Complementary Medicine Exam 2 (Obesity) Flashcards
Typical Body Composition (Male and Female)
Male:
Muscle (45%), Essential Fat (3%), Nonessential fat (12%), Bone (15%), Other (25%)
Female:
Muscle (36%), Essential Fat (12%), Nonessential fat (15%), Bone (12%), Other (25%)
Differences in fat and muscle in males and females
Body Fat: 15% total in men (12% storage, 3% essential), 27% total in women (15% storage, 12% essential)
Muscle: 31% in men, 20.4% in women
Lean Body Mass (LBM)
LBM is an in vivo concept essential for normal physiological functioning throughout the lifespan
In men, FFM includes 3% essential fat and 12% essential fat in women
LBM vs FFM
LBM includes lipid rich essential fat stores in bone marrow, brain, spinal cord and internal organs. FFM does not include this essential fat.
Obesity Key Facts
Doubled worldwide since 1980
More women than men obese
High percentage of children (17%) are obese
What Obesity causes
Energy imbalance between calories consumed and those expended.
Global increase in intake of energy dense foods high in fat.
Increase in inactivity – many causes
Other factors include diet and physical activity patterns, lack of policy, agriculture, food production, distribution and marketing, etc.
Malnutrition
An acute, subacute or chronic state of nutrition in which varying degrees of overnutrition or undernutrition with or without inflammation activity have led to a change in body composition and diminished function.
Malnutrition prevalence
High prevalence in hospitals.
Leads to high rates of cancer (GI, head and neck, lung and pancreatic)
Also increases in COPD and cerebrovascular accident
Obesity can be a long-term, low level _______________
Catabolic Stress
Catabolic stress shifts
Acute phase responses elicit cytokine-mediated responses and favors the catabolic state; obesity is a long-term catabolic stressor
Acute phase metabolic response favors increase in REE, shift towards positive acute phase reactants, export of amino acids from muscle, increase in gluconeogenesis and expansion of ECF
Downregulation of liver proteins such as albumin in order to increase proteins needed for immune response such as clotting and wound healing.
Inflammation promotes
Muscle catabolism, inhibition of protein synthesis and repair, hyperglycemia, decreased visceral proteins, edema, anorexia, deconditioning/sarcopenia
Inflammation in the brain can cause loss of appetite.
Sarcopenia can result from
1 day of bed-rest; or 1 day in space
Starvation-related malnutrition
No inflammation
Limited access to food; anorexia nervosa, marasmus
Chronic disease-related malnutrition
Mild to moderate inflammation
Organ failure, pancreatic cancer, RA, sarcopenic obesity
Acute disease or injury-related malnutrition
Marked inflammatory response present
Infection, burns, trauma or closed head injury
How is malnutrition defined?
By presence or absence of inflammation
Sarcopenic obesity
Low lean body mass and excessive animosity
Main components of malnutrition identification guide
% caloric intake (under 75% for non-severe, or under 50% in severe)
% weight loss (wk, mo or 3 mo)
Decrease in sub q fat, decrease in muscle, increase in fluid/edema
Reduced grip strength (indication of severe malnutrition)
Chronic obesity is ___________ related
Stress related
When you have obesity in a chronic context, particularly if you are sarcopenic and have low LBM, you have chronic disease related malnutiriton.
Define Obesity
Complex multifactorial chronic disease that develops from interaction of genotype and the environment.
Our understanding is incomplete buy involves social, behavioral, cultural, physiological, metabolic and genetic factors.
Between what years did overweight and obesity prevalence spike?
1976 and 1980
Prevalence of obesity based on ethnic background
African American, Mexican American, Native American, Puerto Rican and White
Higher in females than in males in all groups
Geographic relationship in US between obesity and ___________________
Physical inactivity patterns
It has been hypothesized that care of _______________ will break our health system financially
Type 2 Diabetes
Your ___________ is a better predictor of your health than your genetic code
Zip codeq
Obesity and cancer burden
Accounts for 5% of total cancer burden
39% endometrial cancer, 25% kidney, 11% of colon, 9% of postmenopausal breast cancer
______% of cancer burden worldwide associated with infectious agents
17
Diet means
Manner of living
Assessment of risk for co-morbidities due to obesity
BMI, Waist circumference, weight gain since age of 18, level of fitness
BMI values
Underweight (under 18) Normal (20-24) Overweight (25-29) Obese (over 30) Morbid obesity (over 40)
Waist circumference is good estimate of
Central adiposity (this weight wraps around visceral organs)
BMI calculation
Weight (kg) / Height (m)^2
[Weight (lbs) x 703] / height (in)^2
Obesity is caused by…
think general
the superimposition of specific environmental conditions on a susceptible genotype
Obesity prevalence in the US
300,000 deaths per year, 2nd in preventable mortality only to smoking
Consequence of modest weight gain (visceral adipose tissue)
10% increase in weight results in:
Fasting blood glucose increase of 2-3 mg/dL
Systolic blood pressure increase of 6-7 mm Hg
Metabolic syndrome
Clustering of metabolic abnormalities including resistance to insulin-stimulated glucose uptake, hyperglycemia, hyperinsulinemia, increase in triglycerides and decreased HDL-cholesterol
Factors contributing to obesity and being overweight
Socioeconomic status, race/ethnicity, decreased physical activity, diet, earlier puberty, genetics and hereditary
Metabolic syndrome may lead to
Type 2 diabetes, CVD or Cancer
Conditions associated with obesity
Type 2 diabetes, gall bladder disease, stroke, coronary heart disease, gout, osteoarthritis, hypertension, sleep apnea
Central/Visceral Adipose tissue vs Subcutaneous adipose tissue
Central: Excess central or abdominal fat is independent predictor of disease risk, visceral fat is more metabolically active and those with high amounts are more susceptible to metabolic syndrome
SubQ: Minimal risk associated with lower body obesity
Adipose tissue as an endocrine organ
Increases in:
- Lipoprotein lipase (liberates more fat from stores)
- Leptin
- IL-6
- Adipsin
- Serum free fatty acids
- Angiotensinogen (vasoconstrictor)
- Lactate
- PAI-1
–> All of these add up to more viscous blood, clotting tendency, higher BP and contribute to higher LDL and lower HDL
Increase in Lipoprotein Lipase
Causes decreases in HDL and increases in LDL cholesterol; leads to increase in VLDL cholesterol
Eventual insulin resistance resulting in hyperglycemia
Common hormonal abnormalities in obesity
Increase cortisol, insulin resistance, decrease sex hormone binding globulin women (more tissue exposure to estrogen), decreased progesterone in women, decreased testosterone levels in men, decreased growth hormone production
Metabolic disorders associated with obesity
Type 2 diabetes (increases with degree and duration of overweight individuals; also increases in individuals with more central distribution of body fat)
Dyslipidemia
Liver disease
BMI and Type 2 Diabetes
Low BMI = Less risk of developing diabetes mellitus
Diabetes mellitus and weight loss
Weigh loss reduces risk of developing diabetes.
Weight loss of 5-11 kg decreased risk by nearly 50%
Type 2 DM almost nonexistent in those with weight loss of more than 20kg or with BMI under 20
Dyslipidemia finding related to obesity
Inverse relationship between HDL and BMI (may be more important than BMI and TG relationship)
Central fat plays huge role in lipid abnormalities
NAFLD
Nonalcoholic fatty liver disease describes a collection of liver abnormalities associated with obesity.
75% steatosis, 20% steatohepatitis, and 2% cirrhosis
Adipose Tissue
Specialized connective tissue that function as the major storage for fat in the form of triglycerides.
Two forms: White and Brown
Brown vs White adipose tissue
Brown: deeply vascularized, dense with mitochondria, releases energy directly as heat as result of excess caloric intake via diet-induced thermogenesis (heat generation related to mitochondria metabolism)
White: insulation, cushion and major source of stored energy
Describe White Adipose Tissue
Major bulk of adipose tissue in adult mammals is loose associate of lipid-filled cells with adipocytes
Held in framework of collagen fibers
Adipose tissue also contains stromal-vascular cells including fibroblastic connective tissue, leukocytes, macrophages, and pre-adipocytes, which contribute to structure integrity
Each adipocyte is in close proximity to a capillary
Uniqueness of adipose organ
Only body tissue that can markedly change mass in adulthood (2-3% in athlete to 70% in morbidly obese)
Normal 22% men and 32% women
Composed of stromal vascular cells, blood vessels, lymph nodes and nerves
Blood flow lower than other organs (gets 0.2-0.6L/min, or 3-7% of CO; 15-30% in obese)
Adipose tissue locations
SubQ fat, Dermal fat, Intraperitoneal or omental fat
Adipocyte proliferation
They can hypertrophy (increase in size due to excess triglyceride) or hyperplasia (increase in number)
Half life of 8.4 years
As we age adipocytes have blunted ability to proliferate, differentiate, and confer resistance to cell death –> favoring ectopic fat accumulation
Adipose secretions
Adiponectin - sensitizes skeletal muscle; positive mediator for glucose homeostasis; made primarily by subQ adipose tissue; levels drop in those who are morbidly obese
Contribute to risk of increase lipids, increase BP, increase thrombotic tone
Oxygen can diffuse across ____ cell widths
6
Extracellular matrix __________ during obesity and adipocyte expansion
Hardens, or increases in rigidity
Macrophages aggregate to clean up dead adipocytes, followed by inflammatory mediators
Describe fibrotic stage in obesity
ECM changes cause abnormal fibrotic tissue and an increase in collagen 4
Unconstrained adipocyte cell grwoth, hypoxia and no increase in vascularization
Many dead cells and macrophages - macrophages increase number of cytokines
More matrix metalloproteases to help immune cells clear damage
Lipodystrophy
Caused by certain anti-retrovirals
Degeneration of body’s adipose tissue
Lipolysis
Breakdown of lipids and involves hydrolysis of triglycerides into FFA followed by further degradation into acetyl units by beta oxidation
Lipotoxicity
Cellular dysfunction due to lipid imbalance; surplus FFA induction of apoptosis
Macrophage differences in healthy vs not healthy adipose tissue
More M1 macrophages in non-healthy –> associated more often with inflammation
M2 accumulate during negative energy balance
Triangle of approach to obesity treatment
behavioral, pharmacotherapy, diet and exercise
Benefits of modest weight loss
Normalization of BP
Decrease in blood levels of LDL, insulin, glycated hemoglobin (HbA1C), blood glucose and uric acid
Increased HDL
Improved quality of life
Survival paradox
A high BMI can be beneficial (heart disease, cardiac bypass surgery, etc.)
Could be because people lose weight to an unhealthy point, or that the reserves may serve as a buffer for stress or other things.
Obesity treatment pyramid, top to bottoms.
Surgery
Pharmacotherapy
Lifestyle modification –> Diet, Physical activity
Realistic weight loss treatment goals
5-10% weight loss
Focus on health, fitness, and energy level
Positive mood and appearance
Functional and recreational activities
BMI of ____ or above, bariatric surgery is the only option.
40
General guidelines for medical management of overweight or obese patients
Diet, physical activity, behavioral therapy (irregardless of BMI)
For some, pharmacologic (27 with co-morbidities, or BMI over 30) or bariatric surgery (BMI over 35 with co-morbidities or BMI over 40)
Indication for bariatric surgery
BMI over 40 or more than 100 pounds overweight
BMI over 35 with 2 obesity related comorbidities
Inability to achieve a healthy weight loss sustained for a long period of time
Common bariatric procedures
Gastric bypass, sleeve gastrectomy, adjustable gastric band, biliopancreatic diversion with duodenal switch
Many pharmacologic obesity agents target ________________
Appetite
Indications for obesity drugs
Those engaging in behavior therapy, dietary changes, and increased physical activity for at least 6 months without success
Weight loss drugs should never be used without continuous lifestyle modifications and continual assessment
BMI 30 or more OR BMI 27 or more with comorbid condition; should have realistic weight loss expectations and demonstrate readiness to change; are unable to lose weight with lifestyle modifications alone and are willing to comply with medication use; no medical or psychiatric contraindications
Contraindications or cautions for use of obesity drugs
- Pregnancy or lactation
- Unstable cardiac disease
- Uncontrolled hypertension (SBP > 180, DBP > 110)
- Unstable severe systemic illness
- Unstable psychiatric disorder or history of anorexia
- Other drug therapy, if incompatible (MAO inhibitors, migraine drugs, adrenergic agents, arrhythmic potential)
- Closed angle glaucoma
- General anesthesia
Medication types that can cause weight gain
Psychotropic medications (tricyclic antidepressants, MAOIs, SSRIs, atypical antipsychotics, lithium, anticonvulsants)
Beta-blockers
Diabetes medications (insulin, sulfonylureas, thiazolidinediones)
Highly active antiretroviral therapy
Tamoxifen
Steroid hormones (glucocorticoids, progestational steroids)
Strategies for obesity drug action
Reduce food intake
Block nutrient absorption in the intestine
Increase non-shivering thermogenesis (brown adipose tissue)
Modulating fat metabolism/storage through appropriate adjustments in food intake
Modulating the central regulation of body weight
Orlistat/Xenical
120mg / meal
MOA: Peripheral - Blocks absorption of 30% of consumed fat; lipase inhibitor
Side effects: GI symptoms (oily spotting, flatus with discharge, fecal urgency, oily stools, incontinence)
Sibutramine/Meridia
5-15 mg /d
MOA: Central - inhibits synaptic reuptake of NE and serotonin
Side effects: dry mouth, constipation, headache, insomnia, increased blood pressure, tachycardia
Enhances satiety with no cardiac, lung or neurotoxic effects.
Phentermine/Adipex, Fastin, lonamin, etc.
15-37.5 mg/day
MOA: Central - stimulates release of NE
Side effects: CNS stimulation, tachycardia, dry mouth, insomnia, palpitations
Fenfluramine/Phentermine (Fen/Phen)
Patients not properly assessed
Many patients developed valvular heard disease (8-32%) causing withdrawal in 1997
Lorcaserin and Phentermine
Lorcaserin (Serotonin 2C receptor agonist)
phentermine/topimerate (a sympathomimetic amine/antiepileptic drug)
Both used as adjunct to exercise
Very low rates of use
Orlistat, lorcaserin and phentermine/topiramate efficacy
3% | 3% | 9% (additional weight loss from placebo)
35-73% | 37-47% | 67-70% (achieved weight loss of at least 5%)
No obesity agent has shown to ___________
reduce cardiovascular morbidity or mortality
School programs for obesity prevention
Curriculum includes healthy eating, physical activity and body image
Increased physical activity sessions and fundamental movement skills
Improvement in nutritional quality of food in school
Environmental and cultural practices to promote healthier foods and being active
Support for teachers and staff to implement health promotion
Parent support and home activity that encourage children to be more active and nutritious
Changes in dietary behaviors
Increased consumption of sugar sweetened beverages
Continued low consumption of fruits and vegetables (only increased by 1/2 serving in 30 years)
Increased frequency of meals eaten away from home
The food environment
Increased number of fast food restaurants, lack of access to grocery stores selling affordable food, less health food and beverage advertising aimed at children
State of physical activity
35.5% of adults do not engage in recommended levels and 25.4% report no leisure-time activity
in 2009, 81.6% of high school students did not participate in 60 or more minutes of physical activity on any day of the previous 7 days
Only 30% of high school students have daily `PE
Environmental factors that influence physical activity behavior
Lack of infrastructure supporting active transportation (sidewalks)
Access to safe places to play and be active
Access to public transit
Mixed use and transit oriented developments
Target behaviors for change for obesity prevention
Increased physical activity
Increased consumption of fruits and vegetables (helps with satiety)
Increased breastfeeding initiation for at least 6 months, duration and exclusivity
Decrease consumption of sugar sweetened beverages
Decrease consumption of high energy dense, nutrient poor, foods
Decrease television viewing
WHO drivers of obesity
Reduction in time-cost of food and changes in global food system.
Increased food energy supply through increased mechanization
Present systems of monitoring population weight and nutrition are inadequate in most countries. WE NEED POLICY.
Endocrine society clinical practice guidelines for obesity
Diet, exercise and behavior change (BMI 25 or more)
Pharmacotherapy (BMI 27 or more with comorbidity, OR BMI over 30)
Bariatric surgery (GMI 35 or more with comorbidity or BMI over 40)
Assessement of efficacy and safety of pharm therapy monthly for first 3 months, then every 3 months following. If less than 5% weight loss at 3 months, discontinue.
In those who are obese with T2DM, use antidiabetic withadditional weight loss properties (glucagon-like peptide-1 analogs OR SGLT-2 inhibitors) in addition to first-line agent for T2DM
Non-nutritive sweeteners
Reduce intake of carb-rich foods and replace sucrose with non-nutritive (zero calorie) sweetener
*average American adult consumes 64 lbs of sucrose/year, mostly from processed foods
Saccharin, Cyclamate, Aspartame, Neotame, Acesulfane-K, Sucralose, Stevia, Xylitol
Saccharin (Sweet’N Low)
Synthesized in 1878
300-fold sweeter than sucrose; bitter aftertaste
Heat instable, so limited to use in non-baked products
Causes bladder cancer in rads due to micro-crystals which do not develop in humans
Cyclamate (Sucaryl)
Synthesized in 1937
30-50 times sweeter than sucrose with no bitter aftertaste
Heat stable
Initially labeled GRAS but banned by FDA due to risk of bladder cancer (hexylamine suspected carcinogen)
Still sold in many countries
Aspartame (Equal, Nutrasweet)
Methylated dipeptide
200 fold sweeter than sucrose
Not heat-stable; products not toxic
Very popular (use in more than 1200 products)
Aspartame Metabolism
Cleavage into Aspartate and phenylalanine
>Phenylalanine metabolized to yield methyl group
>Methyl group further metabolized to yield formic acid
Phenylalanine usually hydroxylated into tyrosine, mediated by phenyl alanine hydroxylase
.This enzyme is not functional in phenylketonuria (PKU) patients
PKU Patients instead convert phenylalanine into phenylpyruvic acid
>Phenylpyruvic acid converted into phenylactate
»Both cause poor brain development, seizures, etc.
Neotame
Approved in 2002 but not used in foods
7,000-13,000 fold sweeter than sucrose
Less metabolic conversion into amino acids
20-30% absorbed
Negligible effect on PKU patients
Acesulfane-K (Sunette)
200-fold sweeter than sucrose
Heat stable
Not metabolized
Used in some beverages
Combined with other sweeteners due to bitter aftertaste
Sucralose (Splenda)
Chlorinated derivative of sucrose (3 chlorine)
600-fold sweeter than sucrose
Not metabolized; heat stable
general purpose sweetener
(FDA approved since 1999)
Stevia (Truvia, Rebiana)
Stevioside and related diterpene glycosides from Stevia rebausiana
200-fold sweeter than sucrose
No evidence for stevioside and steviol being genotoxic in vivo.
Rebaudioside A determined GRAS by FDA in 2008
n=2, stevioside
n=3, rebaudioside A
Xylitol (Trident)
Polyol
Same sweetness as glucose, 40% fewer calories
Does not promote dental caries or plaque formation
Sweetener in some chewing gums (can still be labeled sugar free)
Can be used by diabetics
Manufactured by hydrogenation of xylose from corncobs and woodpulp
Olestra (Olean)
Sucrose esterified with stearic acid
Not readily hydrolyzed into fatty acids and sucrose and poorly absorbed
Has potential for hypovitaminosis (ADEK)
May cuase GI cramping and loose stools
Used in the manufacture of potato chips, pretzels and microwave popcorn
Orlistat (Alli, Xenical)
Semisynthetic of natural product lipastatin from Streptomyces toxytricini
Irreversible inhibitor of pancreatic lipase (=less fat breakdown = less fat absorption)
MOA: hydroxyl of lipase attacks carboxyl carbon of orlistat.
Not absorbed but interacts with many compounds
AD: GI related (oily stools, cramps, flatulence)
Non-prescription drug: Alli, 60mg taken with each fat-containing meal up to 3x/day
Rx drug: Xenical, 120mg with each fatty meal 3x/day
*used as adjunct to diet and exercise and can be used long-term
Orlistat notable interactions
Cyclosporine, levothyroxine, warfarin, fat soluble vitamins (except E)
Total length of therapy for anorexiants
Usually shorter than 12 weeks, no longer than 6 months
Anorexiants (classes)
Sympathomimetic amines
Serotonergic agents
*most are CNS stimulants with abuse potential
Sympathomimetic amines (adrenergic agents)
Release NE from storage vesicles in adrenergic neuron and block reuptake
Appetite suppression secondary to CNS stimulation and not understood
DO NOT USE WITH OTHER APPETITE SUPPRESSANTS
Withdrawal if suddenly stopped (depression, fatigue)
Amphetamine, Ephedrine and Pseudoephedrine, Phentermine, Mazindol
Amphetamine
Prototypical anorexiant
Use in diet pills banned in 1979
Ephedrine and Pseudoephedrine
Some OTCs contain ephedrine, a natural product in Ephedra (Ma Huang) banned in 2006
Both are common ingredients of cold and allergy meds
Phentermine
Single weight-loss agent to decrease appetite
Schedule 4 (less potential for abuse than amphetamine)
Continued use can lead to tolerance and rebound weight gain
Phentermine/Topiramate (Ionamine)
Approved in 2012
Topiramate originally an anticonvulsant in epileptic patients
MOA unknown
Mazindol (Sanorex)
Schedule 4
Approved for patients with BMI above 30 OR BMI above 27 with comorbidity (hypertension, hyperlipidemia, diabetes)
Tolerance develops over time (useful only during first few weeks)
Serotonergic Agents
Fenfluramine, Sibutramine. Lorcaserin
Fenfluramine (Pondimin)
Became popular in 1992 in combo with phentermine (Fen-Phen combo)
Withdrawn due to risk of heart valve disease
*Proposed MOA: stimulation of 5-HT2B receptors leads to inappropriate valve cell division
No longer marketed worldwide
Sibutramine (Meridia)
Adrenergic/serotonergic agent
MOA: inhibits NT reuptake and stimulation of thermogenesis by activating the B3 adrenergic system in brown adipose tissue
Withdrawn in 2010 due to CV risks and minimal efficacy
Over 60 dietary and herbal supplements adulterated with sibutramine since withdrawal
Lorcaserin (Belviq)
Selective 5-HT2c receptor agonist
Reduced heart valve disease concerns.
Cannabinoid Receptor Antagonist
Cannabinoids stimulate appetite (very useful in those with cancer)
Rimonabant (Acomplia): first centrally acting CB1 receptor blocker approved as anti-obesity drug
Withdrawn due to concerns of psychiatric side effects (increased risk of suicide)
Glucagon-like-peptide-1 (GLP-1) receptor agonists
GLP-1 functions to (1) increase insulin secretion from pancreas; (2) inhibit gastric acid secretion and emptying; (3) increase satiety by acting on the CNS
Liraglutide
Originally for treatment of type 2 diabetes; recently approved for obesity
Long-acting acylated derivative of GLP-1 with half-life of 13 hours (GLP-1 only has half life of a few minutes)
Produced by heterologous expression in Saccharomyces cerevisiae (Baker’s yeast) and attaching one palmitic acid to Lys in the peptide chaine via a Glu spacer
Injected SC once daily
AD: causes thyroid cancer in rats and contraindicated in those with Medullary Thyroid Carcinoma (MTC) or family history
Other GLP-1 mimetics not approved for obesity yet
OTC diet pills and herbal remedies
Many are mixtures of natural products that also contain appetite suppressants such as ephedrine, propanolamine, or sibutramine (non FDA approved) Ex. LipoFuze –> contains 6 patented and 4 clinically tested fat burning ingredients; consumer must be aware of efficacy and safety
SGLT-2 Inhibitors
Inhibit glucose reabsorption in kidney
>loss of glucose in urine >loss of calories = weight loss >indicated for type 2 diabetes >diuretic effect >camaglitozon, dapaglitozon
Phentermine and diethylpropion contraindication(s)
Do not use if history of uncontrolled hypertension or heart disease
*elevations in mean BP and pulse rate in treated populations
**serotonin receptor agonist such as lorcaserin is better choice
***orlistat also safe
First line(s) in diabetic
SGLT-2 or GLP-1
Contraindication for CV disease
Do not use sympathomimetic drug such as lorcascrin and/or orlistat
Consideration for women and contraceptives
BMI over 27 w/ 1 comorbidity OR BMI over 30, use oral contraceptive over injectable due to less potential for weight gain
Consideration for RA or other chronic inflammatory diseases
Use NSAIDs and disease-modifying antirheymatic drugs since corticosteroids commonly produce weight gain
Common endocrine obesity causes
Hypothyroidism
Cushing syndrome
Common Drug-induced obesity causes
Tricylic antidpressants Oral contraceptives Antipsychotics Anticonvulsants Glucocorticoids Sulfonylureas Glitazones Beta-blockers
Gut hormones and satiety?
GLP-1 in ileum in response to glucose promotes insulin release from pancreas and satiety
Lorcaserin contraindication
Do not use in obese and depressed on SSRI or SNRI due to potential for serotonin syndrome
Phentermine/topiramate or phentermine alone better choice
Orlistat also safe
Phentermin resin (MOA, AE and CI)
MOA: NE releasing agent
AD: Elevated BP, anxiety, cardiovascular palpitations, CNS overstimulation
Contraindications: anxiety disorders, uncontrolled hypertension, breast feeding and hyperthyroidism
Lorcaserin 10mg (MOA and Cautions)
MOA: 5HT2c receptor agonist
Use in caution with SSRI, SNRI/MAOI, and St. John’s Wart
Orlistat dosing
OTC: 60mg TID
Rx: 120mg TID
Phentermine/topiramate ER dosing
QD for at least 2 weeks
Dosing escalation at 2 weeks if patient tolerates; further escalation at 12 weeks if 3% body weight not lost
Lorcaserin dosing
10mg bid
Liraglutide dosing
0.6mg SC initially; increase by 0.6mg/week, up to 3.0mg
Metformin induced weight loss MOA
Mediates phenotypic shift away from lipid accretion through AMP-activated protein kinase
GLP-1 agonists
exenatide and liraglutide
SGLT-2 inhibitors
Dapagliflozin and canagliflozin are antidiabetics that reduce renal blood glucose absorption in proximal convoluted tubule, increasing urinary glucose excretion
Consideration with new-age antipsychotics
have weight gain as side effect
Ziprasidone beneficial properties
Less weight gain than olanzapine and less cholesterol increase than olanzapine, quetiapine and risperidone
AEDs associated with weight loss
Felbamate, topiramate and zonisamide
AEDs associated with weight gain
Gabapentin, pregabalin, valproic acid, vigabatrin and carbamazepine
*valproic acid causes weight gain in adults and children
Weight neutral AEDs
Lamotrigine, levetiracetam and phenytoin
Phentermine not approved for _______________
long-term use
*one approach is to try intermittent therapy
Prescribe phentermine off-label for long-term use if…
Patient has no evidence of serious CV disease
Does not have a serious psychiatric disease or history of substance abuse
Has been informed about weight loss medications that are FDA approved for long-term use and told that these are safe and effective while phentermine has not been proven safe or effective long-term
Does not demonstrate a clinically significant increase in pulse or BP when taking phentermine
Demonstrates a significant weight loss while using the medication
