9. DRUG BINDS TO MOA
AMINOGLYCOSIDES 30S mainly FREEZING OF INITIATION
MISREADING OF mRNA code
TETRACYCLINES 30S Inhibit aminoacyl tRNA attachment
to A site.
CHLORAMPHENICOL 50S Inhibits peptidyl transferase that
results in the inhibition of peptide
bond formation and transfer of
peptide chain from P to A site.
MACROLIDES
LINCOSAMIDES
TETRACYCLINES
50S Inhibit translocation of peptide chain
from A to P site
LINEZOLID 50S Inhibit initiation
10. • Buy AT 30 and SELL at 50.
• AT : Aminoglycosides and Tetracyclines-
30S
• SELL:
Streptogramins,Erythromycin,Lincosamide
,Linezolid.-50S
11. DRUGS AFFECTING CELL
MEMBRANE
• These drugs act by causing disruption of cell
membrane and leakage of ions and molecules
from the cell. These drugs include:
• POLYPEPTIDE ANTIBIOTICS: Polymyxin B,
Colistin,
• POLYENE ANTIBIOTICS: Amphotericin B,
nystatin, Natamycin.
• AZOLES: Ketoconazole, fluconazole,
Itraconazole.
12. DRUGS AFFECTING NUCLEIC
ACIDS (DNA and RNA)
• DNA GYRASE INHIBITORS
• RNA POLYMERASE INHIBITORS
• DRUGS DESTROYING DNA
• NUCLEOTIDE/NUCLEOSIDE
ANALOUGES
18. PROBLEMS FROM AMAs.
TOXICITY : Local / Systemic.
HYPERSENSITIVITY REACTIONS.
DRUG RESISTANCE
SUPERINFECTION
NUTRITIONAL DEFICIENCIES
MASKING OF AN INFECTION
19. DRUG RESISTANCE
• Refers to unresponsiveness of a
microorganism to an AMA, similar to the
phenomenon of tolerance seen in higher
organisms.
NATURAL
AQUIRED
20. NATURAL RESISTANCE
Lack of metabolic process or target site
which is affected by the particular drug.
This is characteristic of the group or
species.
Gm-ve bacilli unaffected by penicillin G.
Aerobic organisms unaffected by
metronidazole.
21. ACQUIRED RESISTANCE
Development of resistance due to the use
of an AMA over a period of time.
This is a major clinical problem.
Rapid acquisition of resistance:
Staphylococci,Tubercle Bacilli, Coliforms.
This type of resistance develops either by:
MUTATION
GENE TRANSFER
22. MUTATION
aka : VERTICAL RESISTANCE.
Relatively slow and of low grade.
25. GENE TRANSFER
• The resistance causing gene is passed from
one organism to the other.
• aka HORIZONTAL TRANSFER.
• Rapid and can cause multidrug resistance.
• Occurs via:
# CONJUGATION
# TRANSDUCTION
#TRANSFORMATION
26. THREE TYPES OF
RESISTANT ORGANISMS
DRUG TOLERANT : loss of affinity of the
target biomolecule of the microorganism
for a particular AMA.
DRUG DESTROYING: The resistant
microbe elaborates an enzyme which
inactivates the drug.
DRUG IMPERMEABLE: Loss of certain
specific channels / porins via which AMA
enters into the microorganism.
27. CROSS RESISTANCE
• Aquistion of resistance to one AMA
conferring resistance to another AMA, to
which the organism has not been
exposed.
• Usually occurs between chemically related
drugs.
28. How do we prevent resistance?
Avoid unnecessary use and prolongation
of AMAs.
Prefer rapidly acting and selective (narrow
spectrum ) drugs whenever possible.
Use combined therapy whenever there is
need of prolonged therapy. Eg. TB, SABE.
Intensive treatment of infections which
develop resistance rapidly.
29. SUPERINFECTION
• Refers to the appearance of a new
infection as a result of AMA therapy.
• Mainly due to supression of normal flora of
the body.
• Frequently involved organisms:
Candida Albicans
Resistant staphylococci
Clostridium difficle
Proteus
Pseudomonas
30. Conditions predisposing to
superinfection…
Corticosteroid therapy.
Leukemias and other malignancies.
AIDS.
Agranulocytosis.
Diabetes.
Disseminated lupus erythomatosus(DLE)
31. Choosing an AMA
• PATIENT FACTORS
• ORGANISM RELATED CONSIDERATIONS
• DRUG FACTORS
32. PATIENT FACTORS
Age
Renal and Hepatic function
Local factors like the presence of pus
decreases efficacy;the presence of
necrotic matter or foreign body decreases
penetration of drug.
Drug allergy
Pregnancy
Genetic factors
33. Organism related factors
Clinical diagnosis itself directs choice of
AMA.
Choice based on bacteriological
examinations
34. Drug factors
Spectrum of activity.
Type of activity.
Sensitivity to organism.
Relative toxicity.
Pharmacokinetics of the drug.
Route of administration.
Cost.
35. Combined use of AMA
To achieve synergism
To reduce severity or incidence of adverse
effects.
To prevent emergence of resistance.
To broaden the spectrum of antimicrobial
action
Treat mixed infection.
Initial treatment of severe infections.
Topical application.
36. PROPHYLACTIC USE OF
AMAs.
• Refers to the use of AMAs for preventing
the setting in of an infection, or supressing
contacted infection before it manifests
clinically.
• Difference b/w treating and preventing
infections?
37. treatment is directed against a specific
organism infecting an individual.
Prophylaxis is against all organisms
capable of causing infection.
Prophylaxis against specific organisms.
Prevention of infection in high risk
situations
Prevention of infection in general
38. Rheumatic fever- penicillinG
TB – given to children & HIV +ve : INH+Rmp
MAC – in HIV+ve : azithro/clarithro.
HIV – zidovudine+ lamivudine +/- indinavir
Meningococcal Meningitis : Rmp/
Ceftriaxone/ Suphazidine.
Malaria : travel prophylaxis : chloroquine
Cholera : tetracycline.
40. High risk situations
• Dental extraction, tonsillectomy : there is
ed risk of endocarditis – amoxy / clinda
• Catheterization / instrumentation of urinary
tract : cotrimox / norflox ; In patients with
valvular heart dz: ampi / genta.
• COPD/ Chr. Bronchitis : ampi / doxy/ cipro
• Immunocompromised : penicillin/ cephalo
41. Prevention in general
• Neonates
• Viral URTI : to prevent 2nd ry bacterial
infection.
• Prevent respiratory infections in patients
on ventilators.
