gpat Niper an Over View

Chirag gohil

www.pharmaaspirants.com Page 1

GENERAL OVERVIEW FOR

GPAT & NIPER

Prepared by: Chirag gohil M.Pharm(Chemistry)

Chirag gohil


INDEX :-

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(1) Pharmaceutics

(2) Pharmacognosy

(3) Pharmacology

(4) Pharma-analysis

(5) Microbiology

(6) Forensic pharmacy

(7) Bio.chemistry

“Challenge Is Fun”

Chirag gohil


PHARMACEUTICS C.J.gohil...303

Types of tablets:-

(a) Compressed (For oral) :-

(1) Compressed tablet

(2) Multi compressed tablet(MCT)

(3) Multi layered tablet

(4) Sustained action tablet

(5) Enteric coated tablet

(6) Sugar coated tablet

(7) Film coated tablet

(8) Chewable tablet

(9) Press coated/dry tablet

(b) For oral cavity :-

(1) Buccal tablet

(2) Sublingual tablet

- Glyceryl trinitrate

- Iso-prenaline

- Nifedipine

(3) Lozenge tablet & torches

(4) Dental cones

(c) For other routes :-

(1) Implants(sterile dosage forms)

- Steroid implants

(2) Vaginal tablet(pessaries)

- Mycostatin

(d) Used to prepare solution/moulded tablet :-

(1) Effervescent tablet

(2) Dispensing tablet

(3) Hypodermic tablet(sterile tablet)

(4) Tablet triturates

Granule/bulk density is determine by Pycnometer

Instruments used to evaluate friability of tablet :-

(1) Roche friability tester

(2) Webster friability tester

(3) Van abbe friability tester

F = 10 (1 – W/W0)

- Permissible wt. Loss in friability test = 0.5 – 1 % for 100 RPM

- Permissible wt. Loss in friability test = 1 - 5 % for 10 min revolution

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Instruments used to evaluate Hardness/Crushing strength of tablet :-

(1) Monsanto tester

(2) Strong cob tester

(3) Pfizer tester

(4) Erweka tester

(5) Schleuniger tester

Hardness of tablet :-

(a) 2 kg :- soft tablet

(b) 4 kg :- satisfactory tablet

(c) 6 kg :- hard tablet(may not dissolved/disintegrate)

Disintegration time of vaginal tablet :- 30 min

Disintegration time of soluble & dispersible tablets :- 3 min

Higher the HLB scale,higher will be the polarity of surfactant

Liquid mixer(Propeller type) :-

- Push-pull

- Baffled

Solid mixer(agitator type) :-

- Ribbon blender

Semi-solid mixer(Agitator type) :-

- Sigma blade

(shear type) :-

- Triple roller

- Colloid mill

- Siversion mixer

- Emulsifier

MCC :- direct compresible diluents

Validation of filtration is done by using following micro-organism :-

- Bacillus Stearothermophilus

- Pseudomonas Diminuta

HEPA filter should be change when velocity of air fall below 22 m/min &

Should be started 15 min. Before use

flavours used in granulation step are oils in nature

maximum limit of flavour added in granulation step ----- > 0.5 – 0.75 %

Micro-capsule :- 1 – 500 µ size

For vatirnary use,3 larger capsule shells are available for 5 to 30 gm doses

Bloom strength of gelatine is in b/w 150-250 gm

Gypsum = Caso4

Freezing point of blood serum & tears = 0.52` C

Molarity of body fluid is 0.3 M

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Methyl paraben = water soluble preservative with Ar – Ring

Methyl paraben used in liquid oral preparation

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Alcohol & phenytoin ----- > zero order metabolism & excreation

Creatinine clearance :- women :- 85 – 112 ml/min

Men :- 97 – 140 ml/min

4 half life require to complete elimination of drug

Neosomes made from surfactant like Tween-80

Propellants for inhalation :-

Particular Number of perticualr atoms

Determination of chemical composition of propellant from its number :-

- 1st digit :- No. Of carbon

- 2nd digit :- No. Of hydrogen

- 3rd digit :- No. Of fluorine

Manitol is 72 % as sweet as sucrose

Aspartam(instable in moisture) is 200 times sweet than sucrose

Saccharin is 500 times sweet than sucrose

Propellant 11 3 Cl 1 F Methane

Propellant 12 2 Cl 2 F Methane

Propellant 114 2 Cl 4 F Ethane

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PHARMACOGNOSY

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Precursor Amino acid & Its Product :-

L .Tyrosine ------- > Dopamine

Tyrosine + Phenylalanine ------- > Colchicine

------- > Cinchona

Thebain Ephedrine

L . Thyroxine L.S.D

Tryptophan + Tryptamine ------- > Reserpine

Precursor of Vinca alkaloids

Auxin &

Indole acetic acid

Phenylalanine + Ornithine ------- > Atropine

Tropane alkaloids

Dopamine + Secologanin ------- > Ciphaelin

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Mevalonic acid ------- > Aglycone of Cardiac glycoside

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Shikkimic acid ------- > C6 – C3 units

------- > Amino acid

Glycine ------- > Chlorophyl

Cysteine + Valine ------- > Penicillin ring

Lysine ------- > Lobeline

L . Serine ------- > Ach

Drug – Retonavir & Dapson derived from Phenylalanin

Chemical classification of Alkaloids:-

(1) Quinoline

- Quinine

- Quinidine

(2) Iso-quinoline(Spasmolytic)

- Papaverine

- Emetine

(3) Imidazole

- Pilocarpine

- Jaborandi

(4) Indole

- Reserpine

- Eserine

- Ergot

- colchicine

- Vinca alkaloids

- Nux vomica alkaloids

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(5) Pyridine

- Lobeline

(6) Pyridine-pyroline

- Atropine

- Nicotine

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(7) Phenanthrene(spasmogenic)

- Morphione

- Codeine

- Thebaine

Pseudo alkaloid & proto alkaloid :- ephedrine

Fusion of steroid rings :-

A/B = cis

B/C = trans

C/D = trans

Ring fusion in cardiac glycoside :-

A/B = cis

B/C = trans

C/D = cis

Resin :- organic acid,alcohol,ester & neutral resin

(1) Acid resin(colophony)

(2) Ester resin(benzoin)

(3) Resin alcohols(balsam of peru)

Shellac is resin,which is being used as enteric coating material

Most Plant contain β-glycoside

Ex :-

- Salicin

- Amygladin

Flavonol glycoside

Ex :-

- Rutin

- Hesperidin(Vitamin P/permeability factor)

Alcohol glycoside

Ex :- salicin(anti-rheumatic property)

Terpenoids :-

(1) β-amyrine

(2) α-amyrine

(3) lupol

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Flavones/flavonoids are colouring principle & also have a anti-inflamatory property

Hyoscine = scopolamine

Digoxin is most potent among all cardiac glycoside because it contain additional –OH at C12

position

In cardiac glycoside,less Sugar ----- > more potent

Callus tissue = nurse tissue

Morphine & Heroine diff. By Acetyl group at C3 & C6

Cocaine is amino alkyl ester benzoic acid

Morphine + Con.HCL & 140` C ------- > Apomorphine

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Codeine + NaOH ------- > ppt.

Dipentene ------- > Racemic Limonene

α – terpineol --- dehydration--- > Limonene + nitrosyl chloride ------- > colourless adduct

α – pinene + alcoholic H2SO4

Dibromomenthone + quinoline = thymol

Menthone + Oxi. With KMO4 ------- > keto acid ------- > β – methyl adepic acid

Adipic acid + heating = cyclopentanones

Caffeine + Oxidation = 1,3 – dimethyl alloxan & monomethyl urea

Fructose + Nitric acid = glycolic acid & tartaric acd

Sorbitol & mannitol

Morphine + distillation = phenanthrene

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PHARMACOLOGY C.J.gohil...303

Protein kinase C ------- > release Ca+2 ------- > bind with calmodin

Activates Na. Synthase enzyme

Increase Na. Ions ------- > Vasodilation

Choline + Acetyl group ------- > Ach

Acetylcoenzyme - A + choline acetyl transferase or acetylase ( CAT )

Ach + cholinesterase = choline + acetate

Anti-cholinesterase used in Myesthenia grevis & glaucoma

Anti-cholinesterase act on Neuromuscular junction

Anti-cholinergics act on postganglionic nerve & antagonise muscarinic action,so that they

are anti-muscarinic agents

2 moles of Ach. = succinylcholine

At ganglion level,transmitter is Ach & receptor is Nicotinic

Atropine causes loss of accommodation

Atropine use in narrow angle glaucoma

Loss of accommodation doesn’t happen in sympathomimeticss

Adrenalin produce hypokalemia

Adrenalin & Nor-adrenalin = prevent bleeding after tooth extraction

β 1 receptor present in heart

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β 2 receptor present in smooth muscle

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Plasminogen activated by fibrinolytic agents

Plasmin

Degraded product < --------- > fibrin --------- > splits of fibrin

Penicillamine = metabolite of penicillin & analogue of the amino acid Cysteine

Metal chelating property Used in Wilson’s disease (hepatolenticular degeneration)

Copper poison

Chemotherapeutic Index = Margin of safety

Anorexia = Loss of appetite

Pheochromocytoma = tumor of adrenal medulla

Types of cells in blood & its % :-

(1) Granulocytes –

(a) Basophils = 0 – 1 %

(b) Eosinophils = 0 – 5 %

(c) Neutrophils = 50 – 70 %

(2) Non-granulocytes –

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(a) Monocytes = 0 – 10 %

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(b) Lymphocytes = 20 – 40 %

Hb Con. ----- > women :- 12-14 gm/100ml

Men :- 14-16 gm/100ml

Nitrogen bases in DNA :- GC AT

Nitrogen bases in RNA :- GC AU

Agents act through Ligand-gated ion channel :-

- Nicotinic

- 5-HT

- GABAA

- Insulin

Agents act through G-protein coupled receptor :-

- Epinephrine

- Dopamine

- TSH

- AT1

- Muscarine

- α receptor

- β receptor

- H2 receptor

Aspirin inhibit COX in platelets & vascular endothelium

Aspirin inhibit TXA2

D – isomer of Dextromethorphan is Anti-tussive

L – isomer of Dextromethorphan is Analgesic

Chloramphenicol effective against typhoid/enteric fever

Chloramphenicol is now produce by chemical synthesis process

Phenergant + Chlorpromazine + Pethidine decrease the body temperature 3`C

Lithium is used in maniac depressant illness

Phenothiazides ( chlorpromazine ) & other anti-depressant ------- > Wt. Gain

Serotonin is also known as 5-HT

Serpine’s action = hit & run

Diamond – Blackfan anaemia = congenital (erythoid) hypoplastic anemia

Ig G = Rheumatic factor

Ig A = present in the body secreation such as sweat,tears,nasl secreation

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Monosodium salt of glutamic acid,MSG or Accent used as a condiment & food flavour

enhancer.

MSG/Accent obtain by the hydrolysis of Glutin or Soyabean cake.

Exess of MSG causes “Chinees restaurant syndrome”

D(-) Glutamic acid is not effective in enhancing food flavour

Homovanilic acid is metabolite of Dopamine

Beans contain Dopamine in their pods

Dopamine depleting drugs increase the prolactin secretion

MAO inhibitor increase Na. Level in blood

Patient who is taking Anti-depressant (MAO inhibitor) should not take Cheese,

Because Chees contain Tryptophan & in the body following process occur...

Tryptophan ------- > 5 – HT ------- > increase blood pressure ------- > Haemorhagess

Adr. & 5 – HT act on ------- > MAO – A (in liver & gut)

Dopamine act on ------- > MAO – B (in brain)

Piracetam = cognision enhancer / Nootropic agent

K+ depleting diuretics,steroids,reserpine & catecholamine increase Digitalis toxicity

Human eye do not detect the particle smaller than 50 µ

Quinoline = D - isomer of Quinine

Warfarin inhibit Vit.K in liver

Fibrinolytic agents should be given within 2 Hr of stroke & it should be used with Aspirin

Immune component & its role :-

Ig G = neutralise toxins

Ig A = anti-microbial

Ig M = agglutinating & cytolytic

Ig E = allergic

Stages of allergy :-

- Anaphylaxis

- Cyto-toxic

- Complement system

- T – cell activation

General consideration consider the Diastolic B.P because systolic B.P is fluctuating.

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Ca+2 channel blockers ------- > -ve inotropic & chronotropic effect in heart

1st discovered Ca+2 channel blocker is Verapamil (der. Of papaverine)

Ca+2 channel blocker bind with subunit of L – type of Ca+2 channel

In cardiac muscle,extracellular Ca ion = excitation &

,intracellular Ca ion = contraction

Deposition of lipids in skin & tendons = Xanthomas

Digitalis inotropic action (increase force of contraction of heart)

Negative chronotropic action (decrease heart rate)

Uricosuric drugs = which dissolve & excreate uric acid & decrease uric acid synthesis

Used in Gout

Ex. Of uricosuric drugs :- salicylates

Proben acid

sulphin pyrazole

allopurinol

M.O.A of Salicylates – Inhibit absorption of uric acid by proximal tubule,

Which is greater than inhibition of Urate secretion.

Hence there is a Uricosuric actionLeukotriens antagonist are used in aspirin induce asthma

M.O.A of ketoconazole(antifungal) :- inhibit sterol 14 – α – demethylase

M.O.A of heparin :- binding to anti-thrombin-3

M.O.A of Sildenafil ----- > release NO

Use :- erectile disfunction in men

Decrease blood pressure

Cardio selective β-blocker drug with vasodilating property is Nebivolol

Churg – strauss syndrome = vasculitis with eosinophilia

Inositol deficiency causes loss of hair

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Chemical name of histamine :-

5-(2-aminoethyl) imidazole/β-imidazole ethylamine

L – Histidine ----- > decarboxylation ----- > Histamine

H1 receptor ----- > smooth muscle contraction

Oxytocine,vasopressin & hormone releasing factors are neuro hormones

Anabolic effect :- body growth

Hyper GH in young ----- > Gigantism

In adults ----- > Acromegali

Hypo GH in young ----- > Dwarfism

In adults ----- > Acromicra

Insulin & penicillin-G ----- > hyperkalemia

In insulin,two peptide chains are joined by sulphur bridge b/w cysteine residue

Diabetes :- above 10 % sugar in urine

Fasting blood sugar level above 120 mg % or

post prandial(after meals) – 180 mg %

Diabetes mellitus may be 2nd condition like

Cushing’s syndrome,pheochrochytoma,stress,pregnancy,

Diuretics,analgesics,psychoactive drugs

Types of glucose transporter & its location in body :-

Glut 1 :- in most tissue

Glut 2 :- in liver & pancreatic B-cells

Glut 3 :- in brain

Glut 4 :- in heart,adipose tissue & skeletal muscle

Hypo-Lipidemic Drugs:- M.O.A...

Nicotinic acid = increase HDL level,decrease triglyceride & Lp(a)

Fibrates used in type-3 hyperlipoproteinemia & severe hyper-triglyceridemia

Fibrates act on PPAR-α receptor

decrease triglyceride Con. & increase HDL-C Apo – 1 & 2 = increase plasma HDL Con.

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Niacin = inhibit VLDL secretion,decrease LDL level & increase HDL level

Lipoprotein lipase + VLDL = Clearance

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Anti Diarrhoeal :-

- In Diarhoea,for rehydration “Dhaka Fluid” is Used,which is given through I.V rout Constitution of Dhaka fluid -

Particulars Quantity Nacl 5 gm

Kcl 1 gm

NaHco3 4 gm

For diarrhoea “WHO” recomded “ORS (Oral Rehydration Salt/Solution)”

Constitution of ORS –

Particulars Quantity Nacl 2.6 gm

Kcl 1.5 gm

Trisodium Citrate 2.9 gm

Glucose 13.5 gm

Water 1 lit.

Diuretics :- Acidifying diuretics – irritate & affect gastric mucosa so it is used as a Enteric coating

Acidifying diuretics used in metabolic alkalosis caused by mercurials

M.O.A –

(1) NH4Cl = NH4+ + Cl- (2) H2Co3 = H+ + HCo3

_

converted into the Urea in liver & act as Diuretic

H+ + Cl- -------- > Acidic

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So NH4 secretion is occur & Na+ is reabsorb

NH4Cl ------- > Retain water ------- > Diuresis

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M.O.A of Carbonic anhydrase inhibitor Diuretics –

Co2 + H2o ---- Carbonic anhydrase ---- > H2Co3

H+ + Hco3-

C.A Inhibitors inhibit this step,

so dieresis occur

Secreation of H+ & Na+ reabsorption

So,Na+ & HCo3- retain & take water,so dieresis occur & also K+ excreation is occur

Cause Metabolic acidosis

M.O.A of Loop Diuretics –

Loop diuretics act on “Distal Convulated tubule”

Loop Diuretic inhibit absorption of Na+ & Cl- and it cause Na+,K+,Mg+,Ca+& Cl- excreation,

So Nacl retaintion produce diuretic effect

M.O.A of Thiazide diuretics –

Thiazides contain Unsubstituted Sulfonamide groups & heterocycles

Act on “Distal Convulated tubule”

M.O.A of K+ sparing diuretics –

It antagonise the effect of “aldosteron,Renin or Ag – 2” so Na+ excreation is occur which is

responsible for diuretic effect & it retain K+

- > Effect of Aldosteron = Reabsorb Na+ & K+ excreation

M.O.A of Mercurial diuretics – It is potent diuretic & act on proximal convulated tubule

Mercurial act on Sulph-hydryl enxyme of proximal tubule ------- > Suppress reabsorption of

water ------- > Diuresis

Increase excreation of Na+ & Cl-

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Opioids :-

In stomach,secreation of bicarbonate is control by endogenous opioid peptides,

Like β-endorphin

Vasoactive intestinal petide(VIP)

Pethidine = dolantin = mepiridine =isorepecaine

Opioids = Enkephalins

Analeptics like strychnine & pentylenetetrazole are used to produce practically induce

seizure

The drug which is effective in electrical induce seizure

Beneficial in Grand mal epilepsy

The drug which is effective in Chemical induce seizure

Beneficial in Petit mal epilepsy

Capsacin (pepper) produce pain by releasing substance – P & other peptide from neurons

Endogenous opioid peptides – (1) Enkephalins

(2) Endorphins

(3) Dynorphins

Phenanthrene ------- > spasmogenic

Iso-quinolin -------- > Opioid analgesic

Spasmolytic

Apomorphin :- Dopa agonist

Chlorpromazine :- Dopa antagonist

Inhibition of Dopaminergic neuron ----- > Prolactin secretion

General Anaesthetics :-

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Basal anaesthetics cut off the require quantity of anaesthetics & produce partial

anaesthesia

Basal anaesthetics ------- > bromethol

Paraldehyde

Ultra short acting barbiturates

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Stages of anaesthesia :-

(1) 1st stage :- Analgesia

(2) 2nd stage :- Excitment or Delirium

(3) 3rd stage :- Surgical Anaesthesia

- Plane 1

- Plane 2 :- Ideal stage for surgery

- Plane 3 :- More ideal stage for surgery

- Plane 4

(4) 4th stage :- Respiratory paralysis

Local anaesthetics also produce ------- > anti-epilectic & anti-arrhythmic effect

Treatment of methyl alcohol poisoning ------- > ethyl alcohol (partial treatment)

4 – methyl pyrazole (Complete treatment)

Types of Epilepsy –

(1) Focal Or partial

(a) Cortical or jacksonian motor epilepsy

(b) Temporal or psychomotor epilepsy

(2) Generalised

(a) Grand mal

(b) Petit mal (Ab.seizues)

Chemotherapy :-

Anti-biotic :-

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Penicillin obtain from penicilliume notatum & penicilliume chrysogenum

Penicillin-G :- benzyl penilline

It causes Jarisch Herxheimer reaction(increase sensitivity of syphilitic reaction)

It also causes hyperkalamia

Cephalosporin is obtain from cephalosporium acremonium,

It is substituted 7-amino cephalosporamic acid

Used:- hospital acquired infection

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Erythromycin obtain from streptomyces erythreus,

Destroy by gastric acid ----- > so given as a enteric coated tablet

It causes Arrhythmias

Aminoglycoside

- Streptomycine

It is obtain from streptomyces griseus

In this 2 or more amino sugars joined by glycosidic linkage to a hexose nucleus,

In it Hexose may be streptidin or 2-deoxy streptamine

Tetracyclines obtain from the streptomyces aureofaciens & streptomyces rimosus

Use :- to detect cancer cells of lung or gastric cancer Because it produce brilliant yellow-gold

fluorescence

Chloramphenicol obtain from the streptomyces venezuale

Acetyltranferase inactivate the drug

Adverse effect :- bone marrow dipression

Gray baby syndrome

Antibiotic combination & its effect :-

(1) Synergism :-

Penicillin + streptomycin

Penicillin + sulphonamides

Gentamycin + carbenillin

(2) Additives(not beneficial)

(3) Antagonism :-

Penicillin + chloramphenicol

Ampicillin + chloramphenicol

Sulfonamides act by substrate competition

Sulfonamides antagonise by Pus(pus contain PABA)

Local anaesthetics Procaine

PABA ester

Quinolonea ----- > CNS stimulation

CNS toxicity is increase by NSAID

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Anti-T.B :-

T.B is cause by the microorganism mycobacterium tuberculosis &

Mycobacterium avium

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Newer anti-T.B agents :-

- Clarithromycin

- Azithromycin

- Rifabutin

M.O.A :- (1) Rifamycin :- inhibit DNA dependent RNA polymerase

Protein synthesis at transcription level

(2) Isoniazid :- effective against intracellular macrophages

Inhibit phospholipids & mycolic acid cell wall,

DNA & RNA synthesis.

Chelates with cations for bacterial metabolism

Side effect :-

CNS stimulation – euphoria

(3) Ethambutol :- inhibit mycolic acid incorporation in cell wall & RNA synthesis

It is concentrated in RBC

(4) Pyrazinamid :- act against intracellular macrophages(highly lethal)

It is synthetic analogue of nicotinamide

Inhibit fatty acid synthase-1 gene involve in mycolic acid biosynthesis

(5) Ethionamide :- it is derivative of isonicotinic acid

Act against extra & intra cellular macrophages

Anti-leprosy :- It is cause by mycobacterium Leprae/acid fast – ve bacilli

Dapson is used in leprosy

M.O.A of Dapson is same as sifonamides

Anti-Malaria :-

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Parasite :- genus plasmodium falciparum(cerebral malaria),vivax,ovale & malariae

Carrier – Female Anapheles mosquieto

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Life cycle of malarial parasite –

(1) Schizogony –

Sporozoits(in blood) ------- > cryptozoites(in liver) -------- > schizogony(in RBC)

Schizont(chromatin devide in number of cells) < ------- Trophozoites(ring form)

Merozoites(tiny malarial parasite)

Metacriptozoites(Further infect RBC/liver cells)

(1) Gametogony –

Merozoites

Meiotic divison

Male gametes(microgamets) female gamets(macrogamets)

Zygote(in stomach of female Anapheles)

Oocyst(cyst form of zygote)

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(2) Sporogony –

Oocyst ------- > sporozoites

# M.O.A of anti-malarial drugs –

(1) Quinine –

decrease activity of protoplasm,nutrition,reproduction & motility

inhibit metabolism & carbohydrate metabolism

& decrease C02 uptake

(2) Chloroquine – Curare-mimetic action

Bind with nucleoprotein

Inhibit RNA,DNA activity

Also inhibit dihydrofolate reductase

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(3) Pyrimethamine – inhibit dihydrofolate reductase

& other der. Act on both erythroid & ex0-erythroid so it is suppressive & curative

(4) Mefloquine – bind with haem & form toxic complex ------- > damage membrane

(5) Artemisinin - it is a sesquiterpin lactone of Chinese drug,

bind with haem & form toxic complex ------- > cleavage of peroxide brodge &

generation of an organic free radical

Anti-Viral :- Herpis type 1 Virus cause the genital herpis &

Herpis type 2 Virus causes mucocutaneous(lips & gums) herpis

PCM,nephrotoxic drug,myelosuppressive drug & probenacid increase the toxicity of

Ziduvudine

Azole anti-fungal inhibit ziduvudin metabolism

Interferon is the Host specific drug not virus specific

Interferon receptor :- JAK – STAT tyrosine protein kinase

Anti-retroviral drug combination to be avoided :-

(1) Zidovudine + stavudine :- Ph.dynamic antagonism

(2) Stavudine + dadanosine :- increase toxicity(lactic acidosis)

(3) Lamivudine + didanosine :- clinically not additive

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Anti-Diabetic – Insulin increases the K+ absorption

M.O.A of Insulin secretion inhancers :- Ex :- sulfonyl urease (sensitise β cells to glucose)

meglitinides

Pancreatic β cells ------- > K+ channel blockage

Depolymerisation

Ca+2 influx

Insulin secreation

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Addition disease occur because of Mineralocorticoids

Cushing syndrome occur because of corticoids

Insulin glargin ia same as Insulin aspargine,

But in insulin glargine at A21 is replace by glycine & 2 arginase are added to C- terminus,

The β – chain than human insulin

M.O.A –

(1) Sulfonyl urease is Teratogenic drug & used in type-2 diabetes

(2) Metformin – phenformin withdraw because it cause lactic acidosis

Inhibit gluconeoginesis,increase glucose utilisation & glucose transport,

Increase insulin binding timits receptor,

insulin mediated glucose metabolism,decrease glucose absorption in

type1 & 2

(3) Thiazolidindiones (insulin sensitiser) – potent agonist of PPAR (receptor for insulin

action) & glut-4

It causes upper respiratory tract infection

(4) Meglitinides/repaglinide(pancreatic secretogouges) – increase insulin secreation & β-

cell activity

(5) Acarbose – inhibit α-glucosidase,an enzyme that increase ab. Of glucose at G.I.T

Anti-Cancer :- Cell cycle :-

S phase

(synthesis of DNA occur)

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G 1 phase G 2 phase

(pre DNA synthesis phase) (post DNA synthesis phase)

(cellular components required for

DNA synthesis are synthesis) (synthesis of cellular

components for mitosis)

Mitosis

folinic acid & thymidine reverse toxicity of Methotrexate

thymidine reverse toxicity of fluorouracil

6 – mercaptopurine is metabolise by Xanthine oxidase

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radio active iodine(I131):- fission product of uranium &

neutron irradiation of tellurium

P32 & 198Au are short live isotopes,with 2-7 days half life

M.O.A :-

(1) Pyrimidine antagonist :-

Fluorouracil ----- > nucleotide 5-fluoro-2-deoxy uridine monophosphate(in body)

Inhibit thymidylate synthase

Block conversion of Deoxyuridic acid to deoxythymidylic acid

Failure of DNA synthesis

(2) Cisplatin :- causes cross linking of DNA,

N7 of guanine residue is affected

React with –SH group of protein

(3) Actinomycin-D :- inhibit topoisomerase-2(DNA gyrase)

bind with DNA & forms complex with it,

produce cytotoxicity

(4) Alkylating agents :- produce highly reactive carbonium ion

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Transfer alkyl group to DNA ----- > Forms covalent bond

7 position guanine residue

Cross linking/abnormal base pairing/scission of DNA strand

Cross linking of nucleic acid with proteins

(5) Methotrexate :- inhibit dihydrofolate reductase

blocking conversion of dihydrofolic acid to tetrahydrofolic acid

(dihydrofolate reductase is co-enzyme responsible for 1 carbon transferreaction in

de novo purine synthesis & amino acid interconversion)

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(6) Purine antagonist :- mercaptopurine

Converted in the body to the corresponding monoribonucleotides

Inhibit conversion of Inosine monophosphate to adenine & guanine nucleotide

Feedback inhibition of de novo purine synthesis

Miscelaneous :-

Anti-obesity drugs are 5-HT antagonist & sympathomimetics

Ex – phentermine

Fenfluramine

Orlistat

Sibutramine

Glucocorticoids bound to α-globulin of blood

Mineralocorticoids & sex steroids bound to albumin of blood

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Adrenal gland & its part & secreation –

Zona-glomerula – aldosteron

Zona-fasciculata(radial),it is largest part – cortisol

Zona-reticulata – progesterone & estrogen

Adrenal cortex is rich in Vit.C

About 200 mg of vit.C/100 gm of cortical tissue

Stimulation of adrenal cportex results in depletion of Vit.C

Mineralocorticoids(aldosteron) – conjugation with glucoronic acid

Testosterone = 19 carbon atom

Estradiol = 18 carbon atom

Progesterone = 21 carbon atom

Estrogen receptor & its location :- ER – α = Liver

ER – β = G.I.T

ER – α & β = bone,urogenital tract,breast,C.V.S,C.N.S

Mefepriston = antagonist of progesterone & glucocorticoids

Estrogen & progesterone have a anti-androgenic effect

Gossypol (cottonseed der.) is male contraceptive

Jakob – creutzfeld disease is fatal neurological degenerative disease,

it is occur because of hormonal & biological product

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GH antagonist = somatostatin & octreotide

Prolactin antagonist = pergolide & carbergoline

Leuprolide = anti-secretory of FSH & LH

Atosiban = oxytocin receptor antagonist

Posterior pituitary = neurohypophysis

Renal effect of vasopressin is because of V 2 receptor &

Other effect of vasopressin is because of V1 receptor

Thyroxine is important for the myelination of nerve

Hypo-thyroidism = Cretinism in children

Myxoedema & goiter in adult

Hyperthyroidism = grave’s disease(thyrotoxicosis) & exo-pthalmic goiter,eye bulging

Gitoxigenin :- 3β 14β 16β trihydroxy cardenolide

Digoxigenin :- 3β 14β dihydroxy cardenolide

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PHARMA-ANALYSIS

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Part of Electromagnetic radiation –

(1) ϒ-rays

(2) X-rays :- 10-2 – 102 A`

(3) U.V = (a) vaccum UV :- 120 – 180 nm

(b) Near UV :- 200 – 380 nm

(4) visible :- 380 – 780 nm

(5) I.R ( near & Far IR) :- 780 – 300 µ -- > 2 to 25 µm used

(6) radio wave :- 1 – 1000 m

(7) microwave :- 0.1 – 100 cm

λ = C/V

1/λ = wave number

Where,V = Frequency in hertz

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λ = wavelength

quantum of energy E = hv = hc/λ

chromophore are unsaturated & colour producing compounds

auxochome not Ab. > 200 nm

in Bathochromic,hyperchomic,hypochromic & hypsochromic shift,

if wave length is shorter so its energy is more thats why Absorption is less.

if wave length is longer so its energy is less thats why Ab. Is more.

Longer wave length = Bathochromic (red) shift

Increase intensity of Ab. = hyperchromic shift

Shorter wave length = hypsochromic (blue) shift

Decrease intensity of Ab. = hypochromic shift

Types of band produce in UV spectra :-

K band = π – π* transition ( more absorption)

R band = n – π* transition (intermediate Ab.)

B band = occur in aromatic & hetero-aromatic molecules (weak Ab.)

E band = oscilation of electron in aromatic ring system

Photovoltaic cell = barrier layer cell

In photo or photo emissive tube dark current(small current) is produce

Stray radiation

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Lambert law = intensity of transmitted light decrease exponentially as the thickness of

medium increase arithmetically

-dI/db = kI

It = I0 10-kb

Beer law = intensity of incident light decrease exponentially as the Conc. Of absorbing

medium increase arithmetically

logI0/It = ecb

Dilute solution obey the Beer’s law

Molar absorptivity/absorbance :- E = A1%1cm * mol.wt/10

Most useful range for analytical purpose of IR is 4000 to 400 cm- (fundamental region)

IR used for the fingerprint of chemical functional group

IR change rotational as well as vibrational level

I.R Source :-

(1) Incandescent lamp

(2) Nernst glower

(3) Globar source

(4) Mercury arc lamp

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(5) Tungsten filament lamp

I.R Detector :-

(1) Thermocouple

(2) Bolometer

(3) Thermister

(4) golay

Sampling techniques in IR :-

(a) For solids :-

(1) Solution = Solid dissolve in solvent

(2) As a solid film

(3) Mull technique = nujol is used

(4) Pressed pellet technique or Disk method ----- > solid sample is pressed with Kbr

disk/tablet is being formed

(b) For Liquid :-

(1) Sandwich cell

(2) Demountable cell

(3) Cavity cell

(c) For Gases :- Air tight Sample cell

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In flame photometry = exited atoms & ions ------- > line spectra

exited molecule ------- > band spectra

Molecule produce band spectra because it has rotational,vibrational & axited energy level

Oxidation at anode & reduction at cathode

Indicator electrode ----- > cathode

Reference electrode ----- > anode

Fluorescence is the process of re-emission of radiant energy absorbed in the form of visible

light & emitted light has higher wave length than Ab. Light

& delay emission called phosphorescence

Fluorescence + phosphorescence = Luminescence

In Fluorescence the emited radiation is seen at right angle 90`

Flourimetry :-

(a) Source :- mercury vapour lamp

Xenon lamp

(b) Detector :- PMT

Potentiometry :-

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(1) Indicator electrode :-

(a) H2 electrode

(b) Quinhydrone electrode

(c) Antimony electrode

(d) Glass electrode

(2) Reference electrode :-

(a) Normal H2 electrode

(b) Calomel electrode :- - bell jar type

Side arm test tube type

Test tube type

(c) Ag/Agcl electrode

(d) Hg/HgSo4 electrode

Mass spectroscopy :-

0.1 – 1 mg sample is require

Sample under 10-7 to 10-5 mmhg or 10-5 to 10-6 torr pressure

Energy of Electron beam is 70 eV

To produce electon beam,Tungsten rherium filament is use

Minimum energy require to cause ionisation is called Ionisation potential

Mostly organic compounds are analysed by this method

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Dis-advantage – sample is getting destroy

Ionisation techniques :-

(1) Electron impact

(2) Field ionisation = cathode & anode produce slit

(3) Chemical ionisation

(4) Fast atom bombardment

Types of ions produce in Mass spectroscopy :-

(1) Fragment ions

(2) Molecular ions (parent ion)

(3) Re-arrangement ions

(4) Meta-stable ions

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(5) Multiple charged ions

(6) Isotope ions

(7) Negative ions

- Fragment ions formed by the intra-molecular re-arrangements involving

migration of hydrogen atoms from one part of the ion to another are called

re-arrangement ions

- This process is common in unsaturated compound

Ion separators :-

Based on m/e = H2r2/2V

keep H & r constant,so separation depends on the V = potential

- Types :-

(1) Single focusing magnetic deflection = separation based on their velocity of

ions & it use only magnetic field

(2) Double focusing magnetic deflection = use both magnetic & electrical field

Mass Analyser :-

(1) Time of flight analyser

(2) Cycloidal focusing analyser

(3) Quadropole analyser

(4) Radio frequency analyser

(5) Omegatron analyser

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Mass spectroscopic detectors :-

(1) Faraday cup detector

(2) Electron multiplier

(3) Photo-graphic detection

In the spectrum of CH3Br ------- > double peak ------- > 2 equally intense peaks

(isotopic clusters/isotopic peaks)

1st peak at m/e 94 (CH379Br)

2nd peak at m/e 96 (CH381Br)

Nitrogen rule :-

(1) m/e number is even for parent ion ------- > even Nu. Of nitrogen atoms

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m/e number is odd for parent ion ------- > odd Nu. Of nitrogen atoms

(2) fragmentation of single bond,

even number molecular ion ------- > odd Nu. Fragment ion

odd number molecular ion ------- > even Nu. Fragment ion

Ring Rule:-

R (unsaturated centers) = Nu. Of rings + Nu. Of double bonds + twice Nu. Of triple bonds

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* N.M.R :-

Priciple :-

Nuclei/Protons are charged particles & they are spins ------- > nuclei produce magnetic field

External magnetic field

Align the nuclei :- (1) parallel (lower energy)

(2) Anti-parallel (higher energy)

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Precessing nuclei/Protons

Radiowaves

If the precessional frequency of protons matches with the Radio frequency

Resonance

The exchange of energy takes place b/w radiowaves & spinning nuclei

Transition of nuclei occur & Nuclei will change the Allignment

If nuclei align parallel ------- > energy Ab. ------- > align anti-parallel

If nuclei align anti-parallel ------- > energy release ------- > align parallel

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Precessing protons Ab. The energy if the precessional frequency of nuclei same with appied

external radio beam frequency

& if this occur the nuclei & applied radio beam are said to be in Resonance.

this is called nucleur magnetic resonance

Normally the population of nuclei in lower energy state is slightly greater than that in higher

energy state.

This is responsible for the net Ab. Of the Radiowaves.

So Ab. Of radio radiowaves occur

Felt H(magnetic field) by proton = H = H0(1 – α)

where,H0 = applied external magnetic field

α = shielding parameter

Precessional frequency :-

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W = rH0 W = larmor precession frequency

r = Gyromagnetic ratio

V = precessional frequency

V α H0

In NMR if spin quantum number I > 0

Nu. Of possible orientation of nuclei = (2I + 1)

The atomic nuclei which have the spin quantum number I > 0 will only exhibit the NMR

phenomenon.

In NMR solvent must not contain its own hydrogen & solvent must be non-polar

NMR of Toluene shows 2 picks (signals)

NMR of CH3CH2OH shows 3 picks

α is a Shielding parameter

δ is used for Up field & down field

High δ ------- > down field

Low δ ------- > up field

τ value is opposite to that of δ

High τ ------- > up field

τ = 10 – δ

Chromatography :-

Separation techniques :-

(1) Elution = first mixture is added & then mobile phase

(2) Frontal analysis = mixture added continuously , no mobile phase added

(3) Displacement analysis :- displacement by other constituents of mobile phase

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Elution procedure in column chromatography :-

(1) Isocratic elution = general method

(2) Stepwise or fractional = diff. Solvent is used which have a graduating polarity

(3) Gradient elution = continuous changing eluting medium

Plate size in TLC/HPTLC :- 20 * 20 cm or 5 * 7.5 cm

Absorbent thickness in TLC/HPTCL :- 100 – 250 mm

Diff. b/w TLC & HPTLC is particle size of coated material,

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particle size of coated material:-

TLC :- 5 – 20 µm

HPTLC :- 4 – 8 µm

Particle size of paching in HPLC :- 3 – 10 µm

HPLC work at about 2000 – 8000 psi pressure

In HPLC 1 – 5 µl sample is applicable & detection at 254 nm in UV

Types of pump in HPLC :-

(1) Displacement pump = pulse free,not use for gradient elution

(2) Reciprocating pump = palsatile flow,cause base line noise

Column tube of GC :- D = 2 – 10 mm

L = 2 – 4 metre

In GC, W tubes use for compounds which are sensitive to catalytic action

Thermal conductivity detectors = katharometer detector

Hot wire detector

In Ion-exchange resin chromatography,

Cation exchanger resin is made by sulphonation/phosphorylation of Coal,paper or cotton

Refractive index of organic liquids = 1.2 – 1.8

Refractive index of organic solids = 1.3 – 2.5

Molar refraction = specific refraction * molecular Wt.

rm = (n2 – 1)M/(n2 – 2)d cm3/mole

specific rotation (α)+D = 100 * θ / LC

Nernst Eq. :- E = E0 + RT/nf ln amnt

E = E0 + 0.0591/n log Cmnt

In polarography,DME is called as polarized when it adopts a potential impress upon it with

no change of current & after starting chemical reaction on its surface it is getting

depolarized

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Some important Standerdisation Techniques :-

(1) Ascorbic acid :- Cerric ammonium sulphate :- Oxidation method

(2) PCM :- Cerric ammonium sulphate :- Oxidation method

(3) Thiamine :- Non-Aq. Titration

(4) Pyridoxine HCl :- Non-Aq. Titration

(5) Ranitidine HCl :- HPLC

(6) Piroxicam :- HPLC

(7) Ciprofloxacin :- HPLC

(8) Phenytoin sodium :- tetra butyl ammonium HCl

(9) Sulphamethoxazole :- Dead stop end point method

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Some important Titrants used in Standerdisation technique :-

(1) Ascorbic acid :- Iodine

(2) Pyridoxine HCl :- HClO4

(3) Dapsone :- sodium nitrite

(4) Fluorouracil :- TBAH

(5) Captopril :- 1.8 M H2So4

(6) Glibenclanide :- NaoH

(7) Clorambucil :- NaoH

(8) Cyclizine :- NaoH

(9) Iopanoic acid :- dimethyl formamide with 0.1 M tetra ammonium hydroxide

Chlorthiazide :- Anhydrous formic acid & acetic anhydride with 0.1 N perchloric acid

MICROBIOLOGY C.J.gohil...303

Living bacteria = Parasite

Dead bacteria = Saprophytes

Gram – Ve bacteria produce Indotoxin(Lipo-polysaccharides)

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For turbid & viscous product alternative fluid thioglycolate medium is used that does not

contain Agar & Resazurin

Soyabean Casein digest medium used for Aerobic organism

Clauvanic acid is L – Oxapenam derivative

Streptomycin ------- > Hydrolysis

Streptidine + L – Stteptose + N – Methyl – L – glucosemine

Replication :-

- RNA Polymerase initiate the reaction

- Then DNA Polymerase – 3 proceeds the further reaction

- The Lagging strands are joined together by Ligase

- Gyrase unwind the DNA Helical

Transcription :-

- Transcriptase :- unwind the DNA helical & synthesis the new chain

RIA is most widely used to detect Human Chorionic Gonadotropin(marker for pregnancy)

ELISA :-

(1) Sandwich :- To detect Antigen

Most widely Used to detect Hepatitis-B

(2) Indirect :- To detect Antibody

Most widely used to detect virus,parasites,fungi,rubella & type-2 herpes virus

Ziel Neelsen staining is used to detect acid fast bacilli & T.B organism

Alber stain is used for demonstration of metachromatic & fluorescent dye to bring special

character

Mordant consist of 1 gm phenol

5 gm tannic acid

100 ml Dis.water

Fused oil = Iso-amyl alcohol + butyl alcohol

N – formylmethionine is initiating amino acid in protein synthesis of Prokaryotes

Methionine is initiating amino acid in protein synthesis of Eukaryotic

Termination codon for protein synthesis is UAA,UAG,UGA

Vitamin B can be obtain from Clostridium tetanomorphan

Vitamin B12 can be obtain from S.gracieus & S.aerofaciens

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Aquous solution of formalin contain 37-40 % formaldehyde + 10-15 % methanol

Methanol is added in formaldehyde to avoid polymerization of formaldehyde to

paraformaldehyde

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Ethyl oxide + Co2 = Freon

Cellulose contain β – D – glucose

Inulin contain β – D – fructose

Any other polysaccharides contain α – D – glucose

Cyclic forms of sugar are called pyranose & furanose

Mutarotation of L – D – glucose’s Aq. Sol. Is 52.7`

Chymotrypsin is used in cataract surgery as a proteolytic enzyme

Asparginase is used in Leukamia

For isolation of antibody(sera) from animal following procedure occur –

Blood from animal is taken in the medium containing potassium Citrate

Plasma

Dilute with water

Digested with Pepsin

Fractionated with ammonium sulphate

Immuno-serum

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Classification of Micro-organisms :-

Morphological

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Higher bacteria lower bacteria

Filamentous &

grow by branching uni-cellular

Bacillary/Coccoid Formed in chain

Ex – gram +ve bacteria,

Actinomyces Ex – streptomyces

Cocci bacilli vibrio spirilla spirochaets

(spherical) (rod shape) (coma shape) (spirally flexous) (twisted rods)

Micrococcus diplococcus streptococcus sarcina staphylococcus

Single cell two cells cells are unite in chain form 8 cells cells in cluster

Classification of microbes according to Temperature range –

(1) Psychrophilic :- 0` - 25` C

(2) Mesophilic :- 20` - 44` C

(3) Thermophilic :- 50` - 60` C

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FORENSIC PHARMACY Drug name

Chemical name Non-proprietary name Trade name

(proprietary,brand,registered name)

Exclusive property of Ph.ceutica firm

Official name Approved name

Used in official books, same as adopted or generic name

Identical with generic name Not use in ph.copoeia but

adopted by other body like WHO

Since,drug may be sold under many proprietary names by diff. Firms,

but there is only 1 generic or official name in each country

Constitution of Various Authorities/Boards :-

(1) Ex-officio member of state pharmacy council(SPC) :- chief administrative medical officer

of state

(2) Ex-officio members of Pharmaceutical council of India(PCI) :-

- Director general of health service

- Director of central drug laboratory

- The drug controller general of india

(3) Chairman of drug technical advisory board :- director general of health service

(4) Ex-officio members of the drug technical advisory board under D & C Act :-

- Drug controller general of india

- The president medical council of india

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BIO-CHEMISTRY

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Michaelis-Menton equestion :-

V0 = Vmax[S]/Km + [S]

Where,V0 = initial rate at substrate Con. (S)

Km = Con. Of the specific substrate at which a given enzyme yields ½ its

maximum velocity

Apo-enzyme + Co-enzyme = Holo-enzyme

Co-factor

Prosthetic group/inorganic metal

Bio.chemical test :-

(a) Carbohydrate :-

(1) Benedict test

(2) Fehling test

(3) Molish test

(4) Barfoed test

(5) Seliwanof test (ketones/fructose)

(b) Protein :-

(1) Sulphosalicylic acid test

(2) Heller’s test

(3) Heat coagulation test

(c) Lipid :-

(1) Salkowski’s test (cholesterol)

(2) Libermann burchard test (sterol)

(d) Ketone :-

- Rothera’s test

(e) Blood :-

- Benzidine test

(f) Bile salt :-

(1) Hey’s sulphur flower test

(2) Oliver’s test

(g) Bile pigment :-

(1) Gmelin’s test

(2) Cole’s test

(h) Uric acid :-

- Schiff’s test

(i) Amino acid :-

(1) Sakaguchi test (arginine)

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(2) Millon’s test (tyrosine)

(3) Hopkins – cole reaction (tryptophan)

C.J.gohil...303

Vitamin & its Chemical name & disease cause by its deficiency :-

Vitamin B1 Thiamine Beriberi

Vitamin B2 Riboflavin Cheilosis,cornealopacity

Vitamin B3 Niacin Pellagra

Vitamin B5 Pantathenic acid Chick dermatitis

Vitamin B6 Pyridoxine Merasmas

Vitamin B7 (Vitamin H) Biotin Dermatitis

Vitamin B12 Cyanocobalamines Pernicious anaemia

Vitamin C Ascorbic acid Scurvy

Vitamin K1 Phylloquinone

Vitamin K2 Menaquinone

Vitamin K3 Menadione

Vitamin D Cholecalciferol Reckets

Vitamin E α - tacopherol Haemolytic anaemia,sterility

Vitamin K1 ------ > present in plant

Vitamin K2 ------- > produced by intestinal bacteria

Vitamin K3 ------- > synthetic form

References :- (a) Pharmaceutics :-

(1) Indian Pharmacopoeia 2010

Government of India

Ministry of Health & Family welfare

Published by : The I.P commission,Ghaziabad

(2) Aulton’s Pharmaceutics,

The Design & Mfg. Of Medicines

By Michael.E.Aulton

3rd edition

(b) Pharmacognosy :- (1) Textbook of Pharmacognosy

By T.E.Wallis

5th edition

(2) Textbook of Pharmacognosy

By C.K.Kokate

A.P.Purohit

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(3) Textbook of Pharmacognosy

By Mohammed Ali

2nd edition

(c) Pharmacology :- (1) Goodman & Gilman’s

Pharmacological basis of Therapeutics

By Joel.G.Hardman

Lee.E.Limbird

10th edition

(2) Essentials of Medical Pharmacology

By K.D.Tripathi

6th edition

(3) Elements of Pharmacology

By R.K.Goyal

A.A.Mehta

19th edition

(d) Pharma-Analysis :- (1) Vogel’s

Textbook of Quantitative Chemical Analysis

By J.Mendham

R.C.Denney

6th edition

(2) Textbook of Instrumental Analysis

By Skoog

Holler

(3) Textbook of Pharmaceutical Analysis

By P.S.Kalsi

(4) Elementary Organic Spectroscopic Principle & Chemical Application

By Y.R.Sharma

(5) Instrumental Methods of Chemical Analysis

By G.R.Chatwal

S.K.Anand

(6) Instrumental Methods of Pharmaceutical Analysis

Volume – 2

By A.V.Kasture

K.R.Mahadik

Chirag gohil


(e) Microbiology :- (1) Textbook of Microbiology

By Michael.J.Pelczar

Noel.R.Krieg

E.C.S.Chan

(2) Textbook of Bio.Technology

By S.P.Vyas

Dixit

(f) Forensic Pharmacy :- (1) Textbook of Forensic Pharmacy

By B.S.Kuchekar

A.M.Khadatare

Sachin.C.Itkar

(2) Textbook of Forensic Pharmacy

By N.K.Jain

(g) Bio.Chemistry :- Textbook of Bio.Chemistry

By U.Satyanarayana

U.Chakrapani

“Challenges Never Ends In Life”

By Chirag gohil

gpat Niper an Over View

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