Obesity/Diabetes

Question 0

Phentermine (Adipex-P)

Answer 0

Class: amphetamines
MOA: appetite suppressant, releases NE, DA, inhibits reuptake of NE, DA, SR, increased catecholamines can increase leptin levels in the brain
Special: as a monotherapy, used short-term due to tolerance
ADR: increased HR, BP, h/a, dry mouth, insomnia, constipation, restlessness

Question 1

Orlistat (Xenical, Alli)

Answer 1

MOA: prevents absorption of fats from the human diet, potent inhibitor of gastric and pancreatic lipases, with lipase activity blocked dietary TGs are excreted unhydrolyzed
Indication: obesity, dyslipidemia, reductions in CV risk factors
ADR: GI-steatorrhea (oily, loose stool), fecal incontinence, frequent/urgent bowel movements, this may actually encourage selection of low fat diet
Special: low cost OTC, supplement with fat-soluble vitamins

Question 2

Qysmia

Answer 2

Formula: Phentermine instant release + Topiramate controlled release
Start at low dose, and increase level if no weight lost in 2wks
C.f. Topiramate is teratogenic in 1st trimester, pregnancy X

Question 3

Locaserin (Belviq)

Answer 3

Class: specific agonist of the 5HT-2C serotonin receptor to suppress appetite, increase satiety
ADR: few, most common is h/a, avoids adverse effects assoc with other serotonin agonists, 2A-hallucinogenic effects, 2B-valvulopathy
Special: weight loss is not that impressive

Question 4

Liraglutide (Saxenda)

Answer 4

Class: GLP-1 agonist like Exenatide, modified peptide to resist rapid breakdown by peptidase
MOA: potentiation of glucose-mediated insulin secretion, suppression of postprandial glucagon release, delays gastric emptying, CNS-mediated appetite suppression, reduction in liver fat content
PK: daily s.c. Injection, not for everyone
ADR: nausea, diarrhea, decreases with ongoing usage
Blackbox: thyroid C-cell tumor
Special: expensive

Question 5

Contrave (Buproprion + Naltrexone)

Answer 5

MOA: NE-DA reuptake inhibitor and opioid antagonist, makes food less rewarding decreasing appetite, FDA approved in 2014
C.f. Other drugs in trial: Empatic (Buproprion + Zonisamide;anticonvulsant)

Question 6

Metformin

Answer 6

Indication: type 2 diabetes
MOA: decreases hepatic glucose output
ADR: less wt gain compared to insulin, lactic acidosis with metformin accumulation

Question 7

Sulfonylurea

Answer 7

Indication: type 2 diabetes, with decreased secretion of insulin
MOA: blocks k+ channel on islets of pancreas to cause build up of intracellular k+, depolarizing membrane potential and inducing insulin release
ADR: disulfiram-like rxn, n/v/headache/flushing/tachycardia
Special: can use with metformin for synergistic effect due to complementary mechanism

Question 8

Exenatide

Answer 8

Class: analogue of GLP-1
MOA: enhances insulin secretion, decreases food intake by increasing satiety in brain

Question 9

Thiazolidinedoines (Rosiglitazone)

Answer 9

Indication: type 2 diabetes
MOA: enhances sensitivity of insulin on target tissues, kind of like exercise. Bind to transcription regulator (PPAR).
ADR: wt gain, fluid retention