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2.Chemotherapy
&
Antimicrobial Agents
Dr.Saroj K. Suwal
Contents
 Introduction to chemotherapy
 Chemotherapy terminologies
 Selective Toxicity
 Bacteriostatic
 Bactericidal
 Narrow Spectrum
 Extended Spectrum
 Broad Spectrum
 Antimicrobial agents
CHEMOTHERAPY
 Treatment of disease by chemicals that kill the cells or
microorganism or cancer cells
 If directed to cancer cells→ cancer chemotherapy
 If directed to micro-organism→ Antibiotics
General Principles of Chemotherapy
Diagnosis
Indication of chemotherapy
Selections of drugs , dose
and route of administration
Duration of therapy
Drug therapy
Test for cure
Prophylactic drug
Diagnosis:
Site of Infections
Responsible organism
Sensitivity of drug
Indication of chemotherapy
 May or may not need the antibiotics medicine
→so, need to identify
 Sore throat, common cold may not need the
antibiotics
 If viral→ no need antibiotics, will recover within 5-
7 days
 But if bacterial →may need of antibiotics
Selection of Drugs
 Is based on the cost effectiveness of drug, safety and
toxicity .
 Can be targeted and empirical chemotherapy
 Targeted chemotherapy
 Chemotherapy according to culture sensitivity
 Cancer drugs, treatment after confirmation of organism
 Empirical chemotherapy
 According to practice of doctors
 According to epidemiological pattern to disease
 Extent of disease in community
Selection of dose
 Should be enough to achieve minimum
inhibitory concentration(MIC)
 MIC
 Minimum effect of antibiotics require to
suppress microorganism or to achieve
therapeutic effect
Route of administrations
 In order to achieve MIC
and drug reaches the site
of action
 Different routes has its
own benefits
aminoglycoside like streptomycin if
given orally its not effective( a polar
compound)
Duration of therapy
 Depends of type of disease
 Most drug → minimum 48
hours even after symptoms
subsides
 Antibiotics—>5-10 days
Acute -5-10 days
Subacute-2-3 wks
Chronic – several months
Some chronic disease
Tuberculosis → 6-9 months
Extra pul tuberculosis > 9-12-18 months…
Leprosy > one 1yr
Drug therapy
 Mono drug therapy
 Better tolerated
 Cost effective
 Chance of drug interaction less
 Combination drug therapy
 Eg. Tuberculosis
 Advantage
 Achieve synergism,less side effect,inscrease spectrum
Change of drug during therapy
 Frequent change is not good
 Enough time give so that it can be goodly
absorbed, reach site of action and produce
pharmacological effects
Removal of barriers for site of
administration
 Remove the pus or necrotic tissue
 Drainage of pus incase of abscess
Chemoprophylaxis( Prophylaxis )
 Prevention of disease or infections by chemotherapy
 Non Surgical prophylaxis
 Rheumatic fever →long acting penicillin
 Person travelling endemic area of malaria → mefloquinine or primaquine
 DVT prophylaxis in bed ridden patient
 Surgical
 Purpose is to decrease the adverse effect
 Prevent further infection
 Given if surgical hours is two or more hours(esp. GI surgery, musculoskeletal surgeries etc
Adverse effect of antimicrobial agents(AMAs)
 Toxicity
 Hypersensitivity
 Drug resistance
 Super infection
 Nutritional deficiency
 Masking of infection
Toxicity
 Selective toxicity or no toxicity
 ability to kill an invading microorganism without harming the
cells of host
 Local toxicity
 Local irritation at site of administration
 → pain and abscess by i/m drug
 Thrombophlebitis on iv drug
 Systematic toxicity
 agent which have low Therapeutic index exhibit more toxicity
 Aminoglycoside→ototoxicity
 Chloramphenicol→bonemarrow suppression
Therapeutic Window : Drug
effect between desired
response and adverse respone
Hypersensitivity Reaction
 4 types of reaction (EGGT)
 Skin rash and anaphylactic shock
 Usually seen penicillin and
cephalosporin
Drug Resistance
 Unresponsiveness of microorganism to
antibiotics
 Two types
 Natural resistance
 g positive—not affected g negative
 existed before antibiotic use
 Acquired resistance
 Resistance by prolong use of antibiotics
 mutation in gene(conguation, transduction, transformation of
gene
Super Infection
Leads to superinfection
Change to flora of bacteria
By using more antibiotics
Nutritional deficiency
 Prolong use of antibiotics
alters the normal flora
 Cause different deficiency
of vitamins and minerals
Different Drugs induced nutritional
deficiency
masking of infection
 Short course of antibiotics may be
sufficient to treat one infection
 but suppresses other
 other will mask for short time and cause
severe form
Bacteria
 Gram Positive Bacteria
Takes gram stain
 Gram Negative Bacteria
Don’t take gram stain
• Inhibition of cell wall
synthesis
• Inhibition of protein
synthesis
• Inhibition of nucleic acid
synthesis
• Inhibition of metabolic
pathways
• Interference with cell
membrane integrity
B. Mechanism of Action
D. Spectrum of activity
 Narrow spectrum
 Only effective against certain specific family of bacteria
 gram positive or Negative only
 eg. streptomycin, erythromycin
 Broad Spectrum
 Effective against wide range of microorganism
 Both Gram Positive and Negative
 Tetracycline, chloramphenicol, cephalosporin
 Extended Spectrum
 Gram positive and negative with other microbes
 Tazobactam, meropenam
E. Type of Action
 Bacteriostatic
 inhibit growth of Bacteria
 Clindamycin, tetracyclines
 Bactericidal
 Kill the microbes
 Penicillins, amminogycosides, ciprofloxacin, metronidazole
F. Source of antibiotics

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2.1 Chemotherapy and antimicrobial agents

  • 2. Contents  Introduction to chemotherapy  Chemotherapy terminologies  Selective Toxicity  Bacteriostatic  Bactericidal  Narrow Spectrum  Extended Spectrum  Broad Spectrum  Antimicrobial agents
  • 3. CHEMOTHERAPY  Treatment of disease by chemicals that kill the cells or microorganism or cancer cells  If directed to cancer cells→ cancer chemotherapy  If directed to micro-organism→ Antibiotics
  • 4. General Principles of Chemotherapy Diagnosis Indication of chemotherapy Selections of drugs , dose and route of administration Duration of therapy Drug therapy Test for cure Prophylactic drug
  • 5. Diagnosis: Site of Infections Responsible organism Sensitivity of drug
  • 6. Indication of chemotherapy  May or may not need the antibiotics medicine →so, need to identify  Sore throat, common cold may not need the antibiotics  If viral→ no need antibiotics, will recover within 5- 7 days  But if bacterial →may need of antibiotics
  • 7. Selection of Drugs  Is based on the cost effectiveness of drug, safety and toxicity .  Can be targeted and empirical chemotherapy  Targeted chemotherapy  Chemotherapy according to culture sensitivity  Cancer drugs, treatment after confirmation of organism  Empirical chemotherapy  According to practice of doctors  According to epidemiological pattern to disease  Extent of disease in community
  • 8. Selection of dose  Should be enough to achieve minimum inhibitory concentration(MIC)  MIC  Minimum effect of antibiotics require to suppress microorganism or to achieve therapeutic effect
  • 9. Route of administrations  In order to achieve MIC and drug reaches the site of action  Different routes has its own benefits aminoglycoside like streptomycin if given orally its not effective( a polar compound)
  • 10. Duration of therapy  Depends of type of disease  Most drug → minimum 48 hours even after symptoms subsides  Antibiotics—>5-10 days Acute -5-10 days Subacute-2-3 wks Chronic – several months Some chronic disease Tuberculosis → 6-9 months Extra pul tuberculosis > 9-12-18 months… Leprosy > one 1yr
  • 11. Drug therapy  Mono drug therapy  Better tolerated  Cost effective  Chance of drug interaction less  Combination drug therapy  Eg. Tuberculosis  Advantage  Achieve synergism,less side effect,inscrease spectrum
  • 12. Change of drug during therapy  Frequent change is not good  Enough time give so that it can be goodly absorbed, reach site of action and produce pharmacological effects
  • 13. Removal of barriers for site of administration  Remove the pus or necrotic tissue  Drainage of pus incase of abscess
  • 14. Chemoprophylaxis( Prophylaxis )  Prevention of disease or infections by chemotherapy  Non Surgical prophylaxis  Rheumatic fever →long acting penicillin  Person travelling endemic area of malaria → mefloquinine or primaquine  DVT prophylaxis in bed ridden patient  Surgical  Purpose is to decrease the adverse effect  Prevent further infection  Given if surgical hours is two or more hours(esp. GI surgery, musculoskeletal surgeries etc
  • 15. Adverse effect of antimicrobial agents(AMAs)  Toxicity  Hypersensitivity  Drug resistance  Super infection  Nutritional deficiency  Masking of infection
  • 16. Toxicity  Selective toxicity or no toxicity  ability to kill an invading microorganism without harming the cells of host  Local toxicity  Local irritation at site of administration  → pain and abscess by i/m drug  Thrombophlebitis on iv drug  Systematic toxicity  agent which have low Therapeutic index exhibit more toxicity  Aminoglycoside→ototoxicity  Chloramphenicol→bonemarrow suppression
  • 17. Therapeutic Window : Drug effect between desired response and adverse respone
  • 18. Hypersensitivity Reaction  4 types of reaction (EGGT)  Skin rash and anaphylactic shock  Usually seen penicillin and cephalosporin
  • 19. Drug Resistance  Unresponsiveness of microorganism to antibiotics  Two types  Natural resistance  g positive—not affected g negative  existed before antibiotic use  Acquired resistance  Resistance by prolong use of antibiotics  mutation in gene(conguation, transduction, transformation of gene
  • 20. Super Infection Leads to superinfection Change to flora of bacteria By using more antibiotics
  • 21. Nutritional deficiency  Prolong use of antibiotics alters the normal flora  Cause different deficiency of vitamins and minerals
  • 22. Different Drugs induced nutritional deficiency
  • 23. masking of infection  Short course of antibiotics may be sufficient to treat one infection  but suppresses other  other will mask for short time and cause severe form
  • 24. Bacteria  Gram Positive Bacteria Takes gram stain  Gram Negative Bacteria Don’t take gram stain
  • 25.
  • 26.
  • 27. • Inhibition of cell wall synthesis • Inhibition of protein synthesis • Inhibition of nucleic acid synthesis • Inhibition of metabolic pathways • Interference with cell membrane integrity B. Mechanism of Action
  • 28.
  • 29. D. Spectrum of activity  Narrow spectrum  Only effective against certain specific family of bacteria  gram positive or Negative only  eg. streptomycin, erythromycin  Broad Spectrum  Effective against wide range of microorganism  Both Gram Positive and Negative  Tetracycline, chloramphenicol, cephalosporin  Extended Spectrum  Gram positive and negative with other microbes  Tazobactam, meropenam
  • 30. E. Type of Action  Bacteriostatic  inhibit growth of Bacteria  Clindamycin, tetracyclines  Bactericidal  Kill the microbes  Penicillins, amminogycosides, ciprofloxacin, metronidazole
  • 31. F. Source of antibiotics