Chemotherapy i general consideration

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1. Chemotherapy : General Consideration Dr. Archana Dhavalshankh Prof & Head, Dept of Pharmacology D Y Patil Medical College, Kolhapur

2. CHEMOTHERAPY General Consideration

3. Definition / Terminology Chemotherapy: Treatment of systemic/topical infections/infestations with specific drug that kill/suppress the invading pathogen ( living or multiplying ) without significantly affecting the host. Selective toxicity: A drug that kills harmful microbes without damaging the host

4. Definition / Terminol ogy Antimicrobial agent : Drugs effective against micro-organisms, Naturally or synthetically derived Antibacterial agent: Drugs effective against bacteria Antibiotics : Obtained from fermentation of microorganisms Commensals : Micro-organisms that are parasites without causing disease (may cause disease if host is immuno -compromised)

5. Classification I - [ Type of organism against which primarily active ] Antimicrobial Agents Anti- Bacterial agents – Sulfonamide, F luro -quinolone, Penicillin, Cephalosporin, Macrolide, Aminoglycoside, Tetracycline, Choramphenicol Antibiotic - Penicillin, Cephalosporin. Macrolide Anti- viral agents- Acyclovir, Amantadine, Zidovudine , N evirapine Anti- protozoal agents- Metronidazole, Diloxanide , Chloroquine Anti- fungal agents- Amphotericin-B , Griseofulvin , Ketoconazole Anti- helminthic agents - Mebendazole , Niclosamide , Pyrantel

6. Higher forms Gram + ve , branching filamentous Actinomycetes A. Israelli - Ce rvico -facial, abdominal Nocardia - Pulmonary, brain abscess Streptomycetes Non pathogenic Useful as source of antibiotics Lower forms 1 µm size, Gram + ve or - ve Cocci -Spherical Stapylococci (cluster) Streptococci (chain) Diplococci (pair) Bacilli Straight rod shape Vibrios Curved cylindrical rod Spirilla Elongated spiral shape My. Tuberculosis My. Avium intracellularae My. Kansasii My . Leprae Special group No gram stain , Koch stain + ve BACTERIA

7. Spirochetes Rickettsiae Chlamydiae Atypical No rigid cell wall Contractile cell Stain by silver impregnation Rigid cell wall Gram - ve Rigid cell wall Gram – ve Posses DNA RNA Grow only in other cell Mycoplasma pneumonae Ureaplasma Pneumocystitis cariini Tr. Pallidum Borellia Leptospira Rickettasia Coxiella Chl. Trachomatis Chl. Pneumonae Smallest cellular organism No rigid cell wall Acquire variety of structures Plasma memb . Has cholesterol RNA or DNA present

8. Gram + ve Cocci Infections occur Staph. aureus Abscesses. Septicemia, Bacteremia, Osteomyelitis, Endocarditis Strep. pyogens Pharyngitis, Sinusitis, Otitis Media, Rheumatic Fever, Glomerulonephritis, Septicemia Strep. viridans Bacterial Endocarditis, Bacteremia Strep. facealis Endocarditis, Bacteremia, Urinary Tract Infection Peptostreptococcus Brain, Lung, Puerperal & Dental Abscess Strep. pneumonae Pneumonia, Meningitis, Sinusitis Bacilli Infections occur Clstr . tetani Tetanus Clstr . perfingens Gas gangrene Clstr . difficile Pseudomembranous colitis Clstr . botulinum Botulism/ food poisoning Corne . diphatheriae Diphtheria Listeria monocytogens Meningitis, bacteremia Bacillus anthracis Pneumonia, anthranx

9. Gram - ve Cocci Infections occur Neisseria gonorrhoeae Gonorrhoea Neisseria Meningitidis Meningitis morexella Pneumonia, sinusitis, otitis media Bacilli Infections occur E.Coli UTI, dysentery Salmonella typhi Typhoid & paratyphoid fever, food poisoning Shigella Gastroenteritis, bacillary dysentry Klebsiella Hosptal asso . Pneumonia, UTI Proteus UTI Enterobacteraerogenes UTI H.pylori Peptic ulcer Coliform bacteria Encephalopathy in liver failure

10. OTHERS Organism Infections occur H. influenzae Sinusitis, bronchitis, pneumonia, meningitis H. ducreyi chancroid Ps. aeruginosa Pneumonia, UTI, hospital aq infections Yer . pestis plague Brucella abortus Brucellosis Francisella tuleransis Tularemia Legionella pneumonae Legionnarie’s disorders Campylobacter Gastroenteritis Vibrio chlerae Cholera Organism Infections occur Bordetella pertusis Whooping cough Acinetobacter Nosocomial opportunistic infection Serratia Nosocomial opportunistic infection Fusobacterium Alveolar, lung abscess, gingivitis Bacteroides fragilis Oral,lung , brain, pharyngeal infection Porphyromonas Acute Orofacial infections Prevotella Acute Orofacial infections Burkholderia pseudomallei Melioidosis

11. Classification II - [Type of action] Primarily Bacteriostatic Sulfonamide Tetracycline Chloramphenicol Erythromycin (Macrolide) Clindamycin Ethambutol Linezolid Primarily Bactericidal Penicillin Cephalosporin Aminoglycoside Fluroquinolone Co- trimoxazole Rifampicin Isoniazid Pyrizinamide Metronidazole

12. Static [Bacteriostatic, Fungi-static ] Drugs that arrest the growth / replication of micro-organism (bacteria or fungi) Thus arrest or limit the spread of infection These agents are adequate or sufficient to deal with (to treat) uncomplicated infections. ( Here host defenses usually help to eradicate organisms). But in neutropenic individual, bacteriostatic drugs are ineffective. Sulfonamide, Macrolide, Tetracycline, chloramphenicol

13. Cidal [ Bacteriocidal , fungicidal] Drugs that kill or irreversibly damage the multiplying organisms (bacteria or fungi ). Thus total number of viable organisms decreases. These drugs are preferred for the management of complicated infections. (Tuberculosis, meningitis, endocarditis) Preferred for treating the infection when host defense is impaired. Penicillin, cephalosporin, aminoglycosides, co- trimoxazole,fluroquinolones

14. Chloramphenicol Bacteriostatic Gram – ve rods Pneumococci Bacteriocidal Sulfonamides Trimethoprim Bacteriostatic Co- tri moxazole Bacteriostatic Sulfamethoxazole Trimethoprim Bacteriocidal +

15. Classification III - [Sources of antibiotics] Antibiotics are the drugs that are derived from one micro-organism and effective against another micro-organism .

16. Penicillin Penicillum notatum Penicillum chrysogenum Cephalosporin cephalosporium Griseofulvin Penicillum griseofulvum Aminoglycoside Streptomyces Micromonospora Tetracycline Streptomyces Aureofaciens Chloramphenicol Streptomyces venezuelae Macrolides Streptomyces erythreus Polymyxin –B Bacillus polymyxin Colistin B colistinus Bacitracin Bacillus subtilis

17. Classification IV- [Spectrum of activity]

18. Antimicrobial Spectrum Narrow Spectrum Antimicrobial agents that are active against single or limited group of pathogens are said to have Narrow spectrum. Anti-tubercular drugs are effective against M. tuberculae . Penicillin G & cloxacillin effective against gram + ve organisms. Broad Spectrum Antimicrobial agents that are active against a wide range of pathogens (Gram + ve , Gram – ve , Spirochetes, Chlamydia, Rickettsia) are said to have Broad spectrum. Broad spectrum antibiotics likely to cause super infections. Extended spectrum – Drugs effective against Gram + ve & Gram – ve Ex- Amoxicillin , Ampicillin

19. Classification V- [Mechanism of action]

20. Classification VI- [Chemical Structure]

21. Problems arise with the use of AMAs

22. Practically all AMAs are capable of producing Hypersensitivity Reactions. Sometimes unpredictable and unrelated to dose Occurs in wide range from rash to anaphylactic shock Commonly involved – penicillin, cephalosporin, sulfonamides, fluroquinolone Hypersensitivity Reactions

23. Some of the B complex group vitamins & Vit K is synthesized by intestinal flora (gut flora) is utilized by man Prolonged use of antimicrobials alter this flora result in vitamin deficiencies Neomycin causes morphological abnormalities in the intestinal mucosa which can produce diarrhea and malabsorption syndrome. Nutritional deficiencies

24. A short course of AMAs may be sufficient to treat one infection but only briefly suppress another one contracted concurrently. The other infection will be masked initially, only manifest later in sever form Syphilis masked by single dose of penicillin which is sufficient to treat gonorrhoea . Tuberculosis is masked by short course of streptomycin – sufficient for a minor respiratory infection. Masking of an Infection

25. The native indigenous bacterial flora present in GIT& oral cavity provides resistance to colonization & limits the growth of other pathogenic flora Antibiotic therapy markedly reduces this flora allowing invasion by opportunistic organisms such as proteus , staphylococci & pseudomonas This is termed as superinfecton . Superinfection

26. Superinfection manifests as antibiotic induced diarrhea & colitis Common Superinfections due to clostridium difficile or candida lead to pseudomembranous colitis (PMC)- bloody diarrhoea , abdominal distention, pain, dehydration, blood leukocytosis. Drugs showing – amoycillin , third generation cephalosporin, clindamycin. Manifestations of superinfection

27. Treatment given for superinfection (PMC) Metronidazole 500 mg oral tds x 10 days OR Vancomycin 125 mg qid x 10 days OR Probiotics (to re-establish colonic flora ie lactobacilli & S. boulardii ) Treatment of Superinfection