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When the patient is taking a sulfonylurea
DRUGS AND THE ELDERLY When the Patient Is Taking a Sulfonylurea BETSY TODD The treatment of choice in maturityonset (Type II) diabetes is diet and weight control. If a good diet trial of at least four weeks doesn't bring about a significant decline in blood sugar, either an oral hypoglycemic d r u g - - a sulfonylurea--or insulin is added to the regimen. High blood sugar levels in maturity-onset diabetes seem to be the resuit of a sluggish release of insulin from the pancreas, as well as tissue resistance to insulin. Excess weight and a diet high in refined sugars contribute to this slowdown. The sulfonylurea drugs increase the peripheral utilization of insulin and probably stimulate the pancreas to secrete more insulin. They are a good choice for ketosis-resistant diabetics who can't or won't take insulin injections, or for those few persons who are allergic to insulin. Sulfonylureas are not effective in juvenile-onset diabetes, in maturityonset diabetes with poor pancreatic insulin production, in "brittle" cases, or during periods of stress from surgery, severe infection, or injury. Adverse Effects
The most common side effect of these drugs is hypoglycemia. Although this problem is rarely as acute as it can be with insulin, even mild hypoglycemia can aggravate angina and cardiac arrhythmias. Furthermore, the symptoms of hypoglycemia can develop very slowly and subtly, leading to confusion and disorientation. These symptoms are reversible, but they may lead to a mistaken diagnosis of organic brain syndrome. A few people who take sulfonyl-
ureas are bothered by gastrointestinal distressmanorexia, heartburn, nausea and vomiting, or diarrhea. Occasionally, skin problems such as photosensitivity or a transient rash may develop. The drug should be discontinued if a rash persists. The significance of secondary failure of these agents-=-a kind of drug tolerance--is debatable. The American Medical Association's Department of Drugs suggests that only 6 to 15 percent of diabetics remain well-controlled on sulfonylureas for more than six or seven years(I). However, many "failures" undoubtedly are caused by patients' decreasing attention to diet and weight control over the years. In true secondary failure, a switch to one of the other drugs in the group may end the problem. For some patients, insulin must replace oral drug therapy. The sulfonylureas are chemically related to the sulfonamide antibiotics, so they should be given with particular caution to anyone who has a history of sulfa allergy. A 1970 report of the University Group Diabetes Program, a federally funded, 12-clinic study, main-
tained that patients on tolbutamide (Orinase) had a higher rate of mortality fr~n, cardiovascular disease than did diabetics controlled by diet alone or by diet plus insulin. Among the many criticisms of this study, the most notable is that preexisting cardiovascular disease was not taken into account(2,3). The Food and Drug Administration reviewed the data and "cony firmed" the U G D P conclusions(4). Apparently, t h e FDA had some doubts, however, because the sulfonylureas were not taken off the mark e t w a move that would seem mandatory if the FDA indeed agreed with the research findings. Was the FDA's verification of the study a politically motivated show of support for a federally funded study7 At the very least, the U G D P study indicates that more information is needed about the cardiovascular risks of the sulfonylureas. Nursing Implications Most patients require a lot of support to stick to a diabetic regimen. The nurse can be a strong motivating force if he or she continually reemC o n t i n u e d on p a g e 294
COMPARING THE SULFr )NYI.UREAS Drug
Equivalent Doses
Comments
80
a
Betsy Todd, R.N., B.S., is a p a r t - t i m e s t a f f nurse at C a b r i n i Medical Center, N e w York, N e w York, a n d a lecturer a n d c o n s u l t a n t on d r u g use a m o n g elderly persons.
ELASE~ OINTMENT
(fibdnolysin and desoxyribonuclease, combined [bovine], ointment)
DESCRIPTION. Elase O~ntment is a combination of two lyric enzymes, fibrir',olysin and desoxyribonucfease, supplied in an ointment base of liquid petrolatum and polyethylene. The flbrinorysin component is derived from bovine plasma and the desexyrlbonuclease is isolated in a purified form from bovine pancreas. The flbrinolysin used in the comb/nat~on is activated by chloroform. ACTION. Combination of lhese two enzymes is based on the observation that purulent exudates consist largely of fibrinous material and nuc!eoprotein. Desoxyribonuclease attacks the desoxyribonucleic acid (DNA) and librinolysin attacks principally fibrin of blood clots and fibrinous exudates. ]'he activity of desoxyribonuclease is limited principally to the production of large polynucleotides, which are less likely to be absorbed than the more diffusibTe protein fractions liberated by certain enzyme preparations obtained from bacteria. ]'he fibrinelytic action of the enzymes in Elase Ointment is directed mainly against denatured proleins, such as these found in devitalized tissue, while protein elements of living cells remain relatively unaffected9 Elase Ointment is a combination of active enzymes. This is an important consideration in treating patients suffering from lesions resurting from impaired circulation. The enzymatic action of Elase helps to produce clean surfaces and thus supports healing in a variety of exudalive lesions INDICATIONS. Elase Ointment is indicated for topical 9use as a debriding agent in a variety of inflammato~ and infected lesions9 These include: (1) general surgical wounds; (2) ulcerative lesions--trophic, decubitus. sfasis, arteriosclerotic; (3) second- and third-degree burns; (4) circumcision and episiotomy Elase is used intravaginally in: (1) cervicitis-- benign, postpartum, and postconization, and (2) vaginltis. PRECAUTIONS. The usual precautions against allergic reactions should be observed, particularly in persons with a history of sensitivity to materials of bovine origin or to mercury compounds. ADVERSE REACTIONS. Side effects atlributable to the enzymes have not been a problem at the dose and for the indications recommended herein. Wilh higher concentrations, side effects have been minimal, consisting of local hyperemia Chilis and fever allributable to antigenic action of profibrieolysin activators of bacteria! origin are not a problem with Elase. DOSAGE AND ADMINISTRATION. Since the conditions for which Elase Ointment is helpful vary considerably in severity, dosage must be adjusted to the individual case: however, the following general recommendations can be made: Successful use of enzymatic debridemenl depends on several factors: (I) dense, dry eschar, if present. should be removed surgically before enzymatic debridement is attempted; (2) the enzyme must be in constant contact with the substrate; (3) accumulated necrotic debris must be periodically removed; (4) the enzyme must be replenished at least once daily; and (5) secondary closure or skin grafting must be employed as soon as possible after optimal debridement has been attained. It is further essential that wound-dressing techniques be performed carefully under aseptic conditions and that appropriate systemically acting antibiotics be administered concomitantly if. in the opinion of the physician. they are indicated. General Topical Uses: Local application should be repeated at intervals for as long as enzyme action is desired. After application, Elase Ointment becomes rapidly and progressively less active and is probably exhausted for practical purposes at the end of 24 hours. Intrav~:31nal Use: In mild to moderate vaginitis and cervicitis. 5 ml of Elase Ointment should be deposited deep in the vagi.na once nightly at bedtime for approximately five applications, or until the entire contents of one 30 g tube has been used. The patient should be checked by her physician to determine possible heed for further therapy. In more severe cervicitis and vaginitis, some physicians prefer to initiate therapy with an application of Elase (fibrinolysin and desoxyribonu- clease, combined [bovine]) in solution. See Elase package insert. HOW SUPPLIED.N 0071-4279-13 Elase Ointment. 30g The 30 g tube contains 30 units of hbrinelysin and 20.000 unit s of desoxyribeneclease w:th 0.12 mg thimerosat (mercury derivative) in a special ointment base of liquid petrolatum and polyethylene. N 0071-4279-10 Elase Ointment, 10 g. ].he 10 g tube contains 10 units of fibrinolysin and 6.666 units of desoxynbonuclease with 0.04 mg thimerosal (mercury derivative) in a special ointment base of liquid petrolatum and polyelhylene Th~sproduct also contains sodium chlonde and Sucrose as incidental ingredients. MD
PARKE-DAVIS
Div of Warner-Lambert Co Morris Plains, NJ 07950 USA
DRUGS AND THE ELDERLY Continued f r o m page 291
phasizes the importance of diet, weight control, and exercise in controlling blood sugar and reducing the need for medication. Advise patients to report any serious illness or other stress to the physician, so dosage adjustments or a temporary switch to insulin can be made as indicated. Explain, too, that many factors influence the way the body handles sugar, and that it is dangerous to change the medication DRUGS AFFECTING SULFONYLUREA ACTION Enhance Hypoglycemic Effect alCohOl a-sp~tn
decrease Hypoglycemic 9 Effect bulk laxatives Chlorp~azi~e fmore~.Jne)
cott~osterbidS epineplittne.
coumarin anticoagulants I guanelhl~ne e~r~en {18mel~} I !nsuw tlithlum mono~ine tPh~nytoin oxldase-lahibitor | (o~ntln) antidepressants oxyphenbutazone thiezide {OxaUd. Tandiurelics dearS) phenldbutazone thy~id ~l.u!azQIklin. hormones ~olkO
fonylureas are best taken with meals. Relatively few people experience sulfonylurea-induced photosensitivity, but warn patients to limit exposure to the sun until any change in skin sensitivity has been evaluated. Many drugs potentiate or antagonize the effects of the oral antidiabetic drugs (see chart). Alcohol, for instance, usually exerts a hypoglycemic effect in the nondiabetic person. Also, in combination with a sulfonylurea, alcohol sometimes precipitates a disulfuram (Antabuse) reaction, which causes a throbbing headache, tachycardia, sweating, vomiting, and respiratory difficulties. Because alcohol and sugar ai'e present in many nonprescription preparations, advise patients to consult the pharmacist before purchasing any OTC products. References 1. A m e r i c a n Medical Association, Department of Drugs. AMA Drug Evaluations. 4th ed. Chicago, The Association, 1980, p. 751. 2. Ibid.. pp. 741-742. 3. A m e r i c a n Diabetes Association. F r a n k talk about oral drugs. Diabetes Forecast 33: M a y J u n e 1980. (Reprint available from A m e r i c a n Diabetes Association, 2 Park Ave., N e w York, N.Y. 10016. 4. Audit confirms conclusions of U G D P study on oral diabetes drugs. FDA Drug Bull. 8:34-36, Dec. 1978-Jan. 1979. Correction: The chronic use of stimulant laxatives shortens bowel transit time rather than lengthening it as printed in Drugs and the Elderly, May/June, page 219.
pmben.eclcl,
(Benemid, Pro, ba!a,) proPmnQl~l aulfonardl~e. antibiotics
dose, for example, to "cover" two pieces of birthday cake, without the prescriber's guidance. The symptoms of hypoglycemia include headache, rapid pulse, nervousness, anxiety, shakiness, unusual weakness, drowsiness, chills, cold sweats, excessive hunger, and nausea. Review these with the patient, as well as with family members or neighbors when appropriate. Encourage patients to wear medical identification, such as a Medic-Alert bracelet, particularly the diabetic who lives alone or travels alone. To avoid GI discomfort, the sul-
MOVING?Give us your 9n e w a d d r e s s six weeks ahead
Address your correspondence to Subscription Department, GERIATRIC NURSING, 555 West 57th
Street, New York, N.Y. 10019
The most common side effect of these drugs is hypoglycemia. Although this problem is rarely as acute as it can be with insulin, even mild hypoglycemia can aggravate angina and cardiac arrhythmias. Furthermore, the symptoms of hypoglycemia can develop very slowly and subtly, leading to confusion and disorientation. These symptoms are reversible, but they may lead to a mistaken diagnosis of organic brain syndrome. A few people who take sulfonyl-
ureas are bothered by gastrointestinal distressmanorexia, heartburn, nausea and vomiting, or diarrhea. Occasionally, skin problems such as photosensitivity or a transient rash may develop. The drug should be discontinued if a rash persists. The significance of secondary failure of these agents-=-a kind of drug tolerance--is debatable. The American Medical Association's Department of Drugs suggests that only 6 to 15 percent of diabetics remain well-controlled on sulfonylureas for more than six or seven years(I). However, many "failures" undoubtedly are caused by patients' decreasing attention to diet and weight control over the years. In true secondary failure, a switch to one of the other drugs in the group may end the problem. For some patients, insulin must replace oral drug therapy. The sulfonylureas are chemically related to the sulfonamide antibiotics, so they should be given with particular caution to anyone who has a history of sulfa allergy. A 1970 report of the University Group Diabetes Program, a federally funded, 12-clinic study, main-
tained that patients on tolbutamide (Orinase) had a higher rate of mortality fr~n, cardiovascular disease than did diabetics controlled by diet alone or by diet plus insulin. Among the many criticisms of this study, the most notable is that preexisting cardiovascular disease was not taken into account(2,3). The Food and Drug Administration reviewed the data and "cony firmed" the U G D P conclusions(4). Apparently, t h e FDA had some doubts, however, because the sulfonylureas were not taken off the mark e t w a move that would seem mandatory if the FDA indeed agreed with the research findings. Was the FDA's verification of the study a politically motivated show of support for a federally funded study7 At the very least, the U G D P study indicates that more information is needed about the cardiovascular risks of the sulfonylureas. Nursing Implications Most patients require a lot of support to stick to a diabetic regimen. The nurse can be a strong motivating force if he or she continually reemC o n t i n u e d on p a g e 294
COMPARING THE SULFr )NYI.UREAS Drug
Equivalent Doses
Comments
80
a
Betsy Todd, R.N., B.S., is a p a r t - t i m e s t a f f nurse at C a b r i n i Medical Center, N e w York, N e w York, a n d a lecturer a n d c o n s u l t a n t on d r u g use a m o n g elderly persons.
ELASE~ OINTMENT
(fibdnolysin and desoxyribonuclease, combined [bovine], ointment)
DESCRIPTION. Elase O~ntment is a combination of two lyric enzymes, fibrir',olysin and desoxyribonucfease, supplied in an ointment base of liquid petrolatum and polyethylene. The flbrinorysin component is derived from bovine plasma and the desexyrlbonuclease is isolated in a purified form from bovine pancreas. The flbrinolysin used in the comb/nat~on is activated by chloroform. ACTION. Combination of lhese two enzymes is based on the observation that purulent exudates consist largely of fibrinous material and nuc!eoprotein. Desoxyribonuclease attacks the desoxyribonucleic acid (DNA) and librinolysin attacks principally fibrin of blood clots and fibrinous exudates. ]'he activity of desoxyribonuclease is limited principally to the production of large polynucleotides, which are less likely to be absorbed than the more diffusibTe protein fractions liberated by certain enzyme preparations obtained from bacteria. ]'he fibrinelytic action of the enzymes in Elase Ointment is directed mainly against denatured proleins, such as these found in devitalized tissue, while protein elements of living cells remain relatively unaffected9 Elase Ointment is a combination of active enzymes. This is an important consideration in treating patients suffering from lesions resurting from impaired circulation. The enzymatic action of Elase helps to produce clean surfaces and thus supports healing in a variety of exudalive lesions INDICATIONS. Elase Ointment is indicated for topical 9use as a debriding agent in a variety of inflammato~ and infected lesions9 These include: (1) general surgical wounds; (2) ulcerative lesions--trophic, decubitus. sfasis, arteriosclerotic; (3) second- and third-degree burns; (4) circumcision and episiotomy Elase is used intravaginally in: (1) cervicitis-- benign, postpartum, and postconization, and (2) vaginltis. PRECAUTIONS. The usual precautions against allergic reactions should be observed, particularly in persons with a history of sensitivity to materials of bovine origin or to mercury compounds. ADVERSE REACTIONS. Side effects atlributable to the enzymes have not been a problem at the dose and for the indications recommended herein. Wilh higher concentrations, side effects have been minimal, consisting of local hyperemia Chilis and fever allributable to antigenic action of profibrieolysin activators of bacteria! origin are not a problem with Elase. DOSAGE AND ADMINISTRATION. Since the conditions for which Elase Ointment is helpful vary considerably in severity, dosage must be adjusted to the individual case: however, the following general recommendations can be made: Successful use of enzymatic debridemenl depends on several factors: (I) dense, dry eschar, if present. should be removed surgically before enzymatic debridement is attempted; (2) the enzyme must be in constant contact with the substrate; (3) accumulated necrotic debris must be periodically removed; (4) the enzyme must be replenished at least once daily; and (5) secondary closure or skin grafting must be employed as soon as possible after optimal debridement has been attained. It is further essential that wound-dressing techniques be performed carefully under aseptic conditions and that appropriate systemically acting antibiotics be administered concomitantly if. in the opinion of the physician. they are indicated. General Topical Uses: Local application should be repeated at intervals for as long as enzyme action is desired. After application, Elase Ointment becomes rapidly and progressively less active and is probably exhausted for practical purposes at the end of 24 hours. Intrav~:31nal Use: In mild to moderate vaginitis and cervicitis. 5 ml of Elase Ointment should be deposited deep in the vagi.na once nightly at bedtime for approximately five applications, or until the entire contents of one 30 g tube has been used. The patient should be checked by her physician to determine possible heed for further therapy. In more severe cervicitis and vaginitis, some physicians prefer to initiate therapy with an application of Elase (fibrinolysin and desoxyribonu- clease, combined [bovine]) in solution. See Elase package insert. HOW SUPPLIED.N 0071-4279-13 Elase Ointment. 30g The 30 g tube contains 30 units of hbrinelysin and 20.000 unit s of desoxyribeneclease w:th 0.12 mg thimerosat (mercury derivative) in a special ointment base of liquid petrolatum and polyethylene. N 0071-4279-10 Elase Ointment, 10 g. ].he 10 g tube contains 10 units of fibrinolysin and 6.666 units of desoxynbonuclease with 0.04 mg thimerosal (mercury derivative) in a special ointment base of liquid petrolatum and polyelhylene Th~sproduct also contains sodium chlonde and Sucrose as incidental ingredients. MD
PARKE-DAVIS
Div of Warner-Lambert Co Morris Plains, NJ 07950 USA
DRUGS AND THE ELDERLY Continued f r o m page 291
phasizes the importance of diet, weight control, and exercise in controlling blood sugar and reducing the need for medication. Advise patients to report any serious illness or other stress to the physician, so dosage adjustments or a temporary switch to insulin can be made as indicated. Explain, too, that many factors influence the way the body handles sugar, and that it is dangerous to change the medication DRUGS AFFECTING SULFONYLUREA ACTION Enhance Hypoglycemic Effect alCohOl a-sp~tn
decrease Hypoglycemic 9 Effect bulk laxatives Chlorp~azi~e fmore~.Jne)
cott~osterbidS epineplittne.
coumarin anticoagulants I guanelhl~ne e~r~en {18mel~} I !nsuw tlithlum mono~ine tPh~nytoin oxldase-lahibitor | (o~ntln) antidepressants oxyphenbutazone thiezide {OxaUd. Tandiurelics dearS) phenldbutazone thy~id ~l.u!azQIklin. hormones ~olkO
fonylureas are best taken with meals. Relatively few people experience sulfonylurea-induced photosensitivity, but warn patients to limit exposure to the sun until any change in skin sensitivity has been evaluated. Many drugs potentiate or antagonize the effects of the oral antidiabetic drugs (see chart). Alcohol, for instance, usually exerts a hypoglycemic effect in the nondiabetic person. Also, in combination with a sulfonylurea, alcohol sometimes precipitates a disulfuram (Antabuse) reaction, which causes a throbbing headache, tachycardia, sweating, vomiting, and respiratory difficulties. Because alcohol and sugar ai'e present in many nonprescription preparations, advise patients to consult the pharmacist before purchasing any OTC products. References 1. A m e r i c a n Medical Association, Department of Drugs. AMA Drug Evaluations. 4th ed. Chicago, The Association, 1980, p. 751. 2. Ibid.. pp. 741-742. 3. A m e r i c a n Diabetes Association. F r a n k talk about oral drugs. Diabetes Forecast 33: M a y J u n e 1980. (Reprint available from A m e r i c a n Diabetes Association, 2 Park Ave., N e w York, N.Y. 10016. 4. Audit confirms conclusions of U G D P study on oral diabetes drugs. FDA Drug Bull. 8:34-36, Dec. 1978-Jan. 1979. Correction: The chronic use of stimulant laxatives shortens bowel transit time rather than lengthening it as printed in Drugs and the Elderly, May/June, page 219.
pmben.eclcl,
(Benemid, Pro, ba!a,) proPmnQl~l aulfonardl~e. antibiotics
dose, for example, to "cover" two pieces of birthday cake, without the prescriber's guidance. The symptoms of hypoglycemia include headache, rapid pulse, nervousness, anxiety, shakiness, unusual weakness, drowsiness, chills, cold sweats, excessive hunger, and nausea. Review these with the patient, as well as with family members or neighbors when appropriate. Encourage patients to wear medical identification, such as a Medic-Alert bracelet, particularly the diabetic who lives alone or travels alone. To avoid GI discomfort, the sul-
MOVING?Give us your 9n e w a d d r e s s six weeks ahead
Address your correspondence to Subscription Department, GERIATRIC NURSING, 555 West 57th
Street, New York, N.Y. 10019