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General principles of Chemotherapy.pptx
1.
2. CHEMOTHERAPY
• Treatment of systemic infections with specific drugs
that selectively suppress their growth or kill them
without affecting the host.
• Antibiotic – substances produced by microorganism
which selectively suppress the growth or kill other
microorganism at very low concentration.
• AMA- these are chemotherapeutic substances of
any origin which are used to suppress or kill the
growth of microorganism without affecting the host
3. CLASSIFICATION OF AMA
• Mechanism of action
• Inhibit cell wall synthesis- Penicillin's,
Cephalosporin's
• Inhibit protein synthesis-Tetracycline,
chloramphenicol
• Inhibit DNA gyrase- Floroquinilones
• Inhibit DNA synthesis-Acyclovir, Zidovudine
• Interfere with metabolism- Sulfonamides,,
Pyremethamine
• Cause leakage from cell membrane - Polymixin,
colistin
• Misreading of mRNA - Aminoglycosides
4. • Action on Type of microorganism
• Antibacterial
• Antifungal
• Antiviral
• Antiprotozoal
• Antihelminthic
5. • Spectrum of activity
• Narrow spectrum- Penicillin G, Streptomycin
• Broad spectrum- Tetracycline's, Chloramphenicol
• Type of action
• Bactericidal- Penicillin's, Cephalosporins,
Aminoglycosides
• Bacteriostatic- Sulfonamides, Tetracycline's,
Chloramphenicol
7. PROBLEMS WITH AMA
• Toxicity
• Local irritancy – at site of administration
• Systemic toxicity – Dose related, depend upon
Therapeutic index
• Aminoglycosides- ototoxicity, renal toxicity
• Tetracyclines - Bone marrow depression
• Amphotericin B- Renal, Bone marrow toxcity
• Vancomycin – Hearing loss, Kidney damage
8. • Hypersensitivity reactions
• Penicillins, Cephalosporins,
• Unpredictable and unrelated to dose
• From rash to anaphylactic shock
9. RESISTANCE
• Unresponsiveness of microorganism to AMA
• Natural resistance - not a problem to treatment
• Lack metabolic process or target site at which
drug acts. G- microorganism for penicillin G,
aerobic organism for metronidazole & anaerobic
not affected by aminoglycosides
• Acquired resistance - development of resistance to
AMA over a period of time
• Mechanism – Mutation – Single or multi step process
& by Gene transfer
10. • Mutation
• Heritable, vertical transmission
• stable & occurs spontaneously& randomly
among microorganism
• Single step - single gene mutation . enterococci to
streptomycin
• Multi step – sensitivity decreases gradually in
stepwise manner. Resistance to erythromycin
12. RESULT OF RESISTANCE
• Drug tolerant –loss of affinity of the target molecule
• Drug destroying – B- lactamases for penicillins,
chloramphenicol acetyl transferase
• Drug impermeable
• Cross resistance - acquisition of resistance to AMA
conferring resistance to another AMA to which
organism not exposed
13. PREVENTION OF RESISTANCE
• No indiscriminate & inadequate or prolonged use of
AMA
• Prefer rapidly acting &narrow spectrum AMA
• Use combination of AMA
• Intensive treatment of infections
14. SUPER INFECTIONS
• It is appearance of new infection as a result of
antimicrobial therapy
• Causes alteration in normal microbial flora of body
• Secretion of bacteriocins and nutrition for growth
• Associated with Broad spectrum
• Some conditions like corticosteroid therapy,
Leaukaemias, AIDS, Agranulocytosis, DM, DLE
• Sites –Oropharynx, Intestine, Respiratory &
genitourinary system.
15. Infections like Candida, clostridium difficele,
Proteus& Pseudomonas
Management
Use specific AMA
Do not use for trivial, self limiting infections
Do not unnecessarily prolong AMA therapy
16. PROBLEM CONT…..
• Nutritional deficiencies
• B complex deficiency
• Neomycin causes steatorrohoea & malabsorption
syndrome.
• Masking of infection
• syphilis masked by penicillin used for gonorrhoea
17. GOALS OF AMA THERAPY
• Prophylactic therapy
• Treating pts who are not infected or prevention
of development of disease
• Involved targeted therapy
• Pre- emptive therapy
• Early targeted therapy in infected pt. no
symptom development
• Empirical therapy treatment started without lab
finding
• Definitive therapy specific AMA after culture testing
18. CHOICE OF AMA
• Patient factors
• Age – chloramphenicol causes grey baby
syndrome in new-born, sulfonamides causes
kernicterus in neonate
• Renal and hepatic function
• Local factors - presence of pus, presence of
foreign body, haematoma, anaerobic
environment & penetration barriers
• Drug allergy, pregnancy & genetic factors
19. • Organism related
• Clinical diagnosis of patient
• Good guess of microorganism
• Based on bacteriological examination
• Services not available
• Services are available & treatment can be
delayed
• Services are available & treatment can not be
delayed
20. • Drug factors
• Spectrum of activity
• Type of activity
• Sensitivity of organism
• Relative toxicity
• Dose of drug
• Pharmacokinetic profile
• Route of administration
• Evidence of clinical efficacy
• Cost
21. COMBINATION OF AMA
• Requirement of combination
• Serious infections,
• Critically ill pt,
• Polymicrobial infection,
• Delay resistance
• Objective
• To achieve synergism
• To reduce severity or incidence of ADR
• To prevent resistance
• To broaden the spectrum of action
22. SYNERGISM
• Two bacteriostatic agents are additive
• Sequential block eg. cotrimoxazole
• Inhibition of various stages
• Combination of different mode of action
• Two bactericidal drugs are additive
• Penicillin with gentamycin, ceftazidime with
ciprofloxacin
23. • Decrease of ADR
• Decrease dose in combination
• In low safety margin drugs
• Streptomycin with penicillin
• Amphotercin B with rifampin
• Prevention of emergence of resistance
• Broaden the spectrum
• Treatment of mixed infection
• Initial treatment of sever infection
• Topical use
24. Disadvantages of combination
• Casual rather than rational approach
• Increased incidence & variety of ADR
• Increased chances of super infection
• Emergence of resistance
• Increased cost of therapy
25. Chemoprophylaxs
• It is use of AMA for prevention of setting of infection
or suppressing contacted infection before it
becomes clinically evident
• Against specific organism
• TB – children, HIV positive & susceptible
contacts of positive case (Isoniazid)
• MAC – HIV pts (Azithromycin)
• HIV infection needle injury to HCW (Zidovudine &
lamivudine co)
26. • Gonorrhoea – on contact – (ampicillin)
• Malaria – travellers to endemic areas – mefloquine
or doxycycline
• Cholera – tetracycline to contact
• Plague – doxycycline
27. • Prevention of infection in high risk situations
• Dental extraction, tonsillectomy, endoscopies,
• Catheterisation
• Recurrence of UTI
• COPD
• Immunocompromised patients
• Prophylaxis of infection
• Neonate after instrumental delivery
• To prevent post partum infection
• In unconscious pt
28. Failure of chemotherapy
• Improper selection of AMA
• Too late treatment
• Failure to take necessary adjuvant measures
• Poor host defence
• Trying to treat untreatable
• Presence of dormant organism
29. REFERENCES
• The Pharmacological basis of Therapeutics.
Goodman & Gilman
• Essential of medical pharmacology.
• Medical pharmacology