NAPLEX / Endocrine

Decrease the dose to 100mcg orally daily. The TSH level is below therapeutic range (0.358--3.740 uIUn/mL). The TSH level is generally inversely related to the thyroid hormones’ levels. Bioequivalent of oral to intravenous levothyroxine is 2:1 ratio, so changing any dose to IV above 75mcg dose wound be to increase the dose. Reference: Bahn R, et al. hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the american thyroid association and american association of clinical endocrinologists. Endocr Pract. 2011;17(3). Available at: https://www.aace.com/files/hyper-guidelines-2011.pdf. Accessed May 18, 2016.

Answer C. Diabetic patients are recommended to be on either an ACEI or ARB first line for hypertension therapy per both ADA and AACE/ACE guidelines. The goal BP per ADA guidelines is <140/90 mmHg and <130/80 mmHg per AACE/ACE. The patient’s current BP of 124/78 meets the goal. Answer C is correct because monotherapy of ACEI is a correct option and lisinopril 10 mg once daily is a correct starting dosage. Answer D is incorrect because adding would further drop the BP. Pt is already at goal. Answer B is incorrect because amlodipine alone is not first line recommended for HTN in diabetes. Answer A is irrelevant. Reference: 1. American Diabetes Association. In Standards of Medical Care in Diabetes 2016. Diabetes Care 2016;39(Suppl. 1)
2. Garber AJ, et al. Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Comprehensive Type 2 Diabetes Management Algorithm – 2016 Executive Summary. Endocr Pract. 2016; 22(1):84-113

Answer A. Answer A is correct. Since patient’s estimated 10-y ASCVD risk ≥7.5% and is diabetic classifies him for high intensity statin therapy per 2013 ACC/AHA Cholesterol Guidelines. Option B is not correct since the patient’s TG are 244. Only when >500 does the AACE/ACE recommend adding a fibrate. Option C is incorrect since lovastatin 40 is a moderate intensity statin and this patient needs high intensity. Option D is incorrect since the patient’s ASCVD risk and the fact that patient is diabetic puts him for needing statin. Reference: 1. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63:2889-2934.

Answer A. The only bile acid sequestrant, colesevelam (Welchol), has been shown to increase triglycerides through mechanism of: activation of phosphatidic acid phosphatase with promotes triglyceride synthesis. GLP-1 agonists work on GLP 1 receptors to increase insulin secretion, decrease glucagon secretion, and increase satiety. Thiazolidinediones activate nuclear transcription factor PPAR gamma to increase insulin sensitivity. SGLT2 inhibitors inhibit glucose reabsorption in the kidney. Alpha-glucosidase inhibitors slow down digestion and absorptions of carbs in the gut. Reference: 1. Welchol (colesevelam) tablets and powder for oral suspension package insert. Parsipanny, NJ: Daiiki Sankyo 2014.
2. Sheperd J. Mechanism of action of bile acid sequestrants and other lipid-lowering drugs. Cardiology. 1989; 76 Suppl 1:65-71; discussion 71-74.

Metformin should be stopped when eGFR falls below 30. This is the only cutoff that is recommended for absolute discontinuing. If the eGFR falls between 30-44 while on therapy, benefits and risks of discontinuing should be evaluated. New initiation is only recommended when eGFR >45. Reference: 1. US Food and Drug Administration (FDA) MedWatch for Metformin-containing Drugs: Revised Warnings for Certain Patients With Reduced Kidney Function. Retrieved April 8, 2016. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm494829.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery
2. Eknoyan G, Lameire N, et al. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Journal of International Society of Nephrology. Jan 2013;3(1): 91-111

Acarbose is an alpha glucosidase inhibitor that inhibits carbohydrate breakdown. Metformin is a biguanide that decreases hepatic glucose production. Dapagliflozin is a SGLT2 inhibitor to decrease glucose reabsorption in the kidney. Pioglitazone is a TZD that increases insulin sensitivity. Sitagliptin is a DPP-4 inhibitor that works on incretins/increase insulin secretion/decrease glucagon secretion. Reference: 1. American Diabetes Association. In Standards of Medical Care in Diabetes 2016. Diabetes Care 2016;39(Suppl. 1)

Answer D. Pioglitazone is a TZD that increases insulin sensitivity. Miglitol is an alpha glucosidase inhibitor that inhibits carb breakdown. Saxagliptin is a DPP-4 inhibitor that works on incretins/increase insulin secretion/decrease glucagon secretion. Canagliflozin is a SGLT2 inhibitor to decrease glucose reabsorption in the kidney. Glimepiride is a sulfonylurea which increases insulin secretion. Reference: 1. American Diabetes Association. In Standards of Medical Care in Diabetes 2016. Diabetes Care 2016;39(Suppl. 1)

Answer A. Empagliflozin is a SGLT2 inhibitor to decrease glucose reabsorption in the kidney. Linagliptin is a DPP-4 inhibitor that works on incretins/increase insulin secretion/decrease glucagon secretion. Pioglitazone is a TZD that increases insulin sensitivity. Exenatide is a GLP-1 agonist which increase insulin secretion/decrease glucagon secretion/increase satiety. Reference: 1. American Diabetes Association. In Standards of Medical Care in Diabetes 2016. Diabetes Care 2016;39(Suppl. 1)

Answer E. Incretins work by stimulating synthesis of insulin from the pancreatic beta cells, decrease Glucagon secretion. It works on stomach by slowing gastric emptying and brain by controlling appetite. Reference: 1. American Diabetes Association. In Standards of Medical Care in Diabetes 2016. Diabetes Care 2016;39(Suppl. 1)
2. Prins JB. Incretin mimetics and enhancers: mechanism of action. Aust Prescr: 2008:31:102-4.

Answer A. SGLT2 inhibitors work in the kidney because the SGLT2 receptors are in the nephrons to block glucose reabsorption in the body. Reference: 1. Chao, Edward. SGLT-2 Inhibitors: A New Mechanism for Glycemic Control. Clin Diabetes. 2014 Jan;32(1): 4-11.

Answer C. Glipizide should be discontinued because it works by increasing insulin secretion and one of its main side effects is hypoglycemia. Since the patient does not eat stable meals, this is what is contributing to his episodes of hypoglycemia and this drug should not be used for him. Dapagliflozin would not get to goal A1c. Its A1c reduction capabilities is from 0.5% - 1%. Pioglitazone is not a good option for this patient since there is a black box warning for exacerbating heart failure. Dapagliflozin is not a good option since it works by reducing reabsorption in the kidney which can cause volume depletion in this patient who is already on furosemide. Adding Dulaglutide 0.75mg once weekly would simplify regimen and drop A1c to goal. GLP-1 agonist can drop A1c by average 1%-1.5%. Option D is not ideal either because increasing a long acting insulin glargine in addition to sliding scale will just contribute to hypoglycemia. Sliding scale insulin are potentially inappropriate medication per the beer’s criteria. Reference: 1. American Diabetes Association. In Standards of Medical Care in Diabetes 2016. Diabetes Care 2016;39(Suppl. 1)
2. American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. Journal of the American Geriatrics Society. 2015;63(11):2227-2246. doi:10.1111/jgs.13702.
3. Actos (pioglitazone) package insert. Deerfield, IL: Takeda Pharmaceuticals America, Inc.; 2013 Nov.
4. Farxiga (dapagliflozin) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2016 Aug.
5. Trulicity (dulaglutide) package insert. Indianapolis, IN: Eli Lilly and Company; 2014 Sept.

Answer B. Add Empagliflozin 10mg by mouth daily is the most appropriate answer. Acarbose is not a good option due to possible irritation of patient’s ulcerative colitis. Exenatide is not a good choice since GLP-1 agonists also have high risk of GI side effects. Pioglitazone is not a good option since it can cause weight gain and the patient is already >90% overweight. Add Empagliflozin 10mg by mouth daily is the most appropriate answer since there is no contraindication. Reference: 1. American Diabetes Association. In Standards of Medical Care in Diabetes 2016. Diabetes Care 2016;39(Suppl. 1)
2. Garber AJ, et al. Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Comprehensive Type 2 Diabetes Management Algorithm – 2016 Executive Summary. Endocr Pract. 2016; 22(1):84-113

Answer D. Pioglitazone is not a good option since it can exacerbate his CHF and caries a black box warning. Empagliflozin is not a good option since it is contraindicated in patients with eGFR <30. Exenatide use is not recommended in patients with CrCL<30 mls/hr. Exenatide is not a good option because the patient’s hx of GI bleed is a precaution for use since the drug can slow gastric emptying. Increasing patient’s long acting insulin and adding low dose short acting is an appropriate choice. Reference: 1. American Diabetes Association. In Standards of Medical Care in Diabetes 2016. Diabetes Care 2016;39(Suppl. 1)
2. Garber AJ, et al. Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Comprehensive Type 2 Diabetes Management Algorithm – 2016 Executive Summary. Endocr Pract. 2016; 22(1):84-113

Answer D. TZDs, such as pioglitazone, along with sulfonylureas and insulins are the only anti-diabetic drugs that can cause weight gain. Miglitol, an alpha glucosidase inhibitor, is weight neutral. Linagliptin is a DPP-4 inhibitor and weight neutral. Exenatide is a GLP-1 agonist which can cause weight loss. Empagliflozin is a SGLT2 inhibitor which can cause weight loss. Reference: 1. American Diabetes Association. In Standards of Medical Care in Diabetes 2016. Diabetes Care 2016;39(Suppl. 1)
2. Garber AJ, et al. Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Comprehensive Type 2 Diabetes Management Algorithm – 2016 Executive Summary. Endocr Pract. 2016; 22(1):84-113

Answer E. All antidiabetic meds are neutral for causing hypoglycemia except insulins and sulfonylureas. Glimepiride is a sulfonylurea. Miglitol is an alpha glucosidase inhibitor. Saxagliptin is a DPP-4 inhibitors. Canagliflozin is an SGLT2 inhibitor. Pioglitazone is a TZD. Reference: 1. American Diabetes Association. In Standards of Medical Care in Diabetes 2016. Diabetes Care 2016;39(Suppl. 1)
2. Garber AJ, et al. Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Comprehensive Type 2 Diabetes Management Algorithm – 2016 Executive Summary. Endocr Pract. 2016; 22(1):84-113

Answer B. Only GLP-1 agonists have a black box warning for medullary thyroid tumors so use is contraindicated in patients with personal or family history of it. No other anti-diabetic drugs have this warning. Reference: 1. Nauck, MA, Friedrich N. Do GLP-1 –Based Therapies Increase Cancer Risk? Diabetes Care Aug 2013; Supp 2: S245-52

Answer: C- Because SGLT2 inhibitors work by preventing reabsorption of glucose in the kidneys, this increases frequency of urination. If you take the drug in the morning, it will prevent nocturnal polyuria. SGLT2 inhibitors do not cause hypoglycemia, do not have high risk of nausea/vomiting, and no adverse reactions of insomnia. Reference: 1. Garber AJ, et al. Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Comprehensive Type 2 Diabetes Management Algorithm – 2016 Executive Summary. Endocr Pract. 2016; 22(1):84-113
2. American Diabetes Association. In Standards of Medical Care in Diabetes 2016. Diabetes Care 2016;39(Suppl. 1)

Answer E. Because SGLT2 inhibitors work by preventing reabsorption of glucose in the kidneys, this increases frequency of urination. All of the options are monitoring requirements since the hydration status, blood pressure, blood glucose, and renal function may all be changed from increased urination (from the mechanism of the drug). Reference: 1. Garber AJ, et al. Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Comprehensive Type 2 Diabetes Management Algorithm – 2016 Executive Summary. Endocr Pract. 2016; 22(1):84-113

Answer A. Nausea, vomiting, diarrhea are some of the most common side effects of GLP1 inhibitors. GLP1 inhibitor actually can cause dehydration. Bradycardia is not, they can actually cause increases in heart rate. Dry mouth and polyuria are not side effects of GLP1 Inhibitor. Reference: 1. Bydureon (exenatide extended-release) package insert. San Diego, CA: Amylin Pharmaceuticals, Inc.; 2015 Sep.
2. Garber AJ, et al. Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Comprehensive Type 2 Diabetes Management Algorithm – 2016 Executive Summary. Endocr Pract. 2016; 22(1):84-113

Answer D. SGLT2 inhibitors are the only anti-diabetic drug that works in the kidney to decrease glucose reabsorption in the nephron. Because of the area that these drugs work in, they cause increased risk of UTIs. None of the other anti-diabetic drugs work in the kidney. Reference: 1. Invokana (canagliflozin) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc; 2016 Aug.
2. American Diabetes Association. In Standards of Medical Care in Diabetes 2016. Diabetes Care 2016;39(Suppl. 1)

Answer C. Thiazolidinediones may cause fluid retention through proposed mechanism of increasing reabsorption in the collecting duct of the kidney and increasing vascular permeability in adipose tissue. Bile acid sequestrants work in the intestine to bind bile acids which doesn’t affect fluid retention. GLP-1 receptor agonists work to activate these receptors to secrete insulin from beta pancreatic cells/decrease glucagon secretion/ increase satiety and doesn’t affect fluid retention. SGLT2 inhibitors actually cause increase of fluid elimination through the kidneys. Alpha-glucosidase inhibitors work in the gut to decrease carb absorption/digestion and have no affect on fluid retention. Reference: 1. Yang T, Soodvilai S. Renal and Vascular Mechanisms of Thiazolidinediones- Induced Fluid Retention. PPAR Research. 2008. Article ID 943614.
2. American Diabetes Association. In Standards of Medical Care in Diabetes 2016. Diabetes Care 2016;39(Suppl. 1)

Answer C. Upper respiratory tract infection (8.4—14.9%) with TZDs. The likely mechanism is due to fluid retention. The other answer choices do not have any incidence of them. SGLT2 inhibitors have increased risk of UTI. Reference: Avandia (rosiglitazone) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2016 Sept.
Actos (pioglitazone) package insert. Deerfield, IL: Takeda Pharmaceuticals America, Inc.; 2013 Nov.

Answer E. Metformin is associated with vitamin B12 deficiency because it affects the calcium dependent membrane uptake of it. All other drug classes are not associated with this. Reference: Liu KW, Lok KD, Jean W. Metformin-related vitamin B12 deficiency. Age Aging. 2006. 35(2): 200-201.

All antidiabetic meds are neutral for causing hypoglycemia except insulins and sulfonylureas. Insulins and sulfonylureas are the highest risk.

Answer: A- Empagliflozin is the best option for this patient. Linagliptin is not an option since patient has already tried Sitagliptin (in the same drug class), and patient had pancreatitis. GLP1- agonists also are associated with pancreatitis so use of Exenatide would not be recommended. Pioglitazone should not be used because the patient is ~52% overweight and it can cause weight gain. Increasing the long acting insulin dose and adding short acting sliding scale is an not an appropriate option since sliding scale in elderly adults in on the BEERs list due to potential increased risk of errors/hypoglycemia. Reference: 1. Food and Drug Administration (US FDA) Drug Medwatch-FDA investigating reports of possible increased risk of pancreatitis and pre-cancerous findings of the pancreas from incretin mimetic drugs for type 2 diabetes. Retrieved Mar. 14, 2013. Available on the World Wide Web at http://www.fda.gov/Drugs/DrugSafety/ucm343187.htm.
2. American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 63:2227-2246, 2015.