Pharm Anti-infective agents Flashcards
Classifications of bacteria
- spheres/cocci
- rods/bacilli
- spirals
Gram + or - staining process
- Fixation
- Crystal Violet
- Iodine Treatment
- Decolorisation
- Counter stain with Safranin
Gram + structure
Gram +:
* Cell wall thick multilayered Peptidoglycan outside of cytoplasmic mem
Gram -:
* single layered Peptidoglycan within periplasmic space
* Outer membrane= Lipopolysaccharide which prevents penetration of Gram stain
Penicillin binding proteins: found in both and strengthen peptidoglycan
Beta lactamases: chew up penicillins and cephalosporins
Gram + overview of bacteria
Gram - overview of bacteria
Misc bacterial inf
intracellular bacteria
* chlamydia
* rickettsia
* borellia
Poorly staining
* mycoplasma
* legionella
* helicobacter
Acid fast stain
* mycobacteria
* nocardia
* tuberculosis
Bacterial Growth stages
- Lag phase- adapt to environ, synthesis
- Log phase- doubling per unit time MOST SUSCEPT TO AB bc so fast
- Stationary phase- nutrient depletion, accumulation of byproducts
- Death phase- starvation
Chemotherapy
anticancer tx antibiotics= chemotherapy
BOTH TARGET RAPIDLY DIVIDING CELLS
Antibiotics come from?
- derived from natural biologic products ie environ competing organisms-> fungi
- daily= organisms exposed to these agents in small amounts
- we give significant doses and have consequences= resistance
Ampicillin does work on me?
Agents are specific to microbes not people
* idiosyncratic pharmacokinetics and enzyme induction does differ
* mostly= its bc agents are prescribed indiscriminantely
Choosing a drug
- Host Factors- liver/kid fxn, allergies, age, prego, exposures
- Drug factors- pharmacodynamics, kinetics, tissue penetration, toxicities
- Bug factors- possible resistance patterns, duration of disease, likelihood of multiple organisms
Sensitivity testing
- Zone of inhibition on overnight culture-> Kirby-Bauer Method
Tells you which AB bug will be sens to
GET CULTURES B4 DRUG THERAPY
Susceptibility and Resistance
- Minimum Inhibitory Concentration (MIC)= lowest conc of the AB results in inhibition of visible growth
- Minimum bactericidal conc (MBC)= lowest conc of AB that kills 99.% of original
Pharmacokinetics
- Route: oral preferred but IV/IM for very sick, meningitis, endocarditis, N/V
- Decreased/Increased dosage requirements: Hepatic/Renal, burns, CF, trauma, age, Prego
- Penetration: CSF inflammation
- Monitoring: Peak and trough levels= Ththerapeutic index, substantial interpatient variability
Tissue Specificity- Penetration
- Gut infections= best tx by Oral med- cant be absorbed into body
- CNS infections: some dont penetrate BBB
- Bone: dependent on molecular size, protein binding, fat solubility
- Soft tissues (cellulitis)
- Abscesses: no blood flow= poor penetration (must be drained)
Antimicrobial agents: MOA
- target bacterial cell envelope-> cell wall synthesis and cytoplasmic membrane structure= MC MECHANISM
- Block production of new proteins= bacterial ribosome
- target DNA or DNA replication= antimetabolite activity
Basic mechanisms of resistance
- Drug inactivation or modification-enzymatic deactivation of Penicillin through production of beta lactamases
- Alteration of target site- alt Penicillin binding protein-> binding target site of penicillin MRSA
- Alteration of metabolic pathway-sulfonamide-para aminobenzoic acid = folate precursor
- Reduced drug accumulation- decreasing drug permeability or increasing active efflux of the drugs across the cell surface
Basic mechanisms of resistance
- Drug inactivation or modification-enzymatic deactivation of Penicillin through production of beta lactamases
- Alteration of target site- alt Penicillin binding protein-> binding target site of penicillin MRSA
- Alteration of metabolic pathway-sulfonamide-para aminobenzoic acid = folate precursor
- Reduced drug accumulation- decreasing drug permeability or increasing active efflux of the drugs across the cell surface
MRSA
Methicillin resistant Staph aureus
Mech: mutation by penicillin binding protein PBP
now isolates resistant vancomycin, linezolid
Alternate Classification of Resistance
- Natural or intrinsic resistance
* inaccessibility of the target- lps in gram neg
* multidrug efflux sys- pumping out multiple drugs
* drug inactivation= beta lactamase - Acquired resistance= disseminated by plasmids or transposons
* drug modification
* drug inactivation- beta lactamase
* drug efflux
When cause is known?
interpretation of Culture and Sens-> Monitoring response-> Clinical failures
Classifications of Antibiotics
Mode of action:
* bacteriostatic
* bactericidal
Spectrum of action
* broad
* narrow
Antibacterial agents
Bactericidal: active in killing
Bacteriostatic: limit bacterial growth
Organisms can lose susceptibility to certain drugs= direct result of AB overuse
Clinical use of AB
- Initial concerns: clinical findings, clinical specimens, likely organisms, prevention of secondary cases
- Next level: spectrum based on culture results, combination therapy, dose, route, duration, clinical response