9. Obesity Flashcards
What are the anti-obesity drugs discussed?
Appetite suppressants:
Phentermine/topiramate
Naltrexone/bupropion
Liraglutide
GI lipase inhibitor:
Orlistat
What is obesity?
Body mass index over 30 kg/m^2
Anti-obesity drugs have poor safety record, modifying diet and lifestyle remain the best option
Reduce absorption of calories with GI lipase inhibitors too
Slide 4
What is the hypothalamus and appetite regulation?
The arcuate nucleus has both orexigenic (stimulate appetite) and anorexic (inhibit appetite) Neurons
Orexigenic neurons release neuropeptide Y and agouti related peptide (AgRP)
Stimulated by ghrelin and inhibited by leptin, insulin and peptide YY
Anorexic neurons release alpha melanocyte stimulating hormones to inhibit appetite
Stimulated by leptin and insulin
Hormones- leptin, ghrelin, NPY, AgRP, PYY, cholecystokinin (CCK)
What are the 5 factors that stimulate appetite?
Slide 6
Neuropeptide Y (NPY) Agouti related peptide (AgRP) Orexin Ghrelin Tetrahydrocannabinol and endocannabinoids
What are the 8 factors that inhibit appetite?
Slide 6
Leptin
Cholecyctokinin
Glucagon-like peptide-1 (GLP-1)
Peptide YY (PYY)
Alpha melanocyte stimulating hormone (α-MSH)- derived from proopiomelanocortin (POMC)
Cocaine- and amphetamine- regulated transcript (CART)
Serotonin- stims anorectic neurons and inhibits orexigenic neurons in the arcuate nucleus
Norepinephrine- alpha 1 receptor stimulation
What is phentermine/topiramate’s mechanism of action and adverse effects?
Mechanism:
Phentermine- sympathomimetic (releases norepinephrine)- stimulates anorectic centre
Topiramate- an antiepileptic (increase GABA effect, inhibits glutamate receptors, inhibits carbonic anhydrase)
Adverse effects:
Mood changes, suicidal thoughts, fatigue, insomnia, constipation, increase heart rate, causes birth defects in pregnancy
Slides 8-9
What is naltrexone/bupropion’s mechanism of action and adverse effects?
Mechanisms:
Naltrexone- an opioid receptor antagonist
Bupropion- an antidepressant, weak reuptake inhibitor of dopamine and norepinephrine
Combo of them has effects on the appetite centre in hypothalamus and dopamine reward pathways
Adverse effects:
Suicidal thoughts and behaviour, depression, risk of seizures, increase heart rate and BP, hepatotoxicity, glaucoma
Slides 10-11
What is Orlistat’s mechanism of action and adverse effects?
Mechanism: inhibits pancreatic and intestinal lipases- inhibits breakdown of dietary fat
Adverse effects: bloating, oily spotting, fecal urgency, can reduce absorption of some drugs taken simultaneously
Slide 12
What is liraglutide’s mechanism of action and adverse effects?
Mechanism: recombinant analog of human GLP-1, glucagon-like peptide-1 receptor agonist
Reduced appetite by acting on appetite centre in brain
Stimulated insulin secretion, reduces glucagon secretion depending on blood glucose
Adverse effects: thyroid tumors risk, pancreatitis, gallbladder disease, renal impairment, increase heart rate
Slides 13-14
