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NR 565 Final Exam Study Guide

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Advanced Pharmacology Fundamentals (Chamberlain University)




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NR 565 Final Exam Study Guide:



Chapter 48
Glycemic Goals in Type 2 Diabetes
● Goal:
○ Maintain blood glucose levels to prevent long-term complications like
nephropathy, retinopathy, neuropathy, and cardiovascular disease
● Target A1C:
○ Generally aim for an A1C of <7% for most adults, individualizing based on patient
characteristics.Less than 8% in patients with severe hypoglycemia
■ Some may have a less stringent target, especially elderly patients or
those with severe hypoglycemia risks.
■ The goal of therapy should be individualized based on patient-specific
factors, including the duration of diabetes, age, comorbid conditions, and
other risk factors.
● Fasting Plasma Glucose:
○ Typically aim for 80-130 mg/dL.
○ Diabetes may be diagnosed with a fasting plasma glucose of greater than 126
and a random plasma glucose of greater than 200.
● Postprandial Glucose:
○ Aim for <180 mg/dL at 1-2 hours after meals.
● Patients with A1C greater than 10% and fasting blood glucose of 300 or more may be
started on combination injectable therapy immediately.

Diabetic Nephropathy Prevention
● Approach:
○ Optimize glycemic control (A1C <7%).
○ Control blood pressure (target <140/90 mmHg) using ACE inhibitors or ARBs,
especially if proteinuria is present.
■ These drugs reduce the risk of kidney damage by lowering blood
pressure and reducing proteinuria
○ Monitor renal function regularly, especially in patients with existing diabetes and
hypertension.

Sulfonylureas
● Mechanism of Action (MOA):
○ Stimulate insulin secretion from beta cells in the pancreas by blocking ATP-
sensitive potassium channels, which leads to depolarization of the cell
membrane allowing calcium to enter the cell and promoting insulin release
○ Should not be used in pregnancy, renal impairment, or hepatic impairment




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● Two types 1 & 2 (SEE BELOW)
● Contraindications:
○ Type 1 diabetes.
○ Patients with a history of severe hypoglycemia
○ Diabetic ketoacidosis.
○ Severe renal or hepatic impairment
○ Pregnancy
■ Generally avoided as insulin is preferred due to a better safety profile.
● Side Effects:
○ Hypoglycemia (especially if meals are skipped, or dosage is too high)
○ Weight gain.
○ Increased risk of cardiovascular events (due to electrolyte shifts)
○ Gastrointestinal upset.

1st Generation vs 2nd Generation Sulfonylureas
● 1st Generation:
○ Examples: Tolbutamide, Chlorpropamide.
○ Were the initial class of antidiabetic agents
○ These drugs work by promoting the release of insulin from pancreatic β cells, a
mechanism that effectively lowers blood glucose levels.
○ Require higher doses to achieve therapeutic effects
○ Less potent and have a higher risk of adverse effects.
○ More likely to cause frequent and severe drug interactions
■ Especially drugs that are metabolized by liver or excreted by the kidneys -
leading to unpredictable effects on blood glucose levels
● 2nd Generation:
○ Examples: Glipizide, Glyburide, Glimepiride.
○ More potent, require lower doses, and have fewer side effects.
○ While both generations can cause hypoglycemia, second-generation
sulfonylureas are less likely to lead to severe hypoglycemic episodes when used
appropriately
○ Generally have a longer duration of action, which provides more stable blood
glucose control throughout the day

DDP4 Inhibitors (DPP4I)
● Prototype: Sitagliptin (januvia)
● Mechanism of Action (MOA):
○ Inhibit the enzyme dipeptidyl peptidase-4 (DPP-4), increasing levels of incretin
hormones, which in turn stimulate insulin secretion and decrease glucagon
secretion. By inhibiting DPP-4, these drugs prolong the activity of incretins,
leading to improved insulin secretion, reduced glucagon release, and decreased
hepatic glucose production
■ DPP-4 is responsible for breaking down incretin hormones, which are
essential for glucose homeostasis
● Adverse Effects: Generally well-tolerated; potential side effects include:
○ Mild upper respiratory infections.
○ Headaches
○ Nasopharyngitis




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○ Rare risk of pancreatitis and hypersensitivity reactions

Sitagliptin
● Side Effects: See above.

Glucagon-like Peptide-1 (GLP-1) Receptor Agonists
● Prototype: Exenatidine (Byetta)
● Mechanism of Action (MOA):
○ Mimic the actions of the endogenous incretin hormone glucagon-like peptide-1
(GLP-1)
■ Activate GLP-1 receptors, leading to:
● Slowed gastric emptying.
● Increased glucose-dependent insulin secretion.
● Suppress postprandial glucagon secretion/release
● Appetite suppression.
● Monitoring:
○ Regular blood glucose monitoring to prevent hypoglycemic events
○ Watch for signs of gastrointestinal side effects and pancreatitis
○ Renal function should also be monitored as these drugs can affect kidney
function

Glycemic Control Targets
● General Recommendations:
○ Aim for individualized A1C targets based on age, comorbidities, and risk of
hypoglycemia
○ General target of HbA1C of less than 7% for nonpregnant adults with diabetes
○ Premeal plasma glucose target: 70 - 130 mg/dL
○ Peak Postmeal Plasma Glucose target: less than 180 mg/dL

Incretin Mimetics
● Overview:
○ Mimic incretin hormones (e.g., GLP-1) to enhance insulin secretion in response
to meals, suppress glucagon release, delay gastric emptying, and promote
satiety. These actions improve postprandial glucose levels and may lead to
weight loss
● Pregnancy:
○ Should be used cautiously; risks versus benefits must be evaluated due to limited
data on safety.
■ Insulin is the preferred treatment for managing diabetes during pregnancy
to ensure both maternal and fetal safety

Meglitinides vs Sulfonylureas
● Meglitinides
○ Prototype: Repaglinide
○ MOA:




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