more or
less
definitely diagnosed.
Morton, A. M., Jaffe, H. L., Pordy, L. Ann. intern. Med. 1954, 41, 315. 2. Harrison, T. R. Amer. J. med. Sci. 1944, 207, 561. 3. Parkinson, J. Ann. intern. Med. 1951, 35, 499. 1.