Obesity and diet pills

By Dr. Mohamed Izham Mohamed Ibrahim
The Sun, November 30, 1996

THE HISTORY OF OBESITY DATES back to the Stone Age.

The primary approaches to the treatment of obesity, from the time of Hippocrates until the 20th century , have principally involved changes in diet and exercise. In the current century, many new treatments for obesity, including drugs, have appeared.

In general, obesity is defined as a body mass index greater than 30 kg/square metre. In clinical practice, it is considered a pathological disorder which could possibly lead to various illnesses. Today, weight loss is still of great interest to many and many such attempts to reduce weight by obese individuals are still regarded to be unsafe.

Obesity, also called corpulence or fatness, is by far the most common effect of continued over-consumption of calories, more calories than are required to meet energy expenditure.

Undoubtedly, many will agree that the most common cause of obesity is over-eating and poor eating behaviour.

Indifferent lifestyles, coupled with the lack of physical activities, are frequently correlated to obesity, there is excessive accumulation of body fat in and on the body. This is due to the excessive calories which are stored as fat. Being overweight does not mean being obese. So when is someone considered overweight or obese? In general, if body weight is 10% more than the optimum weight for a certain height, a person is considered overweight. But if the weight us 20% more than the optimum weight, then he or she is considered obese.

Obesity is not a failure of will or behaviour but a chronic medical condition, just like diabetes or hypertension. Furthermore, obesity can be associated with hypertension, heart disease and gallbladder disorders. It is reported that if a person's weight increases by 10% the blood pressure will increase by 7mmHg and the average cholesterol level will increase by 11 mg/100 ml. It is probably true that some people put on fat more readily than others. This could be due to the fact that some people are more interested in food and expend less energy.

Overeating may be a habit culturally imposed by family customs. It may be due to occupational hazards (e.g. cooks), or it may be an expression of boredom or frustration and may be stimulated by certain drugs. Underexpenditure of energy may be determined by the family environment, an inactive and passive lifestyles or temperament. The normal human body only needs approximately 1,800 to 2,500 calories of energy every day.

Many obese people suffer a considerable sense of inferiority. Misdirected attempts at weight reduction may lead to deficiency syndromes and weakness rather than solving the problem.

There are also people who have a phobia of becoming obese. In wealthy communities, many teenage girls and young women go on special diets to stay slim or become slim, though their attempts may not be successful. To a certain extent, diet pills have been used to overcome these problems.

Drugs of this class used in obese patients are commonly known as "anorectics" or "anorexigenics." Patients using weight-loss drugs face a dilemma. The drugs seem promising but the consequences for long-term users remain uncertain. Drugs can only play a limited role and should never be used as the sole element of treatment. Their positive effects tend to be disappointing and the side-effects are dangerous.

The United States Food and Drug Administration (FDA), for example, issuing a final rule establishing that certain active ingredients in over-the-counter (OTC) weight control drug products are not generally recognised as safe and effective or are misbranded.

There are basically two classes of weight control drugs - bulk-forming drugs and central-acting appetite suppressants (refer to Table 1). The most commonly-used bulk-forming drug is methylcellulose. It is said to reduce food intake by producing feelings of satiety but there is little evidence to support this claim. The central-acting appetite suppressants are also of no real value in the treatment of obesity since they do not improve the condition on a long-term basis. They are sympathomimetics and most have pronounced stimulant effects on the central nervous system.

GENERIC NAMES (BRAND NAMES)SIDE-EFFECTS
Central-acting appetite suppressant
1. Dexfenfluramine (Adifex)

Dry mouth, nausea, constipation, diarrhoea, drowsiness, dizziness, headache, weakness, mood disorder, reactive depression insomnia, anxiety
2. Phentermine (Adipex, Duromine, Ionamin, Panbesy) CNS overstimulation, GI disturbance, dry mouth, loss of appetite, palpitations, abnormal heart rhythms, respiratory depression, coma, drowsiness, rash, tremor, insomnia, rise in blood pressure.
3. Fenfluramine (Dietoff, Ponderax) CNS overstimulation, drowsiness, respiratory depression, coma, dry mouth, loss of appetite, palpitations, abnormal heart rhythms.
4. Mazindol (Teronac) Dry mouth, nervousness, gastrointestinal upset, sleep disturbance, headache, sexual function disturbance, rashes, hypertension, abnormal heart rhythms, diarrhoea, unpleasant taste.
5. Fluoxetine (Prozac) Weakness, somnolence, insomnia, nausea, diarrhoea, sweating, nervousness, tremor, difficulty in swallowing, sexual dysfunction, restlessness.
Bulk-forming drugs
1. Methylcellulose (Celevac)

Flatulence, abdominal distension, intestinal obstruction
2. Sterculia (Prefil) Same as methylcellulose.
Table 1: List of weight control (anti-obesity) drugs.
FEATURES
Obesity is a chronic disease.
Obesity has many causes.
Cure us rare; palluation is realistic.
Weight loss is slow.
Relapse is common.
Weight regain may be slow but is often rapid.
Medications do not work if not taken.
Treatment is often more frustrating than the underlying disease.
Table 2: Features of obesity as a disease.

Use of the amphetamine-like drug phentermine is not justified as possible benefits are outweighed by the risks involved. Abuse of the drug may be a problem. It is used in the management of exogenous obesity as a short-term adjunct (a few weeks) in a regimen of weight reduction based on calories restriction. The limited usefulness of this drug should be measured against possible risk factors inherent in its use. Tolerance to anorectic effects usually develops within a few weeks.

The possibility of abuse of phentermine should be kept in mind. There are reports of patients who have taken increased dosages many times to that recommended. This can cause toxicity which will be manifested by dermatoses, insomnia, irritability, hyperactivity and personality changes. The most severe is psychosis. Fatal poisoning usually culminates in convulsion and coma.

Fenfluramine is also related to amphetamine and is a controlled substance. In standard doses, it has a sedative rather than a stimulant effect. It has not been established, however, that its action in treating obesity is primarily one of appetite suppression. Other central nervous system actions or metabolic effects may be involved.

Nevertheless, abuse of fenfluramine has occurred and abrupt withdrawal may induce depression. It should preferably be avoided but may be considered for short-term adjunctive treatment in selected patients with severe obesity, given close support supervision. It should not be given to patients with a past history of epilepsy, drug abuse or psychiatric illness. It is not recommended for periods of treatment beyond three months.

There have been reports of fenfluramine abuse by subjects with a history of abuse of other drugs. Abuse of 80 mg to 400 mg of the drug has been reported to be associated with euphoria, derealisation and perceptual changes.

The possibility that fenfluramine may induce dependence should be kept in mind when evaluating the desirability of including the drug in weight reduction programmes of individual patients. It should not be used for cosmetic reasons in mild to moderate obesity. Anything more than 5 mg/kg is toxic to humans. 5 to 10 mg/kg may produce coma and convulsions. Most deaths are due to respiratory failure and cardiac arrest.

Fenfluramine has two other characteristics, the importance of which is still not clear. First, it decreases the intake of carbohydrate snacks in some individuals and second, it improves carbohydrate tolerance.

Fluoxetine is marketed as an anti-depressant and is reported to produce weight loss. Its recommended daily dose for treating obesity is 60 mg, triple the normal dose for depression. Critics argue that year-long studies carried out on the drug do not offer reassurance that the drug is safe to be prescribed as medication for the rest of a patient's life.

Mazindol is a controlled substance and is indicated in the management of exogenous obesity as a short-term adjunct in weight reduction based on caloric restriction. This drug can cause tolerance and must be discontinued at a certain point in time. In cases where over-dosage have been reported, the symptoms cited include irritability, agitation, hyperactivity, tachycardia, abnormal heart rhythm and abnormal rate of respiration.

Other drugs such as thyroid hormones have no place in the treatment of obesity except in hypothyroid patients. In addiction, there is no convincing data supporting the use of inhibitors of starch digestion or inhibitors of fat absorption. The central-acting appetite suppressant drugs should be avoided in children because of the possibility of growth suppression.

Obesity can be treated using several modalities. Behaviour modification is preferred. Without an inner motivation to reduce weight, it is impossible to make is happen. Such treatments include a series of techniques designed to modify food intake, improve nutritional knowledge and increase exercise.

Diets, from stringent to modest calories restriction and from low-carbohydrate or low-fat regimes to high-protein regimens, provide an additional modality to the behavioural treatment of obesity. An increase in exercise in exercise is also an important component of behaviour modification. So, there is no need to rely too much on drugs, especially when their safety and effectiveness are questionable.

The writer is a pharmacist and an associate at the National Poison Centre. He is also a lecturer in Social Pharmacy at the School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang.


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