01-03 Obesity PHARM Flashcards
Which patients qualify for anti-obesity meds?
A) Have a BMI ≥ 30 kg/m2, OR B) Have a BMI ≥ 27 kg/m2 + 1 obesity-related risk factor or dz: —DM 2 —heart dz —atherosclerosis —sleep apnea —excessive waist circumference —dyslipidemia
What are the FDA-approved obesity drugs?
- Orlistat (Xenical OR Alli)
- Phentermine (Adipex-p)
- Phentermine + Topiramate (Qsymia)
- Lorcaserin (Belviq)
Orlistat
—Mechanism
—Efficacy
—ADRs
MECHANISM
—Blocks fat absorption by inhibiting gastric and pancreatic lipases.
EFFICACY
—mod. wt. loss 9-10kg vs. 3 w/ placebo
—↓ HTN, hyperglycemia, hyperlipidemia
ADRs
—Most common ADRs: steatorrhea (oily, loose stools), fecal incont. and freq/urgent BMs. (depend on amt of dietary fat: ? aversion therapy); not absorbed → few systemic ADRs
—↓ absorption of vitamins A, D, E
Phentermine (Adipex-P)
—Mechanism
—Efficacy
—ADRs
MECHANISM
—similar to amphetamines
—stimulates neurons to release high levels of DA & NE → suppress appetite
—Add’l MOAs likely include inhib of NE, DA & 5-HT reuptake by impacting reuptake transporters and inhibition of MAOs → more neurotransmitter available
—Catecholamine ↑ may also indirectly ↑ [leptin] in brain to signal satiety and ↓ [NPY] that normally signals to initiate eating, ↓ energy expenditure, and ↑ fat storage.
EFFICACY
—As monotherapy it is used short-term (12wks) as tolerance has been demonstrated.
ADRs
—increased heart rate and blood pressure, headache, dry mouth, insomnia, constipation, restlessness.
—Used to be combined with fenfluramine (Phen-fen), withdrawn due to valvulopathy and pulmonary hypertension
Topiramate (Topamax)
—Class
—MoAs
1.Anti-convulsant, mood stabilizer, migraine prevention
2.Exact MoA unknown but may act by combo of:
—Blocking voltage-dependent sodium channels
—augments GABA activity at a subset of GABA-A receptors
—antagonism of the glutamate receptor AMPA/kainate
—carbonic anhydrase enzyme inhibition (isozymes II and IV)
3.Taking topiramate in the 1st trimester of pregnancy may increase risk of cleft lip/cleft palate in infant (part of reason for failure of first FDA application). Pregnancy category X.
Lorcaserin (Belviq)
—Specific agonist of the 5HT-2C serotonin receptor to suppress appetite, increase satiety
—Has met efficacy criteria in Phase III trials, eligible for FDA approval
—Avoids adverse effects associated with other serotonin agonists (Fenfluramine-5HT-2B specific)
—5HT-2A associated with hallucinogenic effects
—5HT-2B associated with valvulopathy
—Weight-loss not that impressive (4-5% in 1yr)
Naltrexone + Bupropion (Contrave)
—Buproprion SR = atypical antidepressant norepinephrine-dopamine reuptake inhibitor, unusual in the class as it does not cause weight gain and can cause weight loss.
—Naltrexone is an opioid antagonist approved for EtOH/opioid addiction.
—Makes food less rewarding-decreases pleasure of food/EtOH consumption.
—Has met both FDA benchmarks, approval denied pending CV evaluation
Zonisamide + Bupropion (Empatic)
Zonisamide: approved anticonvulsant, (as with Topiramate exact mechanism of action unknown; blocks voltage-dependent Na and Ca channels, inhibits carbonic anhydrase, inhibits the uptake of the inhibitory neurotransmitter GABA while enhancing the uptake of the excitatory neurotransmitter glutamate)
—Achieved first FDA benchmark, phase III clinical studies ongoing.
A 45 y/o ♂ requests your opinion on how to lose weight. She has no known complications or associated comorbidities secondary to obesity. She read on the Internet that approaches to weight loss are based on the calculation of BMI. She tells you that because her BMI is 33 kg/m2, medical therapy is indicated. Her sister has had great success taking orlistat, having lost 20lb without having any significant side effects.
Which of the following statements regarding the use of orlistat therapy in this patient is true?
A. Orlistat is generally safe and well tolerated by most patients; the patient should be started on orlistat therapy in conjunction with a diet-and-exercise program
B. The patient can be started on Orlistat therapy OTC; there is no need to prescribe
C. Orlistat is generally safe, but a significant number of patients experience side effects; the patient should be started on orlistat therapy in conjunction with a diet-and-exercise program.
D. Orlistat is poorly tolerated by most patients and has life-threatening side effects
C
A 45-year-old woman comes to your office requesting your opinion on how to lose weight. She is 62 inches tall and weighs 200 lb. giving her a BMI of 37 kg/m2.
She has set herself the goal of getting her BMI into the normal range in 12 months which will require her to lose over 60 lb. She wants to start on an anti-obesity medication as soon as possible.
What would you recommend?
A. You start her on Qsymia with recommendations on diet and exercise and wish her luck.
B. You commend her for her goal and offer to start her on Qsymia. You tell her that any weight she loses will impact her health positively and that she should not be discouraged if she doesn’t lose 60+ lbs. in a year as very few people achieve this. A weight drop of 10-20 lb. would be more likely.
C. You start her on Orlistat with recommendations on diet and exercise.
D. You start her on Lorcaserin with recommendations on diet and exercise.
B
The new FDA approved anti-obesity drug Qsymia is a combination of:
A. An anti-convulsant and an amphetamine.
B. An anti-convulsant and an antidepressant.
C. An amphetamine and an antidepressant.
D. An amphetamine and an opioid antagonist
A: Qsymia = topiramate CR + phentermine IR*
*immediate release
The new FDA approved anti-obesity drug Lorcaserin (Belviq) specifically activates which serotonin receptor?
A. 5HT-1A
B. 5HT-2A
C. 5HT-2B
D. 5HT-2C
What’s happens when activating the others?
D: locaserin is a specific agonist of the 5HT-2C receptor
Activating…
…5HT-1A = anti-depressive effects (buspirone)
…5HT-2A causes hallucinogens
…5HT-2B is assoc’d w/ valvulopathy
For which of the following anti-obesity medications do the embarrassing side effects cause dietary modification encouraging healthy eating habits beyond the end of treatment?
A. Lorcaserin
B. Qsymia
C. Orlistat
D. Phentermine
C
For which anti-obesity medication is there a potential increase in infant cleft lip/cleft palate if taken in the first trimester?
A. Lorcaserin
B. Phentermine
C. Orlistat
D. Topiramate
D: Taking topiramate in the 1st trimester may ↑ risk of cleft lip/cleft palate in infant (part of reason for failure of first FDA application).
—Pregnancy category X.
The FDA has only approved 2 new anti-obesity drugs in the past 13 years. What is the primary benchmark for FDA approval in terms of weight loss?
A. > 5% in 12 months
B. > 10% in 12 months
C. > 15% in 12 months
D. > 20% in 12 months
A > 5% in 12 months
—ALSO evidence needed for improvements in comorbidities e.g. lipids, glycaemia, blood pressure etc.
