latrogenic D isease A. E. SOMERVILLE, MD

latrogenic disorders are not necessarily symptoms of poor practice, but often unavoidable consequences of modern methods of therapy. This article describes some of the avoidable consequences. Dr. Somerville is chief of at Saskatoon City Hospital and clinical assistant professor of medicine at the University of Saskatchewan.

I ATROGENESIS IS becoming one Iatrogenic can be defined as the etiological agents to the patient, of the major problems of our pro- any dysfunction, disorder, or un- and of the apparent shortcomings of fession. But its scope and extent are toward reaction that may befall, or the doctor-patient relationship when not as widely and fully appreciated develop in, a patient as a result of he compares his own experience within the profession as one might visits to, or programs of investigation against the superhuman performance expect - even though the average and treatment by a medical practi- of TV's Welby or Kildare. practicing physician is likely to en- tioner. The disorder may be physical The thalidomide tragedy of a counter examples of it almost daily. or psychological, major or minor, decade ago effectively focused, as A spate of papers published in the transient or permanent. nothing before or since has done, the last decade generally concur that one Some persons have suggested that it public's attention upon the vector role in 20 patients, or five percent of is justifiable to include as iatrogenic of the physician. The popular press hospital admissions, is hospitalized any psychological or physical condi- continues to remind the public of this because of iatrogenesis, and that one tion induced by reading, or listening to in such articles as "A Hospital Stay patient in five, or 20 percent, will medical items and programs in the Could Be Fatal" which I clipped from experience during the course of hospi- various news media. Introspection may a newspaper recently. Those of you talization some type of adverse re- convert what is heard, seen, or read who have Life subscriptions in your action as a consequence of investiga- into neurosis; persuasive example may office waiting rooms may have read, tion and treatment. lead to self , or failure to with as much interest and concern as The term iatrogenesis is derived follow prescribed medical advice, with your patients, the recent article on from the Greek iatros (physician, or physical illness resulting. To my way heart transplants. surgeon), and the Roman genesis of thinking, however, this is too all- One should not, however, assume (production). Since men of medicine encompassing a definition, although that iatrogenic disorders always stem began to practice their art, or science we as medical practitioners may be from malpractice, or poor practice. In (depending upon one's viewpoint), it held to be lax, or derelict, in the many instances they are unavoidable has been clear that they had the performance of our professional consequences of treatment; in other opportunity, and position, to in- obligations when we do nothing to instances, they are unforeseen, or un- fluence the fate of their patients. A refute misleading medical articles and foreseeable, consequences of treat- tradition of conservatism in medical programs. ment. In too many cases, unfor- practice has understandably grown up Man has always had a consuming tunately, careful reflection, or selec- in the centuries since interest in his own wellbeing, although tion, might have prevented or admonished his disciples, "Primum the steps which he may take to ensure minimized a problem. Therefore we non nocere" (first, do no harm). Man that wellbeing are often in a sideways, cannot take a casual or disinterested also has long been aware of the if not in a backwards, direction, from attitude to a problem situation of this hazards of the doctor-patient relation- the physician's viewpoint. Never be- magnitude. Where that problem is ship, as well as the benefits. Napoleon, fore, however, have his expectations foreseeable and predictable, the when advised to consult his physician, been higher than in this era of well- patient must be forewarned; where allegedly declaimed, "I do not want publicized technological and pharma- satisfactory alternatives exist, these two - one nature-made, one ceutical advance, and never before has must be used; where experience is doctor-made", and marched off he been more aware of the role of the new, this should be passed on to one's instead to Russia. physician as a vector who transmits colleagues.

CANADIAN FAMILY PHYSICIAN/JUNE, 1972 85 Fisher, in an article in CMAJ tendencies become dominant in a mantle of humanity and compassion, (November, 1968) pointed out that profession, creativity is stifled and if not of humility, after he becomes routines established for the protection progress blocked. The implications are the servant of the ailing public and the of patient, profession and institution probably more serious in medicine guardian of the sick. had to be logical and thoughtful in than in any other profession since Robert Moser's book, Diseases of purpose and practice. He also quoted a objectivity and self-criticism are the Medical Progress - A Study of truism that to naturally lifeblood of practice and investigation. Iatrogenic Disease exemplifies more occurring substances are uncommon, Where candid scrutiny does not exist, clearly than the spate of articles in the but that allergies and adverse reactions experience deteriorates into an exer- medical literature, the steadily widen- to the mass of synthetic or semi- cise of limited successes and repetitive ing horizons of iatrogenic disease synthetic drugs now in use are becom- errors within limited therapeutic resulting from the use of diagnostic or ing increasingly common and recog- horizons. This perspective explains, I therapeutic measures. The third nized. With over 7,000 brand prepara- hope, the vital importance and neces- edition of this book has grown to a tions to choose from, and an increas- sity of recording the clinician's volume of 985 pages, with 14 con- ing array of sophisticated diagnostic failures, mistakes, and adverse re- tributors aiding the author in his procedures, it is little wonder that the actions - as well as his successes and exposition, and its 16 chapters extend- modern physician frequently finds triumphs. Unfortunately, such honest ing from -induced diseases himself in difficulty. appraisal and reporting leave the pro- through those related to several organ Sometimes, this position is of his fession open to headhunting by those systems, hormone-induced disease, own making; occasionally it is forced with preconceived prejudices, those connective tissue disorders, surgically- upon him. Those of you who recall seeking fame via the purple prose induced disease and those related to your pharmacology lectures at medical route, or those seeking fortune diagnostic procedures, concluding with school, or who are interested in old through litigation. a chapter on psychosomatics. medical textbooks, may recall a In the not too distant past the The reference lists for each chapter certain amusement and disbelief in doctor with the most opportunity for run into the hundreds. Antibiotic contemplating the of inflicting iatrogenic disease upon his therapy is considered in its side-effects herbal days. Unfortunately, we are patients was the surgeon. Within the of direct toxicity, hypersensitivity, seeing a resurgence of polypharmacy last quarter century, however, the role and its biologic effects in permitting in this age of potent synthetic and has reversed, with the physician having overgrowth of other organisms often semi-synthetic agents many of which the dubious distinction of being the resistant to treatment. The congenital have not been available long enough main potential instigator of unneces- effects of drugs transmitted through for the incidence and extent of side sary and unwanted morbidity (and the placenta run the gamut from effects and adverse reactions to be mortality) in the medical community. tobacco, the teratogenic drugs fully appreciated. The cynicism and Consequently, those who prescribe (thalidomide) and the steroids. The amused contempt with which we read and administer physic must become author points to the 'deliberate risk' those old prescriptions containing as fully conversant with any drug they the doctor takes in prescribing drugs many as 12 or more items, should be prescribe,. and must know the inter- for a pregnant women, and points to balanced by an equal concern and actions of combination therapy. At the safety of avoiding the use of new careful evaluation of today's hospital the same time, the public health drugs during pregnancy. In the derma- patient on a dozen or more different section of our profession, the re- tological field the drug eruptions, often containing agents searchers, and the medical educators, intolerance, and toxicity are seemingly with diverse, contrary, or potentiating must accept some share of the blame without end, while the photo-sensitiz- properties and actions. for the present day situation. The ing drugs are of special interest. The Polypharmacy is not necessarily a medical educators, in particular, must chapter on iatrogenic gastrointestinal phenomenon of the doctor's making. bear some of the, blame, albeit in- diseases is of particular significance in It is often a product of excessive direct, for the growth of iatrogenesis. the relationship of drugs to serious demands placed on him by the public, The attitudes acquired in medical hepatic disease. Nearly 400 references and by man's strident demands for the training are those carried into practice. to the chapter on iatrogenic hema- better life in all things (including The budding physician of today is tologic disease indicate the wide escape from the unpleasant realities of nurtured all too frequently on elec- spectrum of the ill-effect of drugs on day-to-day living). The same people tronic devices, multiple investigations, the bone marrow and the red cells who strenuously protest the un- and therapies. He may work in isola- with anemia of one type or another, balanced ecology and pollution of our tion from the patient's family, normal while the hazards of blood trans- external environment often demand environment and regular practitioner, fusions are known to everyone. from their physicians investigation and and is accustomed to frank and free As might be predicted, because of therapy which may constitute com- discussion on all aspects of the their physiologic role in the body's parable hazards to their genes, their patient's care regardless of who may economy, there is hardly a bodily progeny, or their metabolism. be listening. Often tutored by a function which may not be affected in Iatrogenesis should not be regarded clinician with little or no experience an untoward fashion by some steroidal as a dirty word. Mankind's natural outside hospital environs (or a sub- preparation (and over 400 references inclination is to ignore failures and specialist who concerns himself with a point up this fact). The hyper- publicize successes. Doctors are no limited portion of a patient's sensitivity and connective tissue dis- exception. This lack of objectivity, if anatomy) he all too frequently ends orders are especially intriguing, and allowed to persist, leads to smug satis- up as a brash - albeit erudite - young here may lie the answer to the current faction with the status quo; if these practitioner who must acquire a prevalence of diseases such as dis-

CANADIAN FAMILY PHYSICIAN/JUNE, 1972 87 seminated lupus or arteritis - diseases rationalize that therapy will do no drugs three groupings must be thought known for more than a century harm and may perchance do good or of, with there being no hard or fast though rarely encountered (or re- serve as a '. lines of distinction between each. cognized) formerly, but now seem- Iatrogenic disorders can be simply Toxic Effects. These basically re- ingly quite common. The suggestion classified into those of psychogenic present overdosage, intentional or un- has arisen that these are medically origin, and those of physical type. intentional. For example, a physician induced or, at least, related to might increase the dose of digitalis to chemical exposures in daily life and Psychogenic Origin the toxic phase of in order to immunological aberrations induced The induction, or prevention, of ensure that the patient was under thereby. The side effects on the iatrogenic disorders of psychogenic therapeutic effect. At least one third nervous system of the host of sedative- origin is related to the time-honored of patients on reserpine, an effective anxiolytic-tranquillizer-hallucinogenic doctor-patient relationship, abetted hypotensive drug, become mentally drugs are well-known even if such and aggravated in the present day by depressed in greater or lesser degree, widely publicized events as the the widespread dissemination of and in the greater degree may even Manson murder trial did not dramatize medical information in the news attempt suicide. their most horrible consequences. media. Some patients are highly sus- Side Effects. These are defined as Seventy-five pages, and 432 refer- ceptible to psychogenic disorders, an effect on an organ, or function, ences, point up post-surgical complica- particularly anxiety; others are stolid other than the one at which treatment tions whether they be the dumping and impervious. The doctor's problem is aimed. Antihistaminics, useful in syndrome, absorptive disorders of the is to decide into which category his some allergic conditions, were first bowel, , or a host of other patient can be placed' discovered accidentally during research disabling conditions that may follow From the doctor's side, iatrogenic into a new hypnotic. It was found that . Some 500 references empha- neurosis may be a consequence of the new hypnotic was no better than size the illnesses which may follow one many factors. He may be off guard numerous others already available, but or other diagnostic procedure, whether due to fatigue and inattention because that antihistaminic effects occurred as instrumental (endoscopy, biopsy), or of overwork or personal problems, and a side-effect, with the drug then the use of contrast media. Moser's may drop the careless word or gesture developed, registered and marketed for final chapter is devoted to 'psycho- that breeds introspection; he may fail to the antihistaminic qualities, with a semantics' - the psychiatric, or answer the patient's questions ade- warning that it might induce drowsi- psychologic, result of the misused quately or explain the implications ness as a side-effect. The story of word or phrase by the doctor in the of a particular diagnosis; he may be propranolol (Inderal) is somewhat management of his patient. The words mistaken in his diagnosis and present similar, it having been originally which instill fear and foreboding, the an unduly pessimistic prognosis; his developed as a tranquillizer. Anticho- discussions at rounds with house staff reassurance may be unconvincing linergics, commonly used as antispas- and fellows or surgeons - discussions because of inadequate examination modics, have a cerebral stimulant of differential diagnosis and prognosis and investigation, or because a patient effect in *some people. On a longterm in jargon unintelligible even to the has withheld information consciously, basis this drug may produce euphoria, most educated person, which the or subconsciously, because of fear of a flight of ideas, and a carefree attitude patient in his anxiety relates to him- serious underlying disorder. And with obvious risks in industry, com- self. there's a host of other factors. merce, traffic, etc. Steroids are well- Kampmaier, in a 1968 article in the known for the euphoria they may Annals of Internal Medicine, 'The Physical Type produce as a side-effect, and one again Medical Scholar and His Dilemma' Modern drugs have reached a re- wonders how many impetuous deci- points out that the doctor's problems markable degree of efficacy, but any sions, the wisdom of which was are not entirely of his own making. He drug that is efficacious carries risks of debatable afterwards, have been made 'practices in a society that is offered greater or lesser degree. The drug that under the influence of steroid. When an unwelcome paradox: on every hand is entirely safe is almost certainly inert Kennedy and Kruschev were at the our people are bombarded by stories and inefficacious. Even a simple non- height of their power, and Kennedy glorifying the advances in effective analgesic such as reportedly was on cortisone, it was science, in diagnosis, and especially in aspirin is not entirely safe: it can said that the world was controlled by treatment. Lacking discernment in produce severe hematemesis, particu- the three Ks "Kennedy, Kruschev and things medical, and with today's larly in older people and especially if Kortisone". attitude of entitlement to , there is a past history of ulcer, and Adverse Reactions. These are the patient expects action and will not anaphylactic reaction. Penicillin, still adverse effects of drugs, frequently be denied a remedy for every com- the most remarkable drug of the recognized after the drug has been plaint. Therein lies the paradox - the century, has high sensitizing potential marketed and is in wide circulation promise of health or cure, and the and can induce fatal anaphylaxis. One (until regulations were tightened up in inability to provide it. This is a major has to keep in mind that between five the last few years). They commonly dilemma. Time too limited for expla- and 10 percent of the total adult occur in a dose that is safe and nation in a busy practice, the need to population at any one time is on effective for the vast maJority of face a patient's disbelief, the prospect longterm drug therapy - tranquil- patients, and are frequently due to of being branded a therapeutic nihilist, lizers, hypotensive remedies, diabetic interaction between the drug and some or, worse, as one behind the times, agents - all of which can induce other drug, agent or circumstance with may make it simpler to accede to a illness. which they come into chance meeting. patient's wishes or dictates and to In considering adverse effects of One of the best known examples was

CANADIAN FAMILY PHYSICIAN/JUNE, 1972 89 the MAO inhibitors introduced as tran- related substance, and non-immunol- of failure of communication between quillizers, with hypertensive crises in ogic histamine release which mimics basic scientists and clinicians, than patients partaking of aged cheese of typical allergic reactions due to excess indication of neglect or disinterest on high tyramine content. Aggravation of histamine release such as in urticaria, the part of the latter. The truism 'the porphyria by barbiturates, hemolytic bronchospasm and, occasionally, harder you look, the more you fmd' is crises in persons on antimalarials with hypotension. This latter phenomenon never better exemplified than in the enzyme deficiency in the erythrocytes, may follow administration of certain area of drug interactions. Bizarre, or barbiturate inhibition of the couma- drugs such as narcotics, strychnine, atypical, symptoms appearing in the rins' anticoagulant effect, hypotensive stilbamidine, organic arsenicals, and course of a patient's illness, may crises in well-controlled hypertensives protein hydrolysates. It is quite likely become readily understandable if his when hypnotics are added to their that iodide salts used as contrast media drug history is known, and the pos- treatment program, and development in X-ray work possess this ability to sible interactions that might be antici- of resistant organisms, or superinfec- release histamine on a non-immu- pated. Professor Palmer, of the Univer- tions in patients on antibiotic pro- nologic basis. sity of Miami, has stated in a recent grams are other possible adverse re- Substances capable of inducing an publication that any patient receiving actions. The matter of traffic safety immunologic response are of two main four to seven drugs simultaneously and drug therapy has received wide types: large macromolecular materials, ought to have an interaction, and that attention - the euphoria of anticho- and other substances of simpler chemi- a fair proportion of these interactions linergics, steroids and amphetamines cal structure and relatively low molec- should manifest with overt symptom- or the drowsiness of antihistamines ular weight. The high molecular weight atology. Drugs as chemicals can in- and tranquillizers, probably account- biologicals, such as foreign anti-sera teract with each other outside the ing for their share of traffic accidents. and organ extracts, are complete organism, while numerous possibilities Many persons have also suggested that antigens and can induce sensitization. for interaction result when several old age should be regarded as an Skin testing with these materials in drugs are ingested. iatrogenic disorder, due to the fact cases of suspected allergic reaction is that so many elderly people who often of diagnostic value. Most drugs Interactions Outside the Patient previously died of now have are non-protein compounds of a rela- Many reactions can occur in intra- their lives saved by and tively simple chemical nature and low venous solutions. Certain drugs, other drugs, and are thereby enabled molecular weight. For a simple chemi- because of acid or alkaline lability, to live to a much greater age with all cal to induce sensitization it must filrst cannot be mixed with acidic or basic the family and socio-economic prob- bind with macromolecules such as compounds unless the solution is lems that entails. tissue and serum proteins. The result- buffered. Methicillin for instance, is ant hapten-protein conjugate induces acid labile, so the pH of dextrose, Surgery antibody formation, cellular sensitiza- saline, or other solutions, ordinarily The most perfectly carried-out tion, or both. The drug acts as a acid, must be adjusted to the alkaline surgical procedure may lead to dis- hapten, non-antigenic by itself, but range. Levophed, on the contrary, abling complications for the patient. capable of directing the specificity of should be given in acid solution to Post-gastrectomy dumping and malab- sensitization as a drug-protein con- prevent its oxidation. Some solutions, sorption syndromes are examples. In jugate. With some drugs, direct chemi- such as amphotericin, are light sensi- some cases, operations are unwisely (at cal interaction with proteins does not tive; regular insulin binds to glass, least in retrospective evaluation) occur. When allergic reactions occur tetracycline can be photo-oxidized by carried out. Cholecystectomy for non- from these drugs, a degradation the riboflavin in vitamin B complex. specific dyspepsia is one example. product, or a metabolite of the drug, Defects in surgical technique, or super- reacts with tissue or serum proteins to Interference with Absorption imposed infection, may also lead to form a hapten-protein complex. In Drugs with anticholinergic prop- iatrogenic disorders. The psychological those cases where the degradation erties, by decreasing intestinal move- effects of 'multilation' have also to be product is the cause, the unaltered ments, delay or reduce absorption of considered e.g. breast surgery, amputa- drug used for skin testing would fail to drugs. Most of the tricyclic anti-de- tions, colestomy, etc. A session of the react with antibodies induced by a pressants, and many of the major 1969 meeting of the Medical Associa- drug metabolite. tranquillizers, have this property. tion of New Zealand, devoted to Another mechanism of impaired ab- iatrogenic diseases, spoke of iatrogenic Drug Interactions sorption is formation of complexes of suicide, and iatrogenic polysurgery Until the last couple of years, several drugs in the gut such as calcium addiction as well as the syndrome in interest has centered on adverse re- and tetracycline, when antibiotic and which emotionally disturbed patients actions to individual drugs. With antacid are administered together, deliberately mislead unsuspecting multiple drug therapy, however, the with absorption of tetracycline corres- surgical practitioners into performing recognizable incidence of adverse re- pondingly reduced. Cholestyramine, a unnecessary surgical procedures. actions seems to be steadily rising, non-absorbable resin, reduces absorp- reflecting basic pharmacological in- tion of thyroxine. Dilantin, by inhibit- Immunological Factors formation that drugs may, and do, ing an intestinal conjugase, inhibits the In discussing adverse drug reactions interact with one another to alter each absorption of folic acid. Nitro- I made no mention of hypersensitivity others' effects. While it may seem furantoin appears to have a similar reactions where allergic sensitization surprising that this information has effect in man, and can also be asso- develops after previous exposure to not been more widely disseminated ciated with megaloblastic anemia. the same drug or to a chemically and recognized, it is more a reflection More recently, oral contraceptives, and

90 CANADIAN FAMILY PHYSICIAN/JUNE, 1972 triampterine (a diuretic), have been the former case producing toxic mani- stimulus, norepinephrine is released reported to inhibit absorption of folic festations manifested by nystagmus from the mobile pool to interact with acid. and confusion, and in the latter hypo- a receptor, either alpha or beta. Nore- A second mechanism whereby glycemia. As a general rule, a drug that pinephrine can also be synthesized drugs interact is by displacement of is primarily metabolized and that is within these sites from tyrosine and is each other's binding to plasma combined with another drug which is broken down through the participa- proteins. Many drugs, as is well also primarily metabolized, may either tion of MOA. In the extra-cellular known, bind to amino groups of inhibit or enhance the other drug's fluid, norepinephrine is broken down plasma albumen, with the bound com- metabolic effects. by a specific enzyme. Ordinarily, when ponent inactive, but in equilibrium norepinephrine is released, the ma- with a free form. The unbound frac- Inhibition of Renal Secretory jority is taken back up by the nerve tion determines the pharmacologic Mechanism terminal and inactivated, but certain activity of the drug in question. The Drugs can affect each other's rate chemicals such as reserpine and the coumadins and phenylbutazone inter- of elimination by virtue of their com- tricyclic anti-depressants, cocaine, and act in this fashion when given to- petition for weak acid-secreting sites. toxic concentrations of digitalis inhibit gether, with phenylbutazone dis- The thiazide diuretics, penicillin, and this uptake. Exogenous amines can placing the coumadins from binding some sulphonamides will compete for also be taken up by the nerve terminal, sites. Indomethacin, oxyphen- uric acid-secreting sites, thereby elevat- and this explains hypertensive mani- butazone, and clofibrate have similar ing the plasma level of uric acid. festations encountered on occasion in effects. Aspirin can displace protein- Salicylates are notorious in this regard, patients under treatment for hyper- bound penicillin analogs, long-acting since at low doses they act as com- tension with reserpine. These patients sulphonamides, or chlorpropamide. petitors for weak acid-secreting sites in also are receiving phenylephrine nasal This latter is of particular import the kidneys, and elevate the concentra- sprays, certain ephedrine-containing because of the risk of resulting hypo- tion of other acidic drugs. As a general bronchodilator preparations, etc. glycemic episodes. Methotrexate can rule any drug that is acidic, and is not Drugs such as guanethidine, which be displaced by various acidic drugs, metabolized, will be secreted by the must be taken up by the nerve termi- including sulphonamides and sali- kidney and will have the capacity to nal for their action, are also less cylates, with its toxicity accordingly interact with any other non-metabo- effective in the presence of blocking enhanced. lized acidic drug by competing for the agents like the tricyclic anti-depres- It is also possible for drugs to same secretory site. Excretion of a sants. Nervousness and insomnia in displace each other by non-specific drug can be affected by affecting the this group of patients can be related to binding sites and tissues. Pamaquin, an pH of the urine. For instance, diamox, increased circulating cacocholamines. antimalarial that localizes in the liver, by virtue of its ability to alkalinize the Certain compounds present in food, can displace quinacrine, another anti- urine, will enhance the excretion of such as tyramine, can precipitate the malarial, to increase plasma levels of any acidic compound. release of cacocholamines, and the pamaquin, thus reducing the rate of hypertensive crises that have been disappearance of this drug from Alteration of Adrenergic Mechanisms observed in patients on MOA in- plasma. As a corollary, quinacrine This mechanism is the most compli- hibitors such as parnate and autonyl. increases the toxicity of pamaquin. cated of the drug interactions. The False neurohumoral production is catecholamines, principally norepine- used for therapeutic benefit in the case Interference with Metabolism phrine, are stored at post-ganglionic of aldomet (alpha-mathyl-dopa), this Drugs can also interact through nerve terminals and in presynaptic and compound being metabolized to alpha- interference with metabolism, either postsynaptic neurons in the central mathyl norepinephrine and stored in augmenting or inhibiting each other's nervous system. With appropriate the nerve terminal to displace the breakdown. Phenobarb has been more potent norepinephrine. Aramine known for some time to increase liver causes a release of catecholamines size and the amount of endoplasmic ,YC 1 A resulting in a hypertensive effect, but reticulum in animal liver, with a can itself replace norepinephrine in the corresponding but non-specific in- nerve terminal, so that its effects tend crease in enzyme activity. This means to be self-limiting. that not only is the metabolism of the inducing drug increased, but the Indirect Modification of a Drug's metabolism of other drugs as well. Action by Electrolyte Balance This process, known as enzyme in- This last category of drug inter- duction, requires about 48 hours for action involves alterations of acid base onset, and a similar interval for offset. metabolism, with the most classic For. example, phenobarb enhances the example being the combination of metabolism of Warfarin (coumadin). diuretics with digitalis, the diuretics Chloral hydrate has similar effects as producing potassium loss with poten- doriden, meprobamate, dilantin and tiation of toxic effects of digitalis but griseofulvin. not the therapeutic effects. Other Drugs can also inhibit the metabo- CANADIAN FAMILY PHYSICIAN examples include the increased lism of one another, chloramphenicol "And how long have you had this potency of the neuromuscular block- having the ability to inhibit the metab- delusion that people always take ad- ing agents in the presence of low olism of dilantin and tolbutamide, in vantage of you?" potassium levels. 4

CANADIAN FAMILY PHYSICIAN/JUNE, 1972 91