A survey of anorexiants and their function in weight reduction and control
By James D. Colson Prescription and Nonprescription Anorexiants
Various measures are used to lose or control body weight. These may include changes in dietary intake and eating habits, planned physical exercise, individual counseling, group self-help programs, intestinal bypass surgery and various pharmacologic means. The value of pharmacologic intervention in weight reduction is controversial. 1·2·5,6,a, 12,13 This article focuses on the legend and overthe-counter appetite suppressants (anorexiants or anorexigenics) used in weight reduction and maintenance. None of these agents, legend or o-t-c, directly causes weight loss. Their use is indicated for suppressing the desire to eat, when combined with an overall weight reduction program. The use of anorexiants is appropriate only as long as the desired effect results without producing significant, secondary adverse effects. Patients seeking to lose or control their weight need to be aware of the mechanics involved in weight reduction and maintenance and be motivated enough to stay with a program. The pharmacist can assist these patients in understanding the drug and its effects, and he can emphasize and reinforce the need for compliance with the overall weight control regimen. Pharmacists also are in a position to advise patients in cases in which self-medication may be inappropriate or potentially harmful because of the existence of an underlying psychologic or pathologic condition.
Table I
Legend Anorexiants Legend drugs used as anorexiants can be grouped into a single class. (See Table I, above right, for product identification.) Chemically, these agents are all phenethylamine (amphetamine-like) analogs, with the exception of mazindol, an imidazoisoindole compound. 13 The amphetamines, in particular dextroamphetamine, have been used as the standard for comparison of the anorexiants.1 Although differences exist as to the type and degree of secondary effects produced, duration of action and relative potency, no one particular agent has been shown to be significantly any more effective than any other agent in this class. 6 · 13 These agents are thought to act on central mechanisms involved in appetite regulation located in the brain's hypothalamic and limbic regions. The desired anorexiant effect of these agents is accompanied by secondary effects manifested by CNS stimulation and other sympathetic activity. Although there does not seem to be a direct correlation between CNS stimulant and anorexiant potencies, most CNS stimulant drugs do have anorexiant activity. 4 An exception to this general rule is
Vol. NS 16, No. 10, October 1976
Legend Anorexiants
Brand Name
Generic Composition
Remarks
Dexedrine (Others)
Dextroamphetamine S0 4 , P0 4
Desoxyn (Others)
Methamphetamine HCl
More CNS and less cardiovascular effect than amphetamine*; timed-release preparation is available**; Schedule II More pronounced CNS effects than dextroamphetamine; high abuse potential; timedrelease preparation is available**; Schedule II
Didrex
Benzphetamine HCl
Pre-Sate
Chlorphentermine HCl Diethylpropion HCl
Tenuate Tepanil Plegine
Phendimetrazine tartrate
Preludin
Phenmetrazine HCl
Wilpo lonamin Voranil Pondimin San or ex
Phentermine HCL Phentermine Resin Clortermine HCl Fenfluramine HCl Mazindol
Schedule III Long-acting agent; Schedule III Lesser CNS effects; timed-released preparation is available**; Schedule IV Schedule III Timed-release preparation is available**; Schedule II Ion-exchange resin is to provide a more sustained effect; Schedule IV Long-acting agent; Schedule III Produces CNS depression; Schedule IV Long-acting agent; an imidazoisoindole compound; Schedule III
*Racemic amphetamine is not recommended for use as an anorexiant due to its pronounced cardiovascular and lesser CNS effects. **The data are insufficient to adequately evaluate the effectiveness of timed-release preparations in producing a sustained anorex1ant action.l
fenfluramine, an anorexiant which produces significant CNS depression. 7 Anorexiants are indicated for use in exogenous obesity as short-term adjuncts to an overall weight reduction program. The weight loss generally amounts to only a fraction of a pound per week, for roughly five to ten weeks. 6 · 13 Tolerance to the anorexiant effect of these agents develops after short periods of use, often necessitating an increase in the dosage in order to produce a given level of anorexiant effect. Increasing the dose increases the likelihood and occurrence of secondary side effects. When the side effects become significant, the drug has reached its limit of therapeutic value and should be discontinued. Side effects produced by anorexiants used in therapeutic doses are mostly indicative of sympathomimetic activity. They include
headache, dizziness, restlessness, insomnia, tremors, increased pulse rate and blood pressure, nausea, diarrhea, constipation, dry mouth and mydriasis. In situations of acute toxicity or overdose, these effects are accentuated. Chronic use of anorexiants can result in abnormal behavioral changes characterized by increased irritability, aggressiveness, mania, paranoia and delusions (toxic psychosis). Withdrawal of these agents following long-term use often results in generalized mental depression and somnolence. In addition, there is an abuse potential and dependence liability associated with the use of anorexiant agents which must be taken into consideration. In light of these various risk factors, the overall benefit to be derived from use of the anorexiants appears small. Legend anorexiants are also combined
James D. Colson
Captain James D. Colson, MS, is with the U.S. Air Force Biomedical Science Corps, serving as a pharmacy officer at Lackland AFB in Texas where he is the Wing Drug/ Alcohol Abuse Control consultant. He also is affiliated with Wilford Hall USAF Medical Center at the base. Colson received a BS from the University of Washington school of pharmacy in 1972 and an MS from the university's department of pharmacology in 1974. Previously, Colson was a staff pharmacist at Virginia Mason Hospital in Seattle and a clinical instructor at the University of Washington. His background also includes community pharmacy experience. He is a member of ASHP.
565
Prescription and Nonprescription Anorexiants
with other agents such as sedative-hypnotics, antipsychotic tranquilizers, laxatives, antispasmodics, thyroid, diuretics, digitalis, digestives, vitamins and minerals. These combination products, for the most part, are irrational and do more to complicate the potential hazards than increase the effectiveness of the product. 1
Table II
0-t-c Anorexiants*
Brand Name
Manufacturer
Composition
Remarks
Slenderize Weight Control plan
Rieger /Medi-Save
Vitamins and minerals, sodiurn carboxymethylcellulose(SOO mg), benzocaine (9 mg)
Probably subtherapeutic doses
Pretts
Marion
Alginic acid(200 mg), sod ium carboxymethylcellulose (1 00 mg) , sodium bicarbonate(70 mg)
Rationale for using sodiurn bicarbonate is questionable and unspecified
X-11 Reducing Plan
Porter and Dietsch
Phenylpropanolamine(25 mg), methylcellulose(25 mg) , vitamins and minerals, caffeine(25 mg)
Probably subtherapeutic doses
Gobese Diet Plan
Gobese Company
Phenylpropanolamine(SO mg) caffeine(25 mg), vitamins
Timed-release preparation**
Fat-Go
Pruvo Pharmacal
Phenylpropanolamine(25 mg), methylcellulose(25 mg), caffeine(25 mg), vitamins
Probably subtherapeutic doses
E-Lim
Pruvo Pharmacal
Powdered extracts of buchu , juniper , uva ursi and stone root; sodium and potassium nitrate, aloe, oleo resin capsicum
Diuretic and la xative; dose not specified
Hungrex with P.P.A.
Allegheny Pharmacal
Phenylpropanolamine(25 mg)
Probably subtherapeutic dose
Odrinex
Fox Pharmacal
Phenylpropanolamine(25 mg)
Probably subtherapeutic dose
Appedrine Reducing Plan
SDA Pharmaceuticals
Phenylpropanolamine(25 mg) sodium carboxymethylcellulose(SO mg) , caffeine(! 00 mg), vitamins and minerals
Probably subtherapeutic dose
Prolamine
Thompson Medical Company
Phenylpropanolamine(35 mg) , caffeine(l40 mg)
Timed-release preparation **
Figure Aid
Thompson Medical Company
Benzocaine, sodium carboxymethylcellulose, vitamins and minerals
Timed-release preparation; no dose specified
Slim-Mint
Thompson Medical Company
Benzocaine, methylcellulose, dextrose , essential flavors
Dose not specified
Slim-Mint Gum
Thompson Medical Company
Benzocaine, sodium carboxymethylcellulose , dextrose , oils of anise, peppermint , wintergreen, clove and cinnamon
Dose not specified
Aqua Ban
Thompson Medical Company
Ammonium chlorid e, caffeine
Dose not specified
d-Minish Diet Aid Capsules
McKesson Laboratories
Sodium carboxymethylcellulose(300 mg) , benzocaine (9 mg), vitamins and minerals
Timed-released preparation**
0-t-c Anorexiants While there are numerous o+c products available for use in weight reduction, emphasis here will be on those pharmacologic agents which are used as appetite suppressants (as distinguished from the dietary substances such as saccharin, Ayds candy, Metrecal, etc.). These o-t-c anorexiants are thought to act on either central or peripheral mechanisms involved with regulation of appetite. Although there are no guidelines for adequately assessing the relative efficacy of these agents, it can be assumed that the placebo component offered by these agents plays a major role in reinforcing an individual's adherence to an overall weight reduction program. The following represent the different types of o+c anorexiants commonly available. (See Table II, at right, for product identification.) CNS Stimulants-Caffeine and phenylpropanolamine are common agents in this category. The anorexiant effect is thought to be centrally mediated through a mechanism similar to that of the amphetamine-like anorexiants. The dose of phenylpropanolamine that often is used, 25 mg, is probably insufficient to produce the desired effect. 1 Potential secondary effects include manifestations of CNS stimulation, tachycardia, increased blood pressure and gastrointestinal tract disturbances. Patients with cardiovascular disease, hypertension, diabetes and hyperthyroidism should be cautioned against the use of phenylpropanolamine. In addition, caffeine may aggravate Gl tract ulcers and cause disturbances in cardiac rhythm. Caffeinism can also produce signs mimicking neurosis. 11 Laxatives-Bulk-forming agents (e.g., psyllium ,hydrophylic mucilloid, sodium carboxymethylcellulose, methylcellulose, alginic acid) act to produce swelling and distention of the intestines. This peripheral action creates a sense of fullness in the intestinal tract. This fullness, however, is needed more in the stomach, where hunger contractions ("pangs") occur. Other laxatives (e.g., senna, cascara, aloe), in doses producing diarrhea, cause fluid and nutrient loss. Overuse of laxatives can result in severe fluid and electrolyte loss, atony of the colon and other se-
566
*Most of these preparations are t o be taken before or after meals with a glass of water, coffee, tea or a low-calorie beverage. **The s.ignificance of timed-release formulations for some of ttiese·l)reparations is questionable.
rious complications. 3 Patients with Gl tract ulcers or undiagnosed abdominal pain should be warned against the use of laxative agents. Antispasmodics-Belladonna alkaloids (e.g ., hyoscyamine, atropine and hyoscine)
are common to many o+c preparations . Although they are seldom used in o-t-c anorexiant products, these agents supposedly act peripherally to inhibit the Gl contractions often associated with the sensation of hunger, thus reducing appetite. Hunger con-
Journal of the American Pharmaceutical Association
Colson
tractions were once thought to be important in the peripheral regulation of appetite . 10 Animal studies, however, suggest that denervation of the stomach and intestines does not affect food intake.9 The typical atropine-like side effects to expect with these agents include blurred vision , dry mouth, urinary retention , constipation and tachycardia. Those dose-related side effects may well discourage the use of the belladonna alkaloids as anorexiants . Patients with glaucoma , renal hepatic disease or obstructive uropathy should be cautioned against using these types of agents. Local Anesthetics-Benzocaine is commonly used in varied doses. The rationale for use is to suppress appetite by decreasing peripheral sensory desire for food in the mouth. Hypersensitivity reactions are known to occur with benzocaine. 0-t-c anorexiants are often combined with other types of agents, as well as with other anorexiants . For instance, various kinds of diuretics (e .g., powdered extracts of buchu, couch grass, corn silk, uva ursi and hydrangea; sodium or potassium nitrate; caffeine) are used in combinations to produce a relatively rap id, yet small weight loss. (Although this effect is temporary, its immediate onset undoubtedly has a positive psychological impact on the user.) Also, different vitamins and minerals are combined in prophylactic quantities to help supplement those possibly
Clinical Psychiatry ... (Continued from page 559)
mentations and " tardive dyskinesia." The latter is a neurological complication marked by athetoid movements of tongue and mouth in particular. Many " minor" tranquilizers have addictive qualities and may produce serious effects upon withdrawal. This list includes the barbiturates, diazepam, chlordiazepoxide hydrochloride and meprobamate, among others . Here again the pharmacist may fulfill a most important function, alerting the physician who may be unaware of the extent of the patient's dependency. Patient Noncompliance. In recent years, the rate of patient noncompliance has received attention . Published reports indicate that it may run as high as 50 percent, 8 and it is increasingly recognized as a public health problem of great importance.9 It is not altogether clear what the determining factors are, but it is likely that a good work ing all iance between patient and physician aids compliance .10 Simple reinforcement by the pharmacist as he dispenses the prescription
Vol. NS 16, No. 10, October 1976
lost due to dietary restrictions. The merits of many of these o-t-c preparations in contributing significantly to weight reduction and control are based on poorly substantiated claims and inadequately controlled studies . Aside from the question of their efficacy in producing adesired effect, there remains the question of their effectiveness at the comparatively low doses used.
rather limited in scope by comparison. The pharmacist can be instrumental in assisting patients in understanding the fundamental aspects involved in weight reduction and control and how the anorexiant drugs function within the scheme. His attitude can be instrumental in either helping or hindering the patient's efforts at weight reduction.
e
Conclusion
The legend and o-t-c anorexiants have similarities as well as differences. Both types are indicated for short-term use in exogenous obesity as adjuncts to an overall weight reduction program. Their degree of effectiveness in producing weight loss is limited and the maintenance of weight loss is transitory, unless appropriate follow-up measures are taken . Despite this limited effectiveness, the value of anorexiants in psychologically reinforcing and motivating compliance to a weight reduction regimen cannot be overlooked. The potential risk factors differ considerably between legend and o-t-c anorexiants . The legend drugs are capable of a wide range of secondary adverse effects, including CNS hyperexcitability, cardiovascular and Gl tract disturbances, abuse potential and dependence liability. The o-t-c drugs are not without their own risk factors, although these are
References
medication and orally repeats or writes out clear instructions can substantially improve patient compliance. 11 Such factors may determine the success or failure in the conduct of maintenance therapy. The pharmacist occupies a key role among the mental health disciplines by reinforcing medication co!Tlpliance, monitoring drug utilization by the patient, and counseling the physician prescriber. His specialized awareness of drug interactions and incompatibilities adds a crucial dimension to safe and effective drug use.
both health provider and patient by serving as reinforcer, observer, educator, advisor and consultant.
Conclusion
Because of the increasing complexity of cl inical psychopharmacology and because the drugs used are so potent, it is inevitable and desirable that there should develop an increasing collaboration between pharmacist and psychiatrist. The pharmacist who has acquired special training in clinical pharmacology needs to become a full member of the mental health team, adding this professional discipline to others whose skills are dedicated to the care of the mentally ill. The pharmacist can fulfill an important role to
1. AMA Drug Eva luations. 2nd ed .. AMA Counc il on Drugs, Chicago, Ill., 369- 377 (1973) 2. "Anorexiants," FDA Drug Bulletin, U. S. Department of HEW, Rockville, Md. , (Dec. 1972) 3. Babb, R.R., "Constipation and Laxative Abuse, " Wes t. J. Med. 122, 93 (1975) 4. Cox, R.H ., Jr., and Maickel, R.P., "Comparison of Anorexigenic and Behavioral Potency of Phenethylamines," J. Pharmacal. Exp. Ther. 181:1 , (1972) 5. " Dieth ylpropi on," The Medical Letter, 13, 10 1 (Dec. 1971) 6. Dykes, M.H.M., " Evaluation of Three Anorexiants, " JAMA , 230, 270 (1970) 7. " Fenflura mine- Another Appetite Suppressant," The Medical Letter, 15, 33 (Apri l 1973) 8. Fineberg, S.K., " An Appra isal of Anorexiants in the Treatment of Obesity, " J. Am. Geriatr. Soc., 20, 57 6 (Dec. 1972) 9. Ganong, W.F., Review of Medical Physiology, 2nd ed., Lange Medica l Publicat ions, Los Angeles, Calif., 357 (1965) 10. Guyton, A.C .. Textbook of Medical Physiology, 4th ed., W.B. Saunders Co., Philadelphia, Pa., 847- 849 ( 1971 ) 11. Greden, J.F., " Caffe ine Tox ic ity Mimics Neurosis," JAMA , 229, 1563 (1975) 12. Lasagna, L. , " Attitudes Towards Appetite Suppressants- A Survey of U.S. Physic ians," JAMA, 225, 44 (1 973) 13. " Two New Appetite Suppressants," The Medical Letter, 16, 54 (June 197 4)
e
References 1. Ban, T. A., "Clinical Psychopharmacology and Psychiatry," Dis. Nerv. Syst. 36 6 12- 620 ( 1975) 2. Ayd, F.J .. " Phenothiaz ine Therapy During PregnancyEffect on the Newborn," Int. Drug Ther. Newsletter, 3, 39 (1968) 3. Hollister, L.E ., "Clinica l Use of Psychotherapeutic Drugs: Current Status," Clin. Pharmacal. Ther. 8, 249- 255 ( 1967) 4 . Report to Congress: Controls on the Use o f Psychotherapeutic Drugs, Controller General of U.S., M.W.D., 75-4 7, 10- 12 (April 18, 1975) 5. Ayd, F.J., " Recognizing and Treating Depressed Patients," Mod. Med.. 39, 80-86 (1 97 1) 6. Sheppard, C. , and Merl is, S., " Pragmati c Considerati ons of Curren t Models in the Pred icti on of Psychiatric Drug Effects,' ' Dis. Nerv. Syst., 30, 11 - 14 ( 1969) 7. Sarwer- Foner, G., " Comments on the Psychodynamic As-
8.
9.
10.
11 .
56 7
pects of the Extrapyramidal Reactions," Rev. Can. Bioi. , Extrapyramidal System Neuroleptics, 20, 527 - 533 (1961) Davis. M.S., " Variations in Pati ent's Compliance With Doctor's Adv ice: An Empirical Analysis," Am. J. Public Health, 58 , 27 4- 288 (1968) Boyd, J.R., Covington, T.R. , Stanaszek, W.F.. and Cassous, R. , " Drug Defaulting: Detriment of Compliance,'' Am. J. Hasp. Pharm., 31,485 - 49 1 ( 1974) Porter, A.M.W., "Drug Defaulting in a General Practice ," Br. Med. J., 1, 218- 222, ( 1969) Sharpe, T. R.. and Mikea l, R.L., " Patient Compliance With Antibiotic Regi mens," Am. J. Hasp. Pharm., 31 , 479 - 484 (197 4)
By James D. Colson Prescription and Nonprescription Anorexiants
Various measures are used to lose or control body weight. These may include changes in dietary intake and eating habits, planned physical exercise, individual counseling, group self-help programs, intestinal bypass surgery and various pharmacologic means. The value of pharmacologic intervention in weight reduction is controversial. 1·2·5,6,a, 12,13 This article focuses on the legend and overthe-counter appetite suppressants (anorexiants or anorexigenics) used in weight reduction and maintenance. None of these agents, legend or o-t-c, directly causes weight loss. Their use is indicated for suppressing the desire to eat, when combined with an overall weight reduction program. The use of anorexiants is appropriate only as long as the desired effect results without producing significant, secondary adverse effects. Patients seeking to lose or control their weight need to be aware of the mechanics involved in weight reduction and maintenance and be motivated enough to stay with a program. The pharmacist can assist these patients in understanding the drug and its effects, and he can emphasize and reinforce the need for compliance with the overall weight control regimen. Pharmacists also are in a position to advise patients in cases in which self-medication may be inappropriate or potentially harmful because of the existence of an underlying psychologic or pathologic condition.
Table I
Legend Anorexiants Legend drugs used as anorexiants can be grouped into a single class. (See Table I, above right, for product identification.) Chemically, these agents are all phenethylamine (amphetamine-like) analogs, with the exception of mazindol, an imidazoisoindole compound. 13 The amphetamines, in particular dextroamphetamine, have been used as the standard for comparison of the anorexiants.1 Although differences exist as to the type and degree of secondary effects produced, duration of action and relative potency, no one particular agent has been shown to be significantly any more effective than any other agent in this class. 6 · 13 These agents are thought to act on central mechanisms involved in appetite regulation located in the brain's hypothalamic and limbic regions. The desired anorexiant effect of these agents is accompanied by secondary effects manifested by CNS stimulation and other sympathetic activity. Although there does not seem to be a direct correlation between CNS stimulant and anorexiant potencies, most CNS stimulant drugs do have anorexiant activity. 4 An exception to this general rule is
Vol. NS 16, No. 10, October 1976
Legend Anorexiants
Brand Name
Generic Composition
Remarks
Dexedrine (Others)
Dextroamphetamine S0 4 , P0 4
Desoxyn (Others)
Methamphetamine HCl
More CNS and less cardiovascular effect than amphetamine*; timed-release preparation is available**; Schedule II More pronounced CNS effects than dextroamphetamine; high abuse potential; timedrelease preparation is available**; Schedule II
Didrex
Benzphetamine HCl
Pre-Sate
Chlorphentermine HCl Diethylpropion HCl
Tenuate Tepanil Plegine
Phendimetrazine tartrate
Preludin
Phenmetrazine HCl
Wilpo lonamin Voranil Pondimin San or ex
Phentermine HCL Phentermine Resin Clortermine HCl Fenfluramine HCl Mazindol
Schedule III Long-acting agent; Schedule III Lesser CNS effects; timed-released preparation is available**; Schedule IV Schedule III Timed-release preparation is available**; Schedule II Ion-exchange resin is to provide a more sustained effect; Schedule IV Long-acting agent; Schedule III Produces CNS depression; Schedule IV Long-acting agent; an imidazoisoindole compound; Schedule III
*Racemic amphetamine is not recommended for use as an anorexiant due to its pronounced cardiovascular and lesser CNS effects. **The data are insufficient to adequately evaluate the effectiveness of timed-release preparations in producing a sustained anorex1ant action.l
fenfluramine, an anorexiant which produces significant CNS depression. 7 Anorexiants are indicated for use in exogenous obesity as short-term adjuncts to an overall weight reduction program. The weight loss generally amounts to only a fraction of a pound per week, for roughly five to ten weeks. 6 · 13 Tolerance to the anorexiant effect of these agents develops after short periods of use, often necessitating an increase in the dosage in order to produce a given level of anorexiant effect. Increasing the dose increases the likelihood and occurrence of secondary side effects. When the side effects become significant, the drug has reached its limit of therapeutic value and should be discontinued. Side effects produced by anorexiants used in therapeutic doses are mostly indicative of sympathomimetic activity. They include
headache, dizziness, restlessness, insomnia, tremors, increased pulse rate and blood pressure, nausea, diarrhea, constipation, dry mouth and mydriasis. In situations of acute toxicity or overdose, these effects are accentuated. Chronic use of anorexiants can result in abnormal behavioral changes characterized by increased irritability, aggressiveness, mania, paranoia and delusions (toxic psychosis). Withdrawal of these agents following long-term use often results in generalized mental depression and somnolence. In addition, there is an abuse potential and dependence liability associated with the use of anorexiant agents which must be taken into consideration. In light of these various risk factors, the overall benefit to be derived from use of the anorexiants appears small. Legend anorexiants are also combined
James D. Colson
Captain James D. Colson, MS, is with the U.S. Air Force Biomedical Science Corps, serving as a pharmacy officer at Lackland AFB in Texas where he is the Wing Drug/ Alcohol Abuse Control consultant. He also is affiliated with Wilford Hall USAF Medical Center at the base. Colson received a BS from the University of Washington school of pharmacy in 1972 and an MS from the university's department of pharmacology in 1974. Previously, Colson was a staff pharmacist at Virginia Mason Hospital in Seattle and a clinical instructor at the University of Washington. His background also includes community pharmacy experience. He is a member of ASHP.
565
Prescription and Nonprescription Anorexiants
with other agents such as sedative-hypnotics, antipsychotic tranquilizers, laxatives, antispasmodics, thyroid, diuretics, digitalis, digestives, vitamins and minerals. These combination products, for the most part, are irrational and do more to complicate the potential hazards than increase the effectiveness of the product. 1
Table II
0-t-c Anorexiants*
Brand Name
Manufacturer
Composition
Remarks
Slenderize Weight Control plan
Rieger /Medi-Save
Vitamins and minerals, sodiurn carboxymethylcellulose(SOO mg), benzocaine (9 mg)
Probably subtherapeutic doses
Pretts
Marion
Alginic acid(200 mg), sod ium carboxymethylcellulose (1 00 mg) , sodium bicarbonate(70 mg)
Rationale for using sodiurn bicarbonate is questionable and unspecified
X-11 Reducing Plan
Porter and Dietsch
Phenylpropanolamine(25 mg), methylcellulose(25 mg) , vitamins and minerals, caffeine(25 mg)
Probably subtherapeutic doses
Gobese Diet Plan
Gobese Company
Phenylpropanolamine(SO mg) caffeine(25 mg), vitamins
Timed-release preparation**
Fat-Go
Pruvo Pharmacal
Phenylpropanolamine(25 mg), methylcellulose(25 mg), caffeine(25 mg), vitamins
Probably subtherapeutic doses
E-Lim
Pruvo Pharmacal
Powdered extracts of buchu , juniper , uva ursi and stone root; sodium and potassium nitrate, aloe, oleo resin capsicum
Diuretic and la xative; dose not specified
Hungrex with P.P.A.
Allegheny Pharmacal
Phenylpropanolamine(25 mg)
Probably subtherapeutic dose
Odrinex
Fox Pharmacal
Phenylpropanolamine(25 mg)
Probably subtherapeutic dose
Appedrine Reducing Plan
SDA Pharmaceuticals
Phenylpropanolamine(25 mg) sodium carboxymethylcellulose(SO mg) , caffeine(! 00 mg), vitamins and minerals
Probably subtherapeutic dose
Prolamine
Thompson Medical Company
Phenylpropanolamine(35 mg) , caffeine(l40 mg)
Timed-release preparation **
Figure Aid
Thompson Medical Company
Benzocaine, sodium carboxymethylcellulose, vitamins and minerals
Timed-release preparation; no dose specified
Slim-Mint
Thompson Medical Company
Benzocaine, methylcellulose, dextrose , essential flavors
Dose not specified
Slim-Mint Gum
Thompson Medical Company
Benzocaine, sodium carboxymethylcellulose , dextrose , oils of anise, peppermint , wintergreen, clove and cinnamon
Dose not specified
Aqua Ban
Thompson Medical Company
Ammonium chlorid e, caffeine
Dose not specified
d-Minish Diet Aid Capsules
McKesson Laboratories
Sodium carboxymethylcellulose(300 mg) , benzocaine (9 mg), vitamins and minerals
Timed-released preparation**
0-t-c Anorexiants While there are numerous o+c products available for use in weight reduction, emphasis here will be on those pharmacologic agents which are used as appetite suppressants (as distinguished from the dietary substances such as saccharin, Ayds candy, Metrecal, etc.). These o-t-c anorexiants are thought to act on either central or peripheral mechanisms involved with regulation of appetite. Although there are no guidelines for adequately assessing the relative efficacy of these agents, it can be assumed that the placebo component offered by these agents plays a major role in reinforcing an individual's adherence to an overall weight reduction program. The following represent the different types of o+c anorexiants commonly available. (See Table II, at right, for product identification.) CNS Stimulants-Caffeine and phenylpropanolamine are common agents in this category. The anorexiant effect is thought to be centrally mediated through a mechanism similar to that of the amphetamine-like anorexiants. The dose of phenylpropanolamine that often is used, 25 mg, is probably insufficient to produce the desired effect. 1 Potential secondary effects include manifestations of CNS stimulation, tachycardia, increased blood pressure and gastrointestinal tract disturbances. Patients with cardiovascular disease, hypertension, diabetes and hyperthyroidism should be cautioned against the use of phenylpropanolamine. In addition, caffeine may aggravate Gl tract ulcers and cause disturbances in cardiac rhythm. Caffeinism can also produce signs mimicking neurosis. 11 Laxatives-Bulk-forming agents (e.g., psyllium ,hydrophylic mucilloid, sodium carboxymethylcellulose, methylcellulose, alginic acid) act to produce swelling and distention of the intestines. This peripheral action creates a sense of fullness in the intestinal tract. This fullness, however, is needed more in the stomach, where hunger contractions ("pangs") occur. Other laxatives (e.g., senna, cascara, aloe), in doses producing diarrhea, cause fluid and nutrient loss. Overuse of laxatives can result in severe fluid and electrolyte loss, atony of the colon and other se-
566
*Most of these preparations are t o be taken before or after meals with a glass of water, coffee, tea or a low-calorie beverage. **The s.ignificance of timed-release formulations for some of ttiese·l)reparations is questionable.
rious complications. 3 Patients with Gl tract ulcers or undiagnosed abdominal pain should be warned against the use of laxative agents. Antispasmodics-Belladonna alkaloids (e.g ., hyoscyamine, atropine and hyoscine)
are common to many o+c preparations . Although they are seldom used in o-t-c anorexiant products, these agents supposedly act peripherally to inhibit the Gl contractions often associated with the sensation of hunger, thus reducing appetite. Hunger con-
Journal of the American Pharmaceutical Association
Colson
tractions were once thought to be important in the peripheral regulation of appetite . 10 Animal studies, however, suggest that denervation of the stomach and intestines does not affect food intake.9 The typical atropine-like side effects to expect with these agents include blurred vision , dry mouth, urinary retention , constipation and tachycardia. Those dose-related side effects may well discourage the use of the belladonna alkaloids as anorexiants . Patients with glaucoma , renal hepatic disease or obstructive uropathy should be cautioned against using these types of agents. Local Anesthetics-Benzocaine is commonly used in varied doses. The rationale for use is to suppress appetite by decreasing peripheral sensory desire for food in the mouth. Hypersensitivity reactions are known to occur with benzocaine. 0-t-c anorexiants are often combined with other types of agents, as well as with other anorexiants . For instance, various kinds of diuretics (e .g., powdered extracts of buchu, couch grass, corn silk, uva ursi and hydrangea; sodium or potassium nitrate; caffeine) are used in combinations to produce a relatively rap id, yet small weight loss. (Although this effect is temporary, its immediate onset undoubtedly has a positive psychological impact on the user.) Also, different vitamins and minerals are combined in prophylactic quantities to help supplement those possibly
Clinical Psychiatry ... (Continued from page 559)
mentations and " tardive dyskinesia." The latter is a neurological complication marked by athetoid movements of tongue and mouth in particular. Many " minor" tranquilizers have addictive qualities and may produce serious effects upon withdrawal. This list includes the barbiturates, diazepam, chlordiazepoxide hydrochloride and meprobamate, among others . Here again the pharmacist may fulfill a most important function, alerting the physician who may be unaware of the extent of the patient's dependency. Patient Noncompliance. In recent years, the rate of patient noncompliance has received attention . Published reports indicate that it may run as high as 50 percent, 8 and it is increasingly recognized as a public health problem of great importance.9 It is not altogether clear what the determining factors are, but it is likely that a good work ing all iance between patient and physician aids compliance .10 Simple reinforcement by the pharmacist as he dispenses the prescription
Vol. NS 16, No. 10, October 1976
lost due to dietary restrictions. The merits of many of these o-t-c preparations in contributing significantly to weight reduction and control are based on poorly substantiated claims and inadequately controlled studies . Aside from the question of their efficacy in producing adesired effect, there remains the question of their effectiveness at the comparatively low doses used.
rather limited in scope by comparison. The pharmacist can be instrumental in assisting patients in understanding the fundamental aspects involved in weight reduction and control and how the anorexiant drugs function within the scheme. His attitude can be instrumental in either helping or hindering the patient's efforts at weight reduction.
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Conclusion
The legend and o-t-c anorexiants have similarities as well as differences. Both types are indicated for short-term use in exogenous obesity as adjuncts to an overall weight reduction program. Their degree of effectiveness in producing weight loss is limited and the maintenance of weight loss is transitory, unless appropriate follow-up measures are taken . Despite this limited effectiveness, the value of anorexiants in psychologically reinforcing and motivating compliance to a weight reduction regimen cannot be overlooked. The potential risk factors differ considerably between legend and o-t-c anorexiants . The legend drugs are capable of a wide range of secondary adverse effects, including CNS hyperexcitability, cardiovascular and Gl tract disturbances, abuse potential and dependence liability. The o-t-c drugs are not without their own risk factors, although these are
References
medication and orally repeats or writes out clear instructions can substantially improve patient compliance. 11 Such factors may determine the success or failure in the conduct of maintenance therapy. The pharmacist occupies a key role among the mental health disciplines by reinforcing medication co!Tlpliance, monitoring drug utilization by the patient, and counseling the physician prescriber. His specialized awareness of drug interactions and incompatibilities adds a crucial dimension to safe and effective drug use.
both health provider and patient by serving as reinforcer, observer, educator, advisor and consultant.
Conclusion
Because of the increasing complexity of cl inical psychopharmacology and because the drugs used are so potent, it is inevitable and desirable that there should develop an increasing collaboration between pharmacist and psychiatrist. The pharmacist who has acquired special training in clinical pharmacology needs to become a full member of the mental health team, adding this professional discipline to others whose skills are dedicated to the care of the mentally ill. The pharmacist can fulfill an important role to
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