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Block 10 Week 2 > Burkin > Obesity & Satiety Drugzzz > Flashcards

Burkin > Obesity & Satiety Drugzzz Flashcards

1
Q

what % of adults are overweight or obese?

A

over 66%

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2
Q

what are the 4 main categories of obesity complications?

A
  1. sex hormone imbalance
  2. increased FFAs
  3. physical stress
  4. decreased QoL
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3
Q

what are the 3 BROAD manifestations of obesity complications in pts?

A
  1. inc mortality
  2. disability
  3. psychological FX
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4
Q

define orexigenic

A

appetite stimulating

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5
Q

name 4 examples of orexigenic compounds

A
  1. ghrelin
  2. AgRP
  3. NPY
  4. Orexin
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6
Q

define anorexigenic

A

appetite suppressing

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7
Q

name 3 anorexigenic compounds

A

leptin
insulin
incretins

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8
Q

define satiety

A

feeling full

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9
Q

what do incretins do?

A

increase insulin secretion from the pancreas

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10
Q

how does the body modulate hunger & satiety in the “simple model”?

A

by sensing metabolic parameters

  1. blood glucose levels
  2. amts of stored fat
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11
Q

what happens in a normal adult to achieve a close match btwn consumed foods & energy requirements?

A

control processes regulate eating behavior & metabolism of energy-rich molecules

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12
Q

T/F: blood glucose levels are critical to hunger

A

true

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13
Q

what detects a decrease in blood glucose (short term)?

A

liver

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14
Q

what happens when there is a decrease in blood glucose (short term)?

A

the liver signals the hypothalamus & generates “hunger” sensations

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15
Q

what 2 things might regulate hunger long-term?

A
  1. declines in the amt of stored glycogen = orexigenic

2. ratio of utilizing stored carb:lipid

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16
Q

where is ghrelin?

A

stomach

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17
Q

where is leptin?

A

adipose tissue

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18
Q

where is insulin?

A

pancreas

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19
Q

where is PYY?

A

small intestine

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20
Q

where do ghrelin, leptin, insulin, & PYY bind?

A

receptors on orexigenic or anorexigenic neurons in the ARC of the hypothalamus

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21
Q

which 2 molecules are orexigenic neuropeptides from the hypothalamus?

A

NPY

AgRP

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22
Q

which 2 molecules are anorexigenic neuropeptides from the hypothalamus?

A

CART

alpha-MSH

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23
Q

what is the ultimate effect of hormonal circuits involving the gut, fat, & brain?

A

change in the sensations of hunger or satiety

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24
Q

Btwn meals, satiety signals (inc/dec) & hunger signals (inc/dec)

A

satiety signals decrease

hunger signals increase

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25
Q

when does the brain initiate responses to feeding?

A

before ingestion even starts

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26
Q

what does ingestion stimulate?

A

mechanoreceptors > distention & propulsion

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27
Q

how are mechanoreceptor responses transmitted (& to where)?

A

along the VAGUS NERVE

to the dorsal vagal complex in the medulla, which ends in the NTS

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28
Q

where do NTS projections go & what do they do?

A

visceral sensory complex of the thalamus

mediate the perception of satiety

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29
Q

what is hunger the motivation for?

A

eating behavior

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30
Q

what increases hunger?

A

low levels of energy-providing molecules in the body

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31
Q

eating reduces hunger, leading to (______)

A

satiety

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32
Q

what happens when food is readily available?

A

people eat when there is no physiological reason

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33
Q

what is it called when you have the desire to eat when there is no physiological need?

A

appetite

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34
Q

what are dieters doing?

A

attempting to bring eating behavior under cognitive control

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35
Q

how do you become obese?

A

when energy enters the body in greater quantities than are expended

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36
Q

how is most XS energy stored?

A

fat

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37
Q

where is most fat stored?

A

in adipocytes in subQ tissue & intraperitoneal cavity

lesser extent: liver & other organs

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38
Q

when can new adipocytes differentiate from fibroblast-like precursors?

A

whenever they FEEL like it, MOM

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39
Q

T/F: obesity is assoc w/ increased NUMBER of adipocytes ONLY

A

FALSE

NUMBER & SIZE!

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40
Q

what is the range for NORMAL BMI?

A

18.5 - 24.9

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41
Q

what BMI is considered underweight?

A

<18.5

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42
Q

what is the range for overweight BMI?

A

25 - 29.9

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43
Q

what is the range for Obese BMI?

A

> 30

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44
Q

what is the BMI range for class I obesity?

A

30 - 34.9

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45
Q

what is the BMI range for class II obesity?

A

35 - 39.9

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46
Q

what is the BMI range for class III obesity (extreme obesity)?

A

= or > 40

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47
Q

what are 2 assessments besides BMI to evaluate obesity?

A
  1. body fat content

2. index of intra-abdominal fat

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48
Q

how does body fat content measuring work?

A

skin fold thickness measured by calipers

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49
Q

How does the index of intra-abdominal fat work?

A

ratio of waist circumference to height

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50
Q

what are the cutoffs for body fat %?

A

males >20%

females >30%

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51
Q

what are the cutoffs for intra-abdominal fat?

A

males >0.95

females >0.8

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52
Q

how does bariatric surgery work?

A

reduce the size of the stomach to lose weight

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53
Q

T/F: bariatric surgery improves short term CVS risk factors & reduces mortality

A

TRUE

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54
Q

who can get bariatric surgery?

A
  1. pts w/ BMI 40+
  2. pts who have tried & failed adequate diet & exercise program (w/ or w/o drugs)
  3. AND present w/ obesity-related comorbid crap (diabetes, HTN, etc)
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55
Q

what is gastric bypass?

A

resecting & rerouting the small intestine to a small stomach pouch

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56
Q

what is sleeve gastrectomy w/ duodenal switch?

A

removal of a portion of the stomach

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57
Q

what is gastric band?

A

implant a device similar to a pacemaker
electrical leads stimulate the ext surface of the stomach
brain interprets this as satiety
(NO THANK YOU)

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58
Q

what is the complication rate (%) in the first 6 mos of bariatric surgery?

A

40%

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59
Q

what is gastric dumping syndrome?

A

ingested foods bypass the stomach > enter the small int mostly undigested > small int expands too fast > fluid shifts into the gut lumen

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60
Q

what % of bariatric surgery pts have gastric dumping syndrome?

A

20%

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61
Q

what are the early sx of gastric dumping syndrome?

A 
N/V
bloating
cramping
diarrhea
dizziness
fatigue
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62
Q

what are the late sx of gastric dumping syndrome?

A

weakness
sweating
dizziness

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63
Q

when do the early sx of gastric dumping syndrome start?

A

15-30 min (after a meal?)

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64
Q

when do the late sx of gastric dumping syndrome start?

A

1-3 hours (after a meal?)

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65
Q

other than gastric dumping syndrome, what are 4 other common complications of bariatric surgery?

A
  1. leaks at surgical site
  2. incisional hernia
  3. infection
  4. pneumonia
66
Q

what are 2 uncommon complications of bariatric surgery?

A

osteopenia
secondary hyperparathyroidism
gallstones
impaired kidney fxn

67
Q

who can get the vagus nerve stimulator?

A

over 18 yo
BMI 35-40
at least 1 other obesity-related condition

68
Q

what is the vagus nerve stimulator?

A

wire leads & electrodes are surgically implanted in the abdomen > sends intermittent pulse to vagus nerve

69
Q

what signals from the brain to the stomach does the vagus nerve involve?

A
  1. gastric acid secretion
  2. digestive enzyme secretion
  3. gastric capacity
  4. blood glucose
70
Q

what % of vagus fibers go from the brain to the stomach?

A

20%

71
Q

what % of vagus fibers go from the stomach to the brain?

A

80%

72
Q

what signals from the stomach to the brain does the vagus nerve involve?

A
  1. satiety (hunger)
  2. satiation (fullness)
  3. energy metabolism
73
Q

how effective is the vagus nerve stimulator?

A

treatment group lost 8.5% more weight than control group & sustained the weight loss at 18 mos

74
Q

what are the serious adverse FX assoc w/ vagus nerve stimulators?

A 
NV
pain at neuroregulator site
surgical complications
heartburn
pain
trouble swallowing
belching
chest pain
75
Q

what are the 4 classes of the NHLBI grading system for evidence?

A

Evidence A B C D

76
Q

what is evidence A?

A

randomized controlled trials

rich body of data

77
Q

what is evidence B?

A

randomized controlled trials

limited body of data

78
Q

what is evidence C?

A

nonrandomized trials

observational studies

79
Q

what is evidence D?

A

expert panel consensus judgment

80
Q

what evidence level is weight loss meds + diet + activity?

A

evidence level B

81
Q

what are the indications for pts to start weight loss meds + diet + activity?

A
  1. BMI > 30 w/o obesity-related risk factors or dz

2. BMI > 27 w/ obesity-related risk factors or dz

82
Q

how often should you schedule follow ups for obese pts on weight loss meds + diet + activity?

A

2-4 weeks
then monthly for 3 mos
then every 3 mos for the first year

83
Q

what are the 5 drugs that are FDA approved appetite suppressants?

A
  1. phentermine
  2. phentermine + topiramate aka Qsymia
  3. phendimetrazine
  4. lorcaserin/belviq
  5. diethylproprion

(phen phen phen lor die)

84
Q

what is Qsymia?

A

phentermine + extended topiramate

85
Q

what drug is a metabolism accelerator?

A

fexaramine (in dvlpmnt)

86
Q

which drugs are nutrient absorption blockers?

A
  1. orlistat/xenical

2. beloranib (trial)

87
Q

what is phen-fen?

A

phentermine + fenfluramine

highly effective appetite suppressant

88
Q

how is phen-fen an anorectic?

A

agonistic action of the metabolite norfenfluramine on 5-HT 2C receptors

89
Q

why was phen-fen withdrawn?

A

high rates of valvular heart dz & pulmonary HTN

90
Q

what 3 other drugs (besides phen-fen) were also withdrawn?

A

dexfenfluramine/redux
rimonabant (acomplia, zimulti)
sibutramine (meridia)

91
Q

what is phentermine?

A

an amphetamine derivative

92
Q

how does phentermine work?

A

increases 5-HT, noradrenaline, & DA levels in the brain

increases NE in hypothalamus & increases sympathetic tone

93
Q

what is phentermine approved for use as?

A

an adjunct to exercise, behavioral mods, & caloric restriction

94
Q

why would you prescribe phentermine?

A

for SHORT TERM exogenous obesity management (a few weeks)

95
Q

what are the top 10 side FX of phentermine in order from most reported to least reported? (sorry)

A
  1. DRY MOUTH
  2. insomnia
  3. constipation
  4. HA
  5. dizziness
  6. rapid HR
  7. dysphoria (phen rage)
  8. libido issues
  9. urticaria
  10. psychosis
96
Q

what are the top 3 risks of phentermine use?

A
  1. tolerance w/i a few weeks (that’s why you use it short term)
  2. impaired CNS
  3. abuse/addiction potential
97
Q

what side effects of phentermine can happen especially if you use it w/ another anorexigenic like fenfluramine?

A

valvular heart dz

pulmonary HTN

98
Q

what level of evidence is there to support Qsymia?

A

level 2
mid-level
(why not use the ABCD scale???)

99
Q

what is topiramate?

A

sulfamated fructose derivate for addictive behaviors

100
Q

T/F: Qsymia has a high drop-out rate

A

TRUE

101
Q

what are the side FX of Qsymia?

A

paresthesia, dry mouth, constipation, dysgeusia

102
Q

what pregnancy category is Qsymia?

A

D

risk of cleft palate

103
Q

are the effects of Qsymia specific to the hypothalamus?

A

nope

104
Q

what is the mechanism of Lorcaserin/Belviq?

A

selective 5-HT 2C receptor agonist

105
Q

what is the evidence level for Lorcaserin?

A

level 2

mid-level

106
Q

what is serotonin critical for?

A

CNS regulation of appetite & metabolism

107
Q

T/F: serotonin increases satiety

A

TRUE

108
Q

what are the side FX of Lorcaserin in pts w/o diabetes?

A 
HA
dizziness
fatigue
nausea
dry mouth
constipation
109
Q

what are the side FX of Lorcaserin in pts w/ diabetes?

A 
hypoglycemia
HA
back pain
cough
fatigue
110
Q

what are the uncommon but serious/potentially fatal side FX of lorcaserin?

A

serotonin syndrome

attn & memory disturbances

111
Q

what is serotonin syndrome?

A 
mental status changes
autonomic instability
neuromuscular hyperactivity (esp if taken w/ SSRIs)
112
Q

how long does it take for serotonin syndrome to manifest?

A

w/i minutes to hours

113
Q

when should you discontinue use of lorcaserin?

A

if pt does not lose 5% of weight after 12 weeks

114
Q

the safety & efficacy of lorcaserin beyond (?) years is unknown

A

2

115
Q

which things should you NOT use lorcaserin w/?

A

SSRIs
MAOIs
dopamine antagonists
St. John’s Wort

116
Q

can you use Lorcaserin if you’re pregnant?

A

NOPE

it’s category X

117
Q

can you use Lorcaserin if you’re nursing?

A

NOPE

118
Q

what is diethylpropion (tenuate) a derivative of?

A

amphetamine

119
Q

who should you use diethylpropion for?

A

obese women

120
Q

Can you use diethylpropion long term?

A

NOPE

short term only

121
Q

T/F: you can only use diethylpropion as monotherapy

A

TRUE

122
Q

how many times a day should you take diethylpropion?

A

3x daily 1 hour before meals
OR
1x daily (extended release)

123
Q

what are the 3 most important side FX of diethylpropion?

A

insomnia
dry mouth
pulmonary HTN

124
Q

what is the mechanism of phendimetrazine?

A

amphetamine derivative
anorexigenic d/t CNS stimulation
alpha-1 adrenergic receptor agonist
Na-dependent noradrenaline transporter antagonist

125
Q

what is the most common side effect of phendimetrazine?

A

insomnia

126
Q

how old do you have to be to take phendimetrazine?

A

12

127
Q

does phendimetrazine have the same set of contraindications as the other phen drugs?

A

yup

128
Q

what is the mechanism for orlistat?

A

reversible inhibitor of gastric & pancreatic lipases

reduces trygly hydrolysis & fat absorption

129
Q

is orlistat very effective?

A

“moderately effective”

130
Q

what is the evidence level for orlistat?

A

level 2

mid-level

131
Q

what is the ONLY FDA-approved treatment for LONG TERM obesity??

A

ORLISTAT

132
Q

what is the OTC form of orlistat?

A

alli

133
Q

what is the RX form of orlistat?

A

xenical

134
Q

what are the side FX of orlistat?

A

flatus w/ discharge (SHARTING???)
oily spotting
fecal urgency
fecal incontinence

135
Q

how can you reduce the side FX of orlistat?

A

increase fiber intake

decrease fat intake

136
Q

what should your diet be like while you’re taking orlistat?

A

well-balanced

supplements of fat-soluble vitamins (ADEK)

137
Q

what are the 4 contraindications of orlistat?

A
  1. pregnancy category B
  2. chronic malabsorption or cholestasis
  3. do not give w/ cyclosporine
  4. can cause serious liver injury
138
Q

what is the mechanism of beloranib?

A

selective MetAP2 inhibitor to reduce lipid & cholesterol biosynth & increase fat oxidation & lipolysis

139
Q

what is beloranib assoc w/?

A

RAPID weight loss

140
Q

what 3 things also improve on beloranib?

A

lipids
CRP
adiponectin

141
Q

where does fexaramine act?

A

specifically at intestinal FXR

142
Q

how does fexaramine work on metabolic profiles?

A

makes them better

glucose, insulin, leptin, cholesterol

143
Q

how does fexaramine impact VO2?

A

increases VO2 consumption but has similar respiratory exchange ratios to placebo (suggests enhanced use of sugar & fat)

144
Q

how does fexaramine impact body temp?

A

increases it

145
Q

what do the induced metabolic responses do d/t fexaramine?

A

promote lipolysis

mobilize fatty acids for oxidation

146
Q

what does fexaramine do to cells in WAT?

A

browns them

idk wtf this means

147
Q

what 6 drugs are used off-label for obesity (hint: 2 are combos)

A
  1. metformin
  2. zonisamide
  3. bupropion
  4. bupropion + zonisamide
  5. topiramate
  6. naltrexone + bupropion
148
Q

how much weight can you expect to lose on metformin?

A

only a small amount

149
Q

what is metformin particularly useful for?

A

preventing weight gain assoc w/ antipsychotics

150
Q

which off-label drug has level 1 evidence?

A

zonisamide

151
Q

which drug is good for overweight or obese women w/ a binge eating disorder?

A

bupropion

152
Q

what pt population does zonisamide improve weight loss in?

A

obese adults receiving diet & lifestyle counseling

153
Q

which drug is the ONLY FDA-approved non-RX weight loss aid?

A

orlistat (alli)

154
Q

T/F: hydroxycut KILLED SOMEONE

A

true

dude

155
Q

what is the best drug for weight loss in diabetics, even though it only gives pts modest weight loss at 6-12 mos?

A

orlistat (xenical, alli)

156
Q

what drugs can you give to diabetic pts for weight loss, besides orlistat?

A 
canagliflozin
fluoxetine
GLP-1 agonists (exanatide & liragutide)
amylin agonists
bupropion
lorcaserin
157
Q

define “successful weight loss maintainers”

A

individuals who have intentionally lost at least 10% of their body weight & kept it off at least one year

158
Q

is conscious restriction of energy intake usu successful?

A

NOPE

80-90% of the time, the weight is regained

159
Q

in the nat’l weight ctrl registry, how much weight did pts lose on average & how long did they keep it off?

A

~66 lbs & kept it off for 5.5 years

160
Q

how did people in the nat’l weight ctrl registry lose weight?

A

45% did it on their own

55% used a program

161
Q

what 3 behaviors do participants in the nat’l weight ctrl registry do to maintain their weight loss?

A

weigh themselves at least 1x/wk
watch less than 10 hours of TV/wk
exercise ~1 hour/day

162
Q

If individuals can succeed at maintaining their weight loss for (this long), they reduce their risk of subsequent regain by nearly 50%

A

2 years

Block 10 Week 2 (6 decks)

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