L25 Obesity

Question 1

Mechanism of Phentermine/Duromine

Answer 1

increases NA available to receptors suppresses appetite

Phentermine Increases NA
Greater binding to the post synaptic receptors
Inhibition of intake

− Accesses the presynaptic NA levels via reuptake transporter
− Acts as an amphetamine
− Gets into NA vesicles & displaces NA from vesicles
− More NA in presynaptic neuron -> Conc gradient
− NA Leaks out of transporter
Increased NA in the synaptic cleft

Question 2

SE of Phentermine/Duromine

Answer 2

-tolerance
increased BP, HR, insomnia nervousness, headache, dry mouth, cardiovascular disease
Cannot be combined antidepressants (Mao inhibitors SSRI -> increase NA levels) not safe in pregnancy

Question 3

Mechanism of Orlistat

Answer 3

inhibits gastric & pancreatic lipases
Orlistat Binds to lipase-> inhibits lipase, no hydrolysis of triglycerides
Dietary fat is not absorbed, -> Triglycerides- excreted
GI tract-Systemic absorption is not necessary

Must combine with low fat diet & vitamin supplementation (D & E) recommended

Question 4

SE of Orlistat

Answer 4

mainly GI and controlled if adhere to low fat diet

Include explosive diarrhea, faecal fat leakage-> learning experience

Question 5

Glucagon-like peptide-1 (GLP-1) receptor agonist mechanism

Liraglutide

Answer 5

BPGG

• brain
• pancreas, increases insulin secretion
• gastric emptying
• glucagon reduced

GLP-1 receptor agonist 
•	Potentiates glucose mediated insulin secretion 
•	Suppress glucagon secretion 
•	Slows gastric emptying 
•	Loss of appetite( central action) 

• Acts on the pancreas
Increases insulin secretion- insulin causes uptakes glucose, lowers blood glucose

• Reduced glucagon secretion- inhibits the hepatic synthesis of glucose and the breakdown of glycogen into glucose
Reducing glucose levels

• Slower emptying gastric emptying- feel more full sooner, glucose absorption is slower
Lower postprandial rising in glucose
Slowly released from stomach
Weight loss

• Acts within the brain
GLP1 receptors in the brain

Question 6

SEs of Glucagon-like peptide-1 (GLP-1) receptor agonist

Answer 6

• Nausea, vomiting, diarrhea, injection site rxns, small increase in HR
• Pancreatitis

Question 7

How is Glucagon-like peptide-1 (GLP-1) administered?

Answer 7

injected subcutaneously

bc it is a peptide, upon oral-will be broken down

Question 8

Name 3 strategies to target obesity

Answer 8

• targeting fat
• food intake
• thermogenesis

Question 9

Strategies targeting obesity

Fat

Answer 9

Absorption: Longer half-life and better side effect profile of drug
Metabolism: breakdown of fat
− Increase lipolysis-breakdown of fat

Question 10

Strategies targeting obesity

Thermogenesis

Answer 10

Increasing heat production
− Beta 3 adrenoceptors in the skeletal muscle-stimulate heat production in skeletal muscle
− Increase in energy expenditure

Question 11

Strategies targeting obesity

controlling food intake

Answer 11

Central
− antagonists for NPY
− agonist- of peptide that inhibit food intake

Periphery
− Use leptin
− Lose weight, leptin levels reduce-> causes brain to want to increase fat
− Replacing the reduction in leptin, trick the brain that leptin levels have not decreased
− Block compensatory mechanisms