Obestiy Flashcards
What is obestiy?
- Too much body fat
- Too much fat in the wrong place
- Casued by chronic positive energy balance due to:
1. Too much energy intake
2. And/or too little energy expenditure
How do we asess obesity?
- BMI, weight/height
- 25-29.9 pre-obese
- 30-34.9 Grade 1–Moderate (risk of co-morbidity)
- 35-39.9 Grade 2–Severe
- 40+ Grade 3–Very severe
What are the consequences of obesity?
Obesity is a major risk factor for CHD
Also:
* Inc BP
* Inc plasma cholesterol levels
* Inc risk of type II diabetes
- All these are additional factors for CHD
- Inc NHS costs
- Also inc risks of many cancers
How to treat Obesity?
- Weight loss target- 5-10% of original weight with a max weekly loss of 0.5-1Kg
- Dietetic Treatment
- Very low calorie diet
- Drugs
What is Dietetic treatment?
- Based on energy balance equation
- Energy input-energy consumption=Energy balance
- In order to lose weight, energy balance must be negative
What are very low calorie diets(VLCDs)?
- Commercially-prepared diet
- Medical supervision only
- For very obese patients who need to lose weight quickly
- Typically 400-600Kcal/day for several days/weeks(But max 12 weeks)
What are other dietary approaches?
- Individualised modest energy restrictive diet
- Aim to provide 500kcal/day less than calculated amount
- Slower weight loss, based on healthy eating guidelines
What are currently licenced drugs?
- Orlistat
- Liraglutide
- Mysimba
What is Orlistat?
- Tetrahydrolipostatin
1. Synthesised derivative of lipostatin - Inhibits Gastric and Pancreatic lipase
- Irreversible inhibitor
- Forms covalent bonds with serine residues in the active site of lipases
- Minimal absorption
- Needs to be taken before each main meal
- ~30% inhibition of lipases at normal therapeutic doses (lose 200Kcal per day)
- Needs to be combined with low fat diet
What are the side effects of Orlistat?
- Steatorrhea-Fatty, foul smelling faeces
What is OTC Orlistat?
- Reduced dose- 60mg tds
- Max 6 months
- Combined with red fat diet
- BMI>28
What controls appetite?
- The hypothalamus controls appetite.
What are GLP1 agonists? (Saxenda & Wgovy)
Liraglutide and semaglutide are glucagon-like peptide-1 (GLP-1) receptor agonist
S.c. Injection
* Appetite suppression–effects in the hypothalamus
* Inc secretion of neurotransmitters POMC & CART involved in appetite suppression
* GLP-1 can also reduce hugh fat food intake by suppressing dopamine signalling–effect on reward pathways
What is Mysimba?
- Combination of naltrexone & bupropion
- Effects on reward pathway
- Bupropion:
1. Dopamine and noradrenaline reuptake inhibitor.
2. Inc levels of these neurotransmitters in the brain
3. Greater activation of receptors - Naltrexone: Opiod Receptor antagonist
What is the mechanism of Mysimba
- Mechanism not well understood. Possibly:
1. Bupropion activates appetite suppressing neurons
2. Naltrexone: Prevents endogenous negative feedback pathways that would normally counteract this effect
What is Sibutramine?
- Combined NA and 5-HT uptake inhibitor
- 5-HT controls the balance of release of appetite-suppressing and appetite-stimulating neurotransmitters in the brain
- Appetite suppressant
- No longer used due to Inc BP and HR
What are 5-HT receptor systems? (serotonergic)
- 5-HT (serotonin)- number of different receptor subtypes
5-HT1b, 5-HT2c, 5-HT6 all cause weight loss in rodents
Serotonergic compounds alter expression of neurotransmitters in hypothalamus
What is Lorcaserin?
- 5-HT2C receptor antagonist
What is Tesofensine?
- Triple reuptake inhibitor (5-HT, NA, and dopamine)
- But increases HR and BP
What is Rimonabant(Acomplia)?
- CB1 receptor antagonist
- Blocks central and peripheral CB1 receptors
- Dec motivation to eat food
- Inhibition to lipogenesis (liver and adipose)
- Severe side effects: Depression
- No longer licenced
What is Phentermine?
- Not licenced in UK(is US)
- Inc catecholamine levels in brain
- Also inc HR, BP and palpitations
What is Qsymia?
- Used in US but not UK/EU
- Combination of phentermine and topiramate
- Topiramate: agonist at GABA receptors
Summarise anti-obesity treatment.
Anti-obesity treatments are far from ideal
Number of ways of reducing weight:
1. Prevent uptake of energy from diet
2. Reduce appetite
3. Target the reward pathways
4. Focused treatments may not be effective
5. Combinations of drugs may work better—Prevent neg side feedback mechanisms or reduce side effects
