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Transcript of 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
www.pharmaaspirants.com Page 2
INDEX :-
C.J.gohil...303
(1) Pharmaceutics
(2) Pharmacognosy
(3) Pharmacology
(4) Pharma-analysis
(5) Microbiology
(6) Forensic pharmacy
(7) Bio.chemistry
“Challenge Is Fun”
Chirag gohil
www.pharmaaspirants.com Page 3
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
Chirag gohil
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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
Chirag gohil
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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
Chirag gohil
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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
Chirag gohil
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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
Chirag gohil
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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
Chirag gohil
www.pharmaaspirants.com Page 9
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
C.J.gohil...303
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
Chirag gohil
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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
Chirag gohil
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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 %
Chirag gohil
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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
C.J.gohil...303
Chirag gohil
www.pharmaaspirants.com Page 13
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.
Chirag gohil
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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
Chirag gohil
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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.
Chirag gohil
www.pharmaaspirants.com Page 16
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
Chirag gohil
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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-
Chirag gohil
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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 :-
Chirag gohil
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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 :-
Chirag gohil
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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)
Chirag gohil
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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
Chirag gohil
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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)
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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
Chirag gohil
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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
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(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