How to prepare for GPAT?

• If you are reading this article means you have decided to attempt the GPAT.


• Well here I will be explaining step by step how to prepare for the same, so let's start.

1) Prepare your mindset:

• Yes this is the most important step.


• Tell your mind that "I am going to appear and crack GPAT no matter what?"


• Keep yourself away from negative people.


• Forget everything and concentrate only on the study now.

2) Procurement of Study Material:

• Well without weapons how can you fight right?


• Most of the students I have seen started this step by running behind seniors for the collection of so-called NOTES.


• Well I am strictly against this, instead, I strongly recommend READING and Healthy GROUP DISCUSSION.

3) List of books:

• 
  
    Pharmaceutics: Leon Lachman is the most widely used book and most referred for the exam.


• 
  
  Do all the chapters, starting from Milling, mixing to semisolid dosage forms. All the tables of Lachman are important.


• 
  
  Questions will be mostly from Lachman.


• I suggest also read from "Ansel (Capsule)", "Aulton (Tablets)"


• 
  
  
  
  Chapters: Milling, Mixing, Size reduction and separation, Drying, Filtration, Aerosols, Sterilizations, Suspension, Emulsion, Parenterals, Micro-encapsulation, Semisolids, Suppositories, compression and Consolidation, Tablets, Capsules, Coating, Liquid dosage forms, Preformulation etc.
  
  


• 
  
  Martin/Subramanyam: Subramanyam should be referred for all chapters. However, States of matter and last 2 chapters should be referred from Martin.
  
  


• 
  
  Brahmankar: Very very important book Read this book very cautiously as there are many questions prone to come from this book
  
  


• 
  
  ADME chapters, Nonlinear Pharmacokinetics, Compartment modeling (all methods like Wegner Nelson, Residual method, Loo Reigelman, NDDS, All equation of AUC, Tmax, Cmax, Clearance etc.
  
  


• 
  
  Read all dose calculations formula from RM Mehta.
  
  


• 
  
  Cosmetics: Read essential ingredients of each cosmetic formulation and their use.  
  
  
  
  
  2.)  Pharmacology:


• 
  
  Rang and Dale
  
  
  -         Tables and boxes of each chapter, bold letter points from the book.


• 
  
  Initial chapters are very important from the book like receptors, signal transduction.


• 
  
  Everything should be known about receptors.


• 
  
  Mechanism of action of drugs, classification (Refer KDT also for this), adverse effects, Specific use, haematology, vaccines etc from K.D. Tripathi
  
  
  -         Receptor- theories, type: spare, silent, orphan, pre & post synaptic.
  
  
  -          Concept of CGMP, CAMP, desensitization, tachyphylaxis , drug dependence .drug interaction.
  
  
  -         . Detail study –antimalarial, anti TB, antileishmanial, anti-diabetic bioassay


• 
  
  
  
  For detailed study I strongly recommend GOODMAN & GILLMAN,


• Also read from Barar, Satoskar.


• 
  
  
  
  3) Organic Chemistry
  
  
  -Stereochemistry (from all 3 books – Brahmankar, Morrison and Jerry March)
  
  
  - Concepts like hybridization, inductive effect, hyper conjugation, resonance, acidity and basicity comparison between heterocyclic’s, aliphatic and aromatics.
  
  
  -         Name reactions (30-35)
  
  
  -         Bio-molecules from Morrison-Boyd
  
  
  -         Glossary from Mehta and Mehta
  
  
  -         Name and formula of all the catalysts used in chemical processes
  
  
  -          All the rules in chemistry (Markovnikov, Antimarkonikov, Bredt’s etc)
  
  
  -         SN1,SN2,E1,E2, Huckel’s rule,
  
  
  -         Ester Hydrolysis mechanism, tautomerism, pericyclic reactions, Diels Alder reaction.


• 
  
  
  
  For detailed study I strongly recommend Wilson & Grisvold.


• Also read from Foye.


• 
  
  
  
   4.     Analysis:
  
  
  
  
  • Ø NMR (Kemp and Pavia): NMR values, standards, solve simple spectra’s, and instrumentation etc.
  
  
  • Do read Ravishankar.
  
  
  • Mass Spectroscopy(Pavia)
  
  
  • Ø UV (Pavia)
  
  
  • Ø IR(Pavia)
  
  
  Do read Kasture, Ravishankar and Chatwal for all chapters.
  
  
  
  
  • Ø AAS, Fluorimetry, Flame photometry etc. (Kasture, Ravishanakar, Chatwal)
  
  
  • Ø Chromatography (Kasture, Ravishanakar, Chatwal)
  
  
  • Ø Karl-Fischer
  
  
  • Ø Titrations
  
  
  • Ø DSC, TGA, XRD, FTIR
  
  
  • Ø Stability studies and its conditions and zones of stability
  
  
  •  
  
  
  • 5.  Pharmacognosy: 
  
  
  • Kokate (all chapters including marine drugs)
  
  
  Evans: Marine drugs, Quality control, Flavanoids, Caretenoids etc
  
  
  Refer Khandelwal for tables of characteristics of imp drugs, chemical tests, and Microscopies (generally type of stomata, type of leaf is asked).
  
  
  Biosynthetic Pathways, primary and secondary metabolites, Nutraceuticals, Plant growth regulators from Wallace.
  
  
  6.     Biochemistry:


• 
  
  All important chapters like Carbohydrates, protein, lipids, cell structure, vitamins, enzymes, nucleic acids, PCR, Porphyrins, metabolism cycles, Lac operon, biochemical values,


• 
  
  Biochemical Tests, Fermentation etc, industrial enzymes, vaccines and other biotech products, Electrophoresis.


• I recommend you to use Lippincott, Deb, Satyanarayan


• 
  
  
  
  7.     Microbiology:


• 
  
  Bacterial cell wall, growth, Disease-causing organisms from fungi, bacteria, Rickettsiae etc, diagnostic tests, microbial assays, Hypersensitivity, Immunology, Virus, Industrially utilized organisms.


• I recommend you to use Pelzar for microbiology.


• 
  
  
  
  8.     IP: Blue pages in it, Solubility limits, temperature limits, Dissolution apparatus, limits of tablets, capsules, semisolids etc


• 
  
  
  
  Also refer BP, USP, NF.


• 
  
  
  
  What’s NEW????
  
  
   1.     General Knowledge: Read everyday news paper. Remember current happenings.
  
  
  2.     Pharmaceutical News: Subscribe to Fierce pharmaceutical mails, Read pharmaceutical news from Economic times or another site from web.
  
  
  3.     Nobel Prize winners: Name and his work. Recent award getters and all Indian Noble prize winners and their area.
  
  
  4.     New Drugs approvals: Read the drugs approved in last 3 months and their use from USFDA site.
  
  
  5.     Regulatory: Read some guidelines and like 505b2 (Hybrid NDA), 505b1 etc.
  
  
  6.     New Drug application (NDA), Abbreviated New Drug Application (ANDA), Supplementary NDA, Emergency NDA, Treatment NDA
  
  
  7.     Intellectual Property Rights: Patents, Copyrights, Trademarks etc. Fees for patents, duration, time for processing for patent, provisional patent, WIPO, TRIPS, Mail-box applications, Orange book, Hatch-Waxman Act, Para 1,2,3, 4 and what are they used for, compulsory licence, Transfer of Technology and Capture of Technology, TRIMS, Patent Organization Treaty etc.
  
  
  8.     Full forms
  
  
   9.     Synonyms/Antonyms/ Vocabulary
  
  
   10.   Biostatistics: Mean, Median, Mode, Standard deviation, Correlation coefficients, confidence intervals, Probability, Permutation and combination, ANOVA (use, definition, and formula), t-test (Use, definition and formula) etc.
  
  
  11.  Amorphous systems: Definition, methods for amorphous generation, Glass transition (Tg), vitrification, devitrification, Methods for Tg determination etc.
  
  
  12.  Jurisprudence: Schedules, Members in committee, places of institutes, important years related to Act and laws in pharmacy.
  
  
  13.  Bank: various banks in INDIA, their CEO’s, their year of establishment and other information
  
  
  14.  World Regulatory agencies of various countries: INDIA (CDCSCO), ANVISA (Brazil), TGA (Australia), FDA (USA), EMEA (Europe).
  
  
  15.  Gene sequencing, Alignment tools etc.
  
  
   16.  Stages of formulation development
  
  
  17.  Basic knowledge about NABARD, Planning commission etc.
  
  
  18.  Symbols for amino acids
  
  
  19.  Top 10 pharmaceutical companies in India and World
  
  
  20.  Softwares
  
  
  21. Refer all previous years papers

HOW TO STUDY:

• Most of the articles suggest you divide days as per subjects etc.


• But here I will tell you to listen to your heart.


• Open the book you wanted to read start reading it, get the content understood.


• Correlate the content with other subjects.


• e.g. Reading pharmacology of antimalarials. correlate it with chemistry, biochemistry, anatomy, clinical etc.


• Get into a healthy group discussion every 4 hrs with your partner (for practice and to kill boredom).


• Keep mind fresh by changing subjects, attempting online mock tests.


• Keep the habit of daily reading at least 10 pages from random topics from book REMINGTON or SHARGEL.


• Ensure you are done with the above-given list.


• See 100% coverage is essential.

That's it for now, next article I well tell you how to write the paper. All the Best.

GPAT Test Series: Test No. 6

 

Instructions:

1. Please add your name and valid email id, both are compulsory.


2. Try to attempt all questions.


3. After completion don't forget to press "SUBMIT" button.


4. You can attempt the test minimum for 5 times.


5. Total questions are 25.


6. Total test carries 50 marks.

NSAIDs: Non-Steroidal Anti inflammatory Drugs.

NSAIDs

Non-Steroidal Anti-inflammatory Drugs.

• The pharmacological agents which relieve pain lower elevated body temperature and also produces an anti-inflammatory effect by inhibiting an enzyme cyclooxygenase (COX) are known as analgesic-antipyretic or NSAIDs.


• NSAIDs as name indicate lack steroidal nucleus and hence also lack side effects of steroids and hence are safer for use to relieve minor pains.


• Mechanism of action of NSAIDs-


• Any injury to cell cause rupture of cell membrane causing a release of Arachidonic Acid which is a component of the cell membrane.


• The released Arachidonic acid is get converted to the Prostaglandins by actions of a group of enzymes called as "Cyclo-oxygenases".


• The formed prostaglandins cause "nociception" i.e. activation of pain stimulus.


• The formed prostaglandins get circulated through the blood to the hypothalamus and cause shifting of thermal conditions of the body on higher side by acting on temperature regulating center.


• The prostaglandins are known to be main culprits behind the "Inflammation".


• Inflammation is characterized by Swelling, Redness of affected area, Heat on affected area.


• Pathogenesis of inflammation –1) Increased capillary permeability: Exodution of capillary fluid in extracellular space: Swelling.2) Chemotaxis –accumalation  WBCs at the site of injury. (Movement of WBCs (Blood) under chemical signal of body): Redness and Heat at affected area.
  
  3) Suppuration – formation of pus from cell debris
  
  4) Nociception – activation of pain.




• NSAIDs inhibit cyclooxygenase enzyme (COX) an enzyme involved in the synthesis of prostaglandin from arachidonic acid and hence relieve from pain, hyperpyrexia, and inflammation.


• Cyclooxygenase (Prostaglandin Synthetase.):


• Cyclooxygenase exist in 3 isoforms i.e. COX-I, COX-II & COX-III


• COX-I is involved in sercreation of gastric mucus while COX-II mediate inflammatory response.


• Non-selective COX inhibitors inhibit both COX-I & COX-II threby causes gastric acidosis.


• Selective COX-II inhibitors inhibit only COX-II, thereby does not cause gastric acidosis


• Anti-pyretic drugs poorly inhibits COX-II peripherally due to the presence of peroxides but inhibit COX-III in hypothalamus in brain to reduce elevated body temperature up to normal


• Protelytic enzymes viz. chymopapain, serratiopeptidase cause breckdown of collgen at the site of inflammation , when combines with conventional NSAIDs i.e.Nonselective COX- inhibitors increases vascular permeability and reduces swelling.

Classification of NSAIDs:

1) Non-selective COX inhibitors or conventional NSAIDs

1.  Salicylic acid derivatives e.g. Aspirin, sodium salicylate, methyl salicylate


2.  P-amino phenol derivatives e.g. Paracetamol, phenacetin


3. Pyrazolone derivatives e.g. Phenylbutazone, oxyphenbutazone


4. Indole derivatives e.g.Indomethacin, sulindac


5. Propionic acid derivatives e.g. Ibuprofen, naproxen, ketoprofen, fenoprofen


6. Anthranilic acid derivatives / Fenamates e.g. mefenamic acid, flufenamic acid


7. Arylacetic acid derivatives eg. Diclofenac, ketorolac, Flufenac


8. Oxicams e.g. Piroxicam, tenoxicam, meloxicam, Lornoxicam

2) Selective COX –II inhibitors e.g. Celecoxib, Rofecoxib, Valdecoxib, Etoricoxib 

3) sulfanilamide e.g.Nimesulide

4) Anti-inflammatory Potentiator e.g. serratiopeptidase, chymotrypsin, Rutoside(Rutin), Bromelain

5) Miscellaneous e.g. Gold

PHARMACOLOGICAL  ACTIONs OF NSAID’S:  

Prototype drug: Aspirin.

1) Analgesic, Antipyretic and anti-inflammatory action:-

• The analgesic action of NSAID’S is predominantly peripheral i.e. inhibition of prostaglandin synthesis and release.


• They are mainly effective for relieving dull pains related to joints, muscles, nerves, bodyache and toothache.


• NSAID’S reduce elevated body temperature up to normal in fever by resetting thermostatic center in the hypothalamus at a higher level thus their antipyretic action is central.


• It exerts anti-inflammatory action at higher doses (i.e. aspirin 3-6 g/day). Signs of inflammation like pain tenderness, redness and localized swelling are suppressed.

2) Respiration:-

• Salicylates are respiratory stimulants, salicylates stimulate respiration by


• Direct action on medullary respiratory center.


• Indirect action by increasing plasma carbon dioxide concentration.

3) Gastrointestinal Tract:-

• The ingestion of salicylates may produce dyspepsia, epigastric distress, nausea and vomiting as a result of gastric irritation.


• sometimes may produce peptic ulceration with G.I bleeding leading to hematemesis (hemat-blood, emesis-vomitting) at high dose.


• The action is due to two facts,


• 1) Aspirin (Acetyl Salicylic Acid) is itself acid, on an empty stomach if taken causes gastric acidosis.


• 2) Aspirin being a nonselective COX inhibitor inhibits both COX-I and COX-II, as COX-I is needed to maintain gstric integrity of gastric mucosa their lack leads to the gastric ulceration.

4) Blood System:-

• Salicylates reduce platelet aggregation (at low dose), promotes fibrinolysis, prolongs bleeding time by interfering with the formation of thromboxanes (TXA2); a chemical mediator essential for platelet aggregation.


• Hence act as "Antiplatelet" at low dose i.e. 75mg.

5) Uricosuric Effect:-

• Salicylate in small dose  1-2g/day increases plasma urate level by blocking tubular secretion of uric acid. i.e. uric acid retention.


• Salicylates in large doses 5-6g/day increases urate excretion by inhibiting reabsorption of uric acid.  i.e. causing uric acid excretion.


• Thus, the large dose is uricosuric and smaller doses cause retention of uric acid.


• Hence large doses are effective in treatment of "Gout".

6) Metabolic Effect:-

• Salicylate causes conversion of large part of energy (derived from oxidation) into heat by uncoupling of oxidative phosphorylation.


• This is one of the causes of hyperpyrexia following large dose of salicylates. (Salicylte Poisoning).

ADVERSE EFFECTS:-

1) Gastric acidosis leading to epigastric distress, nausea, vomiting and headache long-term therapy may cause a peptic ulcer and G.I hemorrhage.

2) Hypersensitivity reaction like skin rashes, urticaria, pruritus, bronchospasm etc

3) Kidney failure.

4) Liver damage.

5) In pregnant women: by inhibiting prostaglandin synthesis in the uterus may delay the onset of labor & cause greater blood loss at the time of delivery.

CONTRAINDICATIONs:-

1) Known hypersensitivity to any NSAIDS.

2) Peptic ulcer or gastric acidosis or hyperacidity.

3) Liver failure (liver cirrhosis).

4) Kidney failure (renal impairment/acute nephritis).

5) Bronchial asthma.

6) Pregnant women.

THERAPEUTIC USES OF ASPIRIN:-

1) As an analgesic and antipyretic.

2) As Antirheumatic in acute rheumatic fever.

3) As an antiplatelet agent in coronary thrombosis.

4) As anti-inflammatory and anti-gout agent. (at high dose)

5) Local applications as keratolytic, fungistatic and antiseptic. (Salicylic Acid)

6) As counter-irritant and rubefacient eg.methyl salicylate

DRUG INTERACTIONS OF SALICYLATES:-

1) It displaces warfarin, sulfonylurea and phenytoin from plasma protein binding site thus toxicity of these drugs may occur.

2) It reduces effects of diuretics like furosemide and spironolactone by inhibiting tubular chloride reabsorption.

3) Glucocorticoids may decrease salicylate concentration.

Pharmaceutical Calculations

Structure of Proteins

Proteins:

Proteins are large biological molecules consisting of one or more chains of amino acids.

Amino Acids:

Amino acids are biologically important organic compounds made from amine (-NH2) and carboxylic acid (-COOH) functional groups, along with a side-chain specific to each amino acid.

Structure of Proteins:

• A protein function depends upon on its specific conformation.


• The primary structure of a protein is determined by the gene corresponding to the protein. In molecular biology, protein structure describes the various levels of organization of protein molecules, which includes:-

• Primary structure

• Secondary structure


• Tertiary structure


• Quaternary structure

Primary Structure

• The primary structure of proteins is the unique sequence of amino acids.

 

Secondary Structure

• The secondary structure of protein results from hydrogen bond at regular intervals along the polypeptide backbone.


• The typical shapes that develop from the secondary structure are:-

1. An Alpha Helix (Coil)


2. Beta Pleated Sheet (Fold)

 

Tertiary Structure

• Tertiary structure refers to a three-dimensional structure of a single protein molecule.


• The tertiary structure of protein results from varieties of attraction between the R groups or between the R group and the polypeptide backbone.


• The interactions includes

1. Hydrogen Bonds (among polar areas)


2. Ionic Bonds (among charged R – group)


3. Hydrophobic interactions (among hydrophobic R-group)


4. Van Der Waals Interactions (among hydrophobic R-group)


5. Disulfide bridges (Strong covalent bond that forms between sulfhydryl groups (SH) of cysteine monomers, stabilize the structure)

 

Quaternary Structure

• Quaternary structure results from the aggregation of two or more polypeptide subunits.


• The quaternary structure is stabilized by the same non-covalent interactions and disulfide bonds as the tertiary structure.

Examples:

Hemoglobin 

• The protein hemoglobin is made up (primarily) of 4 polypeptides.


• Typically, when a protein is made up of multiple polypeptides, each polypeptide is simply called a protein subunit.


• However, in the case of hemoglobin, the subunits are each called globin.


• 


• The 4 globins are of two types.  2 of them with identical amino acid sequences (primary structure) are called alphaglobins (a-globins), while the other 2 also have identical amino acid sequences and are called beta-globins (b-globins).


• Every hemoglobin molecule contains 2 a-globins and 2 b-globins.


• Each of the globins is folded into a secondary and tertiary structure.


• Then, all four are put together into the hemoglobin molecule's quaternary structure.

Insulin 

• Insulin is composed of two peptide chains referred to as the A chain and B chain.


• 


• A and B chains are linked together by two disulfide bonds, and an additional disulfide is formed within the A chain.


• In most species, the A chain consists of 21 amino acids and the B chain of 30 amino acids.


• It is a dimer of an A-chain and a B-chain, which are linked together by disulfide bonds.

Albumin

• The general structure of albumin is characterized by several long α (alpha) helices, this allows it to maintain a relatively static shape, something essential for regulating blood pressure.


• Serum albumin contains eleven distinct binding domains for hydrophobic compounds. One hemin and six long-chain fatty acids can bind to serum albumin at the same time.

Myoglobin (Does not Possess Quaternary Structure)

• Myoglobin consists of a single protein chain with 153 amino acids and one heme group that stores oxygen in the muscle cells.


• 


• Myoglobin has a stronger affinity for oxygen than hemoglobin, which enables the oxygen to shift from one to the other.

 

Globulin 

• It has helices and strands, 13 and 19 respectively.


• The major beta-sheets of globulin are named the A-sheet and the B-sheet.


• The 13 helices are each lettered beginning with letter A.


• The molecule has five cysteine residues but has no disulfide bonds; so sulfur so is not responsible for holding together globulin structure.