Diabetes I and II Flashcards
Metformin
MOA
Biguanide
- Works in liver to inhibit mitochondrial respiratory chain complex 1 = stops gluconeogenesis (ketone → glucose) therefore less glucose is produced
- Slows glucose absorption into blood stream, thus keeps BSL at a steady, constant state
- Improves cell sensitivity to insulin
- Lowers LDL and increases HDL levels
Metformin
Adverse
Lactic acidosis – rare (DO NOT use with hepatic or renal disease or congestive heart failure) -Nausea, vomiting, diarrhoea, -Vit B12/Folate NOT absorbed -metallic taste -No weight gains -no risk of hypoglycaemia
Metformin
Caution/CrCl
MUST look at CrCl more clearance=
CrCl = 80ml/min = 2g Max
CrCl = 40 ml/min = 1g Max
CrCl = 20ml/min = 500 Max
-Alcohol (↑ lactic acidosis)
-Cimetidine (GORD)
-iodinated contrast media
(↑acidosis)
Sulfonylureas
MOA
- Acts on Beta cells, binding to SUR1 subunit
1. Blocks K-ATP channels = membrane depolarisation =activating L-type calcium channels which stimulates the release of Insulin
2. increase sensitivity of tissues to insulin
3. inhibits gluconeogenesis
Sulfonylureas
Adverse
Increases weight (avoid in obese people)
-hypoglycaemia
(common in elderly/ renal impaired and the longer the half life the more risk )
-Rash, Metallic taste, nausea
Cardiotoxicity (↑ risk of heart failure)
-because is also binds to SUR2 in cardiac muscle
Dipeptidyl peptidase -4 inhibitor
eg Sitagliptin
MOA
- Completely inhibits DPP4
- ↑ endogenous incretins, glucagon-like peptides (GLP-1) and Glucose-dependant insulinotropic polypeptide (GIP)
- ↑ insulin and ↓ glucagon
Glucagon-like peptide -1 analogues
Examples/MOA
eg Exenatide, Liraglutide
- mimics endogenous incretin GLP-1
- activates G-protein coupled receptor, blocking K ATP channels
- ↑ Ca and increase insulin secretion
- Also acts on stomach/hypothalamus to delay gastric emptying
- ↓ glucagon secretion
Sodium-glucose co-transporter 2 inhibitors
examples/MOA
Dapagliflozin
works in proximal convoluted tubule
- inhibits SGLT2 (kidney), thus stop the reabsorption of glucose into blood
- ↑excretion of glucose in urine
Thiazolidinedione
- Binds to Peroxisome proliferator-activated receptor y (PPARy)
- activates a gene that regulates lipid and glucose metabolism
- ↑ insulin sensitivity
- ↓ insulin resistance
- ↑use of insulin
- May also improve beta cell function
a-glucosidease inhibitor
eg Acarbose
-inhibits intestinal a-glucosidase, thus carbohydrate absorption is delayed
