Drugs Used in Obesity Flashcards
What are the limitations of body mass index (BMI)?
Doesn’t take lean muscle mass into account
Age/gender/ethnicity differences
What are the weight classifications of BMI?
Underweight 30
Morbid obese >40
What are some factors contributing to the increasing incidence of obesity?
Susceptibility genes Decline in physical activity Eat more Energy dense food Sleep deprivation Cultural and SE status
What causes obesity to be the second most common cause of preventable death?
Co-morbidities
What are the co-morbidities of obesity?
Diabetes Sleep apnoea Osteoarthritis Cancer Non-alcoholic fatty liver disease Coronary heart disease Hypertension
What are the long-term mechanisms for control of appetite?
Adiposity signals
- Insulin
- Leptin
How does leptin affect appetite?
Accesses hypothalamus
Changes expression and release of various neuropeptides
What are the short-term mechanisms for control of appetite?
Satiety signals
- Nerve input
- CCK
- Other hormones and neurohormones
Where is short-term satiety regulated in the brain?
Medulla
Which hormone increases hunger and how?
Ghrelin released from stomach when its empty > goes to medulla > hunger
What does it mean for drug therapy design since it’s a complex system of peptides that regulates food intake?
Need cocktail of drugs with multiple targets for successful treatment
Which cells predominantly secrete leptin?
Fat cells
What are plasma levels of leptin proportional to?
BMI
Fat
Where are the receptors for leptin located?
Hypothalamus
Are leptin defects relevant to human obesity?
Only in very small number of patients
Why may leptin insensitivity develop in obesity?
Trouble crossing BBB
Down-regulation of leptin receptors
What do beta3-adrenergi receptor agonists do?
Increase thermogenesis > increase energy expenditure
What do all obesity treating drugs need to be combined with?
Very low calorie diet
Increased exercise
What is phentermine?
Amphetamine derivative that increase noradrenaline availability to bind to receptors
Suppresses appetite
How is phentermine used?
BMI >30
Only useful in short-term
- Usually for 4-6 weeks
- Up to 12 weeks
How does phentermine work?
Competes with noradrenaline for neuronal re-uptake receptors > taken up
Displaces noradrenaline from vesicles
Increased noradrenaline intracellularly > Ca-independent release
More noradrenaline binds to post-synaptic receptors
What are the adverse effects of phentermine?
Increased BP and HR Insomnia Nervousness Headache Dry mouth
Does tolerance and dependenc develop to phentermine?
Some dependence
Tolerance, yes > why used in short term
What are the contra-indications for phentermine?
Other weight loss dugs
MAO inhibitors
Pregnancy
What is orlistat?
Gastric and pancreatic lipase inhibitor
Decreases dietary fat absorption
When is orlistat used?
BMI >30
How does orlistat work?
Covalently binds to lipases in gut to inhibit their activity
What does orlistat reduce?
Body weight Waist circumference Blood glucose Insulin Dyslipidaemia Blood pressure
What are the adverse effects of orlistat?
Mainly GI > controlled if adhere to low fat diet
- Explosive diarrhoea
- Faecal fat leakage
What must orlistat be combined with?
Low fat diet
Vitamin E and D supplementation
What is liraglutide?
Glucagon-like peptide-1 (GLP-1) receptor agonist
What are the adverse effects of liraglutide?
Nausea
Diarrhoea
Rare: pancreatitis
What are the actions of GLP-1 agonists?
Increase - Neuroprotection - Insulin - Insulin biosynthesis - Glucose uptake and storag Decrease - Appetite - Gastric emptying - Glucagon secretion - Glucose production
What is topiramate?
Used for epilepsy and migraine
Off-label use for weight loss
What does topimarate do?
Energy expenditure
Appetite suppression
What are the adverse effects of topimarate?
Dizziness
Taste alteration
Teratogenic
