Introduction to Drugs and Medicines

FACULTY OF SCIENCE & ENGINEERING SCHOOL OF PHARMACY EXAMINATION PAPER ___________________________________________________________________ Module Code Module Title Date Examiners : : : : 4PY019 Introduction to Drugs and Medicines May 2023 Drs Zeeneh Elsaid, Ayman Antoun Reyad, Mark Hewitt, Waseem Kaialy, Mathew Palframan and Ben Butler Time Allowed : 2 Hours ___________________________________________________________________ INSTRUCTIONS TO CANDIDATES  Answer ALL sections. o Section A (40 %): Answer all 40 multiple choice questions on the answer grid provided on the last page of the question paper. All questions have ONLY ONE answer. If none or multiple answers are circled, marks will not be awarded. There is no negative marking o Sections B (60 %) Answer all THREE short answer questions. Answer each question (Question 1, 2 and 3) in a SEPARATE answer booklet provided. MATERIALS REQUIRED  You may use a scientific calculator. This must not be programmable.  Periodic Table (is located at the end of the examination paper) ---------------------------------------------------------------------------------------------------------------- Student Number: ___________________________________________________ 1 SECTION A: Answer ALL 40 questions on the answer grid provided at the end of the exam paper. Each question is worth 1 mark. 1. Complete the following sentence: “Pharmacokinetics does NOT include…” A distribution B phase II metabolism C phase I metabolism D adsorption E excretion 2. Which of the following statements describe the term “bioavailability”? A The transfer of the medication from the blood to the site of action B How selective a ligand is to a binding site C Fraction of the drug that reaches the systemic circulation D The time taken for the plasma drug concentration to fall by half E The rate of elimination of the drug from the plasma 3. Which of the following routes of administration involves injecting a solution directly into the vein? A Intravenous B Subcutaneous C Intravitreal D Transdermal E Intraarticular 2 4. Which of the following is NOT an elimination route for drugs? A Skin (through sweat) B Gall bladder C Renal D Faecal E Respiratory 5. In relation to excipients used in compressed tablets, which of the following statements is INCORRECT? A An example of a colouring agent is lactose B An example of a binder is starch C An example of a lubricant is talc D An example of an anti-adherent is magnesium stearate E An example of a glidant is colloidal silica 6. Which of the following statements describes an emulsion? A An oil-in-water dispersion B A solid dosage form enclosed in a shell C A liquid preparation of sugar in water D A liquid preparation that contains a non-aqueous solvent, such as alcohol E A liquid viscous preparation that contains sugars and is mainly used as a demulcent, expectorant, or sedative 3 7. Which of the following is NOT a dosage form used for rectal drug delivery? A Pessary B Enema C Capsule D Cream E Suppository 8. Which of the following statements regarding excipients is CORRECT? A Excipients are ingredients that have pharmacological activity B An example of an excipient is a capsule C A disintegrants is used in tablets to increase the size of the tablet D Excipients are pharmacologically inert ingredients used to give the final dosage form body (mass) or influence its characteristics, delivery and stability. E Enteric coated tablets do not need excipients 9. In relation to acids and bases, which of the following statements is FALSE? A An acid is a substance that contains hydrogen and dissociates in water to yield a hydronium ion B An acid is a substance that will donate a proton C A base is a substance that contains the hydroxyl group and dissociates in water to yield OH- D A base is a substance that will accept a proton E An acid is an electron-pair donor 4 10. You prepared a solution of a weak monoprotic acid by dissolving 0.080 moles of the acid in enough water to make 1.0 litre of solution. The pH of the resulting solution was 4.51. What is the value of Ka for this acid? A 9.5 x 10-10 B 3.9 x 10-4 C 1.2 x 10-8 D 1.8 x 10-5 E 6.1 x 101 11. Which of the following statements describes the criteria for “Lipinski’s rule of 5”? A < 5 hydrogen bond donors, < 10 hydrogen bond acceptors, < 500 molecular weight, log p< 5 B < 5 hydrogen bond acceptors, < 10 hydrogen bond donors, < 500 molecular weight, log p< 0 C > 5 hydrogen bond donors, > 10 hydrogen bond acceptors, > 500 molecular weight, log p> 5 D > 5 hydrogen bond acceptors, > 10 hydrogen bond donors, > 500 molecular weight, log p< 0 E < 5 hydrogen bond donors, < 5 hydrogen bond acceptors, < 5 molecular weight, log p< 5 12. Which of the following is CORRECT? G protein alpha subunits… A contain intrinsic ATPase activity B irreversibly bind to beta gamma subunits C contain intrinsic GDPase activity D contain intrinsic GTPase activity E are highly hydrophilic 5 13. Cyclic adenosine monophosphate (cAMP) is an example of which of the following? A An antagonist B An agonist C An enzyme inhibitor D An enzyme inducer E A second messenger 14. Which of the following statements describes affinity? A How well a drug binds to a receptor B The ‘strength’ of an agonist at eliciting a response C How selective a ligand is for certain receptors D How a drug is metabolised by cytochrome P450 enzymes E Molecules that reduce the actions of agonists 15. Which of the following statements relating to black triangle products is CORRECT? A Black triangle drugs are new medicines/vaccines that are under additional monitoring B Is a mechanism for reporting adverse drug reactions C NICE is responsible for maintaining the list of black triangle products D Black triangle drugs are unsafe and should not be used E The black triangle products are represented by the following symbol: 6 16. If 10 mg of sodium hydroxide (Mr=40 g/mol) is dissolved in 100 ml of water, what is the concentration of this solution? A 0.1 M B 0.01 M C 0.025 M D 0.0025 M E 0.0005 M 17. Which of the following is a set of research ethics principles for human experimentation that was set at the end of the second world war? A Declaration of Hamburg B GPhC standards C Animal (Scientific procedures) Act D Nuremberg Code E Fredricksburg code 18. Which of the following statements regarding the yellow card scheme is INCORRECT? A MHRA and CHM jointly operate this scheme B It is a mechanism of reporting adverse drug reactions of medicines in clinical use C An example of an adverse drug reaction that could be reported on this scheme one which is associated with black triangle drugs D It only applies to drugs during the first year of marketing E All adverse reactions that are not mentioned in the patient information leaflet should be reported 7 19. Which of the following is an example of the ‘Refine’ component of the ‘three Rs’: A Use an ex-vivo model instead of animals B Reduce the number of animal species used in a study C Reduce the number of animals used in a study D Improvements to animal welfare, living facilities and the use of less invasive techniques in the study E Use in silico models instead of animals 20. Which of the following is NOT classified as a secondary metabolite based natural product from a medicinal chemistry perspective? A Taxol B Benzyl penicillin C Digoxin D Adenosine E Testosterone 21. Which of the following is NOT a class of natural product? A Alkaloids B Terpenes C Amides D Steroids E Glycosides 8 22. When considering the two compounds below, which of the following is CORRECT? O Cl A The compounds are not chiral B They are diastereomers C They are enantiomers D They are the same E They are conformers O Cl 23. Which of the following is the CORRECT Newman projection for the following molecule? A B C E D 9 24. When considering the functional groups in the compound shown below, which of the following statements is correct? A The compound contains an amine, amide, ether and ketone B The compound contains an amine, ester, ether ketone C The compound contains an amine, alcohol, ester and ether D The compound contains an amide, ester and ether, ketone E The compound contains an amine, amide, ester and ether 25. How many chiral centres does the compound shown below have? A 1 B 3 C 4 D 5 E 6 10 26. Which of the following compounds is the constitutional isomer to the structure below? A B C D E 27. When considering the reaction below, which of the following statement is TRUE? A The reaction is an addition reaction B The reaction is an elimination reaction C The reaction is a reduction reaction D The reaction is a rearrangement reaction E The reaction is a substitution reaction 11 28. When considering the reaction below, which of the following statement is TRUE? A The iodide is a nucleophile B The alcohol is an electrophile C The product is an ester D The alcohol is a nucleophile E This is a reduction reaction 29. When considering the peptide shown below, which fragment is not likely to be one of the 4 small fragments used in the synthesis of the peptide? A B C D E 12 30. Complete the following statement so that it is correct. “Safety pharmacology is a discipline that aims to…” A …predict the first toxic dose of a drug in man B …predict the risk of rare lethal events C …identify the mechanism(s) of hepatotoxicity in man D …develop new animal models of disease E …assess affinity and efficacy data for new drugs 31. Which of the following statements is INCORRECT? A Glutathione redox cycle protects from oxidative stress caused by toxins B NOAEL is defined as the No Observable Adverse Effect Level When cellular glutathione falls to 20-30% of normal, cellular defence is compromised and cell death can occur leading to severe toxicity The lower the therapeutic index, the higher the relative safety The NOAEL highlights if there is a dose-threshold limit that must be exceeded in order for a toxicity to be observed C D E 32. Which ONE of the following is NOT considered part of a drug molecules pharmacology/toxicological profile during preclinical assessment? A The dose response relationship B Absorption, distribution, metabolism and excretion (ADME) C The effects of co-administration with other drug molecules D The toxicological mechanism of action E The therapeutic index 13 33. Which of the following statements regarding drug toxicity is FALSE? A A drug can act via more than one mechanism of action (both in terms of its pharmacological and toxicological action(s)) B A single drug molecule can lead to multiple adverse reactions in one or more target organs C Changes in biochemistry, physiology and growth are examples of clinical manifestations of adverse drug reactions D The Ames test is an example of an in vitro assay for reproductive toxicity E The NOAEL is defined as the “No Observable Adverse Effect Level” and highlights if there is a dose-threshold that must be exceeded before toxicity is observed 34. Which of the following statements relating to clinical trials is INCORRECT? A Clinical trials are performed to ensure drugs are both efficacious and safe B Clinical trials are performed occur after preclinical testing C There are four phases of clinical trial D E Phase I clinical trials use healthy volunteers and concentrate on establishing efficacy Phase I clinical trials last approximately 6 months 35. Complete the following statement so that it is CORRECT. “Avoidance of bias in clinical trials can be achieved by…” A …using more than 200 patients B …stratification C …using a p value of less than 0.001 D …using a p value of less than 0.005 E …using multiple centres 14 36. Which of the following statements is INCORRECT? A B C D E Black triangle drugs are those requiring additional monitoring Controlled trials make use of a comparative treatment to yield a treatment group and a control group A parallel group study is a simple and commonly used clinical design which compares two treatments A blinded trial is a study whereby people taking part in the trial are not told which group they are placed into There are three types of error in clinical trials termed type 1, 2 and 3 errors 37. Which of the following is NOT a commonly encountered exclusion criterion in relation to clinical trials? A Significantly high BMI B Participation in another study or blood donation in previous 3 months C Evidence or relevant history of drug or alcohol abuse D Sufficient intellectual capacity to understand the information given about the study, and consequent ability to give legally valid informed consent E Clinically relevant cardiovascular abnormality 38. Which of the following statements regarding chemoinformatics is INCORRECT? A Chemoinformatics could be used to rapidly eliminate unsuitable drug candidates B Chemoinformatics involves complex software that requires specialist knowledge to use effectively C Chemoinformatics replaces the need to perform in vitro and in vivo testing D It’s predictions can be inaccurate E Chemoinformatic methods could be used to determine structureactivity relationships 15 39. Complete the following statement so that it is correct. “Movement of drugs by passive diffusion across biological membranes…” A ...relates to natural products B ...relates to compounds to have a large molecular weight C ...requires transporters D ... requires the compound to be lipophilic E ... is likely to occur with polar compounds 40. Which of the following acronyms is INCORRECT? A NCE = New Chemical Entity B FDA = Food and Drug Authority C PCS = Pre-clinical Safety D NICE = National Institute for health and Care Excellence E SAR = Structure Activity Relationships 16 SECTION B: Answer all questions below. Each question is worth 20 marks. Answer Question 1, Question 2 and Question 3 in separate answer booklets provided. Question 1 1A) A new drug candidate for the treatment of Crimean Congo haemorrhagic fever (CCHF) has been submitted to your research team. This disease has a fatality rate of up to 40% and is there is currently no effective treatment. Explain what in silico, in vitro and in vivo preclinical screening techniques exist and how they can be used to assess the safety of this drug candidate. (6 marks) 1B) The drug molecule has passed into the clinical trials phase. Briefly define what is meant by a phase III clinical trial, making reference to its aim(s), participants, data collected and time required to complete. (3 marks) 1C) Concern has been raised about your trial design and the quality and validity of the results it would produce. Explain THREE elements of trial design you would use in such a trial, explaining the advantage of each. (3 marks) 1D) Explain why you think it is important to publish clinical trial data. (3 marks) 1E) The team in your department identified the drug target for this new drug candidate. The pharmacologist tells you this target is a G-Protein coupled receptor. Explain the pharmacological steps following a GPCR agonist binding that lead to the cellular response. (5 marks) 17 Question 2 2A) Discuss the advantages and disadvantages of the following routes of administration. (i) (ii) Transdermal delivery Nasal delivery (5 marks) (5 marks) 2B) A patient is given 75 mg of a drug intravenously. The plasma concentration was monitored to determine the pharmacokinetic behaviour of the drug in order to establish an appropriate dose regime for the patient. The results obtained were as follows: Time (h) Drug concentration in plasma (g cm-3) 2.5 5 10 15 20 26.22 21.24 15.00 9.11 3.82 30 Drug concentration in plasma (µg cm‐3) 25 20 15 10 5 0 0 5 10 15 Time (h) 18 20 25 Please note: All pharmacokinetic formulae are provided below: kel = 0.693 t0.5 DOSE = C0 x Vd Clp = F x DOSE AUCoral Clp = kel x Vd AUC0- = C0 kel F = AUCoral AUCi.v. AUC0- = DOSE Clp Z = F x DOSE x kab Vd(kab – kel) Css = F x DOSE Clp x t interval kab = 0.693 t0.5 AUC0- = Z - Z kel kab Css = rate of infusion Clp Calculate (showing the working out for): i) The concentration at T0 (µgcm-3) (2 marks) ii) The drug’s plasma elimination half-life (h) (2 marks) iii) The elimination rate constant (h-1) (2 marks) iv) The volume of distribution (L) (2 marks) v) The plasma clearance (Lh-1) (2 marks) 19 Question 3 3A) Define the term log P (1 mark) 3B) Explain how a log P value of 4.92 would influence the ADME profile of this drug. (3 marks) 3C) Considering the following compound: i) Draw all possible stereoisomers for the compound (4 marks) ii) Assign all the stereocentres on all stereoisomers using Cahn-Ingold-Prelog rules (4 marks) iii) Define the relationship between the compounds (3 marks) 3D) The compound shown below is a key intermediate in the synthesis of new anticancer medication. The compound can be assembled from 4 fragments. Identify the 4 fragments and propose a possible forward synthesis of the compound (5 marks) O O NH N H O 20 H N O O O 21 STUDENT NUMBER ___________ Module Code and Title: 4PY019 - Introduction to Drugs and Medicines Assessment Date: May 2023 Examiners: Drs. Zeeneh Elsaid, Ayman Antoun Reyad, Mark Hewitt, Waseem Kaialy, Matthew Palframan and Ben Butler This section comprises: 40 Multiple choice questions worth 40 marks in total. All questions have ONLY ONE answer. If none or multiple (i.e. more than one answers) are circled, marks will not be awarded. There is NO negative marking. You may write on the question paper although you MUST transfer all your responses to this single sheet answer grid before the end of the test. Circle your responses (A-E) using a pencil. 1 A B C D E 21 A B C D E 2 A B C D E 22 A B C D E 3 A B C D E 23 A B C D E 4 A B C D E 24 A B C D E 5 A B C D E 25 A B C D E 6 A B C D E 26 A B C D E 7 A B C D E 27 A B C D E 8 A B C D E 28 A B C D E 9 A B C D E 29 A B C D E 10 A B C D E 30 A B C D E 11 A B C D E 31 A B C D E 12 A B C D E 32 A B C D E 13 A B C D E 33 A B C D E 14 A B C D E 34 A B C D E 15 A B C D E 35 A B C D E 16 A B C D E 36 A B C D E 17 A B C D E 37 A B C D E 18 A B C D E 38 A B C D E 19 A B C D E 39 A B C D E 20 A B C D E 40 A B C D E NOTE: This page must be submitted along with all the 3 answer booklets for marking.