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Antibiotics and its preparation

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Antibiotics and its preparation

  2. 2. Antibiotics : • Substance (such as penicillin) that destroys or inhibits the growth of other pathogenic microorganisms and is used in the treatment of external or internal infections. • While some antibiotics are produced by microorganisms, most are now manufactured synthetically
  3. 3. Classification of antibiotics : • Antibiotics are classified several ways. • On the basis of mechanism of action • On the basis of spectrum of activity • On the basis of mode of action
  4. 4. On the basis of mechanism of action: • Cell Wall Synthesis inhibitors: Penicillins Cephalosporins Vancomycin Beta-lactamase Inhibitors Polymycin Bacitracin • Protein Synthesis Inhibitors • Inhibit 30s Subunit Aminoglycosides (gentamycin) Tetracyclines Inhibit 50s Subunit Macrolides Chloramphenicol Clindamycin Streptogramins DNA Synthesis Inhibitors Fluoroquinolones (ciprofloxac illin) Metronidazole • RNA synthesis Inhibitors Rifampin • Mycolic Acid synthesis inhibitors Isoniazid • Folic Acid synthesis inhibitors Sulfonamides Trimethoprim
  5. 5. On the basis of mechanism of action:
  6. 6. On the basis of spectrum activity : • Broad spectrum antibiotics : – Amoxicillin – Tetracycline – cephalosporin – Chlorampenicol – Erythromycin • Short spectrum antibiotics: – Penicillin –G – Cloxacillin – vancomycin – Bacitracin – Fluxacillin
  7. 7. On the basis of mode of action: • Bacteriostatic antibiotics – Tetracycline – Chlorampenicol – Erythromycin – Lincomycin • Bacteriocidal antibiotics – Cephalosporin – Penicillin – Erythromycin – Aminoglycosides – Cotrimoxazole
  8. 8. Antibiotics indications: • Pneumonia • Sepsis • Meningitis • Osteomyelitis • Urinogenital Infections • Gall Infections • Quinsy • Skin Infections • Mucous Membrane Infections • Scarlet Fever • Diphtheria • Siberian Ulcer • Gynecologic Infections • Syphilis • Respiratory Infections • ENT Infections • Fungous Infections
  9. 9. Misuse of antibiotics : • Antibiotic misuse, sometimes called antibiotic abuse or antibiotic overuse. • The misuse or overuse of antibiotics, may produce serious effects on health. • It is a contributing factor to the creation of multidrug-resistant bacteria, informally called "super bugs" relatively harmless bacteria can develop resistance to multiple antibiotics and cause life-threatening infections.
  10. 10. Antibiotics resistance • If the concentration of drug requires to inhibit or kill the microorganism is greater than normal use then the microorganism is considered to be resistant to the drug. OR • The ability of a microorganism to produce a protein that disables an antibiotic or prevents transport of the antibiotic into the cell.
  11. 11. Cross-resistance • Cross-resistance to a particular antibiotic that often results in resistance to other antibiotics, usually from a similar chemical class, to which the bacteria may not have been exposed. • Cross-resistance can occur, for example, to both colistin and polymyxin B or to both clindamycin and lincomycin.
  12. 12. BLOOD PRODUCTS • A blood product is any component of the blood which is collected from a donor for use in a blood transfusion. Whole blood is uncommonly used in transfusion medicine at present; most blood products consist of specific processed components such as red blood cells, blood plasma, or platelets.
  13. 13. VACCINE • Vaccine is a substance that is introduced into the body to prevent the disease produced by certain pathogens.Vaccine consists of dead pathogens or live but attenuated (artificially weakened) organisms. The vaccine induces immunity against the pathogen, either by production of antibodies or by activation of T lymphocytes. • Edward Jenner produced first live vaccine. He produced the vaccine for smallpox from cowpox virus.Nowadays, vaccines are used to prevent many diseases like measles, mumps, poliomyelitis, tuberculosis,smallpox, rubella, yellow fever, rabies, typhoid, influenza,hepatitis B, etc
  14. 14. Vaccination: • The process of distributing and administriting vaccines is reffered to as Vaccination.
  15. 15. Types of vaccine 1. Live-attenuated (weakened) vaccines These vaccines contain modifed strains of a pathogen (bacteria or viruses) that have been weakened but are able to multiply within the body and remain antigenic enough to induce a strong immune response. The varicella-zoster vaccine, oral poliovirus (OPV) vaccine, or yellow fever virus vaccine are some examples of this type of vaccine.
  16. 16. 2.Heterologous vaccines • Heterologous vaccines are a sub-group of live attenuated vaccines produced from strains that are pathogenic in animals but not in humans. It is a vaccine that confers protective immunity against a pathogen that shares cross-reacting antigens with the microorganisms in the vaccine. example cowpox virus that protects against smallpox in humans.
  17. 17. 3. Killed-inactivated vaccines • To produce this type of vaccines, bacteria or viruses are killed or inactivated by a chemical treatment or heat. This group includes for example the inactivated poliovirus (IPV) vaccine, pertussis vaccine, rabies vaccine, or hepatitis A virus vaccine. • 4. Sub-unit vaccines • Instead of the entire microbe, subunit vaccines include only the antigens that best stimulate the immune system.In some cases, these vaccines use epitopes—the very specific parts of the antigen that antibodies or T cells recognize and bind to.Because subunit vaccines contain only the essential antigens and not all the other molecules that make up the microbe, the chances of adverse reactions to the vaccine are lower. 18
  18. 18. 5.DNA Vaccine when the genes for a microbe’s antigens are introduced into the body, some cells will take up that DNA. The DNA then instructs those cells to make the antigen molecules. The cells secrete the antigens and display them on their surfaces. In other words, the body’s own cells become vaccine-making factories, creating the anti gens necessary to stimulate the immune system. • 6.RECOMBINANT VECTOR VACCINES Recombinant vector vaccines are experimental vaccines similar to DNA vaccines, but they use an attenuated virus or bacterium to introduce microbial DNA to cells of the body. “Vector” refers to the virus or bacterium used as the carrier. 19
  19. 19. 7.TOXOID VACCINES These vaccines are used when a bacterial toxin is the main cause of illness.When the immune system receives a vaccine containing a harmless toxoid, it learns how to fight off the natural toxin. The immune system produces antibodies that block the toxin. E.g Vaccines against diphtheria and tetanus. 8.Gene deleted vaccines; These are genetically engineered vaccines which involve the removal or mutation of virulence gene of the pathogen 9.Peptide vaccine: These are the subunit vaccine prepared by chemical synthesis of short immunogenic peptides. 20
  20. 20. Routes of Administration • Deep subcutaneous or intramuscular route (most vaccines) • Oral route (oral BCG vaccine) • Intradermal route (BCG vaccine) • Scarification (small pox vaccine) • Intranasal route (live attenuated influenza vaccine) 21
  21. 21. Tetracycline 22
  22. 22. INTRODUCTION • Tetracyclines is a group of antibotic that include tetracycline. • Tetracyclines are obtained by fermentation from Streptomyces spp. Or by chemical transformation of natural products. • They are derivatives of an octahydro- naphthacene,a hydrocarbon system that comprises four annulated six membre rings. 23
  23. 23. CLASSIFICATION TETRACYCLINES SHORT ACTING: •Tetracycline •Oxytetracycline INTERMEDIATE ACTING: •Demeclocycline •Lymecycline LONG ACTING: •Doxycycline •Minocycline 24
  24. 24. Uses of tetracycline • Tetracycline is used to treat a wide variety of infections, including acne. It is an antibiotic that works by stopping the growth of bacteria. – Used in treatment of infections like septicemia, endocarditis , meningitis. 25
  25. 25. Vit.B12 Chemistry and Mode of Action
  26. 26. Vitamins- general concepts • What are vitamins? Any group of organic compounds that either our own bodies cannot synthesize them, or they are not synthesized in amounts sufficient for our needs. Thus we must obtain them from the foods we eat, or via vitamin supplements. 1 • What is the difference between fat-soluble and water-soluble vitamins? - Fat-soluble vitamins are stored in the liver and fatty tissues. These are not readily excreted from the body such as vitamin A, vitamin D, vitamin E and vitamin K. - Water-soluble vitamins travel in the blood and are stored in limited amounts. These are readily excreted from the body through urine such as, Vit C, Vit B12, thiamin, niacin, riboflavin, tryptophan, pantothenic acid, biotin, and folic acid.
  27. 27. Vit B12 (cobalamin) • Is a complex biochemical structure, but is water soluble. • Vitamin B12 is generic name for group of compounds called corrinoids (four pyrrole rings). – corrin nucleus – atom of cobalt in center – attached are one of following • CN = cyanocobalamin (CNCbl) • OH=hydroxocobalamin (OHCbl) • 5’-adenosyl=adenosylcobalamin*(AdoCbl) • -CH3=methylcobalamin* (MeCbl)
  28. 28. Sources • Seldom found in foods from plants • Synthesis is limited to bacteria. Rumen microbial • synthesis depends on the supply of cobalt in the diet • Animal products ▫ Derive their cobalamin from micro-organisms; Animal derived foods are a primary source since animals eat another animal food, they produces B12 internally due to the intestinal bacteria (not present in humans), and they eat food contaminated with bacteria. ▫ Meat, poultry, fish, shellfish, eggs, milk, milk products ▫ Liver is a good source • Supplements Cyanocobalamin and hydroxycobalamin
  29. 29. Microbial production of vitamin b12 DIRECT FERMENTATION In this process streptomyces olivaceus is grown in nutrient medium conataining glucose as carbon source.cocl2 is added as precursor at the beginning during production.Fermentation is carried out at 27 degree.with aeration for about 5 days. At the end of incubation growth is harvested before mycelial autolysis and destruction of vitamin.The vitamin is recovered from broth by filtration.Filtrate from mycelia;this vitamin is heat labile so heat is applied with caution.During acidification sodium sulphate is added to stabilise the vitamin.Acidified broth is filtered to remove mycelial growth and filtrate is evaporated to dryness.It can further be purified by adding acetone.
  30. 30. INDIRECT FERMENTATION • Vitamin b12 is also obtained as byproduct of various antibiotic fermentation processes such as grisien, streptomycin and aureomycin production. It is also formed during acetone butanol fermentation.
  31. 31. PENICILLIN
  32. 32. 33
  33. 33. 34
  34. 34. First step • is the condensation of three amino acids — L-α- aminoadipic acid, L-cysteine, L-valine into a tripeptide. Before condensing into the tripeptide, the amino acid L-valine must undergo epimerization to become D-valine. The condensed tripeptide is named δ-(L- α-aminoadipyl)-L-cysteine-D-valine (ACV). The condensation reaction and epimerization are both catalyzed by the enzyme δ-(L-α-aminoadipyl)-L-cysteine-D- valine synthetase (ACVS), a nonribosomal peptide synthetase or NRPS.
  35. 35. Second step • The second step in the biosynthesis of penicillin G is the oxidative conversion of linear ACV into the bicyclic intermediate isopenicillin N by isopenicillin N synthase (IPNS), which is encoded by the gene pcbC. Isopenicillin N is a very weak intermediate, because it does not show strong antibiotic activity.
  36. 36. Final step • is an transamidation by isopenicillin N N- acyltransferase, in which the α- aminoadipyl side-chain of isopenicillin N is removed and exchanged for a phenylacetyl side-chain. This reaction is encoded by the gene penDE, which is unique in the process of obtaining penicillins
  37. 37. Production • Penicillin is a secondary metabolite of certain species of Penicillium and is produced when growth of the fungus is inhibited by stress. It is not produced during active growth. Production is also limited by feedback in the synthesis pathway of penicillin. • α-ketoglutarate + AcCoA → homocitrate → L-α-aminoadipic acid → L-lysine + β-lactam The by-product, L-lysine, inhibits the production of homocitrate, so the presence of exogenous lysine should be avoided in penicillin production. • The Penicillium cells are grown using a technique called fed-batch culture, in which the cells are constantly subject to stress, which is required for induction of penicillin production. The available carbon sources are also important: Glucose inhibits penicillin production, whereas lactose does not. The pH and the levels of nitrogen, lysine, phosphate, and oxygen of the batches must also be carefully controlled. • The biotechnological method of directed evolution has been applied to produce by mutation a large number of Penicillium strains. These techniques includeerror-prone PCR, DNA shuffling, ITCHY, and strand-overlap PCR. • Semisynthetic penicillins are prepared starting from the penicillin nucleus 6-APA.
  38. 38. The Industrial Production of Penicillin This can be broadly classified into two processes namely: 1. Upstream Processing - referring to processes before input to the fermenter and encompases any technology that leads to the synthesis of a product. It includes the exploration, development and production. 2. Downstream Processing - referring to processes done to purify the output of the fermenter until it reaches to the desired product, such as extraction and purification of a product from fermentation.
  39. 39. Simplified Flow Chart
  40. 40. 41
  41. 41. STREPTOMYCIN • Streptomycin is an antibiotic (antimycobacterial) drug, the first of a class of drugs called aminoglycosides to be discovered, and it was the first antibiotic remedy for tuberculosis. • It is derived from the actinobacterium ''Streptomyces griseus''. • Streptomycin is a bactericidal antibiotic. • Streptomycin cannot be given orally, but must be administered by regular intramuscular injections. • Adverse effects of this medicine are ototoxicity, nephrotoxicity, fetal auditory toxicity, and neuromuscular paralysis. • Ototoxicity due to neurotoxicity to the 8th cranial nerve can lead to vertigo and irreversible deafness. • Nephrotoxicity due to kidney tubular necrosis may also arise. The reason for these toxicities is the affinity of Aminoglycosides to these tissues and their long t1/2 within these tissues.
  42. 42. Classic fermentation process for the production of streptomycin
  43. 43. • A little additional production of mycelia. The glucose added in the medium & the ammonia released from the soybean meal are consumed during this phase. The Ph remains fairly constant (7.6- 8). It is the final phase of the fermentation, after depletion of carbohydrates from the medium, Streptomycin production ceases & the bacterial cells began to lyse. There is a rapid increase in ph because of the release of ammonia from lysed cells. In the end of fermentation, the mycleium is separated from the broth by filtration & the streptomycin is recovered. The purification consists of adsorbing the streptomycin onto activated charcoal & eluting with acid alcohol.
  44. 44. USES • Treatment of diseases[edit] • Infective endocarditis caused by enterococcus when the organism is not sensitive to Gentamicin • Tuberculosis in combination with other anti-TB drugs. It is not the first-line treatment, except in medically under-served populations where the cost of more expensive treatments is prohibitive. • Plague (Yersinia pestis) has historically been treated with it as the first-line treatment. However It is approved for this purpose only by the U.S. Food and Drug Administration. • In veterinary medicine, streptomycin is the first-line antibiotic for use against gram negative bacteria in large animals (horses, cattle, sheep, etc.). It is commonly combined with procaine penicillin for intramuscular injection. • Tularemia infections have been treated mostly with Streptomycin and some other antibiotic drugs, which is effective, but the infection is resistant to Penicillin. 45
  45. 45. ETHANOL
  46. 46. INTRODUCTION • Ethanol also commonly called ethyl alcohol, drinking alcohol, or simply alcohol is the principal type of alcohol found in alcoholic beverages, produced by the fermentation of sugars by yeasts. It is a neurotoxic psychoactive drug and one of the oldest recreational drugs used by humans. It can cause alcohol intoxicationwhen consumed in sufficient quantity.
  47. 47. USES • Medical • Antiseptic • Ethanol is used in medical wipes and in most common antibacterial hand sanitizer gels at a concentration of about 62% v/v as an antiseptic. Ethanol kills organisms by denaturing their proteins and dissolving their lipids and is effective against most bacteria and fungi, and many viruses. Ethanol is ineffective against bacterial spores.[21] • Antitussive • Ethanol is widely used, clinically and over the counter, as an antitussive agent.[22] • Antidote • Ethanol may be administered as an antidote to methanol[23] and ethylene glycol poisoning. • Medicinal solvent • Ethanol, often in surprisingly high concentrations, is used to dissolve many water- insoluble medications and related compounds. Proprietary liquid preparations of cough and cold remedies, analgesics, and mouth washes may be dissolved in 1 to 25% concentrations of ethanol and may need to be avoided in individuals with adverse reactions to ethanol such as alcohol-induced respiratory reactions.[24]

Editor's Notes

  • Cobalamin enzymes catalyze 3 types of reactions: intramolecular rearrangements, methylations, and the reduction of ribonucleotides to deoxyribonucleotides. The two reactions in mammals that require coenzyme B12 are: (1) the conversion of L-methylmalonyl CoA into succinyl CoA and (2) methylation of homocysteine to form methionine. Reaction (2) is particularly important as Met is necessary for the generation of coenxymes that play a role in the synthesis of purines and thymine. The basic structure of a cobalamin is pictured: the core consists of a corrin ring with a central cobalt atom.

  • Write this down, as this is not mentioned in the slides:
    In mammals, cobalamin is a cofactor for only two enzymes, methionine synthase and L-methylmalonyl-CoA mutase.
    Vitamin B 12 contains a cobalt metal ion bound to a porphyrin ring. Cobalt normally forms six coordinate bonds. Besides the four bonds to the nitrogens of the porphyrin, one bond is to a ring nitrogen of dimethylbenzamidine. The final bond is to a cyanide ion in the vitamin, or to the 5′ carbon of adenosine in the active coenzyme
  • B12 is synthesised in nature by micro-organisms. Animal-derived foods are a primary source because animals eat other animal food, they produce B12 internally due to the intestinal bacteria (not present in humans), and they eat food contaminated with bacteria.