Endo Exam 2: Non-Diebetic Drugs (BBW, MOAs, DDIs)

Molecular Target: SUR receptor (on the KATP channel)

Cellular Change: KATP channel BLOCK → membrane DEPOL

Pharm Response: ↑ INSULIN release, ↓ blood GLUCOSE

Sulfonylureas

Molecular Target: KATP CHANNEL (pancreatic β cells)

Cellular Change: KATP channel BLOCK → membrane DEPOL

Pharm Response: ↑ INSULIN release, ↓ blood GLUCOSE

Meglitinides

Molecular Target: ETC COMPLEX I (hepatocyte mitochondria)

Cellular Change: activation of AMPK

Pharm Response: INHIBITS GLUCOneoGENESIS, ↓ blood GLUCOSE

Metformin (biguanide)

Molecular Target: PPAR-γ receptor

Cellular Change: Receptor ACTIVATION → change in LIPID METABOLISM

Pharm Response: Improved INSULIN SENSITIVITY, ↑ GLUCOSE UPTAKE by tissues, ↓ blood GLUCOSE

TZDs

Molecular Target: GLP-1 receptor on β cells

Cellular Change: ↑ INSULIN release, ↓ APPETITE, SLOWS GASTRIC emptying

Pharm Response: ↓ Blood GLUCOSE

GLP-1 analogs

Cellular Change: ↑ PLASMA GLP-1 and GIP

Pharm Response: ↓ Blood GLUCOS

DPP-4i

Cellular Change: INHIBITS DIGESTION of OLIGOsaccharides

Pharm Response: ↓ GLUCOSE ABSORPTION, ↓ blood GLUCOSE

alpha-glucosidase-i

Cellular Change: INHIBITS GLUCOSE REABSORPTION

Pharm Response: ↓ Blood GLUCOSE

SGLT2i

BBW: Lactic ACIDOSIS

Metformin

BBW: Thyroid C-cell TUMORS (seen in rats)

C/I: personal/family hx of medullary THYROID cancer or MEN2

GLP-1 RA (including oral semaglutide and Tirzepatide)

BBW: May cause or worsen CHF (C/I: NYHA class 3-4).

_____ ONLY: ↑ risk of MI

TZDs, Rosiglitazone

Precautions: bone FRACTURES, Fournier’s gangrene, ketoaACIDOSIS (incl. euglycemic DKA), genital mycotic INFECTIONS, UTIs, HYPOtension/DEhydration, AKI

SGLT2i, Sulfonylureas, and DPP-4i

_____: pancreatitis, GALLBLADDER disease, intestinal blockage with Ozempic),

_____: pancreatitis, HF, JOINT PAIN, bullous pemphigoid)

_____: sulfa hypersensitivity C/I, _____ and all _____ on the BEERS list).

GLP-1 RA, DPP-4i, Sulfonylureas, Glyburide, SUs

DDIs

• _____: 2C9 inhibitors → ↑ HYPOglycemia and 2C9 inducers → poor control

• _____: Hold before iodinated contrast if eGFR 30-60. Limit alcohol

• _____: another form of birth control for 4 weeks after starting and after each dose increase

• _____: Extra hypoglycemia risk with insulin

• _____: ↑ blood glucose

Sulfonylureas, Metformin, Tirzepatide, Pramlintide, Non-Selective BBs