Endocrine System -Oral Antidiabetic drugs

Name of the Oral Antidiabetic drugs Dipeptidyl peptidase-4 inhibitors drugs

• Sitagliptin
• Vildagliptin
• Saxagliptin
• Alogliptin
• Linagliptin

1.Sitagliptin

Mechanism of Action

Inhibits the dipeptidyl peptidase-4 enzyme to slow inactivation of incretin hormones. These hormones are released by the intestine throughout the day but increase in response to a meal. When blood glucose level is normal or increased, incretin hormones increase insulin synthesis and release from pancreatic beta cells. One type of incretin hormone, glucagon-like peptide (GLP-1) also lowers glucagon secretion from pancreatic alpha cells which reduces hepatic glucose production. These combined actions decrease blood glucose level in type 2 diabetes.

Pharmacokinetics

• Bioavailability: 87%
• Peak plasma time: 1-4 hr
• Protein bound: 38%
• Metabolism: Limited; primarily via CYP3A4 and CYP2C8
• Half-life, terminal: 12.4 hr
• Excretion: Urine (87% [79% unchanged]), feces (13%)

Administration

• Assess renal function before starting therapy.
• Before starting drug, ask patient about possible risk factors for pancreatitis, such as history of pancreatitis, alcoholism, gallstones, or hypertriglyceridemia. However, it’s unknown if these conditions make it more likely that pancreatitis will occur.
• Give with or without food.
• Be aware that drug shouldn’t be used to treat type 1 diabetes mellitus or diabetic ketoacidosis.
• Know that when drug is used with a sulfonylurea, a lower dose of sulfonylurea may be required, to reduce risk of hypoglycemia

Contraindications

• History of serious hypersensitivity to drug (such as anaphylaxis or angioedema)

Precautions:

• Concurrent administration of drugs that cause hypoglycemia (such as sulfonylureas or insulin)
• Renal impairment, history of pancreatitis
• Pregnant or breastfeeding patients
• Children younger than age 18 (safety and efficacy not established).

Adverse reactions

• CNS: headache
• EENT: nasopharyngitis
• GI: abdominal pain, nausea, vomiting, diarrhea, pancreatitis
• GU: acute renal failure
• Respiratory: upper respiratory tract infection
• Other: hypersensitivity reactions (including anaphylaxis, angioedema, exfoliative skin conditions such as Stevens-Johnson syndrome)

Patient monitoring

• Monitor renal function periodically.
• Measure patient’s weight and body mass index periodically during therapy.
• Monitor blood glucose and hemoglobin A1c levels periodically during therapy.
• Monitor patient for signs and symptoms of hypersensitivity reactions and immediately stop drug and institute emergency measures if such reactions occur.
• Check for diabetes signs and symptoms and disease progression routinely during therapy. 2Be aware of postmarketing reports of acute pancreatitis, including fatal and nonfatal hemorrhagic or necrotizing pancreatitis. If pancreatitis is suspected, promptly discontinue drug.

Patient teaching

• Instruct patient to take drug with or without food.
• Teach patient about signs and symptoms of hypoglycemia (such as blurred vision, confusion, tremor, sweating, excessive hunger, drowsiness, and fast heart rate).
• Teach patient about signs and symptoms of hypersensitivity reactions (such as rash, throat swelling, or difficulty breathing) and to immediately contact prescriber if these occur.
• Instruct patient to immediately discontinue drug and report if signs and symptoms of pancreatitis occur (persistent severe abdominal pain, sometimes radiating to the back, which may or may not be accompanied by vomiting).
• Instruct patient to routinely monitor blood glucose levels at home.
• As appropriate, review all other significant adverse reactions and interactions, especially those related to the drugs mentioned above.

Nursing Considerations

• Assess patient’s renal function before starting sitagliptin therapy, as ordered, and periodically thereafter. In moderate to severe renal dysfunction, dosage will be reduced.
• Monitor patient for hypersensitivity reactions that, although uncommon, may be severe. If present, notify prescriber and expect sitagliptin to be discontinued.
• Monitor patient’s blood glucose level, as ordered, to determine effectiveness of sitagliptin therapy

2.Vildagliptin (Galvus)

 Administration

• For oral use Galvus can be administered with or without meals (see section PHARMACOKINETICS, absorption).
• The 50 mg dose should be administered once daily in the morning. The 100 mg dose should be administered as two divided doses of 50 mg given in the morning and evening.
• If a dose of Galvus is missed, it should be taken as soon as the patient remembers. A double dose should not be taken on the same day.

Contraindications

Hypersensitivity to the active substance or to any of the excipients.

3.Saxagliptin

Mechanism of Action

Incretin hormones, such as glucosedependent insulintropic polypeptide (GIP) and glucagons-like peptide-1 (GLP-1), are released into bloodstream from small intestine in response to meals. Upon arrival at the pancreas, they stimulate pancreatic beta cells to release insulin. GLP-1 also reduces glucagon secretion from pancreatic alpha cells, which reduces hepatic glucose production. Incretin hormones become inactivated within minutes of release by the enzyme, dipeptidyl peptidase-4. Saxagliptin inhibits this enzyme, thereby slowing inactivation of incretin hormones, which provides more time for them to increase insulin levels and blunt glucagon secretion. More insulin and less hepatic glucose production work together to lower blood glucose levels.

Pharmacokinetics

• Peak plasma time: 2hr (saxagliptin); 4 hr (5-hyroxy saxagliptin)
• Metabolism: Hepatic by CYP450 3A4/5 to active metabolite (50% potency of parent compound)
• Half-life (elimination): 2.5 hr (saxagliptin); 3.1 hr (5-hydroxy saxagliptin)
• Excretion: Urine (75%); feces (22%)

Administration

• Assess renal function before starting therapy.
• Before starting drug, identify possible risk factors for pancreatitis, such as history of pancreatitis, alcoholism, gallstones, or hypertriglyceridemia.
• Administer without regard to meals.
• Be aware that drug shouldn’t be used for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis.

Contraindications

• History of serious hypersensitivity to drug (such as anaphylaxis, angioedema, or exfoliative skin conditions)

Precautions:

• Renal impairment, history of pancreatitis
• Concurrent use of insulin secretagogues or strong CYP450 and CYP3A4/5 inhibitors
• Pregnant or breastfeeding patients
• Children (safety and efficacy not established).

Adverse reactions

• CNS: headache
• EENT: sinusitis
• GI: vomiting, abdominal pain, gastroenteritis, acute pancreatitis
• GU: urinary tract infection
• Metabolic: hypoglycemia
• Respiratory: upper respiratory tract infection
• Skin: urticaria, exfoliative skin conditions
• Other: peripheral edema, facial edema, hypersensitivity (including anaphylaxis and angioedema)

Patient monitoring

• Monitor blood glucose and hemoglobin A1C levels and renal function tests periodically during therapy.
• Monitor CBC with differential, particularly lymphocyte count, in patients with unusual or prolonged infection.
• Observe patient carefully for signs and symptoms of pancreatitis. If pancreatitis is suspected, promptly discontinue drug and initiate appropriate management.

Patient teaching

• Tell patient to take drug with or without food. Tell patient not to split or cut tablet.
• Teach patient about signs and symptoms of hypoglycemia (blurred vision, confusion, tremor, diaphoresis, excessive hunger, drowsiness, increased heart rate) and how to treat it, especially if taking saxagliptin with other drugs that may cause hypoglycemia.
• Instruct patient to discontinue drug and immediately report signs and symptoms of hypersensitivity reaction (such as hives, rash, or swelling of face, lips, or throat) or pancreatitis (persistent severe abdominal pain, sometimes radiating to the back, which may or may not be accompanied by vomiting).
• Instruct patient to routinely monitor blood glucose level at home.
• As appropriate, review all other significant adverse reactions and interactions, especially those related to the drugs, tests, and food mentioned above

Nursing Considerations

• Saxagliptin shouldn’t be used to treat type 1 diabetes mellitus or diabetic ketoacidosis. It hasn’t been studied with insulin.
• Obtain a serum creatinine level, as ordered, before starting saxagliptin therapy and then periodically thereafter to monitor patient’s renal function.
• Monitor patient’s blood glucose level and hemoglobin A1C to assess effectiveness of saxagliptin therapy.
• Watch for hypoglycemia in patients taking antidiabetics, such as sulfonylureas. Expect dosage of insulin secretagogues (such as sulfonylureas) to be reduced to reduce risk of hypoglycemia

4.Alogliptin

Mechanism of Action

Selective dipeptidyl peptidase-4 (DPP-4) inhibitor; slows inactivation of incretin hormones (eg, GLP-1, GIP), thereby reducing fasting and postprandial glucose concentrations in a glucose-dependent manner

Pharmacokinetics

• Bioavailability: ~100%
• Peak plasma time: 1-2 hr
• Protein bound: 20%
• Metabolism: Does not undergo extensive metabolism and 60-71% of the dose is excreted unchanged in the urine
• Half-life: 21 hr
• Renal clearance: 9.6 L/hr
• Excretion: 76% urine; 13% feces

Contraindications

Hypersensitivity to alogliptin, including anaphylaxis, angioedema, or severe cutaneous adverse reactions including Stevens-Johnson syndrome

Cautiously

• Hepatic impairment;
• Renal impairment (dose ↓ required if CCr <60 mL/min);
• HF or renal impairment (↑ risk for worsening HF);
• OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
• Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
• Pedi: Safety and effectiveness not established in children;
• Geri: Older adults may have ↑ sensitivity to effects.

Adverse Reactions/Side Effects

• CV: HF
• Derm: bullous pemphigoid, STEVENS-JOHNSON SYNDROME (SJS)
• GI: ↑ liver enzymes, HEPATOTOXICITY, PANCREATITIS
• MS: arthralgia, RHABDOMYOLYSIS
• Neuro: headache
• Misc: HYPERSENSITIVITY REACTIONS (including anaphylaxis or angioedema)

Assessment

• Observe for signs and symptoms of hypoglycemic reactions (abdominal pain, sweating, hunger, weakness, dizziness, headache, tremor, tachycardia, anxiety).
• Monitor for signs of pancreatitis (nausea, vomiting, anorexia, persistent severe abdominal pain, sometimes radiating to the back) during therapy. If pancreatitis occurs, discontinue alogliptin and monitor serum and urine amylase, amylase/CCr ratio, electrolytes, serum calcium, glucose, and lipase.
• Assess for signs and symptoms of HF (increasing shortness of breath, rapid increase in weight, swelling of feet) periodically during therapy.
• Assess for rash periodically during therapy. May cause SJS. Discontinue therapy if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis, and/or eosinophilia.

Patient/Family Teaching

• Instruct patient to take alogliptin as directed. Take missed doses as soon as remembered, unless it is almost time for next dose; do not double dose. Advise patient to read Medication Guide before starting and with each Rx refill in case of changes.
• Explain to patient that alogliptin helps control hyperglycemia but does not cure diabetes. Therapy is usually long term.
• Instruct patient not to share this medication with others, even if they have the same symptoms; it may harm them.
• Encourage patient to follow prescribed diet, medication, and exercise regimen to prevent hyperglycemic or hypoglycemic episodes
• Review signs of hypoglycemia and hyperglycemia with patient. If hypoglycemia occurs, advise patient to take a glass of orange juice or 2–3 tsp of sugar, honey, or corn syrup dissolved in water, and notify health care professional.
• Instruct patient in proper testing of blood glucose and urine ketones. These tests should be monitored closely during periods of stress or illness and health care professional notified if significant changes occur.
• Advise patient to stop taking alogliptin and notify health care professional promptly if symptoms of hypersensitivity reactions (rash; hives; swelling of face, lips, tongue, and throat; difficulty in breathing or swallowing), liver dysfunction (fatigue, nausea, vomiting, anorexia, right upper abdominal discomfort, dark urine, yellowing of skin or whites of eyes), HF, or pancreatitis occur.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
• Instruct patient to notify health care professional if severe joint pain occurs.

5.Linagliptin

Mechanism of Action

Dipeptidyl peptidase 4 (DPP-4) inhibitor; increases and prolongs incretin hormone activity which is inactivated by DPP-4 enzyme

Incretins regulate glucose homeostasis by increasing insulin synthesis and release from pancreatic beta cells and reducing glucagon secretion from pancreatic alpha cells

Pharmacokinetics

• Bioavailability: 30%
• Peak Plasma Time: 1.5 hr
• Protein Bound: 75-99%; concentration dependent
• Metabolism: Small fraction metabolized to inactive metabolite
• Half-Life: 12 hr
• Renal clearance: 70 mL/min

Contraindications

• Severe renal impairment, end-stage renal disease, or dialysis
• Hypersensitivity to empagliflozin, linagliptin, or excipients (eg, anaphylaxis, angioedema, exfoliative skin conditions, urticaria, bronchial hyperreactivity)

REFERENCES

1. Robert Kizior, Keith Hodgson, Saunders Nursing Drug handbook,1st edition 2024, Elsevier Publications. ISBN-9780443116070
2. McGraw Hill- Drug Handbook, Seventh Edition, 2013, McGraw Hill Education Publications,9780071799430.
3. April Hazard, Cynthia Sanoski, Davi’s Drug Guide for Nurses -Sixteenth Edition 2019, FA Davis Company Publications,9780803669451.
4. Jones and Bartlet, Pharmacology for Nurses, Second Edition, 2020, Jones and Bartlet Learning Publications, ISBN 9781284141986.
5. Nursebro.com, Search – Nursebro

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