Burkin: Obesity & Satiety Drugs Flashcards
Over (blank)% of adults are overweight or obese
66%
Think about some complications of obesity…
sex hormone imbalance
increased free fatty acids –> dyslipidemia, insulin resistance, hypertension
physical stress –> sleep apnea, osteoarthritis, lower back pain, SOB
QOL –> low self esteem, anxiety, disordered eating
Appetite stimulating neurons are called (blank). Here are some examples…
orexigenic; Ghrelin, AgRP, NPY, Orexin
Appetite suppressing neurons are called (blank). Here are some examples…
anorexigenic; leptin, insulin, CCK, CRH, POMC, CART, PYY
These increase insulin secretion from the pancreas
incretins
What is glucostatic hypothesis involving short term hunger regulation
blood glucose levels are critical to hunger –> when blood glucose drops, this signals the hypothalamus to generate a “hunger” sensation to trigger eating behavior
In long term hunger regulation, declines in the amount of stored (blank) might function as orexigenic signals. Also the ratio of utilizing (blank):(blank) is involved
glycogen; carbohydrate:lipid
(List the hormones) bind receptors on orexigenic or anorexigenic neurons in the arcuate nucleus of the hypothalamus. Ultimately, this sends signals that cause changes in sensations of (blank) or (blank)
Ghrelin (stomach), leptin (adipose tissue), insulin (pancreas), PYY (small intestine);
hunger; satiety
In response to hunger, mechanoreceptor responses are transmitted along the (blank) nerve to the dorsal vagal complex in the medulla and terminating in the (NTS)
vagus
What is the difference between hunger & appetite
hunger = motivation for eating behavior
appetite = desire to eat even if there is no physiological reason
Weight loss is achieved by reducing the size of the stomach
Improvement in short term cardiovascular risk factors and reduction in mortality from 23% to 40%
Bariatric surgery
When is bariatric surgery warranted?
pts with BMI greater than 40
have tried adequate diet/exercise, but failed
present with obesity related comorbid condition
resecting and re-routing the small intestine to a small stomach pouch
gastric bypass
removal of a portion of the stomach
sleeve gastrectomy with duodenal switch
device similar to a heart pacemaker is implanted
electrical leads stimulate the external surface of the stomach
interpreted by the brain to give a sense of satiety
gastric band
What are some complications of bariatric surgery?
gastric dumping syndrome (20%) --> ingested foods bypass the stomach rapidly & enter the intestine largely undigested leaks at surgical site (12%) incisional hernia (7%) infection pneumonia
The vagus nerve stimulator is involves wire leads & electrodes that send intermittent electric pulses to the vagus nerve. What are some indications for the vagus nerve stimulator?
over 18yo
BMI 35-40
at least one other obesity-related condition
What are some serious adverse events that occur with vagus nerve stimulators?
nausea pain at neuroregulator site vomiting surgical complications pain heartburn problems swallowing
When are weight loss medications indicated?
BMI greater than 30 without obesity related risk factors
BMI greater than 27 with obesity related risk factors or disease
What was phen-fen & why was it withdrawn?
highly effective appetite suppressant, agonist at 5HT2c receptors; withdrawn due to high rates of valvular heart disease and pulmonary hypertension
What is phentermine? How does it work?
it is an amphetamine derivative - it increases NE, 5HT, and DA levels in the hypothalamus –> increases sympathetic tone
When is phentermine used?
for short term management of exogenous obesity (few weeks)
Used in conjunction with exercise & caloric restriction
Side effects of Phentermine?
dry mouth insomnia costipation headache rapid heartbeat dizziness
Adverse effects of Phentermine?
CNS: impaired alertness or physical coordination Pulmonary HTN Valvular heart disease Tolerance may develop w/i a few weeks Potential for abuse or addiction
What are some contraindications to use of Phentermine?
Don’t use w/ MAOIs or SSRIs
Don’t use w/ other weight loss drugs
Don’t use during pregnancy or breastfeeding
Phentermine can be combined with (blank)
extended topiramate
**controlled release phentermine
Side effects of phentermine + topiramate?
paresthesia dry mouth constipation dysgeusia PREGNANCY CATEGORY D --> can cause cleft palate
This weight loss drug selectively activates 5HT2C receptors
Lorcaserin
What is one uncommon but serious/potentially fatal side effect of Lorcaserin?
seratonin syndrome –> develops within mins-hrs, mental changes, autonomic instability, neuromuscular hyperactivity
Lorcaserin should not be used in these instances…
w/ SSRIs or MAOIs w/ dopamine antagonists w/ St. John's Wort During pregnancy (category X) During nursing
Amphetamine derivative
Associated with weight loss in obese women (level 2, midlevel evidence)
Short term use only
monotherapy only
Orally 3x daily 1 hr before meals or 1x daily (extended release)
Diethylpropion
What is one major side effect of diethylpropion?
pulmonary hypertension!
23x higher risk after 3 mo use with other anorexigenics
Contraindications for diethylpropion?
HTN, pulmonary hypertension
MAOIs
Other anorexigenic drugs
Pregnancy & lactating
Like all amphetamine derivatives, anorexigenic activity likely due to CNS stimulation
Alpha-1 adrenergic receptor agonist
Sodium-dependent noradrenaline transporter antagonist
Phendimetrazine
Side effects of phendimetrazine?
hypertension, pulmonary HTN, advanced arteriosclerosis, hyperthyroidism, glaucoma
Brand names Xenical (prescription) and Alli (OTC)
Reversible inhibitor of gastric and pancreatic lipases
Reduces triglyceride hydrolysis & fat absorption
Reduces Moderately effective (mean weight loss 6.4 lbs) in 15 randomized trials
Level 2 (mid-level) evidence
The ONLY FDA-approved treatment for long-term obesity
Orlistat
What is the MAO of orlistat?
inhibits gastric & pancreatic lipases
reduces TAG hydrolysis & fat absorption (at intestinal brush border)
ONLY FDA approved treatment for long-term obesity
Orlistat
Orlistat side effects? How can you reduce these effects?
flatus with discharge
oily spotting
fecal urgency & incontinence
**increase fiber & decrease fat intake to reduce these symptoms & supplement with fat soluble vits
When should orlistat NOT be used?
pregnancy
chronic malabsorption syndrome
w/ cyclosporine
Experimental drug in Phase 2 trials for obesity
selective inhibitor of methionine aminopeptidase 2 (MetAP2)
reduce lipid & cholesterol biosynthesis
increased fat oxidation and lipolysis
associated with rapid weight loss
improvement in lipids, C-reactive protein, and adiponectin.
Beloranib
When given orally, acts specifically on intestinal FXR
Mice on a high fat diet did not gain weight/ body fat
Had better metabolic profiles (glucose, insulin, leptin, cholesterol)
Had higher VO2 consumption but similar respiratory exchange ratios (suggesting enhanced use of sugar & fat)
Increased core body temperature
Induced metabolic responses that promote lipolysis and mobilize fatty acids for oxidation I
“browning” of cells in WAT
Fexaramine
**works to increase metabolism
What is one med shown to cause modest weight loss at 6-12 months in diabetic pts?
Orlistat
What is considered successful weight loss maintenance?
individuals who have intentionally lost 10% of their body weight & have kept it off for at least one year
If individuals can succeed at maintaining their weight loss for (blank) y, they reduce their risk of subsequent regain by nearly 50%
2
