Drugs Used in Obesity Flashcards
What are the medical complications of obesity?
diabetes, coronary heart disease, hypertension, sleep apnoea, osteoarthritis, asthma and cancer
Where do satiety signals come from and what do they signal via?
satiety signals come from the stomach and liver and signal via the vagus nerve and sympathetic nerves to the medulla and then to the hypothalamus
What are the adiposity signals and where do they signal to?
insulin and leptin - signal to the hypothalamus
What are the central peptides that increase food intake?
NPY, melanin concentrating hormone, agouti-related peptide, orexin A and B, endocannabinoids
What are the central peptides that decrease food intake?
alpha-MSH, urocortin, corticotrophin releasing hormone, serotonin, noradrenaline
What are the peripheral peptides that increase food intake?
ghrelin
What are the peripheral peptides that decrease food intake?
CCK, insulin and leptin
What are the plasma levels of leptin proportional to?
body fat
When in the day are plasma leptin levels highest?
midday
Where is leptin secreted from?
adipocytes
Where are the receptors for leptin?
on the hypothalamus
How does leptin cross the blood brain barrier?
via a transporter (which is saturable)
What factors may lead to leptin resistance in obesity?
saturating the transport process, decreased sensitivity of the receptor and decreased sensitivity of the second messenger system
What are the different strategies to target obesity?
increase the peptides which inhibit food intake, decrease the peptides which stimulate food intake, decrease absorption of fats, increase metabolism of fats, increase thermogenesis
What are the only two current treatments available for obesity?
phentermine and orlistat
What is the mechanism of action of sibutramine and why was it withdrawn as a treatment?
decreases NA and serotonin reuptake - withdrawn because of cardiovascular complications
What is the mechanism of rimonabant and why was it withdrawn as a treatment?
CB1 receptor antagonist - withdrawn because of increased risk of suicide
What is the mechanism of action of phentermine?
blocks neuronal reuptake of NA, DA and 5-HT - although more selective for NA
What are the adverse effects of phentermine?
increased BP, increased HR, insomnia, nervousness, headache, dry mouth
What are the contraindications for phentermine?
use with other weight loss drugs, use with antidepressants, use in pregnancy
Why can phentermine be only used for 3 weeks?
because tolerance develops
What is topiramate, what is it used to treat and what is it used to treat off label?
topiramate is a treatment for epilepsy and migraines but it is used off label for weight loss and to improve insulin sensitivity although the mechanism is unknown
What are the adverse effects of topiramate?
dizziness, taste alteration, teratogenic (cleft palate), parasthesia
What is the mechanism of action of orlistat?
gastric and pancreatic lipase inhibitor - decreases fat absorption by 30% - if lipase can’t act then triglycerides can’t be absorbed so are excreted
