bsc(hons) in pharmacology

8/7/2019 BSc(hons) in Pharmacology

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Background: The necessities for futurescientific and clinical development of themedicine to rely on graduates who have aqualified clinical knowledge as well astrained in research.

These is a program designed for Medicaland Dental undergraduates. Within themedical programme there is the chance tostep aside from the course to undertakefurther study and/or research.



N ewcastle University is home to a diverse andcosmopolitan community with over 3,000 internationalstudents from over 110 countries worldwide. It is one of theUK's leading universities with a reputation built on thequality of our teaching, outstanding research and our work with the community and industry.

¶an impressive academic record· ( The Guardian UniversityGuide 2008)

¶one of the UK·s top 20 universities· ( The Times Good UniversityGuide 2009)

N ewcastle has a long tradition of welcoming students fromall over the world, and provides a well-established anddedicated support and advice services.



The Faculty is part of three faculty in theUniversity. It·s includes Biosciences,Dentistry, Medical Education andPsychology.

It has focused its core research activity atthe basic science/clinical interface, into 7

research institute that containinternationally strong research in: ageing,cancer, genetic, neuroscience, cell andmolecular biosciences, cellular medicine,health and society and stem cells.



is part of the Faculty of Medical Science.The school has responsibility for theundergraduate program, 4 years integratedmasters in biomedical science, and a pre-med study abroad programme.

The school recruits approximately 270

undergraduates per year, who are taught acommon phase 1 during the first year and ahalf of their studies. Then for the next oneand a half year they study their specificprogramme.



Student who wish to intercalate mustsuccessfully complete Stage 3 of their

studies at the first attempt.Have GPA equivalent or above 3.00IELTS min 6.5

Highly motivatedCV



The taught material in semester 1 focuseson the advanced knowledge in the

subject areas, often presenting recentadvances in research and theexperimental basis of our currentunderstanding.

All students also required to takeoptional module at semester 1



Business for the Bioscientist

This module aims to introduce students toenterprise and entrepreneurship in relationto the Biothechnology and Pharmaceuticalindustries. Assessment is entirely by coursework and consist of a test on intellectualproperty rights, a written business plan, anoral presentation and workshop pitchingexercise.



R esearch in Pharmacology

This module provide a broad overview ofscientific research in an academic settingincluding an introduction to postgraduatestudy options. The research theme will befurther explored with an in depth study group inchosen areas of pharmacology, culminating in

a group presentation of a research topic.Further hands on experience of research isassessed by the production of N ews and Viewsstyle article detailing a hot or breaking area ofscience.



Pharmacological Techniques

This module consist of 2 themes. In themeone lectures will cover the theories andgeneral practice of the most relevantanalytical techniques and their applicationin identification and measurement ofxenobiotics in biological matrices. Theme 2will cover the current use and future trend inthe use of laboratory animal.



Clinical Pharmacology

This module introduces the subject ofclinical pharmacology. The module aims toprovide a knowledge and understanding ofthe concepts and principles involved in thedevelopment of new medicine; starting

with drug discovery and culminating in thegranting of a new product license. Studentsalso gain an appreciation of pharmaco-economics, pharmaco-vigilance andrational drug use.



Advanced pharmacogenetics

This module covers aspects of geneticfactors that affect the metabolism offoreign compounds and drug-receptor interactions. Lectures covers current viewson the relationship between

pharmacogenetic polymorphisms anddisease susceptibility. Potential approach todrug design using pharmacogenomics andintroduction to molecular epidemiologyalso considered.



Carsinogenesis and anti-cancer drugs

This module focuses on the process ofcarcinogenesis, the biology of cancer cells, oncogenes and tumours suppressor

genes and the pharmacology of themain anticancer drugs.



Advanced topics in N europharmacology

This module concerns the brain and disease of thebrain examined in the context ofneuropharmacology. Followint the sessions onanatomy and neuroimaging, specific diseases inthe brain also covered; ie. Depretion,anxiety, drug

abuse and addictive behavior. Emphasis areplaced on how to target these pathologies withpharmacological agent in effective way as wellas new approached in therapeuticneuropharmacology.



Toxicology

This module introduces the mechanismsof the toxic effects of chemicals anddrugs in man. Student will learn on how

the chemical enter the body, how it·sbeing metabolised, and how theserelated to their toxic effects.



Integrated Pharmacology

The aims of this module is to test,encourage, and bringing together ofknowledge acquired in the modules thatmake up the honours course. Student willbe expected to know certain ´coreµ ofknowledge on pharmacology but also tosee how the various aspect of the disciplinerelated to each other. Data analysis skill willalso be tested.



Final Project (40 credits)

This module aims to allow student toexperience at first hand in-dept researchwork, either laboratory, library, patient,schools related, or computer based, on anoriginal topic, in a research environment,under the direction of a supervisor. Themajority of student will undertake a projectin one of the research institutes in theuniversity.



Supervised by Dr.Gareth Veal 19



The impact of MDR1 and MRP2 drugtransporters on the intracellular accumulation & anti proliferative activityof anti cancer drug, Actinomycin-D

MethodsWe used Mardin-Darby canine kidney cells (MDCK- II)transfected with various efflux transporter (human MD R 1and M R P2) genes to study trancellular transport and theanti-proliferative activity Actinomycin D, when comparedwith the MDCK II-wild type cells. Later we investigate theimpact of MD R 1 and M R P2 drug transporters in cellviabialityand intracellular accumulation of ActinomycinD.

In order to determined the effect of the drug transporter onthe drug, we focus on two measures:

Growth inhibiton of Actinomycin Dand reversalof resistanceby inhibitor

Intracellularaccumulation of Actinomycin D

1. Veal GJ, Cole M, Errington J, et al (2005) Pharmacokinetics ofDactinomycin in a Pediatric Patient Population: a United KingdomChildren·s Cancer Study Group Study. Clinical Cancer R esearch;11(16):5893-5899

2. Ho RH, Kim R B. Transporter and drug therapy: Implications for drugdisposition and disease. Clinical Pharmacology and Therapeutics;78(3):260-277

3. Melguizo C, Prados J, Fernandez JE et al (1994) Actinomycin Dcauses multidrug resistance and differentiation in a humanrhabdomyosarcomecell line. Cell Molecular Biology: 40(2):137-145

Naila Izzati, Chris Hill, Gareth VealPharmacology Group, Northern Institute of Cancer ResearchUniversity of Newcastle upon Tyne

Background ResultsConclusion

References

Northern Institute of CancerResearch, University of

Newcastle upon Tyne

MDCK- II cells over-expressing MD R 1 andMR P2 were shown to be less sensitive toactinomycin-Dthan MDCK- II WT cell.

Actinomycin-D efflux in MDCK- II MDR 1 celllines was reversed by verapamil, a selectiveMD R 1 inhibitor. Similarly, Actinomycin-D effluxin MDCK- II MR P2 cell lines was reversed byMK571, an inhibitor in M R P cell lines.

MDCK- II MR P2 and MD R 1 cells exhibit asignificant reduction in intracellular accumulation and also decreased sensitivity toActinomycin-D.

The potential role of drug efflux transporter incellular distribution and tumour penetrationmade these transporter important indetermining the pharmacokinetic profile ofanti cancer drug. One of the alternativeapproach to combat the cellular resistant is bydirecting an inhibitor. By identifying the effluxtransporter involved in drug resistance andutilize the anti cancer drug that would benefitfrom the inhibition, hopefully patient prognosiswillrise.

1

2

34

5

The dose-response curve in cell line which has beentransfected with the transporter, MDCK- II MD R1 cellsand MDCK- II MR P2 cells, were shown to be shifting tothe right side (Fig.1A and 1B), with greater effect shownon M D R 1 cell line. These results indicate thatActinomycin D is a substrate for both transporters. Fromthe graph, we can also conclude that higher concentration of Actinomycin D is needed to achieve

the similar cell viability as the parental cell.

1A 1B

In the presence of as low as 1 M of verapamil, MD R 1cells were shown to be more susceptible to cytotoxicityof Actinomycin D, as compared with cells without theverapamil. The similar effect is achieved by theinhibitor, also shown in MDCK- II MR P2 cell line. After

being treated with 40

M of M K-571, the percentage ofcell death is higherthan before treatment.

In cell line transfected with the efflux transporter (MDCK- II MR P2 and MDCK- II MD R 1), the amount ofActinomycin D was significantly low and accountedonly half and a third of the amount that in MDCK- II WTcell respectively.

The role of Drug efflux tr ansporter in cancer

Actinomycin D has been used mostly in paediatric cancer treatment for the following tumour; rhabdomycosarcoma, Willm·sTumor, and Ewing·s sarcoma. Although Actinomycin-D has beenwidely used for treatment of childhood cancer for more than 40years, there is still a lack of knowledge of drug resistancemechanisms whichdev elop in some patients.

The effectiveness of Actinomycin-D can be reduced due tocellular resistance . Although resistance can develop through avariety of mechanisms, some drug transporter including the effluxtransporters which belong to the ABC family (M R P and MD R ), areconsideredto be the cause of drug resistance for many drugs.

Over-expression of P-gp and other efflux drug pumps may resultin lower concentrations of drugs in tumour cells, thus contributingto treatment failure and increased toxicity. In this study we triedto investigate whether Actinomycin-D is a substrate for the MD R 1and M R P2 drug transporter.

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bsc(hons) in pharmacology

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