Download The Pharmacology of Obesity

THE PHARMACOLOGY OF
OBESITY
DR. HANIN OSAMA
DEFINITION OF OBESITY
BMI 25-29.9 (Grade 1, overweight)
BMI 30-39.9 (Grade 2, obese)
BMI > 40 (Grade 3, Morbidly obese)
Increased visceral fat
• Waist > 94 cm in men (waist-to-hip > 0.95)
• Waist > 80 cm in women (waist-to-hip >0.8)
WHY TREAT OBESITY?
Contributes to approximately 300,000 deaths a year,
making it 2nd only to smoking as a cause of death
Contributes or causes to many other diseases including:
• Type 2 Diabetes Mellitus
• Coronary Artery Disease
• Degenerative Joint Disease
• Certain Types of Cancer
• Nonalcoholic Steatohepatitis
INDICATIONS FOR DRUG
THERAPY IN OBESITY
A combined intervention of behavior therapy, dietary changes and
increased physical activity should be maintained for at least 6 months
before considering pharmacotherapy.
• Failure of diet and exercise alone
•
BMI of 30 kg/m² or more or a BMI of 27 kg/m² or more with
comorbid condition
•
Understand that drug therapy is adjunctive to lifestyle intervention
•
Have realistic expectations about weight loss goals and outcomes
•
Demonstrate readiness for change
•
Are unable to lose/maintain weight with lifestyle change alone
•
Comply with medication use
•
Have no medical or psychiatric contraindications
POTENTIAL STRATEGIES FOR ANTIOBESITY DRUG ACTION
• Reducing food intake.
• Blocking nutrient absorption
• Increasing thermogenesis.
• Modulating fat metabolism/storage.
• Modulating the central regulation of body weight.
ADDITIONAL CONSIDERATIONS WHEN USING
ANTI-OBESITY DRUGS
•Weight loss drugs should never be used without continued
concomitant lifestyle modifications and as part of a
comprehensive weight loss program.
•Continual assessment of drug therapy for efficacy and safety is
necessary.
•If the drug is efficacious in helping the patient to lose and/or
maintain weight loss and there are no serious adverse effects, it
can be continued.
•If not, it should be discontinued.
1. SIBUTRAMINE
Mechanism of action:
• Was developed originally as antidepressant
• Inhibit reuptake of serotonin and norepinephrine at nerve
terminals increasing their concentration at postsynaptic
receptors in the brain that affect food intake
• It is also thought to stimulate energy expenditure
Pharmacokinetics
• Rapidly absorbed from the GI
• Extensively metabolized by CYP 3A4 to active metabolites
• With dietary advise this drug is expected to cause loss 57% of the body weight but this tend to be regained after
the drug is stopped
Indications and precautions
• Patients with BMI of 27% who have CVS disease or
BMI >30 with or without CVS disease
• It should be discontinued
• if weight loss at 3monts of starting the drug is
<5% of the initial weight
• the patient regained 3kg after previous weight
loss
• Should not be given more than one year
• Sibutramine is taken once daily with or without food.
Contraindications and D/I
sibutramine should not be used by patients who have:
• uncontrolled hypertension
• coronary heart disease
• congestive heart failure
• Arrhythmias
• stroke
• severe renal or liver dysfunction
• obesity from endocrine disease
• Major eating or psychiatric disorder
Should not be given with TCA because of CNS toxicity
Side Effects
• dry mouth, constipation, headache, insomnia,
increased blood pressure, tachycardia,
sweating, altered taste.
• Should monitor all patients twice weekly in the
first 3 months for hypertension
• Should take in the morning to avoid insomnia
2. ORLISTAT (XENICAL)
Mechanism of action:
• Pancreatic lipase inhibitor that blocks the absorption of
up to one third of ingested fat. (normally 5% of fat is not
absorbed)
• Weight loss is due to calories loss but drug related
adverse effects also contribute by diminishing the food
intake
• Patients who adhere to a low calorie diet and take orlistat
lost an average of 9-10kg after one year (compared to
6kg on placebo)
•
•
Orlistat is taken 3 times daily with meals, if the meal is
missed or contain no fat the dose of orlistat should be
omitted
Treatment should be proceed beyond 3 month only if lost
>5% of the initial body weight and beyond 6 month if lost
>10% should not normally exceed one year and never 2
years
Indications
• Aged 18-75
• Who have lost 2.5kgbody weight by dieting and increasing
physical activity in the previous month
• Patients with BMI of 27% who have CVS disease or BMI
>30 with or without CVS disease
Side effects
• Because it blocks intestinal absorption of fat it can result
in diarrhea and steatorrhea (liquid oily stools), urgency,
abdominal pain. This is minimized by maintaining a strict
low fat diet (<30% of diet)
• Mal-absorption of fat soluble vitamins
C/I
• Chronic intestinal malabsorption
• Cholestasis
INVESTIGATIONAL AGENTS
FOR TREATMENT OF OBESITY
1. TOPIRAMATE
• Topiramate is antiepileptic drug approved by the FDA as
an antiseizure medication.
• When reports surfaced that patients enrolled in initial
trials of the drug and also in clinical practice were
experiencing unexpected weight loss, the effects of the
drug on weight began to be studied.
• Mechanism for weight loss is still poorly understood
2. LEPTIN
•Naturally occurring hormone that plays a role in satiety
and weight maintenance.
•Produced in adipocytes
•Its role in weight regulation is related to its effects on the
hypothalamus, where it leads to:
• satiety
•decreased food intake
•increased energy expenditure in the periphery
•Weight loss was relatively modest.
OTHER DRUGS WITHDRAWN
FROM THE MARKET
• Phentermine, fenfluramnie dexfenfluramine
• Were formerly prescribed appetite suppressants
• Stimulate NE release
• They cause cardiac valve disease and pulmonary
hypertension