lesson eight Flashcards
two antiparasitic agents
- anti-protozoan drugs
- anti-helminthic drugs
quinine and derivatives for malaria
increasing resistance of malaria to the drugs
antifungal agents
- fungi are eukaryotic organisms
- most successful agents affect the plasma membrane of fungi- which contains ergosterol instead of cholesterol
- all drugs have some toxicity (kidney)
- most common drug used for systemic fungal illness: amphotericin B
amphotericin B
inhibits ergosterol synthesis in the cytoplasmic membrane of the fungal cell
antiviral agents
- DNA/RNA synthesis inhibitors
- entry inhibitors
- uncoating inhibitor (M2 proton channel)
- nucleoside analogue
- protease inhibitors
antiviral agent: azidothymidine AZT or zidovudine
inhibits the reverse transcriptase (synthesis of DNA from RNA) treats HIV
bacteriostatic antibiotics
- stop the replication of bacteria
- do not kill the bacteria already present (erythromycin)
bactericidal antibiotics
- kill the bacteria
- stop bacterial metabolism (penicillin)
inhibition of cell wall synthesis
beta lactams:
- penicillins
- cephalosporins
- carbapenems
- monobactams
vancomycin bacitracin
inhibition of protein synthesis
30s subunit
- tetracyclines
- aminoglycosides
50s subunit
- macrolides
- clindamycin
- linezolid
- chloramphenicol
injury to the plasma membrane
polymyxins (topical)
inhibit nucleic acid synthesis
DNA gyrase
- quinolones
RNA polymerase
- rifampin
folate synthesis
- sulfonamides
- trimethoprim
inhibits the synthesis of essential metabolites
specific antibiotics
- inhibit gram - or
- gram + or
- certain bacterial species
broad spectrum antibiotics
- inhibits both gram - and gram + bacteria
most susceptible to bacterial infection
- diabetics
- children
-elderly - burn wound: skin and soft tissue
- immunocompromised
effects of antibiotics
- allergies (penicillin)
- pregnant women (tetracycline)
- children (pharmacokinetic and pharmacodynamic issues)
- people with liver of kidney damage
antimicrobial side effects
- kidney
- liver
- rash, allergy
- GI upsets
- nerve damage
- ototoxicity
- teeth and bone formation in children
- cartilage formation in children
antibiotic=not effective if used too late
- too many bacteria
- too much tissue damage
- formation of walled-off abscesses that can’t be penetrated by antibiotics
- poor absorption of drug
why are IV antibiotics sometimes used
- GI problems
- only drug possible (vancomycin)
- rapid bioavailability
clostridium perfringens
- gram + bacilli
- gangrene
- bacteremia and sepsis
- penicillin, clindamycin, metronidazole (anaerobic)
pseudomonas aeruginosa
- gram -
- opportunistic pathogen
- inhabit soil and water
- needs very few nutrients
- can infect many body sites
- very common in burn patients and patients with cystic fibrosis
- has endotoxin, also produces exotoxins
- require broad spectrum drugs
bacterial mutation to penicillin
- produced enzyme beta-lactamase or penicillinase: inactivation of penicillin by breaking the beta-lactam ring
counteracting bacterial mutation to penicillin
- synthesis of semi-synthetic penicillins with a structure where the active portion of the antibiotics was protected from the enzymes
4 ways bacteria become resistant to antibiotics
- prevent penetration
- destruction of drug
- target site alteration
- ejection of drug from bacterium
r-factors
- plasmids that confer genes for resistance to antimicrobials
- Genes coded on small circular independently replicating pieces of DNA
called plasmids located in the cytoplasm of bacteria - Can be transferred from one bacteria to another by conjugation
- R-factors can be transferred between different bacterial species
why do bugs become resistant
- overuse
- inappropriate treatment
- incomplete treatment regimens
what are superbugs
bacteria that can’t be controlled by antibiotics
what did the staphylococci do after semisynthetic drugs began to be used
- mutated again
- MRSA: methicillin resistant s. aureus (superbug)
- changes the penicillin binding site
- penicillin binding protein 2 mutates to PBP2a
superbug: VRE (vancomycin resistant enterococci)
- genetic mutations-several: in genes Van A, Van B, Van C
- resistance developed after use of avoparcin in animal feed
superbug: ESBL (extended spectrum beta-lactamase)
- Enterobacteriaceae like E. coli:
genetic mutations, many
resistance genes - Increasing problem in ICU,
extended care - Resistance to penicillins and
cephalosporins - ESBL can inactivate even the
new really good beta-lactams
like meropenem - NDM-1 (New Delhi
metallobetalactamase is one of
the latest enzyme variants)
superbug: XDR-TB
- first seen in tugela ferry, south africa
- resistant to both first and second line anti-TB drugs
MIC (minimum inhibitory concentration)
- minimum amount of antimicrobial that will inhibit the growth of the microorganism
- every important bacterial isolate must be tested
- need to know for appropriate dosing levels and intervals
what is a drug of choice
drug that is deemed to be the most effective with the least toxicity for a specific infection
disk diffusion test
- for antimicrobial susceptibility
- routine test, primarily for rapidly growing bacteria as the antibiotics on the disc will deteriorate with time
3 categories of sensitivity:
S= sensitive or susceptible
I= intermediate
R= resistant
kirby bauer or disk diffusion susceptibility test
- Interpretation: measure the zones of inhibition and compare to standard charts to get S,I,R
- This is a one shot concentration of the
antibiotic in each disc - You use this for
infections like urinary tract infections, skin infections, but not for infections in sterile sites (like blood).
e-test for MIC determination
- an easy way to determine MIC for a drug on a specific bacterial strain
monitoring of serum antimicrobial levels
- attain effective levels (over MIC)
- prevent toxic side effects
- ascertain dosing intervals
MIC and SIR
personalize and control the dose
