NR 565 Advanced Pharmacology Fundamentals Week 1-4 &
Midterm Exam Study Guide
Glycemic Goals in DM2
Blood glucose of 80-130 before meals, 180 or less 1-2 hrs post meals, A1C under 7. Long term goals are
to manage BG and preveny long term complications.
Preventing Diabetic Nephropathy
ACE inhibitors, such as lisinopril. Or ARBs such as losartan if patient cannot tolerate ACEs
ADAs Stepped Care Approach to DM Treatment
1. Lifestyle changes plus metformin.
2. Lifestyle plus metformin plus a second drug (GLP-1)
3. Lifestyle plus metformin plus 2 more drugs based on patient characteristics. For example, add SGLT2
inhibitor for patients with cardiovascular or renal disease.
Biguanides
Metformin
Initial therapy for DM2. Inhibits glucose production in liver. Reduces glucose absorption in gut.
Sensitized fat and skeletal muscle receptors to insulin (increased uptake of insulin). Safe in pregnancy. GI
side effects so take with meals. Excreted by kidneys so increased toxicity (lactic acidosis) if renal
impairment. Low risk of hypoglycemia.
1st vs. 2nd Generation Sulfonylurea
All 1st generation have been discontinued. 2nd generation (Glipizide) have shorter duration of action
and increased potency.
Sulfonylureas
glipizide, glyburide, glimepiride. Promote insulin release by beta cells. Block potassium channels of
pancreatic islets to let calcium in, which stimulates insulin release. Do not take with ETOH (disulfiram
reaction includes flushing, palpitations, nausea). Hypoglycemia and weight gain are also common side
effects. Do not take if pregnant or breastfeeding. Increased risk of toxicity if liver or kidneys are
impaired.
Meglitinides MOA
Stimulate a rapid/ short-lived release of insulin from the pancreas.
Meglitinides (Glinides)
Repaglinide (Prandin)
Nateglinide (Starlix)
Meglitinides patient teaching
, Tell patient to eat within 30 minutes.
Meglitinides (Glinides) precautions
Hypoglycemia increased in patients with liver dysfunction 2/2 slower metabolism of the drug.
Meglitinides vs. Sulfonylureas
-meglitinides are rapid acting and will have its effect on a single meal-decreasing post prandial
hyperglycemia. Taken with each meal.
-sulfonylureas continuously stimulate insulin release- having most of its effect on fasting glucose levels.
Both stimulate pancreatic insulin release.
Thiazolidinediones (TZDs)
Pioglitazone (Actos)
Rosiglitazone (Avandia)
Thiazolidinediones (TZDs) MOA
Peroxisome proliferator-activated receptor gamma agonists (PPAR휸 agonists) that increase peripheral
insulin sensitivity. Promotes increased glucose uptake by skeletal and adipose cells.
Thiazolidinediones (TZDs) adverse effects
Renal retention of fluid- so not for patients with stage 3 or 4 heart failure. May also cause upper
respiratory infections, headache, and myalgia. Hepatotoxic. Monitor liver function.
Dipeptidyl Peptidase-4 Inhibitors
Sitagliptin (Januvia), gliptins
Dipeptidyl Peptidase-4 Inhibitors MOA
DDP-4 is an enzyme that inactivate incretin hormones. So, by inhibiting this enzyme, sitagliptin enhances
the activity of incretins, stimulate release of insulin from pancreatic B cells, decrease hepatic glucose
production
Dipeptidyl Peptidase-4 Inhibitors Adverse effects
-Upper respiratory infection
-Headache and inflammation of nasal passages and throat
-Pancreatitis
-hypersensitivity reactions
Sodium Glucose Co-Transporter-2 (SGLT2) Inhibitors
Canagliflozin
Dapagliflozin
Empagliflozin
Midterm Exam Study Guide
Glycemic Goals in DM2
Blood glucose of 80-130 before meals, 180 or less 1-2 hrs post meals, A1C under 7. Long term goals are
to manage BG and preveny long term complications.
Preventing Diabetic Nephropathy
ACE inhibitors, such as lisinopril. Or ARBs such as losartan if patient cannot tolerate ACEs
ADAs Stepped Care Approach to DM Treatment
1. Lifestyle changes plus metformin.
2. Lifestyle plus metformin plus a second drug (GLP-1)
3. Lifestyle plus metformin plus 2 more drugs based on patient characteristics. For example, add SGLT2
inhibitor for patients with cardiovascular or renal disease.
Biguanides
Metformin
Initial therapy for DM2. Inhibits glucose production in liver. Reduces glucose absorption in gut.
Sensitized fat and skeletal muscle receptors to insulin (increased uptake of insulin). Safe in pregnancy. GI
side effects so take with meals. Excreted by kidneys so increased toxicity (lactic acidosis) if renal
impairment. Low risk of hypoglycemia.
1st vs. 2nd Generation Sulfonylurea
All 1st generation have been discontinued. 2nd generation (Glipizide) have shorter duration of action
and increased potency.
Sulfonylureas
glipizide, glyburide, glimepiride. Promote insulin release by beta cells. Block potassium channels of
pancreatic islets to let calcium in, which stimulates insulin release. Do not take with ETOH (disulfiram
reaction includes flushing, palpitations, nausea). Hypoglycemia and weight gain are also common side
effects. Do not take if pregnant or breastfeeding. Increased risk of toxicity if liver or kidneys are
impaired.
Meglitinides MOA
Stimulate a rapid/ short-lived release of insulin from the pancreas.
Meglitinides (Glinides)
Repaglinide (Prandin)
Nateglinide (Starlix)
Meglitinides patient teaching
, Tell patient to eat within 30 minutes.
Meglitinides (Glinides) precautions
Hypoglycemia increased in patients with liver dysfunction 2/2 slower metabolism of the drug.
Meglitinides vs. Sulfonylureas
-meglitinides are rapid acting and will have its effect on a single meal-decreasing post prandial
hyperglycemia. Taken with each meal.
-sulfonylureas continuously stimulate insulin release- having most of its effect on fasting glucose levels.
Both stimulate pancreatic insulin release.
Thiazolidinediones (TZDs)
Pioglitazone (Actos)
Rosiglitazone (Avandia)
Thiazolidinediones (TZDs) MOA
Peroxisome proliferator-activated receptor gamma agonists (PPAR휸 agonists) that increase peripheral
insulin sensitivity. Promotes increased glucose uptake by skeletal and adipose cells.
Thiazolidinediones (TZDs) adverse effects
Renal retention of fluid- so not for patients with stage 3 or 4 heart failure. May also cause upper
respiratory infections, headache, and myalgia. Hepatotoxic. Monitor liver function.
Dipeptidyl Peptidase-4 Inhibitors
Sitagliptin (Januvia), gliptins
Dipeptidyl Peptidase-4 Inhibitors MOA
DDP-4 is an enzyme that inactivate incretin hormones. So, by inhibiting this enzyme, sitagliptin enhances
the activity of incretins, stimulate release of insulin from pancreatic B cells, decrease hepatic glucose
production
Dipeptidyl Peptidase-4 Inhibitors Adverse effects
-Upper respiratory infection
-Headache and inflammation of nasal passages and throat
-Pancreatitis
-hypersensitivity reactions
Sodium Glucose Co-Transporter-2 (SGLT2) Inhibitors
Canagliflozin
Dapagliflozin
Empagliflozin
