Pleno pakar Pc3

Blok GDS

Dr.Datten Bangun MSc,SpFK

Dept.Farmakologi & Therapeutik
Fak.Kedokteran USU
MEDAN
 Definition of Obesity
• Occurs when: energy intake >
energy expenditure
• Body Mass Index = wt (kg)/(ht in meters)2
• BMI 20-23 ideal for teens/adults
• 120% of more of ideal body weight or
BMI > 95% defined as obese
• BMI > 30 = obesity in teens and adults
• BMI >95% = obesity in younger children
 Contributing Factors to Childhood Obesity
• Genetic
• Behavioral Factors
– Energy Intake
– Physical Activity
– Sedentary Lifestyle
• Environmental Factors
– Home
– Childcare
– School
– Community
 Why We Care:
Consequences of Obesity
• Hypertension (2.9 x higher in obese)
• Diabetes (2.9 x higher in obese)
• CAD
• Hypercholesterolemia (2.1x higher)
• Other hyperlipidemias
• Mechanical stress on joints, SCFE
• Blount’s disease (tibia vara)
• Pseudotumor cerebri
• Hepatic steatosis, cholelithiasis
• Social stigma- depression, low self esteem
When To Do an Intervention?
• Won’t work until child is ready to change;
may actually do harm if done before child
ready!

• With the very young child, just need parents’

willingness to modify diet/exercise to ensure
success

• Can use motivational interviewing

• May need family therapy, esp if parent with
eating disorder
 Management/Treatment
• Individualized nutrition prescription Goals and intervention
strategies
– Comprehensive, multicomponent weight management program
• Nutrition counseling and education
• Dietary interventions
– Energy restriction
– Altered macronutrient diets
– Specific foods
• Physical activity interventions
• Behavioral interventions
• Family influences and participation
• Pharmacotherapy (weight loss medications) or bariatric surgery,
when indicated
 Pharmacologic interventions

• Pharmacotherapy is an option available for

extremely obese (ie, body mass index [BMI] ≥ 2
units above the 95th percentile) children older
than 12 years of age who have not responded to
1-year dietary and lifestyle treatments, as well
as for those with impaired glucose tolerance or
insulin resistance, steatohepatitis, ovarian
hyperandrogenism, or a strong family history of
diabetes, myocardial infarction, or stroke
 Drugs approved by the Food and Drug
Administration (FDA) to treat obese adults
• Include phentermine, phendimetrazine, benzphetamine,
diethylpropion (appetite suppressants), and orlistat (intestinal
lipase inhibitor); however, most clinicians prescribe orlistat.
• only orlistat is indicated for the treatment of overweight
adolescents.
• It is approved by the FDA for th for the treatment of obesity in
adolescents aged 12 years and older.
• Until recently, sibutramine was widely used as an antiobesity
medication; however, it has been pulled off of the market.
because of clinical data from the large Sibutramine
Cardiovascular Outcomes (SCOUT) study that indicated
increased risk of cardiovascular adverse events.16
 Orlistat
• Orlistat is the only medication indicated by the US
Food and Drug Administration for the treatment of
obesity in adolescents.
• It is approved by the Food and Drug Administration
for use in adolescents aged 12 years and older.
• There is no single approach to successful treatment
of obesity, and lifestyle modification should be
maintained throughout the pharmacologic
treatment.
 Orlistat:

• Orlistat is a gastrointestinal lipase inhibitor that impairs the

absorption of dietary fat.
• Significant and sustained bodyweight reduction for at least 2
years has been noted in clinical trials
• CHD risk factors have been shown to improve as well.
• Orlistat initially was evaluated as a hypolipidemic agent,
since lipid blood levels improve with orlistat treatment beyond
bodyweight loss alone.
• Orlistat treatment may also favorably affect glucose metabolism
in obese pre-diabetics and in patients with type 2 diabetes
mellitus.
• High blood pressure may be improved as well.
 Orlistat:
• Adverse effects:
• -Gastrointestinal adverse effects such as flatus, oily
stools, fecal urgency and fecal incontinence.
• Abdominal pain particularly among patients who do
not comply with the recommended low fat diet.
• Malabsorption of fat-soluble vitamins (A, D, E, and K)
has rarely, if ever, occurred, but a daily multivitamin
in the evening is recommended concurrently with
orlistat treatment as a preventative measure.
 Orlistat
• in children, orlistat decreased BMI by 0.5 to
4.2 kg/m2 compared with either placebo or
baseline.
 Potential Strategies for Anti-Obesity Drug Action

• Reducing food intake. Either amplify effects of signals/factors that

inhibit food intake or block signals/factors that augment food intake
• Blocking nutrient absorption (especially fat or carbohydrates) in the
intestine.
• Increasing thermogenesis. Either increase metabolism and dissipate
food energy as heat or increase energy expenditure through the enhancement of
physical activity.
• Modulating fat metabolism/storage. Regulate fat
synthesis/breakdown by making appropriate adjustments to food intake or energy
expenditure.
• Modulating the central regulation of body weight. Either
alter the internal set point or modulate the signals presented regarding fat stores.
 Agents sometimes used for Treatment of Obesity NOT Indicated or FDA approved

Generic/Brand Name Usual Dose Mechanism of Action Side Effects

•ephedrine+/-caffeine Varies: usually Central: Stimulates CNS stimulation,
"Elsinore"pill 75-150 mg adrenergic receptors tachycardia, dry
ephedrine and mouth, insomnia,
100-150 mg palpitations
caffeine

•Bupropion/Wellbutrin
100-300 mg/d Central: Inhibits CNS stimulation, dry
reuptake of mouth, headache, GI
effects
dopamine
norepinephrine and
serotonin CNS: paresthesia,
•Topiramate/Topamax fatigue, dizziness,
96-192 mg/d Uncertain: Central ? memory difficulty,
concentration difficulty,
and depression
 Early puberty
Researches:
-----childhood obesity associated with:
-glucose intolerance
-hypertension
-high cholesterol……and ..reproduction
 Kisspeptin

• Kisspeptin (formerly known as metastin) is a

protein that in humans is encoded by the
KISS1 gene.
• Kisspeptin is a G-protein coupled receptor
ligand for GPR54. Kiss1 was originally
identified as a human metastasis suppressor
gene that has the ability to suppress
melanoma and breast cancer metastasis
 Kisspeptin
• It recently became clear that kisspeptin-GPR54
signaling has an important role in initiating
secretion of gonadotropin-releasing hormone
(GnRH) at puberty, the extent of which is an
area of ongoing research.
• Peripheral administration of kisspeptin to
prepubertal, 25-day-old female rats stimulates
LH secretion and induces ovulation in the rat.
 Kisspeptin
• kisspeptin neurons respond to leptin and
expression of Kiss1 mRNA is affected by
leptin status. Kis
• Kisspeptin Cells in the Ewe Brain Respond to
Leptin and Communicate with Neuropeptide
Y and Proopiomelanocortin Cells
• (Kathryn Backholer, Jeremy T. Smith, Alix Rao
,et al.2010
• In addition, reproductive function is
extremely sensitive to the energy status,
signalled through the adipose-derived factor
leptin, as well as other peripheral hormones
and metabolic cues (Casanueva and Dieguez
, 1999;
 Pediatric depression
• Pediatric depression in the form of childhood
and adolescent major depressive disorder
(MDD) is a relatively common psychiatric
condition that generally continues
episodically into adulthood.
• depression is frequently caused by a
combination of genetic, psychological, and
environmental factors.
 Pathophysiology
• Brain abnormalities
• Neuroendocrine abnormalities:
- De Bellis et al, in a study examining nocturnal secretion
of adrenocorticotropin (ACTH), cortisol, growth hormone
(GH), and prolactin in a group of prepubertal children
who were depressed and a control group, reported that
prepubertal children who were depressed had lower
cortisol secretion during the first 4 hours of sleep than
did children in the control group.[9] ACTH, GH, and
prolactin secretion did not differ between the 2 groups.
 Treatment:
The choice of initial acute therapy depends on the
following factors:
• Severity
• Number of prior episodes
• Chronicity
• Subtype
• Patient age
• Contextual issues - Eg, family conflict, academic
problems, exposure to negative life events
 Treatment:
• Mild cases
= psychosocial interventions and
psychotherapies are often recommended as
first-line treatments
the most severe cases, medication in addition
to psychotherapeutic intervention is often
recommended.
 Treatment:
• Selective serotonin reputake inhibitors
(SSRIs) like:
- fluoxetine (eg Prozac),
- paroxetine (Seroxat) and
- sertraline (Lustral) were the first choice to
treat childhood and adolescent depression
for several years
Have a bright day
!!!

Ixora flower----sexuality,passion”