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Pharmacology SBA’s and VSAQ 1: Which is the first line oral glucose-lowering therapy prescribed in type 2 diabetes. A) DPP4 Inhibitors B) Metformin C) Insulin D) Sulfonylureas E) Statins 2: In which TWO situations are the prescription of DPP4 inhibitors contraindicated? A) Crohn’s Disease B) Pancreatitis C) Ulcerative Colitis D) Type 1 Diabetes Mellitus E) Coeliac Disease 3: Which is a RARE complication of SGLT2 inhibitors A) Diabetic Ketoacidosis B) Urogenital infections C) Hyperglycaemia D) Dehydration E) Pruritis4: How would a patient with pre-diabetes commonly present? A) Comatose B) Severely dehydrated C) Left upper quadrant pain D) Asymptomatically E) Dizzy and confused 5: What is the first line recommendation for a person with Pre- diabetes A) Insulin B) Metformin C) ACE-inhibitors D) Statins E) Weight loss and diet 6: How do DPP4 inhibitors help reduce high plasma glucose? A) Enhance the incretin effect B) Cause Alpha cell apoptosis C) Increase serum cortisol D) Enhance glucose excretion in the urine via the nephrons E) Decrease glucose reabsorption from the GI tract 7: What are the pathological mechanisms contributing to the hyperglycaemic state observed in pre-diabetes and type 2 diabetes (Select all that apply) A) Increase Hepatic Glucose Output B) Reduced insulin secretion C) Reduced insulin sensitivity at peripheral tissues D) Autoimmune beta islet cell destruction E) Increased glucose in the circulation8: Mrs Jay is a 64 year old South Asian old female. She lives a very sedentary lifestyle, orders take-away meals 6 times a week and has a 30-pack year smoking history. Her BMI is 31. She gone to her GP for a routine blood test. She is found to have a HBa1c of 47mmol/mol and a fasting plasma glucose of 6.2mmol/L. What is the diagnosis? (VSAQ answer no longer than 4 words). 9: Name 4 risk factors associated with her diagnosis. 10: The GP formulates a management plan for Mrs Jay to help her lower her blood glucose to normal ranges. She is recommended to diet, reduce intake of refined carbohydrates, quit smoking, and lose weight. In addition, she is prescribed the first-line oral-glucose lowering therapy. (A) Identify which drug this is. (B) Describe one way in which this drug will help lower blood glucose. (4 words max, 2 marks) 11: For her follow up appointment Mrs Jay’s Blood HBa1c is checked again however it has now risen to 51mmol/mol. She is prescribed Gliclazide. Explain the mechanism of this drug and how it induces its therapeutic effect. (5 marks available)Pharmacology SBA’s and VSAQ- ANSWERS 1: Which is the first line oral glucose-lowering therapy prescribed in type 2 diabetes. A) DPP4 Inhibitors B) Metformin C) Insulin D) Sulfonylureas E) Statins Metformin is the first-line drug in the treatment of type 2 diabetes. 2: In which TWO situations are the prescription of DPP4 inhibitors contraindicated? A) Crohn’s Disease B) Pancreatitis C) Ulcerative Colitis D) Type 1 Diabetes Mellitus E) Coeliac Disease - DPP4 inhibitors can increase the risk of pancreatitis therefore should not be given to a person who has previously had/ is high risk of developing pancreatitis. - They work by enhancing insulin secretion therefore only work in the presence of residual insulin function so are not effective in type 1 diabetes where there is absolute insulin deficiency.3: Which is a RARE complication of SGLT2 inhibitors A) Diabetic Ketoacidosis B) Urogenital infections C) Hyperglycaemia D) Dehydration E) Pruritis - B and D are both common complications of SGLT2 usage. - C and E are not related to SGLT2 use. 4: How would a patient with pre-diabetes commonly present? A) Comatose B) Severely dehydrated C) Right upper quadrant pain D) Asymptomatically E) Dizzy and confused - Pre-diabetes usually presents asymptomatically. - A, B and E are presentations of SEVERE hyperglycaemia or diabetic ketoacidosis. - C could be due to gallbladder pathology and is unrelated to diabetes.5: What is the first line recommendation for a person with Pre- diabetes A) Insulin B) Metformin C) ACE-inhibitors D) Statins E) Weight loss and diet - Before any medications are given, lifestyles factors should try to be adjusted. This is the most effective manner of reducing plasma glucose to normal levels. 6: How do DPP4 inhibitors help reduce high plasma glucose? A) Enhance the incretin effect B) Cause Alpha cell apoptosis C) Increase serum cortisol D) Enhance glucose excretion in the urine via the nephrons E) Decrease glucose reabsorption from the GI tract - Enhances incretin effect by inhibiting the enzyme DPP4 which is responsible for metabolizing incretins e.g., GLP-1. Enhances insulin secretion and suppressed glucagon.7: What are the pathological mechanisms contributing to the hyperglycaemic state observed in pre-diabetes and type 2 diabetes (Select all that apply) A) Increase Hepatic Glucose Output B) Reduced insulin secretion C) Reduced insulin sensitivity at peripheral tissues D) Autoimmune beta islet cell destruction E) Increased glucose in the circulation - D is the only incorrect answer as that is the pathological mechanism responsible for TYPE 1 diabetes. 8: Mrs Jay is a 64 year South Asian old female. She lives a very sedentary lifestyle, orders take-away meals 6 times a week and has a 30-pack year smoking history. Her BMI is 31. She gone to her GP for a routine blood test. She is found to have a HBa1c of 49mmol/mol and a fasting plasma glucose of 8.2mmol/L. What is the diagnosis? (VSAQ answer no longer than 4 words). Type 2 Diabetes9: Name 4 risk factors associated with her diagnosis. Mrs Jay is a 64 year old South Asian old female. She lives a very sedentary lifestyle, orders take-away meals 6 times a week and has a 30-pack year smoking history. Her BMI is 31. She gone to her GP for a routine blood test. She is found to have a HBa1c of 49mmol/mol and a fasting plasma glucose of 8.2mmol/L. Any of the following: - Age - Ethnicity - Obesity - Smoking History - Sedentary lifestyle - Her Diet 10: The GP formulates a management plan for Mrs Jay to help her lower her blood glucose to normal ranges. She is recommended to diet, reduce intake of refined carbohydrates, quit smoking, and lose weight. In addition, she is prescribed the first-line oral-glucose lowering therapy. - Identify the drug - Describe one way in which this drug will help lower blood glucose (4 words max). - Identify the drug: Metformin (ALWAYS FIRST LINE) - Reduces Hepatic glucose output (via reducing gluconeogenesis and glycogenolysis.) - Increases insulin sensitivity (in peripheral tissue).11: For her follow up appointment Mrs Jay’s Blood HBa1c is checked again however it has now risen to 51mmol/mol. She is prescribed Gliclazide. Explain the mechanism of this drug and how it induces its therapeutic effect. (5 marks available) - Sulfonylurea (one mark for correctly identifying it is a sulfonylurea). An answer that contains any of the following in red: - Mechanism of Action: the drug binds to the sulfonylurea receptor on the Beta islet cell membrane in the pancreas. This inhibits the ATP-sensitive potassium ion channels and blocks potassium efflux. This causes depolarization of the cell membrane which opens Calcium ion channels and Calcium ions enter the cell. This causes exocytosis of vesicles containing insulin. Increased insulin secretion and lower blood glucose.