2: Lecture 7 Drugs Flashcards
Drugs that control insulin resistance (Type 1 Diabetes)
Amylin analogues
Alpha-glucosidase inhibitors
Insulin
First Treatment to treat diabetes
Lifestyle changes, medical nutrition counseling, exercise
Treatment for Type 2 Diabetes
1) Agents that decrease insulin resistance (Metformin, amylin analogs)
2) Insulin secretagogues (Incretin analogues)
3) Insulin
4) Others (Gliflozins, alpha-Glucosidase inhibitors)
Main action of Metformin
Initial choice for hyperglycemia in Type 2 diabetes
Suppresses hepatic glucose production by inhibiting gluconeogenesis (improves insulin sensitivity/increases insulin-mediated glucose utilization in peripheral tissues)
Side effect: strong effect on gut microbiota
Main action of Amylin analogs
ex. Pramlintide
Slow gastric emptying and promote satiety
Also inhibits glucagon secretion from pancreatic alpha cells via hypothalamic receptors
Decrease liver gluconeogenesis and glycogenolysis to improve insulin sensitivity
Used in Type 1 and Type 2 diabetes
Main action of Incretins (insulin secretagogue)
ex. Glucagon-like peptide (GLP-1)
Binds to GPCRs to promote glucose-dependent insulin secretion from beta cells
Also impair glucagon secretion from pancreatic alpha cells
Endogenous incretins are rapidly catabolized by dipeptidyl peptidase-IV
Mechanism of GLP-1
Glucagon-like peptide-1
Delays gastric emptying and promotes feeling of satiety
Also increases thermogenesis and lipolysis via release of atrial natriuretic peptide
Has a POWERFUL impact on obesity reduction
Main action of Exenatide (GLP-1 receptor agonist/incretin analog)
From peptide in Gila monster saliva
Activates GLP1 receptor to increase glucose-dependent insulin secretion by pancreatic beta cells
Exenatide is stable to DPP4 degradation and remains in circulation longer
Main action of Semaglutide (GLP-1 receptor agonist/incretin analog)
Ozempic
Binds to plasma albumin elongating drug’s half life
A GLP1 receptor agonist to increase glucose-dependent insulin secretion
For Type 2 diabetes
Reduction of obesity
Mechanism of Gliflozins (Antihyperglycemic agents)
ex. Canagliflozin
Inhibit sodium-glucose cotransporter 2 (SGLT2)–>induce glucose excretion in urine by osmotic diuresis (also a decrease in sodium reabsorption to increase urine volume)–>decrease in plasma volume (cardiovascular benefit)
Require functioning kidneys but may protect against kidney worsening in Type 2 Diabetes
Side effects of Gliflozins (antihyperglycemic agents)
Increased frequency of urinary tract and genital infections due to increase glucose in urine (favouring bacterial growth)
Benefits of Gliflozins (antihyperglycemic agents)
Prevent heart failure in Type 2 diabetes patients with high cardiovascular risks
SGLT2 inhibitors reduce preload by promoting osmotic diuresis and natriuresis in patients (with or without diabetes)
Mechanism of alpha-glucosidase inhibitors (antihyperglycemic agent)
ex. Acarbose and miglitol
Competitively inhibit alpha-glucosidases enzyme that degrades starch into glucose–>decrease glucose absorption mediated by ion channels and transporters
Usually not used alone (lower efficacy and side effects)
Side effects of alpha-glucosidase inhibitors (antihyperglycemic agents)
ex. Acarbose and Miglitol
Abdominal pair, diarrhea, and flatulence resulting from bacteria fermentation
Avoided in patients with inflammatory bowel disease
