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Pharmacology Exam 1
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Chemotherapy is the use of drugs to eradicate a parasite
with minimal harm to the host organism
Parasites include
viruses
bacteria
fungi
protozoa
insects
cancer cells
Characteristics of chemotherapeutic agents
more toxic to parasite than host
targets biochemical or physiological differences
restricted distribution of the drug to the infected area
Effectiveness of chemotherapy is related to
the extent of differences between the parasite and the host
for less selective drugs
use higher doses
more toxic to host
bacterial chemotherapy is generally ____ ____ than cancer chemotherapy
more successful
Kirby bauer disc diffusion test
bigger zone of inhibition = better efficacy of the drug
MIC
minimal inhibitory concentration
MBC
minimal bacteriocidal concentration
Log cell kill
drug kills a fixed fraction of parasitic cells
Log cell kill =
-log
10
(surviving fraction)
if one cell in a million survives (surviving fraction 10
-6
)
6 log kill
log kill to kill everything in the body
7 log kill
Total cell kill concept is usually not used because of
toxicity
3 log kill, 1 log regrowth used in
cancer chemotherapy
5 major targets of chemotherapy
inhibition of cell wall synthesis
inhibition of protein synthesis
inhibition of nucleic acid replication & transcription
inhibition of synthesis of essential metabolites
injury to plasma cell membrane
Drugs that inhibit cell wall synthesis
PCN
Cephalosporins
bacitracin
vancomycin
Drugs that inhibit protein synthesis
chloramphenicol
erythromycin
tetracyclines
streptomycin
Drugs that inhibit nucleic acid replication and transcription
quinolones
rifampin
drugs that cause injury to plasma membrane
polymyxin B
Drugs that inhibit synthesis of essential metabolites
sulfanilamide
trimethoprim
If there is no immune response
drugs may have to kill every parasitic cell
cancer
Reasons for absence of immune response
impaired immune system (aids)
use of immunosuppressant drugs (inhibition of Tcell activation)
parasite evasion of immune response (helminths)
parasite does not evoke immune response (cancer)
The basis of chemotherapy is that:
A. a drug needs to be more toxic to the parasite than the host.
B. There needs to be a mechanistic difference between parasite and host cells
C. A& B
D. A drug needs to enhance immune response
E. None of the above
C. A&B
If two drugs are given simultaneously or successively and thier mechanisms of action are independant, their log cell kill is
additive
If two drugs are given simultaneously or successively and their mechanisms are complementary the log cell cill may be
synergistic
FIC index =
(MIC A + B)/A + (mic B+A)/B
FIC = 1
additive
FIC < 1
synergistic
FIC > 1
antagonistic
Advantages of combo chemotherapy
treatment of mixed bacerial infections
therapy of severe infection of unknown cause
prevention of resistance
Disadvantages of combo chemotherapy
toxicity
misuse of antibiotics
treatment of untreatable disease
treatment of fever of unknon cause
improper dosage
Combo therapy for TB
4-5 drugs for 6 months
combotherapy for HIV-1
life time therapy
Mechanisms of drug resistance
transformation
conjugation
transduction
Transformation
bacterial cell lysis upon death releases mutated DNA which travels to healthy bacteria
Conjugation
one cell creates resistance and fuses with another to transfer mutated DNA
Transduction
mutated DNA transfered through a viral particle
Sites of drug resistance
drug uptake
drug efflux
increased rate of drug inactivation
altered amount or decreased affinity of target receptor
Decreased drug uptake
methotrexate (cancer)
Chloroquine (bacterial)
Increased efflux of the drug
drugs for TB and Cancer
MRP and ABC
increased rate of drug inactivation example
penicillinase (beta lactamase) in bacteria
Altered amount or decreased affinity of target receptors examples
high levels of dihydrofolate reductase (tumor and methotrexate)
RNA polymerase fails to bind rifampicin (streptomyces)
Toxicity
limiting factor
independent of therapeutic mechanisms
Therapeutic index
LD50/ED50
Standard safety margin (SSM)
LD1-ED99/ED99
SSM vs TI
SSM is more useful
Larger margin between ED99 and LD1 =
better drug
% of drugs eliminated during testing due to toxicity
31%
Cyclophosphamide may be given by what routes?
intravenous
oral
Cyclophosphamide is a prodrug activated by
CYP2D6 in the liver
CYP450 based Gene directed enzyme prodrug therapy allows for
localized delivery of drug to effected cells
drug is activated at the target cell not in liver
effects neighboring cells but not entire body
increased efficacy
Author
Rx2013
ID
59581
Card Set
Pharmacology Exam 1
Description
Intro to chemotherapy I
Updated
2011-01-13T16:04:30Z
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