8. Principles of Chemotherapy Flashcards
What is chemotherapy for infectious diseases?
Use of synthetic, semi-synthetic and naturally occuring chemicals that selectively inhibit specific organisms causing infectious diseases
Chemotherapy of infecitous diseases generally depends on _________?
Selective toxicity
What are the 4 mechanisms of chemotherapy action?
- Antimetabolites
- Inhibitors of cell wall synthesis
- Inhibitors of protein synthesis
- Inhibitors of nucleic acid synthesis
How do antimetabolites work?
Compete with substrate for binding to specific enzymes involved in given metabolic pathway
What is the significance of inhibitors of cell wall synthesis ?
Human cells do not have cell walls like bacteria and fungi.
Allows for very specific targeting for chemotherapy
What is the mechanism of inhibitors of protein synthesis?
Inhibited protein synthesis slows cellular growth.
Inhibitors of nucleic acid synthesis are often used in treating what kinds of condition?
Cancer
Viral infection
What are key laboratory methods in diagnosing infections?
- Gram stain
- Disk diffusion
- Empiric Therapy
What is disk diffusion laboratory diagnosis?
Grow microorganism on plate with several disks of different antibiotics.
Shows which antibiotics are effective against the microorganism
What is empiric therapy?
Initiation of treatment prior to determination of a firm diagnosis.
Used in emergency situation
What are 3 key features of Gram + bacteria?
Thick layer of murein (peptidoglycan)
Hydrophilic molecules can readil diffuse
Retain Stain
What are 3 key features of Gram - bacteria?
Thin layer of murein (peptidoglcan)
Passage of hydrophilic molecules hindered
Lose stain
What is susceptibility?
Minimum concentration (MIC) of antibiotic to inhibit growth of organism in vitro
The concentration of antibiotic in the blood should exceed the MIC by how much to ensure successful treatment?
Exceed by a factor of 2 - 4 fold
What is a narrow spectrum chemtherapeutic?
A chemotherapeutic agent acting only on a single or limited group of microorganisms
i.e. isoniazid
What is an extended spectrum chemotherpeutic?
Agents that are effective against gram + and a singificant number of gram - bacteria
i.e. Ampicillin
What is a broad spectrum chemotherapeutic?
Agent that affects wide variety of microorganisms
i.e. tetracylcline and chloramphenicol
What is a therapeutic index?
An index used to assess the safety of a drug.
TI = TD50/ED50
How does a wide therapeutic index drug’s dynamic differ from a narrow therapeutic index drug’s dynamic?
A wide TI drug has a wide range of doses it can give while still being safe. There is a large gap between the effective dose and toxic dose.
A narrow TI drug has a narrow range of doses it can give while still being safe. There is a narrow gap between the effective dose and toxic dose.
Wide TI drug is safer than narrow TI drug
What precaution must be taken when administering a narrow TI drug?
Check peak and blood levels 30 misn before and after drug administration
Define bacteriostatic drug
Bacteriostatic drugs arrest growth and replication of bacteria at serum levels achievable in patient.
Leave viable organisms to begin second cycle
What do bacteriostatic drugs tend to target in bacteria?
Target metabolic pathways that are necessary for bacterial growth but not survival.
Inhibitors of protein synthesis and antimetabolites
Define bactericidal drugs
Drugs that kill bacteria.
What conditions indicate the use of bactericidal drugs rather than bacteriostatic drugs?
Septicemia or serious infection in patients with impaired host defense
What to bactericidal drugs tend to target in bacteria?
Target metabolic pathways essential for bacterial survival
Cell wall synthesis inhibitors
Inhibitors of nucleic acid synthesis
What is the only inhibitor of protein synthesis that is bactericidal?
Aminoglycosides
Penicillin uses what mechanism of chemotherapy action?
Inhibitor of cell wall synthesis
Cephalosporin uses what mechanism of chemotherapy action?
Cell wall synthesis
What are the 4 bacteriostatic inhibitors of protein synthesis antibiotics?
Chloramphenicol
Clindamycin
Macrolides-erythromycin
Tetracycline
What are 2 bacteriostatic antimetabolite antibiotics?
Sulfonamide
Trimethoprim
When do we use a combinatoin of antimicrobial drugs?
Against organisms resistant to single drug therapy
Severe infection of uncertain etiology or polymicrobial infection
What 3 bacteria are resistant to single drug therapy?
Pseudomonas
Group D streptococci
Tuberculosis
What are 4 adverse effecs of antibiotic therapy?
Drug-drug interactions
Allergic reactions
Superinfections
GI disturbances
Two or more drugs administered in therapeutic dosages at hte same time or in close sequence has what 3 possible outcomes (drug to drug interactions)?
- May act independetly
- May interact to increase or decrease the magnitude or duration of action of one or more drugs
- May interact to cause an unexpeceted reaction
What kinds of antibiotic allergic reactions can occur?
Substantial morbidity and mortality
T cell mediated delayed hypersensitivity
IgE mediated immediate hypersensitivity
Cross allergy between beta-lactam antibacterial agents
What are someclassic GI disturbances from antibiotics?
Nausea, retching, vomiting
Diarrhea
Abdominal cramping
Pseudomembranous colitis
What are the mechanisms of drug resistance?
Treatment with an antibacterial agent affects resistance patterns:
- Genetic mutation causes resistance
- Gene transfer facilitates the spread of resistance
How do you decrease drug resistance?
- Only use when there is a well established need for antibiotics
- Select based on susceptibility tests
- Adequate doses for adequate duration
What is antibacterial prophylaxis?
Administration of a single effective drug to PREVENT infection by a specific organism or to eradicate it soon after it has been established
What are the two purposes of antibacterial prophylaxis?
To protect healthy persons from infection by a specific microorganism to which they have been exposed
To prevent secondary bacterial infection in patients who are ill with other diseases
When must we do SBE (subacute bacterial endocarditis) prophylaxis?
All dental procedures that involve manipulation of gingival tissue or PA region of teeth or perforation of oral mucosa in patients that have reaosnable risk of endocaditis
