A 21-year-old man comes to the emergency department due to several days of dizziness and extreme fatigue. The patient has been drinking a lot of water and urinating more than usual for the past 2 weeks. He developed nausea and vomiting a day ago and has had difficulty keeping food and liquids down since then. The patient has no other medical conditions and takes no medications. Blood pressure is 90/60 mm Hg, pulse is 120/min, and respirations are 20/min. Urinalysis is positive for glucose and ketones. The patient is given intravenous fluids and an intravenous infusion of recombinant human insulin without any amino acid modification. After his condition is stabilized, the insulin infusion is stopped, and the same insulin formulation is administered subcutaneously. Which of the following drug concentration curves is most likely to be obtained after the subcutaneous insulin injection?

Question

A 21-year-old man comes to the emergency department due to several days of dizziness and extreme fatigue.  The patient has been drinking a lot of water and urinating more than usual for the past 2 weeks.  He developed nausea and vomiting a day ago and has had difficulty keeping food and liquids down since then.  The patient has no other medical conditions and takes no medications.  Blood pressure is 90/60 mm Hg, pulse is 120/min, and respirations are 20/min.  Urinalysis is positive for glucose and ketones.  The patient is given intravenous fluids and an intravenous infusion of recombinant human insulin without any amino acid modification.  After his condition is stabilized, the insulin infusion is stopped, and the same insulin formulation is administered subcutaneously.  Which of the following drug concentration curves is most likely to be obtained after the subcutaneous insulin injection?

Quizplus · Accepted Answer

11ec160b_3bad_0a53_9249_01bddeb96518_MD0001_00 This patient's vomiting, volume depletion, glucosuria, and ketonuria are consistent with diabetic ketoacidosis (DKA). DKA is treated with an intravenous infusion of regular insulin that begins to lower serum glucose and ketone levels within minutes of administration. Regular insulin has a half-life of 5 minutes when administered intravenously, allowing rapid adjustment of the infusion rate based on glucose levels. Regular insulin can also be used subcutaneously in the subacute and chronic management of diabetes, usually in combination with an intermediate-acting or a long-acting insulin analog to provide bolus and basal coverage. When given subcutaneously, regular insulin can polymerize into hexamers, which slightly delays systemic absorption; it starts working within 30 minutes, peaks in 2-4 hours, and lasts 5-8 hours. Regular insulin and neutral protamine Hagedorn (NPH) are the only human recombinant insulins without any modifications in the amino acid sequence. All other insulin preparations (eg, detemir, glargine, lispro, aspart, glulisine) have structural modifications (eg, amino acid modifications) and are considered insulin analogs. (Choice A) Insulin lispro, aspart, and glulisine are rapid-acting insulin analogs. Due to various amino acid modifications, they do not form hexamers like regular insulin, and are absorbed more quickly after subcutaneous injection. They have an onset of action of about 15 minutes and peak in 45-75 minutes. (Choice C) NPH insulin is an intermediate-acting insulin composed of a crystalline suspension of insulin with protamine and zinc. This delays absorption of insulin from the subcutaneous injection site. NPH usually starts working within 2 hours, peaks in 4-12 hours, and lasts about 18 hours. (Choice D) Detemir is a long-acting insulin analog with a fatty acid bound to one of the lysine amino acids on the insulin molecule. This fatty acid side chain allows detemir to bind to albumin and slowly dissociate, resulting in prolonged action. It usually starts working within 2 hours, peaks between 3-9 hours, and lasts up to 24 hours. (Choice E) Glargine is an insulin analog with a long duration of action. Glargine has a pH of 4 and forms a microprecipitate in the subcutaneous tissue after injection, resulting in a very slow release of insulin. Glargine lasts about 24 hours and does not have a pronounced peak. Longer-acting basal insulin analogs (eg, insulin degludec and concentrated glargine) with duration of action >24 hours are also available. Educational objective: Diabetic ketoacidosis is initially treated with an intravenous infusion of regular insulin, which allows for rapid adjustments in dose based on blood glucose levels. When given subcutaneously, regular insulin starts working within 30 minutes, peaks in 2-4 hours, and lasts 5-8 hours. __________ References: New insulin preparations: a primer for the clinician. (http://www.ncbi.nlm.nih.gov/pubmed/27176680)

A 21-Year-Old Man Comes to the Emergency Department Due to Several