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
What is the other medical obesity drug?
semaglutide, but not as readily available
What are the 5 requirements to be eligible for bariatric surgery?
- BMI of 40kg/m2 or more, or 35-40kg/m2 with significant co-morbidities
- All appropriate non-surgical measures have been tried
- The person has been receiving or will receive intensive tier 3support
- The person is generally fit for anaesthesia and surgery
- The person commits to the need for long-term follow-up
What are the 4 types of weightloss surgery available?
- intragastric balloon
- adjustable gastric banding
- sleeve gastrectomy
- gastric bypass
What are the 5 operative complications of bariatric surgery?
Thromboembolism
Stenosis
Infection
Hernia
Death (1-2%)
What are the 3 long-term complications of bariatric surgery?
Nutritional deficiencies
Gallstones
Weight Regain
What are the 7 deficiencies associated with bariatric surgery?
Iron, calcium, vitamins B1, B12 and D, and protein deficiency
What are the 4 stages for diet post-bariatric surgery?
Stage 1
- clear liquids only for around 7 days
Stage 2
- pureed foods for days 7-14
Stage 3
- soft food up to 2 month point
Stage 4
- solid food for rest of life
Why do pH changes occur in the stomach post-op and what does this cause?
Partitioning of stomach results in decreased production of HCL
May affect bioavailability of drugs whose absorption is pH-dependent
May be possible to use alternative salt forms or to artificially alter gastric pH
How does gastrointestinal tract motilty affect drug absorption?
- A drug must have a sufficient residence time at its absorption site for absorption to be optimal
- If movement through the GI tract is too fast, the drug will pass through the system without being absorbed
- If movement through the GI tract is too slow, the onset of pharmacological effect will be delayed, the drug may be degraded or the epithelium may be irritated
What are the affects of reduced gastric volume?
- Stomach volume reduced to ~30ml
- Post-op oedema may further reduce stomach volume and opening into stomach
- Avoid effervescent formulations (use orodispersible or allow bubbles to disperse)
- Drugs in aqueous solution more rapidly absorbed than those in oily solutions, suspensions, or solid forms
- Caution with drugs with narrow therapeutic index and sustained/modified release preparations
How does volume of distribution change after bariatric surgery?
Patients may rapidly lose weight post-op -> altered volume of distribution
Increased circulating volume of drugs that are highly lipid-soluble
Close monitoring essential
Dose adjustment may be needed
What are the pre-op considerations for bariatric surgery?
- Often complex polypharmacy due to co-morbidities
- Advise on appropriate peri-operative medicines management
- VTE prophylaxis
- Initiate formulation/drug changes proactively
What are the post-op considerations for bariatric surgery?
- Close monitoring for efficacy of orally administered drug therapy, if lack of efficacy then suspect poor absorption, consider change of formulation or route
- Review drugs with GI side effects e.g. NSAIDs (consider PPI prophylaxis)
- Vitamin B12 deficiency common due to reduction in functioning parietal cells and HCL in stomach (3-Monthly B12 injections effective)
How is VTE prophylaxis provided post op to bariatric surgery patients (not balloon)?
Enoxparin 40mg OD SC (BD if over 100kg)
How is dyspepsia managed post op in bariatric surgery patients?
Lansoprazole 30mg fast tabs OD
Gastric banding: 14 days
Gastric bypass or sleeving: 3 months
Gastric balloon: 6 months
How is pain managed post-op in bariatric surgery patients?
Codeine: 1-2 30mg tabs crushed QDS PRN
Orodispersible tramadol: same as codeine
Soluble paracetamol: 1-2 QDS PRN
How is PONV managed in bariatric surgery patients?
Ondansetron orodispersible 4mg tabs 1 tab TDS
