Drug Treatment and Obesity

General:

• Great controversy over the use of drugs for treatment of obesity.
• Anorexiants can be viewed by doctors, patients, and legislators as:

-- harmful placebos

-- useful treatment in weight control

• Anorexiant is any substance that diminishes or causes loss of appetite.

• It is acceptable to use drugs to control many disease states (not cure):

-- high blood pressure

-- type II diabetes

-- peptice ulcers

• Obesity is a chronic and ongoing problem where it is not acceptable to use drugs to control the disease. A cure is expected by use of the drugs.

• The body defends against weight pertubations:

-- hunger increases

-- metabolism may decrease

-- GI becomes more effecient in absorbing nutrients

-- thyroid hormones may be altered

• Negative image of anorexiants has occurred because of abuse for weight control:

--Schedule II - high abuse potential: dextroamphetamine and methamphetamine

--Schedule III & IV - less abused

-- Fenfluramine (Pondimin) & Dexfenfluramine (Redux) - adverse cardiac effects

 

 

Development of Tolerance to Anorexiant Drugs

"pills or candy"

• Neither tolerance or loss of efficacy occurs for weight loss with drugs.
• A plateau in weight reduction occurs.
• Inappropriate goals or excessive standards in weight loss are what ensure failure.

Increased Control of Anorexiants by FDA

• Poor prescribing by physicians to the general public rather than to obese individuals.
• Physicians cashing in on health care.
• Prescribed to individuals who have no need to lose weight.
• Anorexiants should only be prescribed to individuals when all other methods have failed.
• Scientific evaluation fo the use of drugs for weight loss suffers from poor studies with inadequate controls.
• Physicians really "do not know" how to use drugs to control weight.
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Drugs used for Weight Control

• Amphetamines: Schedule II - sympathetic amines which activte the CNS

--Amphetamine sulfate

--Dextroamphetamine sulfate (Dexedrine, Ferndex, Oxydess II, Spancap No. 1)

--Methamphetamine HCL (Desoxyephedrine HCL, Desoxyn Gradumets

--Amphetamine complex (Biphetamine)

--Amphetamine mixtures(Obetrol)

--Phenmetrazine HCL (Preludin)

 

• Non-amphetamine: Scheduled anorexiants

--Diethylpropion (Tenuate, Tepanil)

--Phenteramine

--Mazindol (Mazanor, Sanorex)

• Contraindications:

--individuals with heart disease, i.e. erteriosclerosis, hypertension

--history of drug abuse

--currently taking or have been taking monoamine oxidase inhibitors (MAO) within 14 days risking a hypertensive crisis.

 

 

• Side Effects:

--cardiovascular, CNS, tolerance, abuse

 

• Administration:

--drugs should only be administered in intermittent courses of therapy 3 to 6 weeks followd by a discontinuation period of half the original treatment.

 

 

 

 

• CNS mediated effects caused by the release of norepinephrine and dopamine.
• Site of appetite suppression is thought to be the lateral hypothalamus feeding center.
• Amphetamine drugs should only be used for:

--short-term treatment of obesity in a regimen of weight control which includes calorie restriction.

--individuals who do not respond to alternative therapy such as repeated diets, group programs, and safer drugs.

--not be used when overeating is a psychological problem, amphetamines have little effect on reducing food intake.

 

Serotonin Reuptake Inhibitors (SSRI)s; Schedule III; and Schedule IV Drugs

• Fenfluramine (Pondimin)

--pulled from the market for cardiac side effects

• Fluoxetine (Prozac)

--inhibits serotonin re-uptake in CNS neurons

--alters weight and appetite in underweitght, depressed patients; 9% expected anorexia

--not approved by the FDA for weight reduction

 

• Dexfenfluramine (Redux)

--pulled from the market for cardiac side effects

• Tryptophan or 5-Hydroxytryptophan

--converted to serotonin after entering the brain reducing the amount of food intake

 

• Phendimetrazine tartrate (Obalan, Plegine, Trimtabs, others)
• Benzphetamine HCL (Didrex)

Thermogenic Drugs

• Thyroid hormone - No current indication for its use; increases protein breakdown, calcium loss, and risk of cardiovascular dysfunction.
• Ephedrine - data are inconclusive but it has been shown to be effective for the treatment of obesity, sympathomimetic amine.
• Beta-adrenergic Agonists - experimental but have been shown to be effective.
• Growth Hormone - controversial and experimental, acromegaly is a serious side effect.

Drugs that Affect the GI Tract

• Focused area of research interest for drug companies

Benzocaine (otc) - (Diet Ayds, Slim-Mint) anesthetize the mouth or GI tract. A 20-kcal piece is taken before meals to decrease hunger and numb tase buds. Reported by the FDA to "probably" be effective.

Fiber - heterogenous substance made of plan wall fibers which may affect weight control.

• delay gastric emptying, promote fullness
• decrease absorption of nutrients
• promote gas, increase stool mass

Enzyme Inhibitors: Orlistat (Xenical)

• Lipase inhibitor for obesity management, including weight loss and weight maintenance, when used in conjunction with a reduced-calorie diet.
• Indicated to reduce the risk of weight regain after prior weight loss.
• Reduces the absorption of fat soluble vitamins, and beta-carotene.
• Counsel patients to take a multivitamin to insure adequate nutrition.
• June 1999 FDA approved, Hoffmann-LaRoche's lipase inhibitor.

Sucrose polyester (Olestra):

• Sucrose esterified with fatty acids
• Indigestible
• Characteristics of cooking oil
• Theory - reduces the absorption of fats
• Mandy Hall's Lecture - Olestra

Hormones:

• Human Gonadotropin and others are experimental and are not proven to be effective.

Regional Fat Mobilization - lipolysis by injections or applications in lotions or creams.

Weight Loss - Lifetime Committment

• You did not put weight on overnight so you will not lose the weight overnight
• Weight loss involves a committment, changes in lifestyle,
• Exercise program
• Behavior modification