問題一覧
1
Which of the following statements is correct regarding insulin glargine?
It is a "peakless" insulin
2
A patient with type 2 diabetes is currently being treated with insulin detemir. The physician determines that the patient needs additional insulin therapy for control of postprandial glucose. Which of the following agents is most appropriate to add at this time?
Insulin lispro
3
A patient with type 1 diabetes is prescribed insulin glulisine as part of his diabetes regimen. How should the patient be advised to take insulin glulisine?
15 to 30 minutes before each meal
4
Which class of oral diabetes drugs is paired most appropriately with its primary mechanism of action?
SGLT2 inhibitor—increases urinary excretion of glucose
5
Which of the following is the most appropriate initial oral agent for management of type 2 diabetes in patients with no other comorbid conditions?
Metformin
6
Which of the following drugs for diabetes is MOST likely to cause hypoglycemia?
Glyburide
7
A 56-year-old man with type 2 diabetes recently experienced a myocardial infarction (heart attack). He takes metformin and canagliflozin for his diabetes, and his Alc is still above goal. Which of the following drugs is most appropriate to initiate for this patient?
Liraglutide
8
A patient with newly diagnosed type 2 diabetes has severe chronic kidney disease (estimated glomerular filtration rate less than 30 mL/min/1.73 m2). Which of the following oral agents for diabetes is most appropriate for this patient?
Linagliptin
9
Which of the following combinations of drugs for type 2 diabetes has an overlapping mechanism of action?
Glipizide—repaglinide
10
A 67-year-old woman with type 2 diabetes also has heart failure with reduced ejection fraction (HFrEF). She takes metformin for diabetes, and she has mild renal impairment. Which of the following may be beneficial to assist with management of both her diabetes and HFrEF?
Dapagliflozin
11
In normal physiology of glucose regulation, beta cells in the pancrease maintain low basal levels of circulating insulin that suppress?
lipolysis, proteolysis, and glycogenolysis
12
Insulin brings glucose into cells by
enzyme-linked receptors (tyrosine kinase)
13
What are the distinguishing physiological differences between type 1 and type 2 diabetes?
Type I – Loss of beta-cell function and Type I DM results from autoimmune-medicated processes. Type II – Lack of sensitivity of target organs to insulin. The pancreas retains some beta-cell function, but insulin secretion is insufficient to maintain glucose homeostasis in the face of increasing peripheral insulin resistance.
14
Explain differences in treatment approaches between type 1 and type 2 diabetes
type 1 is treated with only exogenous insulin, whereas type 2 is treated with weight reduction, exercise, diet modificaitons, and medicaitons
15
Differences in age of onset between type 1 and type 2 diabetes
type 1 is usually during childhood or puberty, whereas type 2 is commonly over age 35
16
Explain the nutritional, prevelence, and genetic predisposition differences among type 1 and type 2 diabetics
Type 1 are usually undernourished, account for 5-10% of diabetics, and have a moderate genetic predisposition Type 2 are usually obese, account for 90-95% of diabetics, and have a very strong genetic predisposition
17
A 58 year old male comes into the clinic as a new patient. He is complaining that is he thirsty all the time, and has frequent urination and low energy. He tells you he has not had anything for breakfast because he knew his labs would be drawn today, but is always hungry. You order labs for him, and shortly after they come back: fasting glucose = 220, A1C = 9.3. You diagnose him with diabetes type 2. What was the criteria used for this diagnosis?
Fasting plasma glucose >/= 126 and A1C >/= 6.5%
18
You have three diabetic patients to see in clinic today. One is a 31 year old female who is reporting a postprandial glucose of 190. The second is 22 year old pregnant woman in her 2nd trimester and reports a fasting glucose of 120. Your third patient is a 79 year old male how is blind and didn't have assistance to take a fasting blood sugar at home, but when he arrives you check it and it is 80. You order an A1C for him and it results shortly after as 7.5%. Based in these findings, what teaching would you include in your after-visit summary for each patient?
31 year old female - Educate her that fasting plasma glucose in the management of diabetes is 80 to 130 mg/dL and that for postprandial glucose is less than 180 mg/dL. 22 year old pregnant female - Educate her that glucose goals are more stringent in patients with gestational diabetes (for example, fasting plasma glucose 70-95 mg/dL, or e, AIC less than 6% if this can be obtained without significant hypoglycemia). 79 year old male - Inform him that he is on track and to keep up the good work since glucose goals may be less stringent in elderly patients (for example, AIC less than 8%)
19
Is a clustering of at least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL).
Metabolic Syndrome
20
Body shape associated Metabolic Syndrome
Apple-shaped
21
Impact of insulin resistance
High triglyceride levels and HDL cholesterol, Atherosclerosis, Hypertension , Elevated glucose levels, Excessive thirst and hunger , Frequent urination , Blurred vision and headaches, Vaginal and skin infections, Slow-healing cuts and sores, Increased risk of stroke and CV disease, Nerve damage in limbs/loss of limbs
22
Jessy is a 45 year old male that is an establlished patient at your clinic, but comes in today with new onset of hyperglycemia and is concerned he might be diabetic. He says he has had nothing for breakfast,so you check his fasting glucose and it is 120. You order an A1C lab and it comes back as 6.3%. Based on ADA criteria, what condition does Jessy have?
Prediabetes because patients with borderline fasting glucose (100-125 mg/dL), postprandial glucose (140-199, AIC 5.7% to 6.4%) are considered to have prediabetes.
23
What is the action (metabolism) of insulin on the liver, muscle, and adipose tissue?
Insulin suppresses hepatic glucose output and adipose tissue lipolysis, lowering blood glucose and fatty acid levels. It also increases hepatic lipid synthesis for subsequent storage in adipose tissue and stimulates glucose uptake into fat and muscle.
24
Discuss the first phase of Insulin release in the body
Is rapidly triggered in response to increased blood glucose levels and lasts about 10 minutes
25
Discuss the second phase of insulin release in the body
Is a sustained, slow release of newly formed vesicles triggered independently of sugar, peaking in 2 to 3 hours
26
What role does Amylin play in glycemic regulation?
By slowing gastric emptying and promoting satiety, thereby preventing post-prandial spikes in blood glucose levels
27
What is the difference in the concept of basal and prandial (bolus) insulin?
Basal insulin suppresses glucose production by the liver (gluconeogenesis) between meals and overnight. Prandial (bolus) insulin covers increases in blood glucose levels following meals
28
Onset: 15 mins; Peak: 1 hour; Duration: 2-4 hours Are indicated to improve glycemic control in patients with T1DM and T2DM along with a proper diet and exercise
Rapid Acting
29
Onset: 30 mins; Peak: 2-3 hours; Duration: 3-6 hours Is indicated for treatment of DMI and DMII and gestational diabetes mellitus. It can also be used in the management of diabetic ketoacidosis.
Short Acting
30
Onset: 2-4 hours; Peak: 4-12 hours; Duration: 12-18 hours Indicated for people with type 1 (T1DM) and type 2 diabetes mellitus (T2DM) along with a proper diet and exercise.
Intermediate Acting
31
Onset: 2 hours; Peak: none; Duration: 24 hours Are indicated to improve glycemic control in patients with T1DM and T2DM along with a proper diet and exercise.
Long Acting
32
Onset: 5-60 minutes; Peak: vary; Duration: 10-16 hours Usually prescribed for patients needing a simple insulin treatment plan, and sliding scale therapy. You may be in this category if you: Are older, with regular meal and activity patterns. Have diminished vision or trouble with dexterity.
Premixed
33
What are the current sources of insulin?
Bacteria and yeast
34
When would you observe for side effect of hypoglycemia with each type of insulin; what if 2 different insulin products are used?
Hypoglycemia could occur starting at the onset of drug action, and if 2 different insulins are used hypoglycemia could occur in the window between onsets.
35
Name at least one Rapid Acting insulin in each category and know when it is used.
Aspart, Lispro, Glulisine; prandial control
36
Name at least one Short Acting insulin in each category and know when it is used.
Regular; prandial control
37
Name at least one Intermediate Acting insulin in each category and know when it is used.
NPH; basal insulin only when dosed at bedtime, or a basal and prandial insulin when dosed in the morning.
38
Name at least one Long Acting insulin in each category and know when it is used.
Glargine, Detemir, Degludec; for basal control
39
Name at least one Premixed insulin in each category and know when it is used.
70/30 NPH/Regular; basal and prandial
40
Contrast standard vs intensive treatment
Standard Therapy: -Involves twice-daily injections -Fewer episodes of hypoglycemia (seizures, coma) -Increased microvascular complications Intensive Treatment: -Involves three or more injections daily -More likely to acheive mean blood glucose level of 154 mg/dL or less (AIC s 7%) -Frequency of hypoglycemic episodes, coma, and seizures is higher -More significant reduction in microvascular complications (retinopathy, nephropathy, and neuropathy) -Not recommended for patients with long-standing diabetes, significant microvascular complications, advanced age, and with hypoglycemic unawareness
41
Which insulins may be given IV? Any special considerations?
Regular insulin; Monitor for quicker onset of hypoglycemia
42
What laboratory monitoring is important for patients with diabetes? How might you use this information to regulate blood sugar?
-HgA1C and fasting and post-prandial blood sugar -Consider other co-morbities and drugs that influence blood sugar
43
How does the hemoglobin A1C work? What is the desired level? How often to you test?
Normal = below 5.7%, Prediabetes = 5.7-6.4%, Diabetes = 6.5% and above; Check every 3-6 months
44
Which insulin(s) can be used in pregnancy?
Regular insulin, insulin aspart, insulin lispro, NPH, and insulin detemir
45
Describe the complications/side effects and drug interactions associated with insulin use?
Headache, Anxiety, Tachycardia, Confusion, Vertigo, Diaphoresis, Shakiness, Increased appetite, Blurred vision, Weakness/fatigue, Lipodystrophy at injection site,Weight gain
46
Mechanism of Action of Biguanides [Metformin]
Reduction of hepatic gluconeogenesis. Metformin also slows intestinal absorption of sugars and improves peripheral glucose uptake and utilization (improves insulin sensitivity). The drug does not promote insulin secretion.
47
Pharmacokinetics of Biguanides [Metformin]
Well absorbed after oral administration, is not bound to serum proteins, and is not metabolized. Excretion is primarily via the kidneys as an unchanged drug
48
Adverse Drug Effects of Biguanides [Metformin]
Largely gastrointestinal, including diarrhea, nausea, and vomiting. Weight loss may occur because it causes loss of appetite. Metformin is contraindicated renal dysfunction due to the risk of lactic acidosis. It should be discontinued in cases of acute myocardial infarction, exacerbation of heart failure, sepsis, or other disorders that can cause renal failure. Should be used with caution in patients older than 80 years and in those with a history of alcohol It should be temporarily discontinued in patients undergoing procedures requiring IV radiographic contrast. Rarely, potential lactic acidosis has occurred. Long-term use may be associated with vitamin B12 deficiency, and periodic measurement of B12 levels is recommended, especially in patients with anemia peripheral neuropathy
49
Mechanism of Action of Sulfonylureas/Glinides
Stimulation of insulin release from the ß cells of the pancreas. Block ATP-sensitive K+ channels on the cells, resulting in depolarization, Ca2+ influx, and exocytosis of insulin. In addition, may reduce hepatic glucose and increase peripheral insulin sensitivity.
50
Pharmacokinetics of Sulfonylureas/Glinides
Given orally, these drugs bind to serum proteins, are metabolized by the liver, and are excreted in the urine and feces. The duration of action ranges from 12 to 24 hours.
51
Adverse Drug Effects of Sulfonylureas/Glinides
Include hypoglycemia, hyperinsulinemia, and weight gain. They should be used with caution in hepatic or renal insufficiency, since accumulation may cause hypoglycemia. Renal impairment is a particular problem for glyburide, as it may increase the duration of action and increase the risk of hypoglycemia significantly.
52
Sulfonylureas/Glinides that are safer options in renal dysfunction and in elderly patients.
Glipizide or glimepiride
53
Sulfonylureas
Glyburide, glipizide, and glimepiride
54
Biguanides
Metformin
55
Mechanism of Action of Thiazolidinediones [TZDs]
Lower insulin resistance by acting as agonists for the peroxisome proliferator—activated receptor-y (PPARy), a nuclear hormone receptor. Activation of PPARY regulates the transcription of several insulin responsive genes, resulting in increased insulin sensitivity in adipose tissue, liver, and skeletal muscle. Can be used as monotherapy or in combination with other glucose-lowering agents or insulin. The dose of insulin may have to be lowered when used in combination with these agents.
56
Thiazolidinediones [TZDs] that are less utilized due to concerns regarding cardiovascular adverse effects
Rosiglitazone
57
Pharmcokinetics of Thiazolidinediones [TZDs]
Are well absorbed after oral administration and are extensively bound to serum albumin. Both drugs undergo extensive metabolism, primarily by CYP2C8. Some metabolites of pioglitazone have activity. Renal elimination of pioglitazone is negligible, with the majority of active drug and metabolites excreted in the bile and eliminated in the feces. Metabolites of rosiglitazone are primarily excreted in the urine. No dosage adjustment is required in renal impairment
58
Adverse Effects of Thiazolidinediones [TZDs]
Weight gain can occur because they may increase subcutaneous fat and cause fluid retention. [Note: Fluid retention can worsen heart failure. These drugs should be avoided in patients with symptomatic heart failure.] Have been associated with osteopenia and increased fracture risk in women. Liver toxicity has occasionally been reported with these drugs, and baseline and periodic monitoring of liver function is recommended.
59
Thiazolidinediones [TZDs] associated with bladder cancer
Pioglitazone
60
Thiazolidinediones [TZDs] that carries a boxed warning about the potential increased risk of myocardial infarction and angina
Rosiglitazone
61
Alpha glucosidase inhibitors
Acarbose and miglitol
62
Mechanism of Action for Alpha glucosidase inhibitors
Located in the intestinal brush border, a-glucosidase enzymes break down carbohydrates into glucose and other simple sugars that can be absorbed. Acarbose and miglitol reversibly inhibit a-glucosidase enzymes. When taken at the start of a meal, these drugs delay the digestion of carbohydrates, resulting in lower postprandial glucose levels.
63
Since they do not stimulate insulin release or increase insulin sensitivity, these agents do not cause hypoglycemia when used as monotherapy. However, when used with insulin secretagogues or insulin, hypoglycemia may develop.
Alpha glucosidase inhibitors
64
Hypoglycemia in this drug can only be treated with glucose rather than sucrose, because sucrase is also inhibited by these drugs
Alpha glucosidase inhibitors
65
Pharmacokinetics of Alpha glucosidase inhibitors
Acarbose is poorly absorbed. It is metabolized primarily by the intestinal bacteria, and some of the metabolites are absorbed and excreted into the urine. Miglitol is very well absorbed but has no systemic effects. It is unchanged by the kidneys.
66
Adverse Effects of Alpha glucosidase inhibitors
The most common adverse effects are flatulence, diarrhea, and abdominal cramping. Patients with inflammatory bowel disease, colonic ulceration, or intestinal obstruction should not use these drugs.
67
Mechanism of Action of DPP4 Inhibitors [gliptins]
These drugs inhibit the enzyme which is responsible for the inactivation of incretin hormones increases release of insulin in response to meals and reduce propriate secretion of glucagon. May be monotherapy or in combination with sulfonylureas, metformin, or insulin.
68
Treatment guidelines do not recommend the combination of these drugs with GLP-I receptor agonists for management of diabetes due to overlapping mechanisms of action and increase potential for toxicity.
DPP4 Inhibitors
69
Unlike GLP-I receptor agonists, these drugs do not cause satiety or fullness and are weight neutral.
DPP4 Inhibitors
70
Pharmacokinetics of DDP-4 inhibitors
Well absorbed after oral administration. Food does not affect the extent of absorption. Alogliptin and sitagliptin are mostly excreted unchanged in the urine. Saxagliptin is metabolized via CYP450 34A/5 to an active metabolite. The primary route of elimination for saxagliptin and the metabolite is renal. Linagliptin is primarily eliminated via the enterohepatic system.
71
All DPP-4 inhibitors except _______ require dosage adjustments in renal dysfunction.
Linagliptin
72
Adverse Drug Effects of DDP-4 inhibitors
Are well tolerated, with nasopharyngitis and headache as the most common adverse effects. Although infrequent, serious hypersensitivity reactions and pancreatitis have occurred. Agents in this class may also increase the risk of joint pain, which is severe and disabling in some cases.
73
_______ has also been shown to increase the risk of heart failure hospitalizations and should be used with caution in patients with or at risk for heart failure.
Saxagliptin
74
Oral intake of glucose results in a higher secretion of insulin than occurs when an equal amount of glucose is administered IV. This effect is referred to as the "____" and is markedly reduced in type 2 diabetes.
Incretin effect
75
The incretin effect occurs because...
The gut releases incretin hormones, notably glucagon-like peptide-I (GLP-I) and glucose dependent insulinotropic polypeptide (GIP), in response to a meal
76
Examples of injectable GLP-I receptor agonists used for the treatment of type 2 diabetes.
Dulaglutide, exenatide, liraglutide, lixisenatide, and semaglutide
77
GLP-1 receptor agonists that are also approved to reduce the risk of cardiovascular mortality in patients with type 2 diabetes and cardiovascular disease
Dulaglutide, liraglutide, and semaglutide
78
Two premixed preparations of long-acting insulins and GLP-I receptor agonists
Insulin glargine plus lixisenatide and insulin degludec plus liraglutide
79
Mechanism of Action of GLP-I receptor agonists
Improve glucose-dependent insulin secretion, slow gastric emptying time, reduce food intake by enhancing satiety (a feeling of fullness), decrease postprandial glucagon secretion, and promote ß-cell proliferation. Consequently, postprandial hyperglycemia is reduced, AIC levels decrease, and weight loss may occur
80
Pharmacokinetics of GLP-I receptor agonists
Administered subcutaneously, since they are polypeptides. Dulaglutide, liraglutide, and semaglutide are considered long-acting GLP-I receptor agonists. Dulaglutide and semaglutide are dosed once weekly, while liraglutide is available as a once-daily injection. The oral formulation of semaglutide is dosed once daily. Lixisenatide is a short-acting GLP-I receptor agonist that is dosed once daily. Exenatide is available as both a short-acting (dosed twice daily) and extended-release preparation (dosed once weekly). Exenatide should be avoided in patients with severe renal impairment.
81
Adverse Drug Effects of GLP-I receptor agonists
Nausea, vomiting, diarrhea, and constipation. These agents have been associated with pancreatitis and should be avoided in patients with chronic pancreatitis. Longer-acting agents have been associated with thyroid C-cell tumors in rodents. It is unknown if GLP-I receptor agonists cause these tumors or thyroid carcinoma in humans although they are contraindicated in patients with a history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2.
82
Amylinomimetics—What makes this new drug unique? What is the MOA? Who can use it? How administered? Kinetics? Adverse Effects and drug interactions?
Amylin is a hormone that is co-secreted with insulin from ß cells following food intake. It delays gastric emptying, decreases postprandial glucagon secretion, and improves satiety. Pramlintide is a synthetic amylin analog that is indicated as an adjunct to mealtime insulin in patients with type I and type 2 diabetes. Pramlintide is administered by subcutaneous injection immediately before meals. When pramlintide is initiated, the dose of mealtime insulin should be decreased by 50% to avoid a risk of severe hypoglycemia. Other adverse effects include nausea, anorexia, and vomiting. Pramlintide may not be mixed in the same syringe with insulin, and it should be avoided in patients with diabetic gastroparesis (delayed stomach emptying), cresol hypersensitivity, or hypoglycemic unawareness.
83
Discuss SGLT2 Inhibitors and their special indications
Canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin are oral sodium—glucose cotransporter 2 inhibitors for the treatment of type 2 diabetes. Canagliflozin and empagliflozin are also indicated to reduce the risk of cardiovascular death in patients with type 2 diabetes and cardiovascular disease. In addition, canagliflozin and dapagliflozin have been shown to reduce the risk of heart failure hospitalizations and end-stage kidney disease in patients with type 2 diabetes.
84
Mechanism of Action of SGLT2 inhibitors
Reabsorbing filtered glucose in the tubular lumen of the kidney. By inhibiting SGLT2, these agents decrease reabsorption of glucose, increase urinary glucose excretion, and lower blood glucose. Inhibition of SGLT2 also decreases reabsorption of sodium and causes osmotic diuresis.
85
GLP-1 Agonists/Incretin Mimetics
Dulaglutide, exenatide, liraglutide, lixisenatide, and semaglutide
86
Amylinomimetics
Pramlintide
87
SGLT2 Inhibitors
Canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin
88
Pharmacokinetics of SGLT2 Inhibitors
These agents are given once daily in the morning. Canagliflozin should be taken before the first meal of the day. All drugs are mainly metabolized by glucuronidation to inactive metabolites. These agents should be avoided in patients with severe renal dysfunction.
89
Adverse Drug Effects of SGLT2 Inhibitors
Female genital mycotic infections (for example, vulvovaginal candidiasis), urinary tract infections, and urinary frequency. Hypotension has also occurred, particularly in the elderly or patients on diuretics. Thus, volume status should be evaluated prior to starting these agents. Ketoacidosis has been reported with use of SGLT2 inhibitors, and these agents should be used with caution in patients with risk factors that predispose to ketoacidosis (for example, alcohol abuse and caloric restriction related to surgery or illness). SGLT2 inhibitors are also associated with an increased risk of bone fractures and Fournier gangrene.
90
Activates dopamine receptors but exact mechanism of action in DM is unknown. Morning administration improves glycemic control in patients with type 2 diabetes without increasing plasma insulin concentrations.
Dopamine Agonist (Cycloset)
91
Binds to bile acids in the intestine which reduces the amount of bile acids that are returned to the liver via enterohepatic circulation. Removing these bile acids helps to lower blood cholesterol to improve glycemic control in type 2 diabetes
Bile Acid Sequestrants (Colesevelam)
92
Discuss how combinations of insulin and the oral agents are used to obtain diabetic treatment goals
-Using a combination of treatments (ie, an oral medication plus insulin) generally lowers the dose of insulin compared with taking insulin only -Since insulin can cause weight gain, combination therapy may reduce the risk of weight gain
93
Who is a Candidate for Insulin Glargine?
All above and below
94
John a type 1 diabetic is on insulin glargine at HS and insulin lispro ac each meal. He is having his wisdom teeth removed. How should he manage his insulin?
continue the glargine and take lispro only as a supplement
95
John recovers—prior to being on Lantus, he was on BID NPH and he needed an afternoon snack. Does he need to continue the snack, now that he is on Lantus?
eliminate the snack
96
Which of the following should be used with caution in a person with Sulfa allergy?
Glyburide
97
What is the most common adverse effect noted with alpha-glucosidase inhibitor use?
Gastrointestinal upset
98
Which of the following should be periodically monitored with the use of a TZD?
ALT
99
The meglitinides are particularly helpful adjuncts in Type 2 Diabetes Mellitus care to minimize the risk of:
Postprandial hyperglycemia
100
Are linked with increased with of HF exacerbations and hospitalizations—so do not use
TZDs, and DPP4 inhibitors—Saxagliptin and Alogliptin