PHAY2002

UCL SCHOOL OF PHARMACY

M. PHARM. EXAMINATION

PHAY2002
MEDICINES FROM THE BENCH TO THE CLINIC

May 2016

TIME ALLOWED: 3 HOURS

The Examination is comprised of TWO (2) sections. You must answer BOTH
sections of the paper.

Section A.

 Answer SIX (6) of the EIGHT (8) questions.

 Use ONE (1) answer book for all the questions you select.
 Each question has the same value.
 The marks distribution is shown clearly for each section of the question. Answer
all parts of each of the individual questions you select.
 This section contributes 50 % of the total paper marks. You are advised to spend
one and a half hours on this section.
 You are advised to spend no more than 15 minutes on each question.

Section B.

 Answer TWO (2) of the THREE (3) questions.

 Use a separate answer book for each question you select.
 Each question has the same value.
 The marks distribution is shown clearly for each section of the question. Answer
all parts of each of the individual questions you select.
 This section contributes 50 % of the total paper marks. You are advised to spend
one and a half hours on this section.
 You are advised to spend no more than 45 minutes on each question.

 Notes are not permitted in this examination.

 Dictionaries are not permitted in this examination.
 Calculators may be used in this examination.
 Do not turn over until you are told to do so by the invigilator.
 Do not take this question paper out of the examinations room.

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SECTION A

Answer SIX (6) questions. Spend ONE AND A HALF hours on this section.

1. Answer BOTH parts of the question.

a) Clinical researchers discovered a single nucleotide change (mutation) in the

human genome that correlates with the occurrence of colon cancer. Their
evidence came from "Linkage Analysis". Briefly explain the meaning of
"Linkage Analysis" research. (25 % of marks)

b) Laboratory scientists showed that this mutation caused over-expression of a

growth factor receptor in human colonic tumour tissue. Their evidence came
from "DNA microarray analysis". Briefly explain the technique of "DNA
microarray analysis". (75 % of marks)

2. Answer ALL parts of the question.

a) What are preclinical carcinogenesis studies? (5 % of marks)

b) Briefly describe the long-term animal study carried out to determine if a new
drug has the potential to cause cancer. (45 % of marks)

c) Give FOUR (4) observations you could make in the animal study to distinguish
if tumours occurring are a result of treatment with the drug or due to
spontaneous disease. (50 % of marks)

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3. Answer ALL parts of the question.

a) Why is the compound below referred to as a cardenolide?

(20 % of marks)

b) Give TWO (2) examples of drugs from the cardenolide class. For EACH, state
its therapeutic use and source organism. (30 % of marks)

c) Give the names of compounds 1 and 2 below, their producing organism and
their biological activities. (30 % of marks)

d) Give the source organism and use of compound 3 below. (20 % of marks].

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4. A compound has the formula C4H8O2. Determine its structure using the proton
and carbon NMR spectra provided below, explaining your rationale. Draw its
correct structure in your answer book. (100 % of marks)

Solvent
Peak

PPM

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5. Answer BOTH parts of the question.

The physical structure of a drug is extremely important pharmaceutically.

a) Define the terms "crystal", "polymorphism" and "amorphous" in relation to the

physical structure of a drug. (40 % of marks)

b) Explain the significance of polymorphic and amorphous forms of a drug in orally

administered pharmaceutical products, including a discussion of relevant
underpinning physical parameters and processes. (60 % of marks)

6. List TWO (2) formulation approaches that can be used to prolong the release
of a drug from an orally administered capsule. Explain the advantages of EACH
approach. (100 % of marks)

7. With the aid of appropriate diagrams, describe the principles of BOTH of the
following methods of drying: fluidised-bed drying and freeze-drying. Include in
your answer the types of samples that each method is suited to drying.
(100 % of marks)

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8. Answer BOTH parts of the question.

a) A patient with respiratory disease is clinically stabilised with oral theophylline

200 mg daily. His average theophylline plasma levels are 15 mg/L (target range
10 to 20 mg/L). The patient is later co-prescribed oral carbamazepine. Some
months later, his respiratory symptoms begin to worsen and TDM indicates a
theophylline plasma concentration of 7 mg/L. Provide a plausible explanation
for these observations. (50 % of marks)

b) Amikacin is an aminoglycoside antibiotic drug. Following a single intravenous

bolus injection of 100 mg, and serial plasma sampling, the following profile was
obtained (plasma drug concentration is plotted on a logarithmic Log 10 scale).
Provide a good estimate of the elimination rate constant (to 3 decimal places)
and the apparent volume of distribution of amikacin (to 1 decimal place).(50 %
of marks)

END OF SECTION A

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Section B

Answer TWO (2) questions. Spend ONE AND A HALF hours on this section.

9. Answer ALL parts of the question.

You are a community pharmacist and have an interest in the development of

medicines.

a) A patient of yours has purchased a product for the treatment of minor lower
back pain. The product has the following logo on its packaging. She has asked
you to explain what this means. Provide a detailed answer for this patient,
covering aspects such as quality, safety and efficacy/tradition of use of the
product.

(40 % of marks)

b) Discuss how the approval process for a conventional, new small molecular-
weight drug to treat the same condition will differ from that described in your
answer to (a) above. Include in your answer details of the various stages
involved in this process. (40 % of marks)

c) Discuss the unique production requirements for herbal medical products in

terms of quality assurance from source to final product. (20 % of marks)

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10. Answer ALL parts of the question

a) The binding of a specific transcription factor X to its DNA response element

(XRE) is believed to be a key stage in uncontrolled mitosis. Describe and
explain ONE (1) assay that could be used in High Throughput Screening to
identify potential inhibitors of this interaction in a chemical compound library.
(30 % of marks)

b) What are the notable features and advantages of High Throughput Screening?
(20 % of marks)

c) In the process of discovering one or more compounds that were inhibitors,

explain how you might identify the "pharmacophore" and explain what this
feature actually represents. (25 % of marks)

d) During this process of the identification of the pharmacophore, the following

compound was identified. Using TWO (2) retrosynthetic steps and ONE (1)
functional group disconnection, demonstrate how this compound could be
obtained. (25 % of marks)

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11. Answer ALL parts of the question

Oral modified-release technologies are used to control drug release in the

gastrointestinal tract.

a) What are the differences between "delayed-release" and "extended-release"

dosage forms in relation to their therapeutic use? Sketch a plasma-
concentration profile that would be expected from EACH of these dosage forms.
(15 % of marks)

b) Discuss in detail the formulation principles of an osmotic modified-release

tablet. (25 % of marks)

c) Give FIVE (5) reasons why a tablet may be film coated, other than in order to
modify its drug-release rate. (10 % of marks)

d) With the aid of an appropriate diagram, describe the film coating process. What
parameters are monitored during the process and why?
(25 % of marks)

e) You have manufactured an osmotic modified-release tablet and subjected it to

dissolution testing. What is meant by the term "dissolution testing"? Comment
briefly on the advantages and disadvantages of standard dissolution tests as
defined in pharmacopoeias. (15 % of marks)

f) The results of the dissolution test on your osmotic modified-release tablet are
given in the figure below. Given these data, do you think that the formulation
is suitable for modified release? Explain your answer. (10 % of marks)

END OF PAPER