UNIVERSITY OF EAST ANGLIA School of Pharmacy Main Series UG Examination 2012-2013 CLINICAL THERAPEUTICS I: ENDOCRINOLOGY PHA-2TKY Time allowed: 2 hours Part ONE. Answer ALL questions. Write/mark the correct answer CLEARLY in the answer grid provided. Part TWO. Answer THREE (3) of the FOUR (4) questions. Use a SEPARATE answer book for EACH question in Part TWO. Each question has the same value. The marks distribution is shown as a percentage for each section of each question. Answer all part of each of the individual questions you select. The mark allocation for the paper is: Part ONE carries 40% of the total mark Part TWO carries 60% of the total mark You are advised to spend approximately 50 minutes on Part ONE and 70 minutes on Part TWO. The paper consists of 11 pages in total. Dictionaries are not permitted in this examination. Notes are not permitted in this examination. Do not take this question paper out of the examinations room. Do not turn over until you are told to do so by the invigilator. (PHA-2TKY) Module contact: Mrs Catherine Heywood (PHA) Copyright of the University of East Anglia Version 1
2 PART ONE For each question ONE answer is correct. 1. Which ONE of the following statements is true about ALL hormones? A) They are of similar chemical composition B) They combine with specific receptors on or in the target cell C) They are secreted at a constant rate D) They act by activating adenylate cyclase, which transforms ATP into camp E) They are secreted by endocrine glands through ducts into the blood 2. Which ONE of the following is the source of energy used by the brain? A) Glutamate B) Fatty Acids C) Amino Acids D) Glycerol E) Glucose 3. Which ONE of the following statements is CORRECT? The proportion of the UK adult population that has Type 2 diabetes is: A) About 50% B) About 10% C) About 2% D) About 4% E) About 30% 4. Which ONE of the following is NOT a sign or symptom of diabetic ketoacidosis? A) Hypokalaemia (low potassium) B) Ketone breath C) Hypertension D) Hyperventilation E) Reduced consciousness
3 5. Which ONE of the following is NOT a World Health Organisation diagnostic criterion for the diagnosis of Diabetes mellitus? A) Patient has symptoms and has a random venous blood glucose of 11.1 mmol/l B) Patient has symptoms and has a fasting venous blood glucose of 7.0 mmol/l C) Patient has no symptoms and has two separate measurements of either a random venous blood glucose of 11.1 mmol/l or a fasting venous blood glucose of 7.0 mmol/l D) Patient has symptoms and has a blood glucose of 11.1 mmol/l two hours after a 75 g anhydrous glucose tolerance test. E) Patient has symptoms and has a fasting venous blood glucose of 4.0 mmol/l 6. Which ONE of the following is CORRECT regarding the BP specifications of conventional insulin products? A) The ph should be between 7.5 and 8.0 B) The maximum content of dissolved insulin in crystalline insulin suspensions is 5% C) The maximum particle size of crystalline insulin suspensions is 10 m D) The maximum content of zinc in soluble insulin solutions is 40.0 g per 100 units of insulin E) Insulin products should be pale golden brown in colour 7. Which ONE of the following is NOT an appropriate route or method of administration for insulin? A) Subcutaneous injection with disposable pen device (e.g. Flexpen ) B) Intramuscular injection with vial and syringe C) Intravenous infusion with syringe pump D) Subcutaneous injection with insulin pump E) Subcutaneous injection with reusable pen device (e.g. NovoPen ) 8. Which ONE of the following is a side-effect of metformin therapy? A) Gastrointestinal disturbances B) Increased heart rate C) Weight gain D) Eczema E) Shortness of breath TURN OVER
4 9. Which ONE of the following occurs in response to glucagon? A) Decreased lipolysis B) Increased gluconeogenesis C) Decreased blood sugar D) Increased glycogenesis E) Increased triglyceride synthesis 10. Which ONE of the following is inhibited by sulphonylureas? A) The insulin receptor B) The GLUT-4 transporter C) The PPARgamma receptor D) The ATP-sensitive K + channel E) The voltage-gated Ca 2+ channel 11. With respect to blood glucose monitoring which ONE of the following statements is INCORRECT? A) Pre-prandial (before meals) blood glucose levels should be between 4-6 mmol/l B) Blood glucose meters cannot be prescribed on FP10s C) Type 2 diabetics should monitor their blood glucose before each meal D) During illness Type 1 diabetics should increase the number of times a day they monitor their blood glucose to 4 or more E) Blood glucose should always be above 4 mmol/l to avoid hypoglycaemia 12. Which ONE of the following statements is CORRECT? The cells of the retina, kidney and peripheral nervous system are particularly vulnerable to damage from high levels of blood glucose because: A) Blood travelling directly to these cells from the pancreas carries the highest concentration of glucose B) These cells become resistant to the effect of insulin earlier than other types of cell C) These cells are able to respond to lower levels of insulin D) These cells are vulnerable to damage from high blood pressure which often accompanies high blood glucose E) Glucose can enter these cells even in the absence of insulin
5 13. Regarding the normal functioning thyroid, which ONE of these is synthesised by the organ? A) Tyrosine B) Calcitonin C) Leucine D) Calcium E) Thyrodoxine 14. Which ONE of the following is appropriate second line drug therapy for the treatment of hyperthyroidism in a patient intolerant of carbimazole? A) Pantoprazole B) Penicillin C) Paroxetine D) Propylthiouracil E) Probenecid 15. Which ONE of the following is NOT a potential symptom in hypothyroid disorders? A) Low metabolic rate B) Weight loss C) Weakness D) Bradycardia E) Myxoedema coma 16. The release of a hormone from the anterior pituitary stimulates the release of which ONE of the following? A) Parathyroid hormone B) Oxytocin C) Cortisol D) Insulin E) ADH 17. Which ONE of the following statements is INCORRECT? Cushing's disease: A) is due to excessive secretion of ACTH from the anterior pituitary B) is characterised by hypertension C) is due to a deficiency of corticosteroids D) is caused by therapeutic use of corticosteroids E) is a disease which can cause diabetes TURN OVER
6 18. Cholesterol is NOT a precursor of which ONE of the following? A) Glucocorticoids B) Mineralocorticoids C) Oestrogens D) Androgens E) Adrenaline 19. Which ONE of the following statements is INCORRECT regarding the androgens and their pharmaceutical applications? A) Testosterone esters are used as slow release prodrugs in androgen replacement therapy B) 17-α-methyltestosterone is orally active whereas testosterone is not C) Introduction of a 1,2-double bond into the structure of an androgen drug increases anabolic activity and decreases androgenic activity D) Introduction of a 9-α-fluoro substituent into an androgen drug increases anabolic activity and has no effect on the androgenic activity E) Cyproterone acetate is an androgen antagonist that is used to treat hypersexuality and sexual deviation in men 20. Which of the following molecules could be predicted to have agonist activity at the cortisol receptor? A) Molecules 1, 2 and 3 B) Molecules 1, 2 and 4 C) Molecules 2 and 3 D) Molecules 3 and 4 E) Molecules 1 and 3
7 21. Which ONE of the following statements is INCORRECT regarding the progestogens and their pharmaceutical applications? A) Introduction of a 6-α-substituent will decrease the oral availability of synthetic progesterones B) During pregnancy, progesterone prevents further ovulation and relaxes the uterus to prevent the fertilised egg being dislodged C) Anti-progestogens are used for terminations D) Norethisterone is a synthetic progesterone that is orally active because it contains a 17-α-ethynyl group that prevents metabolism at this position E) The absence of a C19 methyl group in a synthetic progesterone results in increased activity 22. Which ONE of the following occurs during the follicular phase of the female menstrual cycle? A) Oestrogen stimulates thickening of the endometrium B) The egg travels down the Fallopian tube C) The corpus luteum secretes oestrogen D) There is bleeding and loss of uterine lining E) LH and FSH levels are high 23. Which ONE of the following is NOT a cause of stress incontinence? A) Pregnancy B) Oestrogen deficiency due to menopause C) Spinal cord injury D) Obesity E) Weak pelvic floor muscles 24. Which ONE of the following is INCORRECT with respect to the use of transdermal contraceptive patch (Evra )? A) The patch is applied once weekly B) The effectiveness of the patch is not reduced by diarrhoea and vomiting C) Withdrawal bleeding starts on average one day later than with the combined oral contraceptive pill D) The patch should not be used in woman who smoke and are over the age of 35 years E) The patch can be used in women who weigh more than 90 kg TURN OVER
8 25. Which ONE of the following is NOT a mechanism of action of the combined oral contraceptive pill? A) Inhibition of ovulation B) Reduction in levels of progesterone C) Suppression of FSH secretion D) Thickening of cervical mucus E) Reduction in endometrial receptiveness 26. Which ONE of the following is a characteristic of drugs that are least likely to cross the placenta and reach the developing foetus? A) Molecules that have a small volume of distribution B) Molecules that are lipophilic C) Molecules that are highly ionised D) Molecules that not metabolised by the placenta E) Drugs that have a small molecular size 27. Which ONE of the following is INCORRECT with regard to osteoporosis? A) It is diagnosed with a T-score of -2.5 or less B) There is an increased risk with treatment with long term prednisolone therapy at >7.5 mg daily C) The most common form of fragility fracture is the pelvis D) It is characterised by a reduction in bone mass and thinning of the trabecular bone E) Vitamin D and calcium supplements should be used for housebound people 28. Which ONE of the following is NOT a sign or symptom of the menopause? A) Weight loss B) Hot flushes C) Dyspareunia D) Osteoporosis E) Urinary incontinence 29. Which ONE of the following is INCORRECT with respect to hormone replacement therapy (HRT)? A) HRT can be used as a form of contraception as it contains oestrogen B) Progesterone is used in women with an intact uterus to reduce the risk of cancer C) Transdermal HRT is less likely to be associated with thromboembolism as it avoids first pass metabolism in the liver D) HRT increases the risk of stroke E) Oestrogen-only HRT is used in women who have had a hysterectomy
9 30. Which ONE of the following statements is CORRECT? The Body Mass Index (BMI) is calculated as? A) Weight (in kilograms) and height (in metres) as weight / height 2 B) Height (in metres) and weight (in kilograms) as height / weight 2 C) Weight (in kilograms) and height (in metres) as weight / height D) Weight (in pounds) and height (in inches) as weight / height 2 E) Height (in inches) and weight (in pounds) as height / weight END OF PART ONE TURN OVER
10 PART TWO 31. Answer ALL parts: (a), (b) and (c). a) Outline the main physiological and pharmacological effects of cortisol in the body. Describe the main factors that influence the levels of cortisol in the body. [50%] b) Give FOUR (4) examples of common conditions that glucocorticosteroids are used to treat. [10%] c) Describe THREE (3) structural modifications that can be made to adrenocorticoids to improve activity. [40%] 32. Answer BOTH parts: (a) and (b). a) With the aid of a diagram describe the pathway of insulin synthesis in the pancreatic β-cell. [50 %] b) Describe in detail the chemical and physico-chemical properties of native human insulin and how these are altered in the modified human insulin analogues Insulin Aspart, Insulin Lispro and Insulin Glargine. What effect do these alterations have on the onset and duration of action of the analogues compared to the native material? [50 %]
11 33. Answer ALL parts: (a), (b) and (c) Mrs DS is an 80 year old lady who presents at your pharmacy asking if you can recommend a "tonic" as she is feeling run down. You check her records and find that her current prescription is: Propranolol beta blocker for hypertension Bendroflumethiazide thiazide diuretic for hypertension Glibenclamide sulphonylurea for type II diabetes She has a BMI of 31. a) Describe the signs and symptoms of poorly controlled (or undiagnosed) diabetes. Differentiate between those usually seen in Type 1 and Type 2 diabetes, and those which are common to both. [20 %] b) Comment on the appropriateness of her current treatment for hypertension and diabetes. Outline any changes to her current prescription that you would recommend, including any additional drug therapy that is indicated. Explain your reasoning. [70 %] c) Describe the lifestyle changes that Mrs DS should adopt [10 %] 34. Answer BOTH parts: (a) and (b). a) Describe the actions and roles in the female of the following hormones: i) Oestrogen ii) Progesterone [30 %] b) Compare and contrast the advantages and disadvantages of the Combined Oral Contraceptive Pill (COC) and the Progestogen Only Contraceptive Pill (POP).Your answer should include consideration of side-effects, contraindications and drug interactions. [70 %] END OF PAPER