CHEMOTHERAPY Antimicrobial chemotherapy Antiviral chemotherapy Antiparasitic Drugs Cancer Chemotherapy.
Post on 24-Dec-2015
285 Views
Preview:
Transcript
CHEMOTHERAPYCHEMOTHERAPY
Antimicrobial chemotherapyAntimicrobial chemotherapy
Antiviral chemotherapyAntiviral chemotherapy
Antiparasitic DrugsAntiparasitic Drugs
Cancer ChemotherapyCancer Chemotherapy
CHEMOTHERAPYCHEMOTHERAPY
Concepts easy to understand.Concepts easy to understand.
Many distinct diseases so less Many distinct diseases so less prototype drugs.prototype drugs.
ANTIBIOTICSANTIBIOTICS
General PrinciplesGeneral Principles
Mechanism of Action Mechanism of Action
Pharmacokinetics/Therapeutic UsesPharmacokinetics/Therapeutic Uses
Adverse effectsAdverse effects
STUDY AIDSSTUDY AIDS
ObjectivesObjectives
Summary tablesSummary tables
STUDY AIDSSTUDY AIDS
Review questions on web: Review questions on web: http://info.unmc.edu/scholarchemo1/http://info.unmc.edu/scholarchemo1/AntiBio/AntibioTestframe.htmAntiBio/AntibioTestframe.htm
STUDY AIDSSTUDY AIDS
http://dev1.unmc.edu/JeopardyGame/Antibiotics.htm
http://dev1.unmc.edu/JeopardyGame/AntibioticsDouble.htm
ANTIMICROBIAL ANTIMICROBIAL CHEMOTHERAPYCHEMOTHERAPY
Selective ToxicitySelective Toxicity
CHEMOTHERAPYCHEMOTHERAPY
Allows the normal host-Allows the normal host-defense mechanisms to defense mechanisms to gain control.gain control.
CLASSIFICATION OF CLASSIFICATION OF CHEMOTHERAPEUTIC CHEMOTHERAPEUTIC AGENTSAGENTS
TimeTime
Nu
mb
er o
f N
um
ber
of
bac
teri
ab
acte
ria
ControlControl
Bacteriostatic agentBacteriostatic agent
Bactericidal agentBactericidal agent
BACTERIOSTATIC DRUGSBACTERIOSTATIC DRUGS
SulfonamidesSulfonamides
ErythromycinErythromycin
TetracyclinesTetracyclines
BACTERICIDAL DRUGSBACTERICIDAL DRUGS
Trimethoprim +SulfamethoxazoleTrimethoprim +Sulfamethoxazole
AminoglycosidesAminoglycosides
ββ-lactams-lactams
TT
AntimetabolitesCell Wall Synthesis
Inhibit Protein SynthesisNucleic acid synthesis
XXXXXXXX
Cell membrane Permeability
CHOICE OF THE CHOICE OF THE ANTIBIOTICANTIBIOTIC
First determine etiology of the First determine etiology of the infection.infection.
CHOICE OF THE CHOICE OF THE ANTIBIOTICANTIBIOTIC
Sensitivity pattern of the infecting Sensitivity pattern of the infecting organism must be determined.organism must be determined.
Consider pharmacokinetics and host Consider pharmacokinetics and host factors.factors.
PHARMACOKINETIC PHARMACOKINETIC FACTORSFACTORS
Location of Infection.Location of Infection.
Route of Administration.Route of Administration.
Pattern of excretion, metabolism, and Pattern of excretion, metabolism, and degree of protein binding.degree of protein binding.
HOST FACTORSHOST FACTORS
Host defense (Immunocompetence).Host defense (Immunocompetence).
Local factors.Local factors.
Age. Age.
Genetic factors.Genetic factors.
Drug Allergy.Drug Allergy.
HOST FACTORSHOST FACTORS
Renal disease and liver disease.Renal disease and liver disease.
AIDSAIDS
Pregnancy.Pregnancy.
USES OF ANTIBIOTICSUSES OF ANTIBIOTICS
Empirical antimicrobial therapy- Empirical antimicrobial therapy- before the pathogen is known.before the pathogen is known.
Infections with known etiology.Infections with known etiology.
MISUSES OF ANTIBIOTICSMISUSES OF ANTIBIOTICS
Treatment of nonresponsive Treatment of nonresponsive infections.infections.
Therapy of fever of unknown originTherapy of fever of unknown origin
Fever of short durationFever of short durationFever persisting for 2 or more weeks.Fever persisting for 2 or more weeks.
MISUSES OF ANTIBIOTICSMISUSES OF ANTIBIOTICS
Dosing errorsDosing errorsWrong frequencyWrong frequencyExcessive or subtherapeutic dosesExcessive or subtherapeutic doses
MISUSES OF ANTIBIOTICSMISUSES OF ANTIBIOTICS
Inappropriate reliance on Inappropriate reliance on chemotherapy alone (e.g. chemotherapy alone (e.g. abscesses).abscesses).
MISUSES OF ANTIBIOTICSMISUSES OF ANTIBIOTICS
Lack of adequate bacteriological Lack of adequate bacteriological information.information.
• Absence of supporting dataAbsence of supporting data
• Agents selected by habitAgents selected by habit
• Doses are routine, rather than individualizedDoses are routine, rather than individualized
COMBINATION COMBINATION CHEMOTHERAPYCHEMOTHERAPY
Separate but simultaneous Separate but simultaneous administration.administration.
Combination Chemotherapy- Combination Chemotherapy- AdvantagesAdvantages
Treatment of polymicrobial Treatment of polymicrobial infections.infections.
Prevent or delay resistance.Prevent or delay resistance.
Synergy.Synergy.
Combination Chemotherapy- Combination Chemotherapy- AdvantagesAdvantages
Severe infections of unknown Severe infections of unknown etiology-empirical therapy.etiology-empirical therapy.
DISADVANTAGESDISADVANTAGES
Increased risk of toxicity.Increased risk of toxicity.
Increased likelihood of Increased likelihood of superinfections.superinfections.
Increased cost.Increased cost.
Antagonism of an antibacterial effect.Antagonism of an antibacterial effect.
FIXED DOSE FIXED DOSE COMBINATIONSCOMBINATIONS
Ratio and dose of antibiotics are Ratio and dose of antibiotics are determined based on determined based on in vitroin vitro studies. studies.
Encourages inadequate treatment.Encourages inadequate treatment.
PROPHYLAXIS OF INFECTIONPROPHYLAXIS OF INFECTION
This should be used only in This should be used only in circumstances in which efficacy has circumstances in which efficacy has been demonstrated and the benefits been demonstrated and the benefits outweigh the risks.outweigh the risks.
PROPHYLAXIS OF PROPHYLAXIS OF INFECTIONINFECTION
Effective when a single drug is used Effective when a single drug is used to prevent infection from a specific to prevent infection from a specific microorganism. microorganism.
In patients undergoing organ In patients undergoing organ transplantation or receiving cancer transplantation or receiving cancer chemotherapy.chemotherapy.
PROPHYLAXIS OF INFECTIONPROPHYLAXIS OF INFECTION
Primary and 2ndary prevention of Primary and 2ndary prevention of opportunistic infections in AIDS opportunistic infections in AIDS patients when CD4 counts are below patients when CD4 counts are below certain threshholds.certain threshholds.
PROPHYLAXIS OF INFECTIONPROPHYLAXIS OF INFECTION
To prevent wound infections after To prevent wound infections after various surgical procedures.various surgical procedures.
Complications of Antimicrobial Complications of Antimicrobial TherapyTherapy
Drug ResistanceDrug Resistance
SuperinfectionsSuperinfections
ToxicityToxicity
DRUG RESISTANCEDRUG RESISTANCE
Involves a stable genetic change in Involves a stable genetic change in the bacteria.the bacteria.
DRUG RESISTANCEDRUG RESISTANCE
Mutation and selection with passage Mutation and selection with passage vertically.vertically.
Horizontal transfer from a donor cell Horizontal transfer from a donor cell by transduction, transformation or by transduction, transformation or conjugation. conjugation.
MUTATION-SELECTIONMUTATION-SELECTION
Occurs in many different genes.Occurs in many different genes.
Random events that confer a survival Random events that confer a survival advantage when a drug is present.advantage when a drug is present.
CHROMOSOMAL MUTATIONSCHROMOSOMAL MUTATIONS
Antibiotics are acting as selecting Antibiotics are acting as selecting agents.agents.
+ Antibiotic+ Antibiotic
Resistant PopulationResistant Population
HORIZONTAL GENE HORIZONTAL GENE TRANSFERTRANSFER
Mobile genetic elements (plasmids, Mobile genetic elements (plasmids, transposable elements, integrons, transposable elements, integrons, gene cassettes).gene cassettes).
TransductionTransduction
TransformationTransformation
CONJUGATIONCONJUGATION
Direct cell to cell contact through a sex Direct cell to cell contact through a sex pilus or bridgepilus or bridge
Very important for the spread of Very important for the spread of resistance because multiple resistance resistance because multiple resistance genes can be transferred genes can be transferred simultaneously.simultaneously.
Enzyme Inactivation
Altered Permeability
Mod. of target siteand reduced affinity
CROSS-RESISTANCECROSS-RESISTANCE
e.g. sulfonamides, penicillinse.g. sulfonamides, penicillins
PREVENTION OR DELAY OF PREVENTION OR DELAY OF RESISTANCERESISTANCE
Judicious (appropriate) or careful Judicious (appropriate) or careful use of antibioticsuse of antibiotics
Adequate DosageAdequate Dosage
Combination ChemotherapyCombination Chemotherapy
SUPERINFECTIONSSUPERINFECTIONS
A new infection appearing during the A new infection appearing during the chemotherapy of a primary one.chemotherapy of a primary one.
Caused by removing inhibitory Caused by removing inhibitory influence of the normal flora.influence of the normal flora.
+ Antibiotic + Antibiotic (Broad spectrum)(Broad spectrum)
Resistant pathogenResistant pathogen
Secondary infection from Secondary infection from resistant organismsresistant organisms
TREATMENT OF THE TREATMENT OF THE SUPERINFECTIONSUPERINFECTION
Stop present therapy.Stop present therapy.
Culture infected area.Culture infected area.
Treat against the offending Treat against the offending microorganism.microorganism.
TOXICITYTOXICITY
HypersensitivityHypersensitivity
Direct Toxicity- GIDirect Toxicity- GI
BACTERICIDAL AGENTSBACTERICIDAL AGENTS
Drugs whose killing action is time Drugs whose killing action is time dependent don’t show increased dependent don’t show increased killing above MBC; bactericidal killing above MBC; bactericidal activity continues as long as the activity continues as long as the serum concns. exceed MBC.serum concns. exceed MBC.
GramGram++
GramGram__
GramGram++
GramGram
__
RickettsiaRickettsia
AmoebaAmoeba
Drug Concentration on Drug Concentration on microbial killingmicrobial killing
AUC:MIC (area under the serum AUC:MIC (area under the serum concentration time curve: minimal concentration time curve: minimal inhibitory concentration).inhibitory concentration).
Peak serum concentration:MICPeak serum concentration:MIC
Appropriate Dose of Appropriate Dose of Antimicrobial AgentAntimicrobial Agent
Principles of pharmacokinetics and Principles of pharmacokinetics and pharmacodynamics are used to pharmacodynamics are used to determine this.determine this.
Appropriate Dose of Antimicrobial Appropriate Dose of Antimicrobial AgentAgent
Pharmacodynamic factors include Pharmacodynamic factors include cidal vs static activity and cidal vs static activity and postantibiotic effects.postantibiotic effects.
CIDAL VS STATIC CIDAL VS STATIC
For primarily static agents inhibitory For primarily static agents inhibitory drug concn’s are much lower than drug concn’s are much lower than cidal concn’s.cidal concn’s.
Usually cell wall active drugs are Usually cell wall active drugs are cidal and protein synthesis inhibitors cidal and protein synthesis inhibitors are static.are static.
CIDAL VS STATICCIDAL VS STATIC
Some agents that are considered to Some agents that are considered to be static may be cidal vs selected be static may be cidal vs selected organisms.organisms.
CIDAL VS STATICCIDAL VS STATIC
Static and cidal agents are equivalent Static and cidal agents are equivalent for immunocompetent hosts.for immunocompetent hosts.
Cidal agents should be used when Cidal agents should be used when host defenses are impaired.host defenses are impaired.
CIDAL VS STATICCIDAL VS STATIC
Bactericidal agents can be divided Bactericidal agents can be divided into 2 groups (1) concentration into 2 groups (1) concentration dependent e.g. aminoglycosides and dependent e.g. aminoglycosides and quinolones and (2)time dependent quinolones and (2)time dependent killing e.g. beta lactams and killing e.g. beta lactams and vancomycin.vancomycin.
POSTANTIBIOTIC EFFECTPOSTANTIBIOTIC EFFECT
Persistent suppression of bacterial Persistent suppression of bacterial regrowth after brief exposure.regrowth after brief exposure.
Mechanism is likely multifactorial Mechanism is likely multifactorial and may vary with the specific and may vary with the specific antimicrobial drug and organism antimicrobial drug and organism combination.combination.
HoursHours
No
. o
f V
iab
le
No
. o
f V
iab
le
bac
teri
a/m
l.b
acte
ria/
ml.
Postantibiotic effectPostantibiotic effect
Drug addedDrug added Drug removedDrug removed
00 8844
POSTANTIBIOTIC EFFECTPOSTANTIBIOTIC EFFECT
With aminoglycosides it has allowed With aminoglycosides it has allowed once daily dosing and less once daily dosing and less monitoring.monitoring.
top related