Discuss the historical uses of weight loss agents in
the US
Evaluate the Rx approved agents for Weight loss
Assess the Rx agents that has the potential to cause weight loss
Gauge the natural medicines that can be used for weight loss
Objectives
Mid 1900’s
Late 1930s - 1950s:
Doctors began prescribing amphetamines for its side effect of appetite suppression
1959:
Phentermine approved by the FDA
1960’s:
"Rainbow pill" regimes were being used. They were a combination of multiple pills to help weight loss, such as amphetamines, diuretics, and laxatives.
1965:
Appetite suppressant aminorex fumarate was developed as treatment for obesity.
Withdrawn from the market two years later due to pulmonary hypertension side effects.
1970’s
1970:
Adderall® was used as a diet drug, marketed under the name Obetrol.
1973: the Food and Drug
Administration approved the drug fenfluramine
FDA began the recall of diet drugs containing amphetamines.
1979: Fenfluramine and phetermine
have been combined into Fen-Phen® and gained popularity.
1990’s
1992
Fen-Phen® gained more popularity when a report stated that it caused a 10% weight loss.
1994 Dietary Supplement Health and Education Act is passed, which
adds the "dietary supplement" category.
Ephedra classified as a herb and use for weight loss increases.
1995
Dexfenfluramine (Redux®) was developed as an alternative to fenfluramine with less side-effects.
1990’s
1997
Removal of Fen-Phen® is called for by the FDA after reports linking fen-phen with heart valve problems.
Redux® removed from the market due to similar problems relating to cardiovascular health.
1998
Meridia® is put on the market.
2000’s
2004: Ephedra removed from the US market from concerns with
raising blood pressure which could lead to strokes and death.
2009
Hydroxycut® diet supplements pulled off the market after reports of liver damage.
Meridia® (sibutramine) is removed from the US market from concerns that it could raise blood pressure and cause stroke or heart attack.
2000’s
2010
Orlistat (prescription as Xenical®, over-the-counter as Alli®) is available.
Orlistat is taken to reduce the amount of dietary fat that is absorbed by the digestive tract.
MOA: sympathomimetic amine (amphetamine)
Dose: IR- 25mg TID-QID once hour before meals CR- 75mg once a day
Weight Loss: 6.6 lbs. in 6-12 months
AE: pulmonary Hypertension, valvular heart disease, dependence
CI: pulmonary hypertension, hypertension, hyperthyroidism, glaucoma, MAOIs
DI: MAOI, alcohol, anesthetics,
Cautions: consider cardiac evaluation. d/c 4 weeks if not effective.
Diethylpropion (Tenuate®, Tenuate® Dospan®)
MOA: Adrenergic- increase norepinephrine levels
Approved for short term use
Dose- 18.75-37.5 mg before breakfast or 1-2 hours after breakfast or 18.75mg BID
Weight loss- 7.92 lbs 2-24 weeks
AE: over-stimulation and nervousness, insomnia, and headache
DI: alpha adrenergic blockers, SSRI, MAOIs,
CI: PPH, valvular heart disease, symptomatic cardiovascular disease, glaucoma, moderate hypertension
Phentermine (Adipex®, Ionomin®, Fastin®)
• Basic Function: Prevents the absorption of fats,
reducing caloric intake Inhibits pancreatic lipases
which break down fat molecules
• Dose: 160mg TID with meals • Weight loss: 7.6 lbs/5% of
baseline fat at 1 year • OTC version: Alli® Half the dose of prescription
• DI: cyclosporine, warfarin, lowers absorption of many medicaitons and fat soluable vitamins
Side Effects: Oily discharge/fatty stools
Liver failure
Orlistat (Xenical®, Alli® OTC)
Dose-300-400 mg per day divided twice daily
Weight loss- 6.1 lbs in obese patients with depression 6-12 months
AE: dry mouth, nausea, CNS stimulation, tremor, seizures, increased BP
CI: seizure disorder, bulemia, MAOIs
Cautions: drugs that decrease seizure threshold, Strong CYP2D6 inhibitor
Bupropion(Wellbutrin SR®)
Dose-5-10mcg SQ twice daily, 1 hour prior to two main
meals, al least 6 hours apart
Weight loss: 5.94-6.38 lbs over 24 weeks in diabetes patients in diabetes trials
AE: N/V, hypoglycemia, renal impairment, HA
CI: hypersensitivity to exenatide
DI: APAP, anti-infective agents, sulfonylureas, lovastatin
Caution: lower dose if coadministration with sulfonylurea, renal impairment. Do not use if have severe GI disease such as gastroparesis
Exenatide (Byetta®)
Dose: 125 IU IM once daily, plus fat-free 500 Kcal per
day diet
Weight loss- no reliable evidence
AE: ovarian hyperstimulation, edema, HA, depression , fatigue, arterial thromboembolism
CI: precocious puberty, prostate cancer, androgen-dependant cancer,
Cautions: heart disease, renal impairment, seizure disorders, migrane, and asthma
Human Chorionic Gonadotropin (Novarel®, Pregnyl®)
Dose- 60-120 mcg just before major meals (250 kcal or
30g carbohydrate)
Weight loss- 3.74 lbs after 6 months
AE: severe hypoglycemia, N/V, allergic reactions
CI: gastroparesis, hypoglycemic unawareness,
Cautions: May delay drug absorption (may need to separate dose especially for drugs requiring rapid onset)
Pramlintide (Symlin®)
Dose- Variable; most commonly about 100-200 mg
per day divided twice daily
Weight loss- 6.5% baseline wieght loss in 6 months
AE- paresthesia, dysgeusia, irritability, constipation, dry mouth, hyperammonemia,
CI: hypersensitivity
Caution- d/c slowly to prevent seizures, dosage adjustment for renal insufficiency, decreased efficacy of OC
Topiramate (Topamax®)
Dose- 100-600mg daily or divided twice daily based
on response and no faster increase of 100mg every 2 weeks.
Weight loss- 5% of baseline weight loss in 16 weeks
AE: serious skin an dhematologic reactions, mood disorders, psychosis, cognitive impairment, somnolence, dizziness, headache, agitation
Cautions: teratogen, avoid if CrCL<50 ml/min, CYP3A4 substrate
Zonisamide (Zonegran®)
5-Hydroxytryptophan
5-HTP is the precursor to serotonin.
MOA: increase seratonin levels to decrease appetite or cause a feeling of fullness or satiety
Made from L-tryptophan, a natural amino acid found in most dietary proteins
Three studies show appetite reduction and weight loss with 600-900mg daily (avg. 11 lbs. In 12 weeks)
SE: GI effects, linked to Eosinophilia Myalgia Syndrome (EMS)
DI: anything that increases seratonin levels (ie SSRI)
called "fat burning" drugs that increase energy
expenditure
Lots of patients try herbal products touted as "natural" thermogenic enhancers. Patients are often enticed by their savvy brand names...Metabolife...Slenderite...GlycoLEAN Accelerator 2...Fen-Tastic...Naturally Herbal Phen...Thermo Sculpt...and on and on.
Most contain Ephedra but with the FDA controversy some were replaced with bitter orange and Hoodia
Thermogenic agents
Ephedra/Ephedrine
Ephedra: plant with 2 active constituents: Ephedrine
Pseudoephedrine
Ephedrine is normally paired with caffeine in OTC diet supplements
Basic function of Ephedrine: Appetite suppressant
Acts on adrenergic receptors
Weight loss of 0.9kg/month for up to 6 months
Dose: 15-20mg three times daily
Side Effects: High blood pressure
Heart attacks, strokes (can be fatal)
Tremors/seizures
Insomnia
Banned by FDA Drugs now contain
“legal ephedra”
Epehdra without ephedrine
DI: caffeine, QT prolongation, stimulants,
South African spiny succulent plant
MOA: Increases hypothalamic ATP
It's claimed that the San Bushmen eat hoodia to stave off hunger during long hunts.
Effectiveness: No published scientific evidence demonstrating use as appetite suppressant
AR: none reported
DI: none reported
Dose: no typical dose
Hoodi gordonii
Contains 1-6% synephrine
(adrenergic agonist related to ephedrine) Dose of 150mg daily
Essential oil from an type of orange
Similar health concerns and SE as ephedrine
Lack of evidence about effectiveness
DI: It is a CYP3A4 Inhibitor, MAOIs, SSRI, QT prolonging drugs,stimulants,
Bitter Orange
Chitosan
Made from chitin, the main component of crustacean shells (e.g. shrimp, crab, lobsters)
No scientific data confirming its effects as a “fat blocker” or “fat binder” or in promoting weight loss
0.5kg weight loss 1-6 months. Dose: 1-5 grams/day
AR: gi upset, nausea, flatulance, consti
Pation
DI: warfarin
Barley 3-6 grams
barley oil extract, flakes, flour
Digestion Inhibitors
Blond psyllium- 6-12 grams daily
Caution: Theoretically fiber can reduce the absorption of some drugs by reducing GI transit time.
Both Not well studied for weight loss
7-Keto
7-keto DHEA-metabolite of DHEA MOA: Boosts basal metabolism and
thermogenesis In one double bind study, participants were
given either 7-keto or placebo for 8 weeks along with 1800 kcal diet and exercise 3x/week for 45 minutes.
6.34 pounds lost vs 2.3 pounds Increased weight loss associated with higher
levels of T3 Dose: 100mg bid AR: decreased hemoglobin and hematocrit DI: None known
MOA: theorized that CLA might shrink adipose tissue by
inducing apoptosis of fat cells. Also seems to reduce hunger and improve satiety and feeling of fullness
AR:gastrointestinal upset including diarrhea, nausea, loose stools, and dyspepsia
Dose: CLA 0.7-4.5 grams/day seems to significantly decrease body fat mass (BFM) and might increase lean body mass (LBM) in some patients
Caution: Some evidence indicates that the isolated trans-10, cis-12 isomer of CLA increases hyperproinsulinemia and insulin resistance in patients with abdominal obesity.
Conjugated Linoleic Acid
Adults and children with low calcium intake are
more likely to gain weight, have a higher body mass index (BMI), and be overweight or obese compared to people with higher calcium intake
intake of 800-1200 mg seems to increase weight reduction, lean body mass, and body fat loss
Some evidence suggests that increasing calcium consumption by 900-1000 mg/day is associated with an 8-9 kg reduction in body weight
Calcium
People are using it for related for hyperlipidemia,
diabetes, and obesity.
American diets are deficient in chromium, which leads to diabetes, weight gain, and other metabolic abnormalities.
MOA: evidence that chromium can help reduce lipid and glucose levels in patients with diabetes
chromium picolinate produces modest weight loss of about 1.1 kg compared to placebo over 72-90 days
AR: cognitive, perceptual, and motor dysfunction, headaches, insomnia, sleep disturbances, irritability, and mood changes
Chromium
AKA “African Mango” or “bush mango” a tree from
Africa that produces a mango-like fruit MOA: seeds have high soluble fiber content and function
as a bulk-forming laxative. reduces the accumulation of fat in fat cells called adipocytes
in several weight loss products such as Integra-Lean, Vitagetics Vita Lean, Dr. Sears Private Label Primal Force Primal Lean etc.
Clinical research shows that taking a standardized seed extract (IGOB131) 150 mg twice daily for 10 weeks reduces weight by about 13 kilograms compared 0.7 kilograms in overweight patients taking placebo.
AR: flatulence, headaches, and difficulty sleeping DI: none known
Irvingia gabonensis
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Work Cited
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