This document discusses various anti-obesity agents. It begins by defining obesity and describing factors that contribute to obesity such as genetics, environment, lifestyle and certain drugs. It then discusses various FDA-approved anti-obesity drugs including Lorcaserin, Naltrexone/Bupropion, Liraglutide, Phentermine/Topiramate, and Orlistat. For each drug, it provides information on type, mechanism of action, dosing, effects, pharmacokinetics, adverse effects, precautions and contraindications. The document emphasizes that anti-obesity drugs should be used along with lifestyle modifications and are not intended for long-term use or weight maintenance.

1. ANTI-OBESITY AGNETS
DR. PRERNA SINGH
JUNIOR RESIDENT- 2ND YEAR
DEPARTMENT OF PHARMACOLOGY
JNMC,AMU

2. INTRODUCTION
 Intermittent food supply- storage is important (as triglycerides in adipose
tissue)
 Imbalance between nutrition and usage (sedentary lifestyle)
 State of excess tissue mass
Energy
Expenditure
Calorie intake

3. BMI- AN INDICATOR OF BODY FAT
Exception: athletes – lean muscle mass is high

4. CRITERIA
 Other method – skin fold thickness
 Waist to hip ratio- >1 in men and > 0.9 in women is abnormal

5. Less risk of metabolic disease in pear shaped obes

6.  80- 90-% fat in subcutaneous depots
 10-20 % in visceral depots (mesenteric, omental)
 More health risk with visceral and abdominal
subcutaneous fat

7.  Ectopic fat- when excess calories cannot be
accumulated in adipose , they spill to muscle,
liver
 Ectopic fat is associated with insulin resistance

8. OBESITY ASSOCIATE WITH HIGH RISK OF
 Diabetes mellites
 Hypercholesterinemia
 High plasma triglycerides
 Hypertension
 Heart disease
 Cancers
 Gallstones, arthritis, gout
 Mortality

9. FACTORS CONTRIBUTING TO OBESITY
 Genetics
 Environment and behavioral
 Women
 Lack of activity
 Depression
 Alcohol
 Drug induced- TCA’s, steroids

10. PHYSIOLOGICAL REGULATION OF WEIGHT
 Regulated by endocrine and neural components
 Vagal input- information from viscera like distention of gut

13. ENERGY EXPENDITURE
 BMR- 70% of daily intake `
 Exercise

14. WHEN PHARMACOTHERAPY?

15. CLASSIFICATION OF ANTI OBESITY
 Appetite suppressant- target monoamine receptor in hypothalamus
Locarserin
Phentramine/topiramate
 GI fat blockers

16. FDA APPROVED DRUGS/COMBINATIONS
Lorcaserin
Naltrexone SR /Bupropion SR
Liraglutide
Phentermine/Topiramate ER (Qsymia®)
Orlistat

17. LORCASERIN (BELVIQ®)
 Type of drug: Selective serotonin 2c (5HT-2c)
receptor agonist
 MOA- stimulates 5HT-2c receptors in the
appetite center of the brain. Results in increased
release of alpha-melanocortin stimulating
hormone(α-MSH)
 Dosing: 10 mg twice daily.Discontinue if the
patient does not lose 5% of weight after 12
weeks.

18. Pharmacokinetics-
Well absorbed orally
Metabolized in liver
Excreted more in urine and less in faeces
Effects-
Average weight loss 8%; improved blood pressure, lipids, glycemic control

19. Adverse effects: Headache, dizziness, fatigue,
nausea, dry mouth, constipation; hypoglycemia
with concomitant anti-diabetic agents.
Precautions: Risk for serotonergic syndrome/
neuroleptic malignant syndrome if the patient is
taking serotonergic or antidopaminergic agent.
Caution in patients with valvular heart disease,
congestive heart failure, psychiatric disorders;
Contraindications: Pregnancy

20. NALTREXONE SR/BUPROPION SR
Type of drug:
Bupropion :a dopamine and norepinephrine reuptake
inhibitor
naltrexone :an opioid receptor antagonist used to
treat addiction
Mechanism of action
Bupropion: reduces the activity of dopamine mediated
reward system in the mesolimbic dopaminergic
neurocircuitry
Naltrexone:produces aversion to food by blocking mu
opiod receptors

21. Dosing: Week 1: one pill (8 mg naltrexone/90 mg
bupropion) daily; escalate weekly to target dose
of two pills twice daily (total, 32/360 mg) by
week 4. Evaluate response after 12 weeks on
target dose; stop treatment if weight loss < 5%.
Effect: Long-term use; combination produces > 8%
weight loss (diminished appetite and cravings); >
12% weight loss when combined with intensive
lifestyle intervention. Also improves glycemic
control

22. Adverse effects: Nausea, constipation, diarrhea, headache; most resolve in days
to weeks and do not recur.
Precautions: Warning about suicidal thoughts in patients < 24 years.
Contraindications: Uncontrolled hypertension; seizure disorders; chronic opioid
use; MAOI use; pregnancy.
Other considerations: May be a good choice for patients with co-morbid
depression, as well as those who wish to quit smoking

23. LIRAGLUTIDE (SAXENDA®)
Type of drug: Glucagon-like peptide 1 (GLP-1) receptor agonist
Dosing: 0.6 mg SC once daily injection;
titrate by 0.6 mg/week for 5 weeks to target dose of 3.0 mg.
Evaluate response after 16 weeks; stop treatment if weight loss < 4%.

24. Pk : Binds to serum and tissue albumin
T⅟2 -12 hours
Effect: Achieved 9% weight loss; 71% maintained at 3 years.
Adverse effects: Nausea, vomitting, diarrhoea, constipation, hypoglycaemia

25. Precautions: Hypoglycemia can occur in patients on antidiabetic medications;
may be severe with sulfonylureas or insulin.
Contraindications: acute pancreatitis, pregnancy, breastfeeding.
Other considerations: good choice for patients with or at risk of diabetes and
those unlikely to become pregnant.

26. PHENTERMINE/TOPIRAMATE ER (QSYMIA®)
Type of drug/Mechanism of action:
Phentermine- amphetamine derivative sympatho-
mimetic amine, exerts anorexic effect by
increasing the release of NA and DA from central
nerve terminals as well as by blocking reuptake
of these monoamines.An increase in NA in
hypothalamus decreases appetite
Topiramate- antiepileptic, D-fructose derivative,
weight loss is a side effect

27. Dosing: 3.75 mg phentermine/23 mg topiramate ER; escalate to 7.5/46 mg after
2 weeks. Response evaluated after 12 weeks, treatment should either be
escalated to a higher dose or discontinued if patients do not achieve ≥ 3%
weight loss.
Effects: Additive effect of drug combination leads to more weight loss than
either agent alone

28. Adverse effects
Phentermine may cause HTN, tachycardia, insomnia, anxiety, dizziness
Topiramate may cause, urolithiasis, metabolic acidosis, angle closure glaucoma
Contraindications:
Topiramate is a known teratogen; pregnancy should be ruled out before
starting the medication

29. ORLISTAT (RX: XENICAL®; OTC: ALLI®)
 Type of drug/action: Peripherally acting pancreatic lipase inhibitor;
reduces absorption of ingested fat.
 Effects: Orlistat plus behavioral counseling doubled weight loss
seen with placebo/counseling.
 Dosing: 120 mg three times daily with meals (or over-the-counter
alli® at half dose, 60 mg)

30. Adverse effects:
Gastrointestinal (diarrhea, flatulence), especially if
large amounts fat are ingested.
Binds fat-soluble vitamins A D E K
Contraindications:
Pregnancy
cholestasis
chronic malabsorption syndromes

31. Thank you