Obesity Flashcards
What are the physiological changes associated with obesity?
- Excess of fat tissue
- Increased mortality (HTN, atherosclerosis, CAD, diabetes, cancers)
- IBW: height, gender (obese: actual BW> IBW more than 20%)
How is obesity classified?
Classification (WHO):
- BMI ≥25 to 29.9 kg/m2 (overweight)
- BMI ≥30 kg/m2 (obesity)
- moderate (BMI 30.0 to 34.9)
- severe (BMI 35.0 to 39.9)
- morbid (BMI ≥ 40.0)*
What are the 2 factors affecting distribution in obesity?
- higher percentage of body fat
- lower percentage of lean tissue and body water
What are the two factors affecting metabolism in obesity?
- higher cardiac output and liver blood flow
- enlarged liver with altered histologic status
What are the two factors affecting excretion in obesity?
- higher renal blood flow
- higher glomerular filtration rate
How does distribution change in obesity?
- Distribution between fat and lean tissues influences PK
- Drugs with weak or moderate lipophilicity have limited distribution in excess body fat
- Lipophilic compounds have increased Vd in obesity
How does metabolism change in obesity?
- Fatty infiltration of liver which influence metabolic activity
- CYP 450 isoforms altered, no clear overview of drug hepatic metabolism
- Increased glucuronidation
- Changes for antioxidant systems
How does renal function change in obesity?
- Differing data caused by extent of obesity
- Ciprofloxacin, lithium and gentamicin have significant difference in creatinine clearance (CLcr) between obese and those with normal bodyweight
- Vancomycin has a significant increase in CLcr in morbidly obese patients
What are the 3 causes of obesity?
- overeating
- low energy expenditure
- physical inactivity
What are the three GI hormones associated with GI motility and regulation?
Ghrelin
- responsible for appetite stimulation
- obesity associated with post-prandial ghrelin suppression
Anorexigenic intestinal hormones
- Include glucagon-like peptide 1(GLP1), cholecystokinin (CCK)
- Secreted in response to food intake
- obesity is associated with delayed or reduced activity
Leptin
- Predominantly secreted by white adipose tissue
- increased in people with obesity
What are the 4 tiers of the UK Obesity care pathway?
Tier 1
- universal interventions: healthy eating + exercise
Tier 2
- Lifestyle weight management: GP led weight management services
Tier 3
- Specialist weight management services: clinician-led MDT
Tier 4
- Hospital based specialist care: surgery
What are the 4 requirements for liraglutide to be used as management for obesity?
- They have a BMI of at least 35kg/m2 and
- They have non-diabetic hyperglycaemia (42mmol/mol to 47mmol/mol or a fasting plasma glucose level of 5.5mmol/litre to 6.9mmol/litre) and
- They have a high risk of CVD based and
- It is prescribed in secondary care by a specialist multidisciplinary tier3 weight management service
What are the properties of liraglutide as a good obesity treatment?
Liraglutide is an analogue of (GLP-1) which stimulates insulin and inhibits glucagon release.
GLP-1 can suppress food intake and appetite and decelerate gastric emptying and induce satiety
Attached acyl chain allows non-covalent binding to albumin:
Delays both the inactivation of liraglutide, extending the half-life of GLP-1 from one to two minutes for native GLP-1 to 11–15 hours allowing once daily administration.
What are the 3 positive effects of liraglutide?
- increased biosynthesis
- increased beta cell proliferation
- decreased beta cell apoptosis
What are the 3 negative effects of liraglutide?
- risk of nausea and vomiting
- increased heart rate
- risk of pancreatitis
