Transcript Side-effects

Drug therapy in obesity
Safarian.m MD,PhD
Associate professor in nutrition
Obesity Trends* Among U.S. Adults
BRFSS, 1990, 1998, 2007
(*BMI 30, or about 30 lbs. overweight for 5’4” person)
1998
1990
2007
No Data
<10%
10%–14%
15%–19%
20%–24%
25%–29%
≥30%
Treatment strategies
-
Diet
Exercise
Behavior modification
Drug
Surgery
Treatment strategies
‫مکانیسم اثر‬
‫‪ ‬کاهش دهنده اشتها‬
‫‪ ‬کاهش دهنده جذب غذا‬
‫‪ ‬افزایش دهنده تولید حرارت ‪thermogenesis‬‬
‫‪ ‬کاهش دهنده هضم و جذب چربی‬
Pharmacotherapy
•
•
Increased energy expenditure: caffeine
Centrally acting medications:
– Seretonergic pathways: phenfluramine
– Cathecholamine pathways: phentermine
– Nor-adrenergic and serotonergic: sibutramine
– Cannabinoid antagonist: rimonbant

Drugs acting on gastrointestinal tract:
– Pancreatic lipase inhibitor: orlistat
– Bulk forming agents: fiber clear
– Glucosidase inhibitor: acarbose
– Fat polymers: formoline
Currently Available Agents Indicated for
Treatment of Obesity
Generic/Brand Name
Usual Dose
Mechanism of Action
Side Effects
•Belviq/Locaserine
10 mg bid
selective 5-HT2C
receptor agonist
headache, insomnia
•Orlistat/Xenical
120 mg with
each meal
Peripheral: Blocks
absorption of about
30% of consumed fat
GI symptoms (oily
5-15 mg/d
Central: Inhibits
synaptic reuptake of
norepinephrine and
serotonin
Dry mouth,
constipation,
headache, insomnia,
increased blood
pressure, tachycardia
15-37.5 mg per
day as a single or
split dose
Central: Stimulates
release of
norepinephrine
•Sibutramine/Merid
ia
•Phentermine/
Adipex, Fastin,
Ionamin and others
spotting, flatus with
discharge, fecal urgency,
oily stools, incontinence)
CNS stimulation,
tachycardia, dry
mouth, insomnia,
palpitations
Agents sometimes used for Treatment of
Obesity NOT Indicated or FDA approved
Generic/Brand Name
Usual Dose
•ephedrine+/caffeine "Elsinore"pill
Varies: usually
75-150 mg
ephedrine and
100-150 mg
caffeine
Central: Stimulates
CNS stimulation,
adrenergic receptors tachycardia, dry
mouth, insomnia,
palpitations
•Bupropion/Wellbutri
n
100-300 mg/d
Central: Inhibits
reuptake of
dopamine
norepinephrine and
serotonin
•Topiramate/Topama
x
96-192 mg/d
Mechanism of Action
Side Effects
CNS stimulation,
dry mouth,
headache, GI
effects
CNS: paresthesia,
Uncertain: Central ? fatigue, dizziness,
memory difficulty,
concentration
difficulty, and
depression
INDICATIONS FOR USE OF OBESITY DRUGS
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
 Demonstrate readiness for change
 Are unable to lose/maintain weight with
lifestyle change alone
 Comply with medication use
 Have no medical or psychiatric
contraindications

CONTRAINDICATIONS OR CAUTIONS TO THE
USE OF OBESITY DRUGS
Pregnancy or lactation
 Unstable cardiac disease
 Uncontrolled hypertension (SBP >180, DBP > 110 mmHg)
 Unstable severe systemic illness
 Unstable psychiatric disorder or history of anorexia
 Other drug therapy, if incompatible (eg MAO inhibitors,

migraine drugs, adrenergic agents, arrhythmic potential)
Closed angle glaucoma (caution)
 General anesthesia

NHLBI Obesity Education Initiative, Expert Panel on
the Identification, Evaluation, and Treatment of
Overweight and Obesity in Adults


Sibutramine (Meridia)
Approved : 1998
Mechanism: Serotonin, norepinephrine and
dopamine reuptake inhibitor, does not
promote serotonin release
 Responders lose >4 pounds in the first 4
weeks of treatment
 Side-effects: hypertension, increased heart
rate, dry mouth, constipation, insomnia,
and headache
Sibutramine – Side Effects
Can result in dry mouth, constipation,
headache, insomnia, increased blood
pressure, tachycardia.
 Should monitor all patients once a month
for hypertension and side effects
 Should take in the morning to avoid
insomnia

Sibutramine Contraindications

Contraindicated with BPH, valvular heart
disease, MAOI or serotoninergics
 With anorexia nervosa
 Using any other centrally-acting appetite
suppressant
 With hypersensitivity to ingredients of
sibutramine
Orlistat (Xenical)






Approved: 1999
Mechanism: non-absorbed inhibitor of
pancreatic lipase.
Administered with meals
Side-effects: GI bloating, flatus, oily stools,
urgency, fat leakage, deficiency of Bcarotene and A,D,E,K vitamins
Improves lipid status and slows progression
to diabetes
Contraindicated in chronic malabsorbtion,
cholestasis, known hypersensitivity
Orlistat

Pancreatic lipase inhibitor that blocks the absorption of
up to one third of ingested fat.

In addition to helping reduce weight, orlistat has been
shown to also:
– lower plasma low-density lipoprotein cholesterol (LDL)
cholesterol levels.
– The decline in LDL cholesterol is greater than that expected due
to weight loss alone.
– Lower HgbA1C in diabetic patients
Orlistat: complications
Fat soluble vitamins
 ?neurodegenerative disease
 ?NAFLD

Phentermine
(Adipex, Ionomin, Fastin)
 Approved for short-term
 Mechanism: Adrenergic
 Side-effects:
use only
over-stimulation and
nervousness, insomnia, and headache
 Contraindicated with PPH, valvular heart
disease, symptomatic cardiovascular
disease, glaucoma, moderate
hypertension
Lorcaserin (Belviq)
selective 5-HT2C receptor agonist
 to activate proopiomelanocortin (POMC)
production and consequently promote
weight loss through satiety
 side effects of: headaches, dizziness,
fatigue, nausea, dry mouth and
constipation.
 pregnant women shouldn't take lorcaserin.

Phentermine-topiramate
(Qsymia)

Phentermine is an appetite suppressant.

Topiramate is an anticonvulsant that has
weight loss side effects.
GLP-1 analogues (Liraglutide)
Adjuvant therapy in diabetic patients
 Weight loss property
 GLP-1:

– GI hormone
– Improved satiety feeling
– Improved non-pancreatic insulin secretion

Problems:
– Subcutaneous administration
– expensive
‫داروهاي غير مجاز‬
‫‪ ‬قيمت مناسب و ارزان‬
‫‪ ‬تبليغات وسيع در رسانه ها و مکانهاي جمعي‬
‫‪ ‬اثر سريع در کاهش وزن‬
‫– عدم امکان کاهش وزن بيش از ‪ 2‬کيلوگرم در هفته‬
‫‪ ‬فروش با نام داروي گياهي‬
‫داروهاي غير مجاز‬
‫‪ ‬عدم تثبيت وزن‬
‫‪ ‬عدم تغيير در روش زندگي و رژيم غذايي‬
‫‪ ‬مخلوطي از داروهاي ديورتيک و محرک مرکز سيری‪ ،‬لووتيروکسين و‬
‫متفورمين‬
‫‪ ‬عوارض متعدد گوارش ي‪ ،‬عصبي‪ ،‬کبدي و طوفان تيروئید‬
Drugs not indicated
 Fluoxetine (Prozac)
 Thyroid hormone
 Androgens
 Growth hormones
 Amphetamines
 Diueritcs
‫ترکيبات داروهاي غير مجاز‬
Bumetanide
 Flouxetine
 Furosemide
 Phenophetalein
 Phenytoin
 Levothyroxin
 Metformin
 Sibutramine
 Rimnobandt

‫داروهاي غير مجاز‬
‫‪ ‬نامهاي جذاب مانند‪fat burner, Slimming, Magic :‬‬
‫‪slim, Perfect slim, natural model, body‬‬
‫‪shaping‬‬
‫‪ ‬بر روي برچسب نام کارخانه سازنده ديده نمي شود‪.‬‬
‫‪ ‬توليد اکثر اين داروها در چين و تحت عنوان گياهي است‪.‬‬
‫‪ ‬ورود به کشور با عنوان مکملهاي غذايي‪ :‬عدم کنترل کيفيت و آناليز‬
‫مواد تشکيل دهنده‬
FDA:
These products contain undeclared, active
pharmaceutical ingredients that may put
consumers' health at risk.
 Some of the amounts of active
pharmaceutical ingredients far exceed
FDA-recommended levels.

FDA

Some of the products claim to be "natural"
or to contain only "herbal" ingredients, but
actually contain potentially harmful
ingredients not listed on the product labels
or in promotional advertisements.
‫‪Fat burner‬‬
‫‪ ‬مصرف در باشگاههای بدن سازی‬
‫‪ ‬حاوی ماده ‪ DNP‬که ماده ممنوعه است‪.‬‬
‫‪ ‬سه مورد مرگ در تابستان در کشور انگلستان‪.‬‬
‫‪ ‬تجویزدارو کمک کننده است‪.‬‬
‫‪ ‬باعث افزایش ميزان پاسخ به درمان می شود‪.‬‬
‫‪ ‬توجه کنید که رژیم غذایی و فعالیت بدنی پایه اصلی درمان است‪.‬‬
‫‪ ‬مراقب داروهای غير استاندارد چاقی باشیم‪.‬‬
Thank you for your
attention