a) Diet Therapy

In a weight management program, diet therapy is planned on an individual

basis. But this diet should be put into overweight patient status. It aims to make a 50
to 100 kcal / day deficit an integral part of any weight loss program. According to
Rani, et al, ed., There are several dietary management such as:
Low calorie diet
Low-calorie diets consist of very low when the number of calories less than
800 kcal per day, low when 800-1500 kcal per day and moderate when the
number of calories per day lower about 800 kcal from the calorie income at that
time.
Low-fat diet
Usually low-fat diet composition is the content of fat in the diet is less than
30% of total calories.
Low carbohydrate diet
Called low carbohydrates in foods less than 60 grams per day. The
effectiveness of carbohydrate-based diet to lose weight is still a debate, at least
when viewed from the body's metabolism.
High protein diet
High-protein diets are usually also high in fat. Proteins can spur thermogenesis
so that it can withstand lean body mass and this lowers energy efficiency.
Provision of protein as a substitute for carbohydrates in low-calorie diet,
resulting in more weight loss.

b) Physical activity
Increased physical activity is an important component of a weight loss
program, although physical activity does not lead to more weight loss within six
months of long physical activity is helpful in preventing weight gain. An additional
benefit of physical activity is a reduction in cardiovascular and diabetes risk more
than weight loss without physical activity alone.
For obese patients, therapy should start slowly, and the intensity should be
increased gradually. Laughter can be done entirely at one time or gradually
throughout the day.
Patient can start physical activity by walking 30 minutes with a period of 3
times a week and can be increased intensity for 45 minutes with a period of 5 times a
week. With this regimen, additional energy expenditures of 100-200 calories per day
can be achieved.
These regimens can be adapted into other forms of physical activity, but
walking is more attractive because of its safety and ease. Another strategy to increase
physical activity is to reduce sedentary time by performing other routine physical
activities with low risk of injury.

c) Behavioral therapy
 To achieve weight loss and maintain it, a strategy is needed to overcome the
obstacles that arise during diet and physical activity. Specific strategies include self-
monitoring of the habits of physical activity, stress management, stimulus control,
problem solving, contigency management, cognitive restructuring, and social support

d) Pharmacotherapy
Pharmacotherapy is one of the important components in a weight management
program. Sibutramine and orlistat are weight loss medications that have been
approved by the FDA in the United States for long-term use. In patients with obesity
indications, Sibutramine and orlistat are very useful.
Antiobesity drugs can be divided into the following groups:
1. Noradrenergic groups: amphetamines, fentermin, diethylpropion, and mazindol.
2. Serotonergic groups: fenfluramine and fluoxetine.
3. Noradrenergic and serotonergic mixtures: sibutramin (inhibiting serotonin
reuptake and NE).
4. Gastrointestinal lipase inhibitor: orlistat (inhibits gastric lipase and pancreas).

1. Noradrenergic group
a) Amphetamines
Amphetamine is a stimulant drug (usually available only by
prescription) which is usually used only to treat attention-deficit hyperactivity
disorder (ADHD) in adult and children. It is also used to treat symptoms of
traumatic wounds in the brain and daytime drowsiness in cases of narcolepsy
and chronic fatigue syndrome.
Amphetamines cause the release of norefinephrine, dopamine and
serotonin from presynaptic neurons. The amphetamines also inhibit reuptake
of norefinephrine and dopamine.
At first, amphetamines are very popularly used to reduce appetite and
control weight. Amphetamine trademarks (in the US) include Adderall, and
Dexedrine. While in Indonesia sold in injection packaging with generic
trademark. The drug is also used illegally as a recreational drug (Recreational
Club Drug) and as a performance enhancer (adds confidence or PD). The term
"amphetamine" is often used in mixtures derived from amphetamines.

b) Fentermine
Phentermine, also known as ,-dimethylphenethylamine, is a
psychostimulant drug of the substituted amphetamine chemical class, with
pharmacology similar to amphetamine. It is used medically as an appetite
suppressant for short term use, as an adjunct to exercise and reducing calorie
intake.

Mechanism of action
Phentermine has some similarity in its pharmacodynamics with
its parent compound, amphetamine, as they both are TAAR1 agonists,
 where the activation of TAAR1 in monoamine neurons facilitates the
efflux or, release into the synapse, of these neurochemicals; at
clinically relevant doses, phentermine primarily acts as a releasing
agent of norepinephrine in neurons, although, to a lesser extent, it
releases dopamine and serotonin into synapses as well. Phentermine
may also trigger the release of monoamines from VMAT2, which is a
common pharmacodynamic effect among substituted amphetamines.
The primary mechanism of phentermine's action in treating obesity is
the reduction of hunger perception, which is a cognitive process
mediated primarily through several nuclei within the hypothalamus (in
particular, the lateral hypothalamic nucleus, arcuate nucleus, and
ventromedial nucleus). Outside the brain, phentermine releases
norepinephrine and epinephrine also known as noradrenaline and
adrenaline respectively causing fat cells to break down stored fat as
well.

Contraindications
Phentermine use is contraindicated in those who:
have a history of drug abuse.
are allergic to sympathomimetic amine drugs.
are taking a monoamine oxidase inhibitor (MAOI) or have
taken one within the last 14 days.
have cardiovascular disease, hyperthyroidism, or glaucoma.
are pregnant, planning to become pregnant, or breast-feeding.
Phentermine may prevent drugs like clonidine, methyldopa,
and guanethidine from having any effect. Drugs to treat
hypothyroidism may increase the effect of phentermine.

Adverse effects
Rare cases of pulmonary hypertension and cardiac valvular
disease have been reported. Tolerance usually occurs however risks of
dependence and addiction are considered negligible. People taking
phentermine may be impaired when driving or operating machinery.
Consumption of alcohol with phentermine may produce adverse
effects.

Other adverse effects include:

Cardiovascular effects like palpitations, tachycardia, high blood
pressure, precordial pain; rare cases of stroke, angina, myocardial
infarction, cardiac failure and cardiac arrest have been reported.
Central Nervous System effects like overstimulation,
restlessness, nervousness, insomnia, tremor, dizziness and headache;
 there are rare reports of euphoria followed by fatigue and depression,
and very rarely, psychotic episodes and hallucinations.
Gastrointestinal effects include nausea, vomiting, dry mouth,
cramps, unpleasant taste, diarrhea, and constipation.
Other adverse effects include trouble urinating, rash,
impotence, changes in libido, and facial swelling.

c) Mazindol

Indications

Mazindol is used in short-term treatment of exogenous obesity,

in combination with a regimen of weight reduction based on caloric
restriction, exercise, and behavior modification in patients with a body
mass index of 30 kg of body weight per height in meters squared
(kg/m), or in patients with a body mass index of 27 kg/m2 in the
presence of risk factors such as hypertension, diabetes, or
kghyperlipidemia. Mazindol is not currently available as a
commercially marketed and FDA regulated prescription agent for the
treatment of obesity.

Pharmacology

Mazindol is a sympathomimetic amine, which is similar to

amphetamine. It stimulates the central nervous system, which increases
heart rate and blood pressure, and decreases appetite.
Sympathomimetic anoretics (appetite suppressants) are used in the
short-term treatment of obesity. Their appetite-reducing effect tends to
decrease after a few weeks of treatment. Because of this, these
medicines are useful only during the first few weeks of a weight-loss
program.

Although the mechanism of action of the sympathomimetics in

the treatment of obesity is not fully known, these medications have
pharmacological effects similar to those of amphetamines. Like other
sympathomimetic appetite suppressants, mazindol is thought to act as a
reuptake inhibitor of norepinephrine. In addition, it inhibits dopamine
and serotonin reuptake. The recommended dosage is 2 mg per day for
90 days in patients 40 kg overweight and under; 4 mg a day in patients
 more than 50 kg overweight; separated into two doses separated by a
12-hour window between each 2 mg dose.

2. Serotonergic group

a) Fenfluramine

Fenfluramine (former brand names Pondimin, Ponderax and Adifax),

also known as 3-trifluoromethyl-N-ethylamphetamine, is an anorectic that is
no longer marketed. In combination with phentermine, it was part of the anti-
obesity medication Fen-phen.

Fenfluramine was introduced on the U.S. market in 1973 and

withdrawn in 1997. It is the racemic mixture of two enantiomers,
dexfenfluramine and levofenfluramine. The drug increases the level of
serotonin, a neurotransmitter that regulates mood, appetite and other functions.
Fenfluramine causes the release of serotonin by disrupting vesicular storage of
the neurotransmitter, and reversing serotonin transporter function.[1] The result
is a feeling of fullness and reduced appetite.

3. Noradrenergic and serotonergic group

a) Sibutramine

In 1997, the FDA allowed the market of Meridia-containing sibutramin

drug brands in it. Drugs that have the molecular formula C17H29Cl2NO this
works by inhibiting reuptake norepinephrine, serotonin, and dopamine in the
central nervous system; With inhibition occurring in norepinephrine reuptake
and serotonin 3 times greater than in dopamine. Two molecules of active
metabolite sibutramin (M1 and M2) are also inhibitors of norepinephrine and
serotonin reuptake.

Sibutramin inhibits norepinephrine that will lead to satiety and

suppress appetite and reduce caloric intake due to the anorexane effects
contained by this drug. In addition, sibutramin also increases energy
expenditure and reduces the metabolic rate associated with weight loss.
Sibutramin is suitable if given to patients with uncontrolled appetite, snacking,
frequent feeding at night, requiring short-term weight loss for medical reasons,
low HDL levels, or no contraindications to the use of sibutramin (especially
cardiac abnormalities Or high blood pressure)
 Pharmacokinetics

The drug is rapidly absorbed by oral administration. The time

taken for sibutramin to reach its peak is 1 to 2 hours. First cross
metabolism occurs in the liver, especially by CYP3A4. This drug is
excreted mainly through urine. Foods can reduce the peak levels of M1
(27%) and M2 (32%) in the blood, and the time to reach the peak level
extends to 3 hours.

Indication

Drugs used obese patients to reduce weight can reduce the risk
of obesity-related health problems, with hypertensive records should
be controlled. Sibutramin is recommended for obese people with BMI
greater than 30 kg / m2, or with BMI 27 and with other risk factors
such as diabetes, hypertension, arthritis, sleep apneu, and dyslipidemia.
Peak weight loss occurs after about 6 months of use and weight can be
maintained for at least 1 year. Sibutramin is known to be effective for
maintaining weight loss. Because the sibutramin effect lasts for at least
1 year, then sibutramin is recommended for long-term obesity
treatment.

Dose

The initial dose of 10 mg is given once / day with or without

meals. If weight loss is not significant, then the dose may be increased
after 4 weeks of use to a total of 15 mg once / day. Blood pressure and
heart frequency of the patient should be considered during dose
titration. Not recommended for use with doses above 15 mg. In most
clinical trials, medication is administered in the morning.

Side effects

Side effects of sibutramin include: dry mouth, anorexia,

headache, constipation, insomnia, increased blood pressure and heart
rate, and arrhythmia (requires further monitoring). Patients with a
history of drug abuse need more attention for signs of certain disorders.
 Contraindications

Contraindications from sibutramin include: uncontrolled

hypertension; Patients with a history of myocardial infarction, angina,
heart failure, cardiac arrhythmias, stroke or a transient ischemic attack
(Transient Ischaemic Attack), or peripheral arterial disease.

Drug Interactions

Sibutramin will interact if given along with sympathomimetic

drugs, for example nasal decongestants. If given together with a
serotonergic drug, for example the Selective Serotonin Reuptake
inhibitors (SSRI) antidepressants, such as fluoxetine or sertalin, may
produce potentially fatal serotonin syndrome, so it is also
contraindicated.

4. Gastrointestinal lipase inhibitor

a) Orlistat
Orlistat is a synthetic lipstatin derivative (a lipase inhibitor) produced
by Streptomyces toxytricini. Gastrointestinal lipases (pancreas and stomach)
are important for the absorption of long-chain triglycerides and facilitate
gastric emptying. Orlistat works selectively in inhibiting gastrointestinal lipase
by inhibiting the formation of free fatty acids from food triglycerides, so that
dietary fat absorption decreases and body weight may be reduced. These drugs
are very little absorbed and used with foods containing fat to show the desired
results.
The weight loss that occurs in patients taking orlistat may be due to the
individual reducing their fat intake to avoid severe gastrointestinal effects such
as steatorrhea. Vitamin supplements (especially vitamin D) can be given in the
event of a deficiency of fat soluble vitamins. Orlistat can not be given longer
than 2 years due to lack of experience in that period.
Orlistat is suitable if administered to patients who have lost weight at
least 2.5 kg as a result of drug use, requiring long-term therapy, which in its
dietary therapy requires a high fat intake, has high LDL levels, has impaired
glucose tolerance, has repeatedly lost Weight gain lately and quickly restore it,
or have the ability to undergo a low fat diet for a long time.

Dose
 Provision of orlistat at a dose of 120 mg given immediately
before, during, and up to 1 hour after each large meal (maximum 360
mg / day). Giving the dose gives the result that fat can be reduced to
30%. A maximum of 2 years treatment therapy. Not recommended for
children.

Side effects
Side effects of orlistat include: soft feces, abdominal pain,
flatus, fecal urgency or incontinence most commonly occurring during
the first 1-2 months with mild to moderate degrees and tend to improve
with continued use.

Contraindications
Contraindications from orlistat administration include: chronic
malabsoprsi syndrome, cholestasis, pregnancy and lactation.

e) Surgical therapy
Surgical therapy is one option to lose weight badab. This therapy is only given
to patients with clinically severe obesity with a BMI 40 or 35 with comorbid
conditions. This surgical therapy should be done as a last resort for patients who fail
with pharmacotherapy and suffer from extreme obesity complications.
According to Oswari (1995), during this time there has been considerable
controversy about any type of surgical policy to control obesity, surgical measures
that have been tried with varying degrees of success include three main types:
Jejunal shortcut actions are initially stimulated by knowledge of the fact that
massive bowel resection usually causes severe weight loss, imanisi, san
extreme case greeting, lethal. For this reason, shortcut intestines are
introduced for management of morbid obesity. End-to-end jejunoileostomy
has been performed in many patients as well as end-to-end jejunoileum
shortcuts.
Gastroplastic action is characterized by the formation of small gastric pouches
on the esophagogaster junction with the placement of stitches or staples
across the cardia and leaving only a small channel (1cm).
Gastric bypass action is generally characterized by the formation of a small
proximal gastric sac with a gastrojejunum 'roux-en-Y' also with a channel of
about 1cm to reduce the capacity

Source :

o Sugondo, sidartawan. 2014. Buku Ajar Ilmu Penyakit Dalam jild II 6th edition.
Jakarta: Interna Publishing. Page 2569-2570
o Indrayoga, Andrika. 2015. Terapi farmakologi obesitas. Page 4-5
www.medicinesia.com/kedokteran-klinis/obat/penatalaksanaan-obesitas/ 6/12