Antidiabetic Drugs II Flashcards
mechanism of action of sulfonylureas and their use in diabetes
- binds to SUR1 subunit –> blocks ATP sensitive K channel in beta cell membrane –> depolarization –> opening of voltage gated calcium channel –> influx of calcium –> release of preformed insulin from beta cells
- reduction of serum glucagon levels
- both of the above leads to reduction of fasting glucose levels and HbA1c
what is AE of the first generation sulfonylurea (name it)
Chlorpropamide (SHHJ)
SIADH (potentiates action of vasopressor)
Hyperemic Flush (increased acetaldehyde conc)
Hematological toxicity
Jaundice if given in excess
who is the first generation of sulfonylurea contraindicated in (name it)
Chlorpropamide (HER)
Hepatic insufficiency
Elderly
Renal insufficiency
what are the second generation sulfonylureas and how they differ from first generation
Glyburide (Glibenclamide)
Glimepiride
Glipizide
second generation lack some of the adverse effects and drug interactions seen in first generation Chlorpropamide and are more potent
which of the second generation sulfonylurea is most likely to cause hypoglycemia
Glyburide (Glibenclamide)
AE of second generation sulfonylurea
Glyburide, Glimepiride, Glipizide
Hypoglycemia
Weight gain
what are the meglitinides
Repaglinide
Nateglinide
mechanism of meglitinides (name them)
repaglinide and nateglinide
same as sulfonylurea: binds to different location on SUR1 –> inhibit beta cell ATP sensitive K+ channel –> depolarization –> opening of voltage gated calcium channel –> influx of calcium –> release of insulin
when are meglitinides taken (name them)
repaglinide and nateglinide
they are post prandial glucose regulators which are rapid onset and short duration so must be taken right before a meal
who are meglitinides indicated for
repaglinide and nateglinide
those with sulfur or sulfonylurea allergy
how do you get rid of meglitinides
metabolized by CYP3A4 and excreted in bile
AE of meglitinides (name them)
repaglinide and nateglinide
same AE as sulfonylurea:
Hypoglycemia
Weight gain
what is the bigaunides
Metformin
mechanism of action of biguanides
- metformin reduces blood glucose by inhibiting gluconeogenesis by reducing the expression of gluconeogenic enzymes
- increases insulin mediated glucose utilization by peripheral tissues such as liver and muscle after meals
first line therapy in type II DM
metformin
what are some big difference between biguanide (metformin) and insulin secretagogues (meglitinides and sulfonylureas)
- metformin causes weight loss while insulin secretagogues cause weight gain
- metformin inhibits gluconeogenesis and increases uptake of glucose of peripheral tissues after meals while insulin secretagogues increase insulin release by inhibiting ATP K channels leading to depolarization and opening of Ca channels
AE of metformin
LBL
Largely GI: anorexia, vomiting, nausea etc
B12 malabsorption if long term use
Lactic acidosis –> MI, heart failure
what should be avoided if taking metformin
alcohol
contraindications of metformin
HHAR
Hepatic disease
Hypoxia
Alcoholism
Renal disease
best treatment for polycycstic ovarian syndrome and what has become the leading treatment
best: clomiphene
leading: metformin
what are the thiazolidinediones (TZDs)
Pioglitazone
Rosiglitazone
mechanism of action of thiazolidinediones (name them)
pioglitazone and rosiglitazone
- decrease insulin resistance
- agonist of peroxisome proliferator activated receptor-gamma found in muscle, fat, liver
what are thiazolidinediones slower onset (name them)
pioglitazone and rosiglitazone
because they work on gene regulations which takes weeks or even months to see their results
AE of thiazolidinediones (name them)
pioglitazone and rosiglitazone
WERC
Weight gain
Edema
Retention of fluid
Congestive Heart Failure
contraindication of thiazolidinediones (name them)
pioglitazone and rosiglitazone
class III and IV heart failure
what is the alpha glucosidase inhibitor
Acarbose and Miglitol
mechanism of alpha glucosidase inhibitor (name it)
acarbose and miglitol –> competitive inhibitor of intestinal alpha glucosidase –> reduces the post prandial digestion and absorption of starch and disaccharides –> inhibits upper intestinal digestion and absorption –> defer it to distal SI –> reduce post prandial hyperglycemia and hyperinsulinemia
AE of alpha glucosidase inhibitor
acarbose and miglitol
mainly GI: flatulence, diarrhea, abdominal pain,
this is due to the fact that the undigested carbs from the upper GI are getting into the colon but eventually the distal SI start to express alpha glucosidase and the AEs are no longer an issue
what would you give a patient who expresses hypoglycemia because they are taken sulfonylurea along with acarbose
you give them glucose and not sucrose because the disaccharide breakdown might be blocked with the acarbose
contraindication of acarbose and miglitol
chronic or IBD
intestinal conditions
Kidney diease
Hepatic disease
anything that might be worsened with gas or flatulence
what is the incretin analogue
Exenatide
mechanism of incretin analogue
exanatide is an agonist of glucagon like peptide-1 receptor –> enhances glucose dependent insulin secretion, suppresses post prandial glucagon release, slows gastric emptying which slows nutrients entry into circulation, decreases appetite, and stimulates beta cells proliferation
AE of exenatide
VAND
Vomiting
ACUTE PANCREATITIS
Nausea
Diarrhea
contraindication of exenatide
gastroparesis (spontaneous movement of muscle in stomach not functioning properly)
DPP IV inhibitor
Sitagliptin
mechanism of DPP IV inhibitor
Sitagliptin –> increases circulating GLP-1 and insulin levels and decreases glucagon levels
AE of DPP IV inhibitor
Sitagliptin
Pancreatitis
Hypersensitivity reaction
amylin analogue
Pramlintide
mechanism of amylin analog
Pramlintide inhibits food intake, gastric emptying, and glucagon release
AE of amylin analog
Pramlintide
ANOREXIA
nausea
headache
vomiting
Contraindication of Pramlintide
gastroparesis just like Exenatide
