Therapeutics Iv Exam 3- Obesity

Front 1

what is a healthy body weight? normal, overweight range, morbid obesity

Back 1

defined by BMI- normal is 18.5-24.9
overweight is 25-29.9

morbid obesity is > 40

Front 2

disease risk and central obesity

Back 2

central obesity is higher risk of disease even if 2 people have same BMI

Front 3

excessive weight circumference range in men vs. women

abdominal adiposity as predictor of risk (what type of factor)

Back 3

Abdominal adiposity is BAD
Independent predictor of risk
Men >40 inch
Women >35 inch

Front 4

how to measure waist circumference

Back 4

measure right above iliac crest (hip bone) and measure horizontally

Front 5

% of americans obese
% overweight +

% of children obese

Back 5

33% of american pop is obese
70% overweight+ wtf

17% of age 2-19 obese

Front 6

metabolic changes that occur when you become obese: duration

Back 6

FOREVA

Front 7

why the rapid change in obesity rates over the last 30 years? (3)

can't be explained by what?

Back 7

ENVIRONMENT!! “Obesogenic” environment
this means...Less exercise/activity
More “unhealthy” diets
cannot be explained by genetics because 30 years is too quick for evolution

Front 8

5 major consequences of obesity that put ppl at risk for serious health issues

3 other consequences

Back 8

Major risk for serious health consequences

Hypertension
Dyslipidemia
Type 2 Diabetes
CAD
Sleep Apnea
Other consequences:
Gall bladder disease
Certain cancers
Death

Front 9

why causes obesity
#kcal that = 1 lb of fat

Back 9

Imbalance in calories ingested versus calories burned

3500 kcal = 1 lb fat

Front 10

discrepancy between reported and actual energy intake and expenditure: significant difference

Back 10

most people think they are eating way less calories than they are actually eating, and reporting higher amts of energy expenditure

Front 11

greatest areas for prevention and treatment actions (2)

Back 11

Behavior and environment play a large role causing people to be overweight and obese.

Front 12

Process of metabolism is mediated by ______ and _____ influenced by _______

Back 12

endocrine and neural pathways and influenced by genetics

Front 13

In the setting of excess caloric intake and deficient caloric expenditure what happens? (3)

Back 13

excess fat is deposited

over time this = weight gain

Even small changes can have large effects

Front 14

5 things that regulate appetite

name 2 hormones

Back 14

psych factors involved (emotions, reward, learning...)
cultural factors
hormones/peptides in gut (grelin- "grr" and leptin which tells you when you're full)
neural afferents
metabolites

Front 15

4 things that affect caloric expenditure

Back 15

Resting or basic metabolic rate (~70% of daily energy expenditure)
Energy cost of metabolizing and storing food
Thermic effect of exercise (only 10-20%)
Adaptive thermogenesis aka regulation of heat (varies in response to chronic caloric intake)

Front 16

adipocytes are also what?

Back 16

also an endocrine cell that releases numerous molecules in a regulated fashion

Front 17

4 hormones/stuff that adipocytes excrete

Back 17

leptin
adiponectin
resistin

cytokines

Front 18

leptin- in fasted vs. fed state

in obesity

(say what it does- 2 things)

Back 18

fasted state = decreased in leptin, increase in grelin- stimulates appetite and decreases energy expenditure

fed state = increased leptin = decrease apptetite and increase energy expenditure

different in obesity- leptin resistance so it doesn't decrease appetite and increase energy expenditure

Front 19

4 roles of leptin

Back 19

glucose and lipid metabolism
hunter/satiety
thermogenesis/autonomic system
neuroendocrine fxn

Front 20

Body weight is the result of (6)

Back 20

genes, metabolism, behavior, environment, culture, and socioeconomic status

Front 21

obesity and genetics- what makes it hard to determine role of genes?

Back 21

Obesity is commonly seen in families so it's difficult to distinguish role of genes vs. environment

Front 22

genetics affects both...(2)

Back 22

appear to affect both appetite and energy expenditure

Front 23

environmental causes of obesity (3)

Back 23

cultural/societal things like:
availability of food
types of activities

economic drivers- marketing/profits (cheap, fast food makes more profits)

Front 24

in addition to environment and genes, 2 things that affect obesity

Back 24

medications

diseases

Front 25

diseases that cause obesity (6)

Back 25

Cushing disease, growth hormone deficiency, hypothyroidism, insulinoma (insulin causes glucose to be taken up into cells and stored as fat), leptin deficiency, and various psychiatric disorders,

Front 26

5 categories of meds that cause obesity

Back 26

atypical antipsychotics
anticonvulsants
antidepressants
conventional antipsychotics (haloperidol)
hormones

Front 27

4 anticonvulsants that cause fattiness

Back 27

carbamazepine, gabapentin, pregabalin, and valproic acid

Front 28

2 antidepressants that cause obesity

Back 28

mirtazapine and tricyclic antidepressants

Front 29

4 atypical antipsychotics that cause obesity

Back 29

clozapine, olanzapine, quetiepine, and risperidone

Front 30

3 hormone meds that cause obesity

Back 30

corticosteroids, insulin, and medroxyprogesterone

Front 31

who should be advised on weight? (4)

Back 31

basically anyone who meets overweight

BMI 25-29.9 OR waist circumference >40”male/>35”female AND >2 risk factors

OR

BMI>30

but actually...everyone should be...wtf

Front 32

initial eval of someone's obesity (questions to ask) related to the patient's past/why he's fat (6)

Back 32

History of weight gain
Maximum body weight
Any meds causing/worsening weight gain
Previous approaches to quit
Patterns of food intake (including binge eating)
Physical activity

Front 33

evaluation of patient- questions to ask/things to note regarding patient's current status and ability to succeed at weight loss (5)

Back 33

Current BMI & waist circumference
Presence of comorbidities
Assess the patient’s readiness to lose weight
Identify barriers to success
Identify reasonable approaches to weight loss for individual patient

Front 34

risk factors for major comorbidities (6)

Back 34

Cardiovascular disease
Type 2 Diabetes
(includes pre-diabetes: Impaired fasting glucose (100-125 mg/dL) and Impaired glucose tolerance (post-prandial 140-200 mg/dL)
HTN
Hyperlipidemia
Obstructive Sleep Apnea
Increased waist circumference

Front 35

3 weight loss goals

Back 35

Prevent further weight gain
Reduce body weight
Maintain a lower body weight over the long term

Front 36

how much weight to lose? (per week? per 6 months? maintain for how long?)

overall, in terms of patterns of weight loss what is better?

Back 36

Recommend 10% weight loss at 6 months
1-2 pound loss per week
Maintain for 6-12 months and then set goals for further weight loss

Better to lose a little weight and maintain the lower weight than lose a lot only to regain it over time

Front 37

gradual weight loss and maintenance is associated with... (4)

Back 37

Associated with decrease in obesity- associated risk factors (BP, lipids, sugars, waist circumference)

Front 38

lifestyle approaches to weight loss/maintenance (3)

difficulty?

Back 38

Dietary approaches
Physical activity
Behavior modification


MOST DIFFICULT TO ADHERE TO

Front 39

which diet to choose for weight loss?

diets and rapid weight loss- what do studies suggest about these? do people normally maintain this weight loss?

Back 39

NONE IT'S THE CALORIES THAT COUNT

Some diets may result in more rapid weight loss but most studies suggest that weight loss is similar at one year with some studies showing different results

Most people will lose weight on a diet at 6 months; however, most will regain weight by 12 to 24 months.

Front 40

well balanced diet shit

Back 40

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Front 41

daily caloric requirements- what is it made up of? name of formula (don't have to calculate)

if obese how do you use this formula?

Back 41

Basal Metabolic Rate plus Activity Factor (harris benedict formula)

if obese- will overestimate, so may help to use IBW

Front 42

For healthy weight loss, what caloric deficit do you need?

women daily kcals
men daily kcals

never go below...

how you would go about reaching these levels of kcals

Back 42

Need a caloric deficit of ~500 kcal/day
Women: 1,000-1,200 kcal/day
Men: 1,200-1,600 kcal/day
Never <800 kcal/day

make sure to "titrate" to these lvls depending on person's current intake

Front 43

physical activity properties (2)

Back 43

Very important to overall health/maintenance of weight and should be part of weight loss plan

Activity alone is often insufficient to lose weight

Front 44

how much physical activity (time, frequency per week)

good way to reach goal

Back 44

>30 minutes for >5 days/week
May need to set small goals and work up to this target

Front 45

4 benefits of physical activity beyond weight loss

Back 45

Decrease in blood pressure
Decrease in triglycerides & LDL
Increase in HDL
Decrease in mortality

Front 46

5 behavioral modifications to make

Back 46

Goal setting
Self-monitoring: diet diary
Stimulus control
Cognitive restructuring
Prevention of relapse

Front 47

when does weight loss pharmacotherapy come into play? (2)

Back 47

If weight loss goals are not met after 6 months of lifestyle modification, then pharmacotherapy for weight loss may be considered as an adjunct

also if they are at certain BMIs (obese, >=30) weight loss meds are indicated as adjunct therapy

Front 48

eligibility criteria for weight loss meds (2 tiers)

Back 48

BMI 27-29.9 plus 2 comorbid conditions &/or risk factors

BMI>30 with or without comorbid conditions &/or risk factors

Front 49

biggest failure in the past with weight loss drugs

major issues (2) with this drug

Back 49

in the 90s, with phen-fen

pulmonary hypertension, valvulopathies in almost a third of pts

Front 50

4 drug categories/types currently out on market for WL

Back 50

Sympathomimetic Amines
Lipase inhibitor (Orlistat)
Belviq (lorcaserin)
Qsymia (phentermine & topiramate)

Front 51

4 sympathomimetic amines for WL

Back 51

Phentermine, Diethylpropion, Benzphetamine, Phendimetrazine

Front 52

sympathomimetic amines- duration of use

Back 52

Indicated for short-term (up to 12 weeks) treatment (often used >12 weeks)

Front 53

efficacy of sympathomimetic amines

tolerance?
permanence of effect?

side effects prominent?

controlled?

Back 53

~3 kg placebo adjusted weight loss
Tolerance to effects develops over time
Weight is typically regained after therapy
Associated with clinically significant side effects
All are controlled substances

Front 54

indication of sympatho amines (duration of treatment and age)

Back 54

adults and adolescents>16 y.o.a. for short-term (8-12 weeks) treatment of obesity

Front 55

MoA of sympathomimetic amines (2)

Back 55

Increase NE transmission, decrease NE reuptake
Decrease appetite by stimulating satiety centers in the brain

Front 56

when to dose sympatho amines
(don't have to know actual dosing? he said for reference)

Back 56

Avoid dosing later in the day to minimize risk for insomnia

Front 57

Phentermine dosing

Back 57

15-37.5 mg/day

Front 58

AE of sympatho amines (6)

Back 58

Dry mouth
Constipation
Elevated blood pressure
Elevated heart rate
Insomnia
Nervousness

Front 59

PPH (primary pulmonary hypertension) and appetite suppressants

Back 59

PPH incidence in appetite suppressant use is slightly higher but consider that obesity itself increases risk. therefore the absolute risk of PPH is pretty small when using these drugs.

Front 60

8 conditions to avoid sympatho amines

Back 60

Cardiovascular disease (PPH, HF) hypertension, valvulopathy
Anxiety/agitated states
History of drug abuse, addictive tendency
Hyperthyroidism
glaucoma
Pregnancy, nursing or lactating women

Front 61

drug interactions with sympatho amines (2)

Back 61

MAOI’s (at least 14 days between use must be observed)-
SSRI’s

Front 62

when to stop sympatho amines (2)

long term success?

Back 62

Stop if intolerable side effects
Stop if <4 pound weight loss at 4 weeks=unlikely to respond
Evidence for long-term success is limited

Front 63

orlistat indication (include age)

Back 63

Weight loss and maintenance in adults and adolescents >12 yoa

Front 64

MoA/absorption of orlistat

Back 64

GI Lipase inhibitor-decreases fat absorption
Little to no systemic absorption of drug

Front 65

orlistat- when to dose
efficacy depends on what?

Back 65

only works if taken within an hour of food

if pt wasn't eating high fats then this won't help

Front 66

orlistat in clinical trials- efficacy

long term use

Back 66

patients on orlistat achieved 2-4 kg weight loss in1 year- most trials favored treatment with orlistat

little better data for long term use- 2 year trial of pt switching from orlistat to placebo, staying on orlistat, etc. showed weight maintenance

Front 67

orlistat effect on LDL and visceral fat

Back 67

LDL cholesterol mean percent change higher in orlistat users...duh.

also significant decrease in abdominal (visceral) fat

Front 68

2 forms of orlistat and dosing

cost

Back 68

Xenical 120 mg TID with meals

Alli 60 mg TID with meals

$$$$$

Front 69

6 AE of orlistat

Back 69

fatty/oily stool
oily spotting
fecal urgency
fecal incontinence
increased pooping
flatulance

Front 70

orlistat AEs over time...

Back 70

AE decreases over time- may be because pt stop eating high fats

Front 71

avoid using orlistat in pt with...(3)

Back 71

Cholestasis
Chronic malabsorption syndrome
Very high fat meal-increase GI toxicity

Front 72

orlistat and vitamin/drug absorption- which ones does it affect? (5 vitamins, 1 drug)

how to remedy this? (2)

Back 72

Reduced absorption of Vitamins ADEK, beta-carotene- ie the fatty ones-and cyclosporine (interferes with absorption): separate other drugs by 2 hours & take multivitamin

Front 73

Strict FDA Approval Criteria for Treatment of Obesity (3)

Back 73

Induce statistically significant placebo-adjusted weight loss of >5% at 1 year OR

>35% of patients should achieve >5% weight loss (which must be at least twice that induced by placebo)

also requires that the medication show evidence of improvement in metabolic biomarkers, including blood pressure, lipids, and glycemia.

Front 74

lorcaserin indication- when/how to use

patient criteria (BMI, 2 tiers)

Back 74

adjunct to diet & exercise for chronic weight management in adults with BMI >30 or >27 with >1 comorbid condition (HTN, HL, T2DM) what about sleep apnea and shiz?

Front 75

lorcaserin MoA

Back 75

5-HT2C receptor agonist-decreases appetite and increases satiety

Front 76

dosing of lorcaserin

when do you d/c

Back 76

10 mg twice daily; stop at week 12 if 5% weight loss has not been achieved

Front 77

common AE of lorcaserin (5)

Back 77

Nausea, dizziness, headache, fatigue, nasopharyngitis

Front 78

serious AE of lorcaserin (4)

Back 78

hypoglycemia (T2DM pt incidence is ~29%- idk serotonin regulates insulin), serotonin syndrome, heart valve disorder (2.4%), suicidal thoughts (0.6%)

Front 79

lorcaserin DDIs (2 categories of drugs- 2 in the first one, 3 in the second)

Back 79

Drugs with serotonin activity: SSRI’s, SNRI’s, TCA’s

Drugs metabolized by CYP2D6: metoprolol, codeine, tamoxifen

Front 80

CI for lorcaserin

caution in...(4)

Back 80

Avoid in pregnancy
Caution in CKD, heart block, heart failure, depression

Front 81

trials for lorcaserin- duration, pt population,# of trials

avg weight loss

% that achieved at least 5% weight loss

weight maintained if stop drug?

Back 81

3 R,DB,PC trials 1-2 years in duration (2 trials without DM, 1 with DM)

avg weight loss was 3-3.7%

50% pt lost at least 5% in study with no T2Dm...kind of shit

pt who stop drug regain weight

Front 82

locarserin effect on LDL/BP/glucose

Back 82

small but statistically significant difference in LDL/BP/glucose

...not sure if clinically significant

Front 83

benefits of using combo therapy (2)

Back 83

Lower doses of multiple agents may decrease risk for toxicity from higher doses of single agents
Some drugs in combo have been used as single agents so may have a track record of safety or least more well known than an entirely new drug

Front 84

topiramate MoA for WL?

efficacy

Back 84

~5 to 7% placebo adjusted weight loss

MoA unknown but controls satiety

Front 85

Qsymia (formerly QNEXA) what is it

Back 85

Topiramate and phentermine

Front 86

WL treatment algorithm...

Back 86

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Front 87

Qsymia indication- when to use?

criteria for use in adults (2)

Back 87

adjunct to a reduced calorie diet and increased physical activity for chronic weight management in adults with BMI >30 or >27 and >1 comorbidity (HTN, T2DM, HL)

Front 88

Qsymia MoA (2)

Back 88

decreased appetite and increased satiety (exact MOA is unknown)

Front 89

dosing of Qsymia- initial dosing (have to titrate due to topamax)
maintenance dosing

max dose

Back 89

Initial: phentermine 3.75 mg/topiramate 23 mg once daily in the morning X 14 days
Maintenance: P-7.5 mg/T-46 mg once daily
Maximum: P-15 mg/T-92 mg once daily

Front 90

6 AE of Qsymia

Back 90

Paresthesia, dizziness, altered taste (these are topamax)

insomnia, constipation, dry mouth (phentermine)

Front 91

Qsymia 6 DDIs and why

Back 91

MAOI’s: avoid within 14 days-HTN crisis
Oral contraceptives
CNS depressants including alcohol
Non-K+ sparing diuretics: risk of hypokalemia
Antiepileptic drugs
Carbonic anhydrase inhibitors: increased metabolic acidosis

Front 92

CI Qsymia (4)

Back 92

Avoid in pregnancy, glaucoma, hyperthyroidism, within 14 days of MAIOI

Front 93

Qsymia can cause an increase in...(5)

Back 93

Increase in heart rate, suicidal behavior, mood & sleep disorder, metabolic acidosis,

Front 94

Qsymia precautions (4)

Back 94

caution in CKD-increased SCr & max dose
risk of hypoglycemia with T2DM on meds
hypotension with anti-HTN meds?? wtf
potential seizures with abrupt withdrawal (topamax)

Front 95

Qsymia- # of trials
efficacy in trials
% of pt that lost > 5%

effects on comorbidities

Back 95

Two Phase III trials
>5% placebo adjusted weight loss
~45-70% of patients lost >5% still shitty

Improvements in comorbidities

Front 96

using the highest dose of Qsymia was associated with what (heart issue)

Back 96

Highest dose=increase heart rate of 1.5 bpm

Front 97

Contrave (in approval process)- what is it

Back 97

Buproprion (NDRI) and Naltrexone (opioid antagonist)

Front 98

Buproprion - what's it do for pt?

efficacy of WL

Back 98

decrease appetite and food cravings: ~2.8 kg at 52 weeks

Front 99

Contrave at 48 weeks- how much WL?

Back 99

~10 kg wt loss

Front 100

Contrave # of clinical trials

Back 100

4 phase III trials=fairly good results

Front 101

last line for WL

Back 101

surgery!

Front 102

4 types of WL surgery
which is most common

goal of all of these surgeries

Back 102

Vertical banded gastroplasty (VBG)
Roux-en-Y gastric bypass (RYGB)**most common- bypasses the stomach decreasing absorption, and metabolic/hormonal changes

Gastric banding- band the stomach
Biliopancreatic diversion- Part of the stomach is resected, creating a smaller stomach (however the patient can eat a free diet as there is no restrictive component). The distal part of the small intestine is then connected to the pouch, bypassing the duodenum and jejunum.

all restrict capacity in stomach and decrease absorption

Front 103

efficacy of WL surgery

Back 103

Currently most effective method
~40-70% weight loss

Front 104

WL surgery effect on comorbidities (3)

Back 104

Diabetes: 89% resolved
HTN: 66% resolved
OSA (obstructive sleep apnea): 40% resolved

Front 105

complications of WL surgery (4)

Back 105

Nutritional deficiencies, obstruction, infection, death

Front 106

pt on WL surgery- really important to advice them on what? (2)

Back 106

Advise patient on multivitamin and vitamin D supplements

Front 107

CAM (complementary/alternative medications) for WL- (3) good bad?

Back 107

CAM are not regulated like meds
Not tested for safety or efficacy
Some may be dangerous

e.g. ephedra was a stimulant similar to amphetamine that fucked people up

Front 108

7 CAMS and their MoA (for some)

Back 108

Bitter orange- noradrenergic
calcium pyruvate
chromium
chitosan- cationic polypeptide that blocks fat absorption
garcinia
guarana- noradrenergic (Caffeine)
hoodia
tea extracts- noradrenergic (caffeine)

Front 109

stupid summary slide

Back 109

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