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CHEMOTHERAPY
Antimicrobial
Antiviral
chemotherapy
Antiparasitic
Cancer
chemotherapy
Drugs
Chemotherapy
CHEMOTHERAPY
Concepts
Many
easy to understand.
distinct diseases so less
prototype drugs.
ANTIBIOTICS
General
Principles
Mechanism
of Action
Pharmacokinetics/Therapeutic
Adverse
effects
Uses
STUDY AIDS
Objectives
Summary
tables
STUDY AIDS
Review
questions on web:
http://info.unmc.edu/scholarchemo1/
AntiBio/AntibioTestframe.htm
STUDY AIDS
http://dev1.unmc.edu/JeopardyGame/A
ntibiotics.htm
http://dev1.unmc.edu/JeopardyGame/A
ntibioticsDouble.htm
ANTIMICROBIAL
CHEMOTHERAPY
Selective
Toxicity
CHEMOTHERAPY
Allows
the normal hostdefense mechanisms to
gain control.
CLASSIFICATION OF
CHEMOTHERAPEUTIC
AGENTS
Control
Number of
bacteria
Bacteriostatic agent
Bactericidal agent
Time
BACTERIOSTATIC DRUGS
Sulfonamides
Erythromycin
Tetracyclines
BACTERICIDAL DRUGS
Trimethoprim
+Sulfamethoxazole
Aminoglycosides
β-lactams
Inhibit Protein Synthesis
Nucleic acid synthesis
Cell membrane
Permeability
T
XXXX
Cell Wall Synthesis
Antimetabolites
CHOICE OF THE
ANTIBIOTIC
First
determine etiology of the
infection.
CHOICE OF THE
ANTIBIOTIC
Sensitivity
pattern of the infecting
organism must be determined.
Consider pharmacokinetics and host
factors.
PHARMACOKINETIC
FACTORS
Location
Route
of Infection.
of Administration.
Pattern
of excretion, metabolism, and
degree of protein binding.
HOST FACTORS
Host
defense (Immunocompetence).
Local factors.
Age.
Genetic
Drug
factors.
Allergy.
HOST FACTORS
Renal
disease and liver disease.
AIDS
Pregnancy.
USES OF ANTIBIOTICS
Empirical
antimicrobial therapybefore the pathogen is known.
Infections
with known etiology.
MISUSES OF ANTIBIOTICS
Treatment
of nonresponsive
infections.
Therapy
of fever of unknown origin
Fever of short duration
Fever persisting for 2 or more weeks.
MISUSES OF ANTIBIOTICS
Dosing
errors
Wrong frequency
Excessive or subtherapeutic doses
MISUSES OF ANTIBIOTICS
Inappropriate
reliance on
chemotherapy alone (e.g.
abscesses).
MISUSES OF ANTIBIOTICS
Lack
of adequate bacteriological
information.
• Absence of supporting data
• Agents selected by habit
• Doses are routine, rather than individualized
COMBINATION
CHEMOTHERAPY
Separate
but simultaneous
administration.
Combination ChemotherapyAdvantages
Treatment
of polymicrobial
infections.
Prevent
or delay resistance.
Synergy.
Combination ChemotherapyAdvantages
Severe
infections of unknown
etiology-empirical therapy.
DISADVANTAGES
Increased
risk of toxicity.
Increased
likelihood of
superinfections.
Increased
cost.
Antagonism
of an antibacterial effect.
FIXED DOSE
COMBINATIONS
Ratio
and dose of antibiotics are
determined based on in vitro studies.
Encourages
inadequate treatment.
PROPHYLAXIS OF INFECTION
This
should be used only in
circumstances in which efficacy has
been demonstrated and the benefits
outweigh the risks.
PROPHYLAXIS OF
INFECTION
Effective
when a single drug is used
to prevent infection from a specific
microorganism.
In
patients undergoing organ
transplantation or receiving cancer
chemotherapy.
PROPHYLAXIS OF INFECTION
Primary
and 2ndary prevention of
opportunistic infections in AIDS
patients when CD4 counts are below
certain threshholds.
PROPHYLAXIS OF INFECTION
To
prevent wound infections after
various surgical procedures.
Complications of Antimicrobial
Therapy
Drug
Resistance
Superinfections
Toxicity
DRUG RESISTANCE
Involves
a stable genetic change in
the bacteria.
DRUG RESISTANCE
Mutation
and selection with passage
vertically.
Horizontal
transfer from a donor cell
by transduction, transformation or
conjugation.
MUTATION-SELECTION
Occurs
in many different genes.
Random
events that confer a survival
advantage when a drug is present.
CHROMOSOMAL MUTATIONS
Antibiotics
agents.
are acting as selecting
+ Antibiotic
Resistant Population
HORIZONTAL GENE TRANSFER
Mobile
genetic elements (plasmids,
transposable elements, integrons,
gene cassettes).
Transduction
Transformation
CONJUGATION
Direct cell to cell contact through a sex
pilus or bridge
Very important for the spread of
resistance because multiple resistance
genes can be transferred
simultaneously.
Enzyme Inactivation
Altered Permeability
Mod. of target site
and reduced affinity
CROSS-RESISTANCE
e.g. sulfonamides, penicillins
PREVENTION OR DELAY OF
RESISTANCE
Judicious
(appropriate) or careful
use of antibiotics
Adequate
Dosage
Combination
Chemotherapy
SUPERINFECTIONS
A
new infection appearing during the
chemotherapy of a primary one.
Caused
by removing inhibitory
influence of the normal flora.
+ Antibiotic
(Broad spectrum)
Resistant pathogen
Secondary infection from
resistant organisms
TREATMENT OF THE
SUPERINFECTION
Stop
present therapy.
Culture
Treat
infected area.
against the offending
microorganism.
TOXICITY
Hypersensitivity
Direct
Toxicity- GI