PHARMACEUTICAL MEDICINAL CHEMISTRY- Dealing with the structure- Part- II

         PHARMACEUTICAL MEDICINAL CHEMISTRY- Dealing with the structure- Part- II
      In the previous post we covered some basic funda's regarding chemistry. Now with the basics done its time to move ahead and master the subject of interest- "Pharmaceutical Medicinal Chemistry". This subject basically will deal with the SAR- Structure Activity Relationship, MOA- Mechanism of Action and chemical synthesis of pharmaceutical agents or simply 'drugs'.
      In SAR, we should try to focus on the functional groups in a particular moiety which are responsible for the action of the drug/ binding with the receptors. It can also include the 'prodrug' approach as well. E.g. Which functional group is susceptible for the making prodrug.
      In MOA, it is sometimes essential to know the sequence of reactions which actually take place with the drug (especially prodrug) in the body on administration. MOA is more of concern in 'pharmacology' which we would cover in the upcoming posts. Rather, I would personally suggest to study pharmacology and medicinal chemistry at the same time. It will serve 2 purposes-
1. Time-saving activity.
2. After knowing structure, SAR and chemical synthesis of particular class of drugs in chemistry (for e.g. anti-viral agents), you can look its MOA, ADR (Adverse Drug Reactions), S/E (Side-effects) and other aspects in pharmacology. Thus, you will immediately link the chemistry and pharmacological actions of the drug instantly and trust me, it really helps a lot.. Its like hitting 2 bird with a single stone !!
       In this post we will also try to cover 'Biochemistry'. Most of the questions regarding with biochemistry is more centered around the biochemical pathways. Glycolysis, TCA cycle are favourite ones. Questions may or may not be asked on enzyme kinetics, enzyme immobilization, nucleic acids- DNA, RNA etc.,  genetic mutations etc. These topics are more of a concern in NIPER-JEE preparation. We would also cover guidance and tips about NIPER-JEE too once GPAT series ends.

Recommended books for reading-

PHARMACEUTICAL MEDICINAL CHEMISTRY
1. Thomas L. Lemke, David A. Williams, Victoria F. Roche, S. William Zito, "Foye's Principles of Medicinal Chemistry", 7th Edition, Lippincott Williams and Wilkins Publishers, 2013.

2. John M. Beale Jr., John H. Block, "Wilson and Gisvold's Textbook of Organic Medicinal and Pharmaceutical Chemistry", 12th Edition, South Asian Edition, Lippincott Williams and Wilkins Publishers, 2010.

The above books were for referring SAR, MOA, uses etc. stuff of drugs. Now for synthesis of drugs we would recommend to refer-

3. Daniel Lednicer, "The Organic Chemistry of Drug Synthesis",  Wiley, Volumes- 1 to 7.

4. Douglas S. Johnson and Jie Jack Li, "The Art of Drug Synthesis".Wiley Interscience, 2007.

PHARMACEUTICAL MEDICINAL CHEMISTRY
Basic Principles- 1

Drug metabolism and Concept of Prodrugs; Principles of Drug Design (Theoretical Aspects)- 1

Synthetic Procedures, Mode of Action, Uses, Structure Activity Relationships including Physicochemical Properties of the Following Classes of Drugs:

a. Drugs acting at synaptic and neuro-effector junction sites: Cholinergics, anti-cholinergics and cholinesterase inhibitors, Adrenergic drugs, Antispasmodic and anti-ulcer drugs, Local Anesthetics, Neuromuscular blocking agents- 1,2

b, Autacoids- 1,2

c. Steroidal Drugs- 2

d. Drugs acting on the central nervous system- 1,2

e. Diuretics; Cardiovascular drugs- 1,2

f. Thyroid and Anti thyroid drugs; Insulin and oral hypoglycemic agents- 1

g. Chemotherapeutic Agents used in bacterial, fungal, viral, protozoal, parasitic and other infections, Antibiotics: ß-Lactam, macrolides, tetracyclines, aminoglycosides, polypeptide
antibiotics, fluoroquinolones- 1,2

h. Anti-metabolites (including sulfonamides); Anti-neoplastic agents; Anti-viral agents (including anti–HIV);
Immunosuppressives and immunostimulants; Diagnostic agents; Pharmaceutical Aids- 1,2


BIOCHEMISTRY-
1. David L. Nelson and Michael M. Fox, "Lehninger Principles of Biochemistry", 6th Edition, Macmillan Publishers, 2013,

2. Robert K. Murray, Peter J. Kenelly, David A. Bender, Kethleen M. Bothan, P. Anthony Weil, Victor W. Rodwell, "Harpers Illustrated Biochemistry", 29th Edition, Tata Mc-Graw Hill Publishers, 2012.

BIOCHEMISTRY-
Biochemistry in pharmaceutical sciences- 1,2

Enzymes- 1,2

Co-enzymes- 1,2

Carbohydrate Metabolism- 1,2

The Citric Acid Cycle- 1,2

Lipids Metabolism- 1,2

Essential fatty acids & eicosanoids-  Refer Foye and Wilson of Medicinal Chemistry.

Biological Oxidation- 1,2

Metabolism of ammonia and nitrogen containing monomers- 1,2

Purine biosynthesis- 1,2

Pyrimidine biosynthesis and formation of deoxyribounucleotides.
Biosynthesis of Nucleic Acids- 1,2

Mutation- 2

Genetic Code and Protein Synthesis- 1,2

Enzyme Immobilization- 1,2.

            This was all about 'MEDICINAL CHEMISTRY' and 'BIOCHEMISTRY'. In the next part we would cover all of 'PHARMACEUTICAL ANALYSIS'.
             Hope you would have liked this part, too.. Any kind of feedback and suggestions are welcome by our team !!!
                                                                                           -Darwin
                                                                  [GPAT-2014- All India Rank (AIR)- 619)
                                                                        NIPER-JEE-2014 AIR-25 and

                                                                          ICT-BPT-CET-2014 AIR-7 ]
                                                      Ist year M, Tech (Bioprocess Technology-BPT)-2014-16,
                                                            Institute of Chemical Technology, Matunga, Mumbai.

                                                                                   

PHARMACEUTICAL MEDICINAL CHEMISTRY- Dealing with the structure- Part- I

         PHARMACEUTICAL MEDICINAL CHEMISTRY- Dealing with the structure- Part- I
         Chemistry is one subject in which your logic and basic concepts are tested to the core. Mugging up the whole subject is not a solution to master this subject. However, mugging up the structure of some pharmaceutical compounds and reagents/ reaction conditions in synthesis of some pharmaceutical drugs is the only option sometimes (sorry you really can't help some times!!!). But some time a little common sense and logic can save you in GPAT.
        So in order to clear certain basic concepts, we will include the guidance in subjects like "INORGANIC MEDICINAL CHEMISTRY", "PHYSICAL CHEMISTRY" and "ORGANIC CHEMISTRY".
INORGANIC MEDICINAL CHEMISTRY- This subject mainly deals with inorganic medicinal compounds like gastrointestinal drug products like laxatives, dental products, pharmaceutical aids like excipients, suspending agents etc. Not much theoretical questions are expected from this subjects. However, some numerical problems about isotonic solution adjustments, radiopharmaceutical activity and half-life measurements can be asked.
PHYSICAL CHEMISTRY- A subject that cannot be neglected, it deals with important topics like thermodynamics, solutions, chemical kinetics, phase rule etc. Many questions can be asked like that of physical pharmacy as mentioned in my previous part. Actually it is also a part of physical, but has been included in this part due to much relevance to chemistry.
ORGANIC CHEMISTRY- A subject that almost completely deals with reactions, structures, mechanisms etc. is hated by most of the students (maybe since this subject is volatile). Having said that, you really need to practice it everyday with paper-pencil just like you solve mathematical problems. You just can't do chemical reactions in air by reading and mugging and if you try to do they are easily forgotten at the time of exam.Again many questions can be asked particularly regarding name reactions like Hoffman, Beckmann reaction and many more. Mechanism of each reactions like whether that reaction is electrophilic, nucleophilic and whether it is addition, substitution or elimination reaction should be clear.

RECOMMENDED BOOKS FOR STUDYING-
1. A.H. Beckett and J.B. Stanlake, "Practical Pharmaceutical Chemistry", 4th Edition, CBS Publishers and Distributors, 1997.

2. J. H. Block, E.B. Roche, T.O. Soine and C.O. Wilson, "Inorganic Medicinal and Pharmaceutical Chemistry", Lea Febiger Publishers, 1974.

3. Indian Pharmacopoeia, 2014.

4. David B. Troy, Paul Beringer, "Remington ; The Science and Practice of Pharmacy", Lippincott Williams and Wilkins, 2006.

5. Patrick J. Sinko, "Martin's Physical Pharmacy and Pharmaceutical Sciences", 6th Edition, Lippincott Williams and Wilkins, 2010.

6.  Arun Bahl, B.S. Bahl, G.D. Tuli, "Essentials of Physical Chemistry", S. Chand Publishers, 2009.

7. R.T. Morrison , R.N. Boyd and S.K. Bhattacharjee, "Organic Chemistry", 7th edition, Pearson India Publishers, 2011.

8. P.S. Kalsi, "Stereochemistry- Conformation and Mechanism", Anshan Publishers, 2009.

9. G. Brahmachari, "Organic Name Reactions- A Unified Approach", 1st edition, Narosa Book Distributors Pvt. Ltd., 2011.

10. S.H. Pine, "Organic Chemistry",5th edition, McGraw Hill Publishing Co. Ltd., 2007.

11. J.A. Joule and K. Mills, "Heterocyclic Chemistry", 4th edition, Blackwell Publishing, 2005.

A) INORGANIC MEDICINAL CHEMISTRY
Importance of inorganic compounds in pharmacy and medicine- 1,3

Gastrointestinal Agents- 2

Major Intra- and Extra-cellular Electrolytes- 2

Essential and Trace Elements- 2

Topical Agents- 2, 4

Gases and Vapors- 2, 4

Dental Products- 2,4

Miscellaneous Agents- 2,4

Pharmaceutical Aids Used in Pharmaceutical Industry- 2, 3, 4

Acids, Bases and Buffers- 1

Inorganic Radiopharmaceuticals- 4

PHYSICAL CHEMISTRY-
Importance of basic fundamentals of physical chemistry in pharmacy- 5,6

The Liquid State- 5,6

Solutions- 5,6

Thermodynamics- 5,6

Thermochemical equations; Phase rule; Adsorption- 5,6

Photochemistry- 6

Chemical Kinetics- 5,6

Quantum Mechanics- 6

ORGANIC CHEMISTRY-
Importance of fundamentals of organic chemistry in pharmaceutical sciences; Structure and Properties- 6, 7, 10

Stereochemistry- 7, 8

Stereoselective and stereospecific reactions; Structure, Nomenclature, Preparation and Reactions-  7,10

Nucleophilic and Electrophilic Aromatic Substitution Reactions- 7, 10

Electrophilic and Nucleophilic Addition Reactions; Rearrangements- 7, 9, 10

Elimination reactions; Conservation of Orbital Symmetry and Rules- 7, 10

Neighboring group effects; Catalysis by transition metal complexes; Heterocyclic Compounds- 7, 11.

          This was all about the basics which we should be clear of, when we deal with the detail chemistry of pharmaceutical drugs. In the next part we will provide guidelines and tips about 'MEDICINAL CHEMISTRY' and 'BIOCHEMISTRY'.
          Hope you would have liked this part, too.. Any kind of feedback and suggestions are welcome by our team !!!
                                                                                           -Darwin
                                                                  [GPAT-2014- All India Rank (AIR)- 619)
                                                                        NIPER-JEE-2014 AIR-25 and

                                                                          ICT-BPT-CET-2014 AIR-7 ]
                                                      Ist year M, Tech (Bioprocess Technology-BPT)-2014-16,
                                                            Institute of Chemical Technology, Matunga, Mumbai.

                                                                                     

LEMTRADA (Alemtuzumab)- Only FDA approved drug of November- 2014

                  LEMTRADA (Alemtuzumab)- Only FDA approved drug of November- 2014
TRADE (BRAND) NAME- LEMTRADA
ACTIVE PHARMACEUTICAL INGREDIENT- Alemtuzumab
COMPANY- Genzyme
USE- Treatment of T-cell lymphoma and chronic lymphocytic leukemia
Alemtuzumab has been in use for the above diseases from a long time ago. In 2008 ,at Cambridge University, it was suggested that it can be used in the treatment of relapsing multiple sclerosis (MS) and also reversing its effects. But it was not approved by FDA due to lack of solid proof and results in treating multiple sclerosis. However, thanks to the persistent fight by Genzyme, it was finally granted FDA approval in November 2014.
It is a humanized monoclonal antibody obtained from rat. It attacks CD52 protein present on T- and B- cells. The inflammatory responses observed in MS were due to the abundance of T- and B-cells and alemtuzumab depletes these cells after every dose. However, it is used as a secondary choice of drug in MS therapy due to its low safety profile. Various life-threatening side effects include auto-immune disorders, prone to malignancies like thyroid cancer. rashes, fatigue etc. are observed with alemtuzumab.

                                                                                                                              - Darwin

PHARMACEUTICS- Heart Of Pharmacy- Part- II

                                           PHARMACEUTICS- Heart Of Pharmacy-
                                                                        Part II
In the previous post, we covered about some basic concepts in subjects like Physical Pharmacy, Dispensing Pharmacy and Pharmaceutical Engineering, which are essential beforehand in order to start our actual "PHARMACEUTICS" preparation.
In this post we will actually cover the guidance about actual subject- PHARMACEUTICS and its allied courses which are also important like 'Community Pharmacy / Hospital Pharmacy and Drug Store Management' and 'Biopharmaceutics and Pharmacokinetics'.
PHARMACEUTICS- This subject, as we are well aware of, deals with the science behind various dosage forms ranging from liquid orals, semi-solid dosage forms to solid dosage forms like tablets, capsules till parenteral products. A lot many questions can be asked on this subject. Typical questions asked will be discussed chapter-wise below.
COMMUNITY PHARMACY / HOSPITAL PHARMACY AND DRUG STORE PHARMACY-
From this topic hardly any questions are asked. Maximum 2-3 questions. But a general knowledge about the role of pharmacist in drug store and hospitals, working and management of hospital and its services should be remembered.
BIOPHARMACEUTICS AND PHARMACOKINETICS- Biopharmaceutics particularly focuses more on the changes we need to make in the dosage form to increase bioavailability; whereas pharmacokinetics deals with what happens to the drug once it is inside in the body. Minimum 1-2 numerical problems are definitely asked from this subject about bioavailability, plasma drug concentration kinetics such as calculation of tmax, Cmax, AUC (Area Under the Curve) etc. So even if you are not much thorough with theoretical knowledge of these subjects, concepts must be clear regarding numerical calculations of pharmacokinetics. There should not be any confusion in remembering the formulaes. Try to practice as much as you can regarding all numerical problems as these are easy gains during the GPAT exam if the formulas are crystal clear in your mind.
 (NOTE- Calculators are not allowed during GPAT examination, so it is very much essential that you should try to practice numerical problems WITHOUT calculators or atleast you should be able to approximately predict the nearest correct answer.
In GATE examination, calculators are allowed... This is another plus point in GATE exam)

Books recommended for studying-
1. Leon Lachman and Herbert A. Lieberman, " The Theory and Practice of Industrial Pharmacy", Special Indian Edition, CBS Publishers and Distributors Pvt Ltd., 2009.

2. David B. Troy, Paul Beringer, "Remington ; The Science and Practice of Pharmacy", Lippincott Williams and Wilkins, 2006.

3. S.J. Carter, "Cooper and Gunns Tutorial Pharmacy",1st Edition, CBS Publishers, 2005.

4. P.P. Sharma, "Cosmetics- Formulations, Manufacturing & Quality Control", 3rd Edition, Vandana Publications Pvt. Ltd., 2005.

5. J.B. Wilkinson & R.J. Moore, "Harry's Cosmeticology", 7th Edition, Longman Singapore Publishers Pvt. Ltd.

6. Dr. H.P. Tipnis and Dr. Amrita Bajaj, "Hospital Pharmacy", Career Publications, 2008.

7. Leon Shargel, Sussana Wu-Pong, Andrew Yu, "Applied Biopharmaceutics and Pharmacokinetics", 6th Edition, McGraw Hill Professional Publishers, 2012 (RECOMMENDED FOR PHARMACOKINETICS).

8. D.M. Brahmankar,  Sunil B. Jaiswal, "Biopharmaceutics and Pharmacokinetics- A Treatise", 2nd Edition, Vallabh Prakashan/ Publishers (RECOMMENDED FOR BIOPHARMACEUTICS).

PHARMACEUTICS (In GPAT syllabus they have mentioned under the heading- Dosage Forms, designing & evaluation)

1.Liquid Dosages Forms: 1,2 (Remember various ingredients and its properties).

2.Semisolid Dosage Forms: 1,2 (Stress more on ointment bases, creams and gels).

3. Suppositories: 1 (Focus on suppository bases and its properties)

4. Extraction and Galenical Products: 2

5. Blood Products and Plasma Substitutes: 3

6. Pharmaceutical Aerosols: 1 (Stress more on the evaluation tests, its temperatures and pressures, nomenclature of propellants and various parts of aerosol container)

7. Ophthalmic Preparations: 2 (Stress more on labelling conditions, preservatives and other formulation aspects of ophthalmic products)

8. Cosmeticology and Cosmetic Preparations: 4,5 (Focus more on formulation and evaluation of lipstick, nail paints, dental products and skin car products).

9. Capsules: 1 (Remember the capsule sizes and the corresponding volumes)

10. Micro-encapsulation: 1

11. Tablets: 1 (Almost everything is important from this topic)

12. Parenteral Products: 2 (Same applies as that of tablets)

13. Surgical products: 2, 3

14. Packaging of Pharmaceutical Products: 1,2 (Try to remember which conatainer and which packing material is used for that particular dosage form).

15. Designing of dosage forms: 1 (Important topic, too !!)

16. Performance evaluation methods: 8 (Remember the I.P, B.P, U.S.P dissolution apparatus types and its application for that particular dosage form).

HOSPITAL PHARMACY AND DRUG STORE MANAGEMENT

1. Community Pharmacy: 2,6

2. Organization and Structure of hospital pharmacy: 2,6

3. Hospital Formulary: 2,6

4. Drug Store Management and Inventory Control: 2,6

5. Drug distribution Systems in Hospitals: 2,6

6. Central Sterile Supply Unit and their Management: 2,6

7. Manufacture of Sterile and Non-sterile Products: 2,6

8. Drug Information Services: 2,6

9. Records and Reports: 2,6

10. Nuclear Pharmacy: 2

BIOPHARMACEUTICS AND PHARMACOKINETICS

1. Introduction to biopharmaceutics: 8

2. Pharmacokinetics: 7,8

3. Clinical Pharmacokinetics: 7,8

4. Bioavailability and bioequivalence: 7,8

This was all for today. Here we complete our guidance about PHARMACEUTICS !! In the next week ,i.e, 17th December 2014, we will start PHARMACEUTICAL MEDICINAL CHEMISTRY guidance section.
Hope you would have liked this part...!!! Any kind of feedback and suggestions are most welcome to our team.
                                                                                          -Darwin
                                                                  [GPAT-2014- All India Rank (AIR)- 619)
                                                                        NIPER-JEE-2014 AIR-25 and

                                                                          ICT-BPT-CET-2014 AIR-7 ]
                                               Ist year M, Tech (Bioprocess Technology-BPT)-2014-16,
                                                      Institute of Chemical Technology, Matunga, Mumbai
                                                 (WITH INPUTS FROM 'CURIE'- GPAT-2014 QUALIFIED)

GPAT-2015 - 'GUIDANCE AND TIPS SERIES' -- PHARMACEUTICS- The Heart of Pharmacy- Part- I

                                            PHARMACEUTICS- The Heart of Pharmacy-
                                                                        Part- I
Pharmaceutics is one subject that pharmacy students just cannot ignore. It is that subject which runs from the first year to final year of the Bachelors in Pharmacy. Since this subject being very vast we will try to cover the guidance, tips, books to recommend etc. in 2 parts.
This part will try to focus on some basic aspects or concepts which are applicable in almost all subjects in pharmacy and thus they act as the pillar on which our GPAT preparation will stand on. They include physical pharmacy, dispensing pharmacy and pharmaceutical engineering which are learnt in the first 2 years of the Bachelors course.
It has been observed that many questions are asked from PHYSICAL PHARMACY and PHARMACEUTICAL ENGINEERING in the recent 2-3 years. On an average 15-20 questions are asked from these subjects out of total 125 questions thus accounting to 12-16% of the paper.
These two subjects were the most neglected ones since they were a part of first year and second year.B. Pharma curriculum and it is a particular notion amongst the students that one should focus more on third and final years of the course for GPAT preparation. But this notion is slowly fading away with the experience of past 2-3 years.
In PHYSICAL PHARMACY, try to emphasize more on the concepts and principle of the methods. Thus, 'X' method is applicable for the determination of 'Z'  becomes crystal clear if the concepts are understood. If anybody is not comfortable remembering concepts in English, they can try to translate the thoughts in their mother-tongue and easily remember the concepts since in GPAT or other competitive exams, our concepts, approach and perspective matters a lot instead of the language. 
The applications and the principle behind the working of a particular unit operation, process should be more focused in case of PHARMACEUTICAL ENGINEERING.
Specific and special constants, their values with units and formulas should be memorized.
For e.g. Viscosity of water is 0.001 Pa.s,
Reynolds number is a dimensionless unit
Sieve number and their corresponding mesh aperture size are important should also be remembered.

DISPENSING PHARMACY- Calculations of dose of drug for adult, children, infants and their subsequent formulas and a few theory are important. Atleast one of the slot may contain such numerical problems.
    Here are the topic-wise books which I would like to personally recommend for particular topics. NOTE- (APPLICABLE FOR ALL THE UPCOMING POSTS INCLUDING THIS ONE) The final right to select the book for a particular subject / topic remains with the student itself according to his needs, language, understanding of the concepts and the time and money which he would like to spend.
GPAT-2015 syllabus is a bit unorganized e.g. Microbiology, pharmaceutical jurisprudence have been included in pharmaceutics section and that too just after physical pharmacy !!!!!!!!!
So I have organized the subjects on my own way of importance but the order of sub-topics remain the same as that is mentioned in the official syllabus of GPAT-2015..

The numbers indicates here the books to refer ; the list according to the numbers is provided at the bottom.

PHYSICAL PHARMACY

Matter, Properties of Matter- 1,2

Micromeretics and Powder Rheology- 1,3

Surface and Interfacial Phenomenon- 1,3

Viscosity and Rheology- 1

Dispersion Systems- 1,2

Complexation- 1,3

Kinetics and Drug Stability- 1,3

DISPENSING PHARMACY

Prescription- 4

Pharmaceutical calculations- 5

Principles involved and procedures adopted in dispensing of :
Typical prescriptions like mixtures, solutions, emulsions, creams, ointments, powders, capsules, pastes, jellies, suppositories, ophthalmic, pastilles, lozenges, pills, lotions, liniments, inhalations,
paints, sprays, tablet triturates-  4

Incompatibilities- 4

PHARMACEUTICAL ENGINEERING (In syllabus they have mentioned under the heading- Importance of unit operations in manufacturing, Stoichiometry)

Unit processes-2, 6, 7

Fluid Flow- 6

Heat transfer- 6

Evaporation- 6

Distillation- 6, 7

Drying- 6

Size Reduction- 6

Mixing- 6

Filtration and Centrifugation- 6, 7

Crystallization-6, 7

Dehumidification and Humidity Control- 6,7

Refrigeration and Air Conditioning- 6,7

Material of Construction- 6

Material Handling Systems-6

Corrosion- 6,7

Plant location- 6,7

Industrial Hazards and Safety Precautions- 6, 7

Automated Process Control Systems- 7


BOOK REFERENCES-

1. Patrick J. Sinko, "Martin's Physical Pharmacy and Pharmaceutical Sciences", 6th Edition, Lippincott Williams and Wilkins, 2010.

2. Arun Bahl, B.S. Bahl, G.D. Tuli, "Essentials of Physical Chemistry", S. Chand Publishers, 2009.

3. C.V.S. Subrahmanyam, "Textbook of Physical Pharmaceutics", 2nd Edition, Vallabh Prakashan, 2000.

4. S.J. Carter, "Cooper and Gunns Dispensing For Pharmaceutical Students", 12th Edition, CBS Publishers, 2008.

5. H.C. Ansel and M.J. Stoklosa, "Pharmaceutical Calculations", Lippincott Williams and Wilkins, 2006.

6. C.V.S. Subrahmanyam, J. Thimma Shetty, Sarasija Suresh, V. Kusum Devi, "Pharmaceutical Engineering- Principles and Practices", 1st Edition, Vallabh Prakashan, 2002.

7. K. Sambamurthy, "Pharmaceutical Engineering", 1st Edition, New Age International Publishers, 2002.

8. David B. Troy, Paul Beringer, "Remington ; The Science and Practice of Pharmacy", Lippincott Williams and Wilkins, 2006.

This was all for today. See you next week -10th December 2014- with the next part in which we would cover- Dosage forms, Community Pharmacy and Biopharmaceutics and Pharmacokinetics.
Hope you would have liked this part...!!! Any kind of feedback and suggestions are most welcome to our team.
                                                                                          -Darwin
                                                                  [GPAT-2014- All India Rank (AIR)- 619)
                                                                        NIPER-JEE-2014 AIR-25 and

                                                                          ICT-BPT-CET-2014 AIR-7 ]
                                               Ist year M, Tech (Bioprocess Technology-BPT)-2014-16,
                                                      Institute of Chemical Technology, Matunga, Mumbai

GRADUATE PHARMACY APTITUDE TEST (GPAT)-2015 'GUIDANCE AND TIPS' SERIES

                                                              GPAT- AN OVERVIEW

       GPAT is a well-known all-India level exam conducted by All India Council for Technical Education (AICTE)- a statutory body of Govt. of India for selection of meritorious students for the post-graduate in pharmacy (M. Pharm). From the year 2013, it has been conducted as an online exam and 2015 being the third year. Previously till 2009, it was conducted in the name of Graduate Aptitude Test in Engineering (GATE) in the 'Pharmaceutical Sciences' category. Thus, GPAT came into force from 2010 for pharmacy students.
      The exam which comprises of 125 questions follows a simple formula- +4 for each correct answer, -1 for each incorrect answer and 0 for no answer . The candidate who qualifies GPAT and takes up the admission for M. Pharmacy in the selected course in a particular college receives a monthly stipend of Rs 8000/- per month from the Ministry of Human Resources and Development (HRD)- Govt. of India. However, there is buzz nowadays that the stipend amount is going to increase but that we can leave up to the government, student bodies etc. and lets not try to touch the sensitive issue surrounding it.
      Till 2012, GPAT was conducted all over India in a SINGLE SLOT on a pen-paper mode by darkening the circles of the appropriate option and comprised of 150 questions. Single slot here it means the exam was conducted all over the nation at the same time at the same day decided in the selected examination cities. But from 2013 onwards, the exam was conducted online on MULTIPLE SLOTS. Multiple slots being- Exam schedule spanning over 2-3 days (depending upon the students appearing) and each day comprising of 2 slots- one in morning and one in the afternoon.
       For OPEN and OBC category candidates, the qualifying marks are 125 out of 500 while for SC, ST and PD candidates the qualifying marks are 100 out of 500. In general, almost first All India Ranks (AIR) upto 4000 out of all the candidates appearing  qualify GPAT every year (although this is not a rule, they are estimated figures and may vary each year).
      This change of pattern was in some ways a boon for the students while for some others a curse. Lets first see the ADVANTAGES offered due to the change in pattern-

1. Less number of questions as the number reduced from 150 to 125 (anytime a welcome gift for any kind of student !!!)
2. The candidate can actually choose the day of the examination with respect to his/her preparation (many choose the last day as the get an extra day to study!!!)
3. The time taken for darkening the circles during the exam is significantly reduced giving more time to think over in the 3-hour exam.
4. Moreover, although you have selected the option previously, if you want to change your option you can easily change it by just a click.
5. There is a special bar in the right corner which shows the questions you have attempted and those you have left out. On clicking that particular question number, the question appears and thus you can view it easily. Again a significant time-saving activity instead of searching the questions left out and thinking over it.

Now for some DISADVANTAGES.....

1. Although the number of questions are reduced to 125, the exam being conducted on multiple-slot basis, the probability of questions being asked from various pharma fields/ subjects increases drastically since no question is repeated in any of the slots. E.g. Questions are nowadays asked from much neglected secondary subjects (by students) like Forensic Pharmacy and Jurisprudence, Pharmaceutical Management, Anatomy,Physiology and Pathophysiology, Pharmaceutical Engineering, Clinical Pharmacy, Hospital Pharmacy and Drug Store Management etc.
2. Although the candidate has the option to select the particular day, the chances of getting an easy or difficult paper is a total-luck based game. For e.g. it has so happened that both the slots on a particular day presented an easy paper to the aspiring students. But on the next day, the overall level of the paper was slightly difficult in the morning slot and in the afternoon slot, the level of the paper was again easy. (my personal experience !!)
3. The examination committee has to chose around unique and non-repetitive 500-750 questions. Thus focussing on only 5 main subjects- Pharmaceutics, Pharmacology, Pharmacognosy, Pharmaceutical Medicinal Chemistry and Pharmaceutical Analysis is not a good option. (If you have less time in your hand, you can really focus on these subjects and qualify).
4. No one can actually predict the number of questions coming from a particular subject in a particular paper because if around 40-50 questions are to be included from a particular subject, they are not distributed equally (most of the cases) in a particular slot. Thus if a candidate has that particular subject as his/her favorite , has studied a lot about it and unfortunately in the paper if he finds only around 4-5 questions then he/she is in a deep trouble.
5. There is a provision in GATE exam, to account for the difficulty level of question paper. GPAT doesn't take this into account. From a particular mathematical and statistical equations, all the students appearing at different slots are brought at the same platform. Thus in crude terms , we can say that overall marks are deducted from students appearing in easy exam slots and overall marks are added in students overall marks appearing in the difficult exam slots.
6. Till GPAT-2013, the examination was held in May; but from GPAT-2014, the trend is set to schedule the exam in last week of February (on the similar lines as that of GATE). Since a B. Pharmacy student can give all the three exams- GPAT and GATE (Life Sciences- XL and Biotechnology- BT), it is a really a difficult time to study for both and qualify in addition to final year study workload.     (NOTE- B. Pharma Students aspiring to do M.Tech in Biotechnology and allied course from IITs (Indian Institute of Technology) and NITs (National Institute of Technology) have to GATE only.  For others aspiring to do M.Tech in Biomedical Enginnering from IIT-Bombay, M.Tech in Bioprocess Technology (BPT) or in Green Technology from Institute of Chemical Technology, Mumbai ( ICT- formerly UDCT/ UICT ), GPAT score is acceptable.  Please check further requirements on the concerned institutes websites in eligibility criteria section).  

See you all on next Wednesday - 3rd December-2014 !! We will be starting the guidance and tips session with the most beloved and favourite subject of most pharma guys out there - PHARMACEUTICS- Heart of Pharmacy !!!
                                                                                                     -Darwin
                                                                             [GPAT-2014- All India Rank (AIR)- 619)
                                                                                            NIPER-JEE-2014 AIR-25 and
                                                                                            ICT-BPT-CET-2014 AIR-7 ]
                                                                Ist year M, Tech (Bioprocess Technology-BPT)-2014-16,
                                                                  Institute of Chemical Technology, Matunga, Mumbai

The Outbreak.

Between 1 September and 24 October 1976, 318 cases of acute viral hemorrhagic fever occurred in northern Zaire. The outbreak was centred in the Bumba Zone of the equator region and most of the cases were recorded within a radius of 70 km of Yambuku, although a few patients sought medical attention in Bumba, Abumombazi, and the capital city of Kinshasa, where individual secondary and tertiary cases occurred. There were 280 deaths, and only 38 serologically confirmed survivors. 

The index case in this outbreak had onset of symptoms on 1 September 1976, five days after receiving an injection of chloroquine for presumptive malaria at the outpatient clinic at Yambuku Mission Hospital (YMH). He had a clinical remission of his malaria symptoms. Within one week several other persons who had received injections at YMH also suffered from the same haemorrhagic fever. On further research by  United States Army Medical Research Institute of Infectious Diseases (USAMRIID) at Fort Detrick, Maryland, it was found to be a virus known as Ebola virus, whose name originates from river named Ebola which runs through Democratic Republic of Congo(then Zaire). 

    Ebola virus(Also known as EBOV) is a zoonotic virus included in genus Ebolavirus of family Filoviridae. It is a single stranded RNA virus which encodes seven structural proteins namely nucleoprotein(NP), polymerase cofactor(VP35) and (VP40), glycoprotein transcription factor (VP 30) and (VP24) and enzyme RNA polymerase. The genome of the virus is 19kb in length. It has a characteristic thread like structure and is cylindrical in shape. It contains a viral envelope, matrix and nucleocaspid components. Viral proteins VP 40 and VP24 are located in the matrix space. The nucleocaspid contains negative sense RNA without 3'-polyadenylation and 5'-capping. The RNA is hellically wounded and complexed with the NP, VP 35, VP 30 and L proteins. 

Each virion contains 18959 to 18961 nucleotides. It is found that 472 nucleotides from 3' end and 731 nucleotides from 5' end are sufficient for replication. The gene order is 3- leader- NP- VP35- VP40- sGP- VP30- VP24- L- trailer- 5'. It is found that the host encoded Neiman-Pick C1, a cholesterol transporter protein is essential for entry of virions in to the host cell and for its further replication. So, NPC1 can be a potential drug target for an Ebola anti-viral drug.

       
On infection, the virus causes an extremely hemorrhagic fever in humans and other primates. the infection mainly spreads through-

 1. Direct contact with blood or the secretions of infected person. OR

 2. The exposure to the objects like needle that have been contaminated with                                       the infected secretions.

The fatality rate of the disease was found to be 64%. The vector which was found to spread the virus is a type of fruit bat which drops partially eaten fruits and pulp on which land mammals feed. Symptoms may appear anywhere from 2 to 21 days after exposure to Ebolavirus though 8-10 days is most common.

Symptoms of Ebola HF typically include:

• Fever

• Headache

• Joint and muscle aches

• Weakness

• Diarrhea

• Vomiting

• Stomach pain

• Lack of appetite

• Rash

• Red Eyes

The main targets of the virus are endothellial cells, mono nuclear phagocytes and hepatocytes. After infection the virus synthesizes a secret glycoprotein called bola glycoprotein which takes over the protein synthesis of infected cells and host's immune defenses. The GP forms a trimeric complex which binds the virus to the endothellial cells lining. Further it forms a dimeric protein that interferes with the signalling of neutrophila which allows the virus to evade the immune system. These leukocytes also serve as carriers to transport the virions through out the body especially lymph nodes and spleen. This triggers release of cytokines like TNF-α, IL-6,IL-8 etc. which elevate body temperature and inflammation and lead to loss of vascular integrity. 

          
The diagnosis of the disease is usually done by Polymerase Chain Reaction(PCR) or ELISA. The treatment is primarily supportive in nature which includes balancing fluids and electrolytes to counter dehydration, administration of anticoagulants to prevent or control disseminated intravascular coagulation, administration of procoagulant to control bleeding, maintain oxygen levels, pain management and use of medications to treat secondary bacterial and fungal infections. Currently, many NCEs are under investigation. One July 31, 2014, an experimental drug ZMapp was first tested on two infected Americans and gave positive results. Other promising reatments rely on anti sense technology. TKPF-Ebola is a small interfering RNA compound currently tested in Phase 1 clinical trails in people. The only preventive measure which can be taken is by keeping as many infected patients as possible in the quarantine.

     The following table is the timeline of the Ebola virus outbreaks.-

Year	Country	Type	Reported human cases	Reported deaths	Fatality	Description
1976	Zaire (Democratic Republic of Congo)	ZEBOV	318	280	88%	Occurred in Yambuku and surrounding area. Disease was spread by close personal contact and by use of contaminated needles and syringes in hospitals/clinics. This outbreak was the first recognition of the disease.[10]
1976	Sudan	SEBOV	284	151	53%	Occurred in Nzara, Maridi and the surrounding area. Disease was spread mainly through close personal contact within hospitals. Many medical care personnel were infected.[11]
1977	Zaire (Democratic Republic of Congo)	ZEBOV	1	1	100%	Noted retroactively in the village of Tandala.[12]
1979	Sudan	SEBOV	34	22	65%	Occurred in Nzara, Maridi. Recurrent outbreak at the same site as the 1976 Sudan epidemic.[13]
1989	USA	REBOV	0	0	0%	REBOV was introduced into quarantine facilities in Virginia and Pennsylvania by monkeys imported from the Philippines.[14]
1990	USA	REBOV	4 (asymptomatic)	0	0%	REBOV was introduced once again into quarantine facilities in Virginia and Texas by monkeys imported from the Philippines. Four humans developed antibodies but did not get sick.[15]
1989–1990	Philippines	REBOV	3 (asymptomatic)	0	0%	High mortality among cynomolgus macaques in a primate facility responsible for exporting animals in the USA.[16] Three workers in the animal facility developed antibodies but did not get sick.[17]
1992	Italy	REBOV	0	0	0%	REBOV was introduced into quarantine facilities in Siena by monkeys imported from the same export facility in the Philippines that was involved in the episodes in the United States. No humans were infected.[18]
1994	Gabon	ZEBOV	52	31	60%	Occurred in Mékouka and other gold-mining camps deep in the rain forest. Initially thought to be yellow fever; identified as Ebola hemorrhagic fever in 1995.[19]
1994	Ivory Coast[nb 1]	CIEBOV	1	0	0%	Scientist became ill after conducting an necropsy on a wild chimpanzee in the Tai Forest.
1995	Zaire (Democratic Republic of Congo)	ZEBOV	315	250	79%	Occurred in Kikwit and surrounding area. Traced to index case-patient who worked in forest adjoining the city. Epidemic spread through families and hospitals.[21]
1996 Jan–Apr	Gabon	ZEBOV	37	21	57%	Occurred in Mayibout area. A chimpanzee found dead in the forest was eaten by people hunting for food. Nineteen people who were involved in the butchery of the animal became ill; other cases occurred in family members.[19]
1996–1997 Jul–Jan	Gabon	ZEBOV	60	45	75%	Occurred in Booué area with transport of patients to Libreville. Index case-patient was a hunter who lived in a forest camp. Disease was spread by close contact with infected persons. A dead chimpanzee found in the forest at the time was determined to be infected.[19]
1996	South Africa	ZEBOV	2	1	50%	A medical professional traveled from Gabon to Johannesburg, South Africa, after having treated Ebola virus-infected patients and thus having been exposed to the virus. He was hospitalized, and a nurse who took care of him became infected and died.[22]
1996	USA	REBOV	0	0	0%	REBOV was introduced into a quarantine facility in Texas by monkeys imported from the Philippines. No human infections were identified.[23]
1996	Philippines	REBOV	0	0	0%	REBOV was identified in a monkey export facility in the Philippines. No human infections were identified.[24]
2000–2001	Uganda	SEBOV	425	224	53%	Occurred in Gulu, Masindi, and Mbarara districts of Uganda. The three most important risks associated with Ebola virus infection were attending funerals of Ebola hemorrhagic fever case-patients, having contact with case-patients in one's family, and providing medical care to Ebola case-patients without using adequate personal protective measures.[25]
2001–2002 Oct–Mar	Gabon	ZEBOV	65	53	82%	Outbreak occurred over the border of Gabon and the Republic of the Congo.[26]
2001–2002 Oct–Mar	Republic of Congo	ZEBOV	57	43	75%	Outbreak occurred over the border of Gabon and the Republic of the Congo. This was the first time that Ebola hemorrhagic fever was reported in the Republic of the Congo.[26]
2002–2003 Dec–Apr	Republic of Congo	ZEBOV	143	128	90%	Outbreak occurred in the districts of Mbomo and Kéllé in Cuvette Ouest Département.[27]
2003 Nov–Dec	Republic of Congo	ZEBOV	35	29	83%	Outbreak occurred in Mbomo and Mbandza villages located in Mbomo district, Cuvette Ouest Département.[28]
2004	Sudan	SEBOV	17	7	41%	Outbreak occurred in Yambio county in Western Equatoria of southern Sudan. This outbreak was concurrent with an outbreak of measles in the same area, and several suspected EHF cases were later reclassified as measles cases.[29]
2007	Democratic Republic of Congo	ZEBOV	264	187	71%	Outbreak occurred in Kasai-Occidental Province. The outbreak was declared over on November 20. Last confirmed case on October 4 and last death on October 10.[30]
2007–2008 Dec–Jan	Uganda	BDBV	149	37	25%	Outbreak occurred in Bundibugyo District in western Uganda. First reported occurrence of a new strain.[2][3][4]
2008 Nov	Philippines	REBOV	6 (asymptomatic)	0	0%	Outbreak in the Philippines and the first known occurrence of REBOV in pigs. Strain closely similar to earlier strains. Six workers from the pig farm and slaughterhouse developed antibodies but did not become sick.[31][32]
2008–2009 Dec–Feb	Democratic Republic of Congo	ZEBOV	32	14	45%	Outbreak occurred in the Mweka and Luebo health zones of the Province of Kasai-Occidental.[33]
2012 Jun–Aug	Uganda	SEBOV	24	17	71%	Outbreak occurred in the Kibaale District.[34]
2012 Jun–Nov	Democratic Republic of Congo	BDBV	77	36	47%	Outbreak occurred in Province Orientale.[35][36]
2014 Mar–present	Guinea Liberia[nb 2] Sierra Leone Nigeria	ZEBOV	1779	961	54%	Outbreak is currently ongoing in Guinea (the country of origin), and the neighboring countries of Sierra Leone and Liberia. Several cases have occurred in Nigeria, in travelers from infected areas, and subsequently in health care workers.[38] This outbreak is the most severe in recorded history in regards to both the number of human cases and fatalities.[39]

  Many other countries like Germany, India, Saudi Arabia, Spain are suspected to have the Infected cases.

World Health Organization head Margaret Chan admitted that the Ebola outbreak is spreading faster than the efforts to control it. Stay Safe.

                                                                                                                 -CURIE.

(P.S.- Some of the images & information is taken from en.wikipedia.org and www.cdc.gov/vhf/ebola/resources/pdfs/ebola-factsheet.pdf)