Pharmacology & Treatment of Eating Disorders Flashcards
What happens to the appetite during acute stress? Why?
It decreases due to the release of adrenaline
How is obesity determined?
By calculating the BMI
What is the calculation for BMI?
(Weight)/ (Height)^2
What is the initial treatment for obesity?
Comprehensive lifestyle intervention: a combination of diet, exercise and behavioral modification.
What dietary changes are made during initial treatment for obesity?
Lower calorie intake, cut down on sugars and fats
How long does initial treatment continue?
Depends on the patient, usually they are monitored and based on their process you choose to continue or not
When is subsequent treatment initiated?
When patients are unable to achieve weight loss goals with a comprehensive lifestyle intervention alone
What is the indication that the initial treatment is successful?
The patient loses about 5% of body weight in the time period of 3 to 6 months
What are the options of the subsequent treatment?
Pharmacologic treatment
Surgery
What is the goal of therapy?
To prevent, reverse or improve the complications of obesity and improve quality of life
What are the characteristics required by an obese individual to initiate pharmacological therapy?
BMI > 30
OR
BMI > 27 with at least one weight-related comorbidity
Are most drugs long or short- term?
Short-term
Which drugs are used for long-term weight management?
The newer medications
When are drugs considered effective?
If they demonstrate at least a 5% greater reduction in body weight than placebo
What kind of comorbidities is obesity associated with?
Type 2 DM
HTN
Dyslipidemia
CHD
What is the correlation between BMI and morbidity/mortality?
The higher the BMI, the greater the risk of morbidity and mortality
Why has the role of drug therapy been questioned?
Concerns regarding efficacy, potential abuse, side effects and cost
What are examples of GLP1 receptor agonists?
Semaglutide
Liraglutide
What is the mechanism of action of GLP1 receptor agonists?
Chemically modified versions of GLP1, stimulating binding to GLP1 receptors
Where do GLP1 receptor agonists act?
CNS, areas of the brain like hypothalamus which are involved in the regulation of appetite and calorie intake.
Stomach, short period of satiety and loss of appetite by slowing gastric emptying.
How does slower gastric emptying help reduce weight?
Food remains in the stomach for longer, the stomach takes longer to empty out and thus sends a “hunger” signal (ghrelin). Slower rate of absorption of food in the bloodstream.
What do GLP1 agonists also stimulate secretion of?
Secretion of incretin which increases glucose-dependent insulin secretion
What is the effect of incretin?
Decreases inappropriate glucagon secretion.
Which kind of patients are GLP1 agonists preferred to be given to because of incretin?
Type 2 diabetes patients –> improve glycemic levels and reduce weight
Is semaglutide long or short-term use?
Chronic weight management
What are the main side effects of GLP1 agonists?
GI side effects: nausea and vomiting
Diarrhea
Anorexia
What is the example of dual-acting GLP1 & GIP receptor agonist?
Tirzepatide
What is Tirzepatide?
A dual-acting GLP1 and GIP receptor agonist that is used as first-line medication
What is the function of GIP?
GIP increases insulin secretion, improves glucose tolerance and reduces gastric acid secretion
What is the mechanism of action of Tirzepatide?
The dual agonism decreases hyperglycemia severely more than just GLP1 agonists on their own, and reduces patient’s appetite
What was the body weight percentage drop after giving Tirzepatide to patients with no diabetes?
16.5 % to 22.4% over 72 weeks
What are the PK of Trizepatide?
Subcutaneously given by weekly injection
What are the adverse effects of Trizepatide?
Nausea, Vomiting, Diarrhoea, Constipation and Increased Heart Rate
What should patients on GLP1 or dual acting GLP1/GIP agonists be monitored for?
Depressive symptoms and suicidal thoughts
Unusual changes in mood or behaviour
What are the contraindications for both GLP1 and GLP1/GIP agonists?
Patients with personal or family history of medullary thyroid carcinoma
Patients with multiple endocrine neoplasia syndrome type 2
Pregnancy
Why are GLP1 and GLP1/GIP agonists contraindicated during pregnancy?
Can cause teratogenicity, fetotoxicity and abortion (seen in animals)
What is an example of lipase inhibitors?
Orlistat
When are lipase inhibitors taken?
Only after fatty meals, it prevents the lipase enzymes from breaking down fats and being absorbed and stored in the body
What is the MOA of Orlistat?
Decreases the breakdown of fat into smaller molecules and therefore, decreases fat absorption by about 30% and increases fecal fat excretion
What are the pharmacokinetics of Orlistat?
Administered orally with each mean that contains fat
Minimal systemic absorption, excreted in the feces
No dosage adjustments required in patients with renal/hepatic dysfunction
What are the side effects of lipase inhibitors ?
Oily stool
Diarrhea
Decreased absorption of lipid soluble vitamins
What does Orlistat interfere with the absorption of?
Fat-soluble vitamins (vitamins A, D, E, and K) and β-carotene, patients should be advised to take a multivitamin supplement at bedtime
Other medications
What other medications does Orlistat interfere with?
Amiodarone
Cyclosporine
Levothyroxine
Is Orlistat a short or long-term medication?
Available for long-term treatment of obesity but clinical utility is limited due to GI side effects
How are the GI side effects of Orlistat minimised?
Though low-fat diet and cholestyramine
What is cholestyramine?
A drug that reduces the re-absorption of bile in the body
What are the contraindication of Orlistat?
Pregnancy
Patients with chronic malabsorption syndrome
What are anorexiants?
Appetite suppressants; sympathomimetic drugs and are classified as controlled substances
Why are anorexiants classified as controlled substances?
Due to dependence and abuse potential
What are examples of Anorexiants?
Phentermine
Diethylpropion
Benzphetamine
Phendimetrazine
Are anorexiants approved as long or short-term medication treatments?
Short-term because of their potential side effects and potential abuse
What is the MOA of Phenetrmine?
Increases the release of norepinephrine and dopamine and inhibits their uptake in nerve terminals
What is the result of increasing levels of dopamine and norepinephrine?
Decrease appetite which facilitates weight loss
When does weight loss plateau?
When tolerance is achieved, discontinuation of drug should be progressive and not immediate
What re the pharmacokinetics of anorexiants?
Rapidly absorbed after oral administration
Peak plasma concentration within 1 to 2 hours
Undergo extensive first pass metabolism
Metabolised to inactive compounds by the liver
Elimination via the kidneys
What is the half life of anorexiants?
Short, 4 to 8 hours
What are the side effects of anorexiants?
Increase HR and BP
Dizziness, headache and insomnia
Changes in libido
Constipation, diarrhoea and nausea
What are the contraindications fro anorexiants?
Patients with HTN, CVD, arrhythmias, HF or stroke and history of drug abuse
Which is the most widely prescribed weight loss drug?
Phentermine
What are combination drug treatments?
Combining two drugs with different mechanisms of action that improve efficacy
What are examples of combination drugs?
Phentermine-Topiramate
Bupropion-Naltrexone
Is the combination drug Phentermine- Topiramate long or short term use?
Long term use
What is the MOA of Phentermine- Topiramate?
Topiramate affects the activity of two neurotransmitters: GABA enhancement and glutamate decrease
Phentermine is a stimulant to contradict the sedation
What is the effect of Topiramate on its own?
Induction of sedation
What are the side effects of Phentermine- Topiramate?
Suicidal ideation, cognitive function decrease and dry mouth
What are the contraindication of Phentermine- Topiramate?
Contraindicated in pregnancy
Patients with history of renal stones
Patients with CVD
Why is Phentermine- Topiramate not given to patients with history of renal stones?
Topiramate is a weak carbonic anhydrase inhibitor, increases calcium excretion and decreases citrate in urine
Discontinuation of Phentermine- Topiramate?
Should not be stopped abruptly, can cause seizures
When was Bupropion-Nalterxone FDA-approved?
September 2014
Is Bupropion-Nalterxone first line treatment? Which kind of patients is it suggested to?
No, it could be prescribed for the obese smokers who desire pharmacology therapy for smoking cessation and obesity
What is Bupropion?
A weak dopamine and norepinephrine reuptake inhibitor
What is Bupropion used for?
Treatment of depression and smoking cessation.
What is Naltrexone?
Opioid-receptor antagonist used to treat alcohol and opioid dependence
What is the MOA of Bupropion-Nalterxone?
Stimulate POMC neurons through bupropion,
Blocking the auto-inhibitory mechanisms of POMC with naltrexone
What is Bupropion-Nalterxone metabolised by?
By CYP2B6, low risk of drug to drug interactions
What are the side effects of Bupropion-Nalterxone?
Nausea, headache, seizure, constipation.
Low risk of young adults becoming suicidal during initial treatment
Is Setmelanotide long or short term use?
Chronic weight management
Who is Setmelanotide used for?
Adult and paediatric patients 6 years of age and above with monogenic or syndromic obesity
What kind of deficiencies allow for Setmelanotide use?
POMC
OCSK1
LEPR
Bardet-Biedl Syndrome
What is the Bardet-Biedl syndrome?
Inherited disease that causes loss of night and peripheral vision
What is the MOA of Setmelanotide?
Acts on the MC4R agonist
Potentially restores the function of an impaired MC4R pathway, reduces hunger
What is the MC4R?
Key part of the biological pathway that regulates hunger, calorie intake and energy expenditure
What is an example of serotonin agonists?
Lorcaserin
What is the effect of serotonin?
Reduces food intake in animals and human beings
What is the MOA of Lorcaserin?
Selective agonist that activates serotonin 2C receptors.
Activation of POMC –> activation of melanocortin receptors
Decrease in appetite
Was Lorcaserin used long or short term?
Long-term use
What drug does Lorcaserin have similar efficacy but lower side effects with?
Orlistat
Where are serotonin 2C receptors found?
Most in the central nervous system
When was Lorcaserin discontinued and why?
February 2020 because of an increased occurrence of cancer
What types of cancers were associated with Lorcaserin?
Colorectal, pancreatic and lung cancers
What were the side effects of Lorcaserin?
Nausea
Headache
Dry mouth
Dizziness
Constipation
Mood changes and Suicidal Ideation
What are the pharmacokinetics of Lorcasterin?
Extensively metabolised in the liver to inactive metabolites and eliminated in the urine
What is the effect of Lorcaserin on Type 2 DM patients?
Higher risk of hypoglycemia
What are the contraindication of Lorcaserin?
Pregnancy
What are some examples of not recommended therapies?
Green tea, garcinia cambogia, conjugated lionelic acid chitosan
calcium
chromium, gambisan, hoodie gordonii
What are orexigenic drugs?
Appetite stimulants, increase appetite and enhance food consumption
When are orexigenics prescribed?
Severe appetite loss or muscle eating due to CF, anorexia, old age, cancer or AIDS
What are examples of oexigenics?
Corticosteroids
Progesterone analogues
Cannabinoids
Serotonin antagonists
Anabolic steroid
Mirtazapine
What is an example of corticosteroids (orexigenic)?
Dexamethasone
What is the difference between glucocorticoids and progesterone analogues?
Progesterone analogues have fewer side effects
What is an example of serotonin antagonist?
Cyproheptadine
What is an example of cannabinoid?
Dronabinol
MOA of Dronabinol:
A synthetic version of THC acts on cannabinoid receptors in the brain.
Relieves nausea
Which kind of patients are androgens given to?
Older persons to increase muscle mass or to help patients recovering from severe illness or injury
What is an example of an androgen?
Oxandrolone
What is an example of tetracyclic antidepressant?
Mirtazapine
What is the MOA of Mirtazapine?
Treatment for major depression, weight gain is a side effect
