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38 Cards in this Set

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Selective Toxicity
kill or inhibit pathogen while damaging host as little as possible
Degree of selective toxicity depends on (3)
- Therapeutic dose
- Toxic dose
- Therapeutic index
Therapeutic dose:
drug level required for clinical treatment of a particular infection
Toxic dose
drug level when undesirable effects produced
Most drugs are what spectrum?
Narrow
Disadvantage of Broad spectrum:
could kill good bacteria
Examples of broad spectrum drugs
Neomycin: effective against G+/-
Zeocin: anti bacterial and anti fungal
Sulfonamides: antibacterial, fungal, protozoal
Difference between bactericidal and bacteriostatic
bactericidal: bacteria can't grow
bacteriostatic: inhibits growth and slows it down, buys time for your immune system to get rid of it
Origin of antibiotics (3)
Natural, Synthetic, Semi-synthetic
Natural
produced by living organism
Streptomyces: streptomycin, chlortetrarcycline, erythromycin
Penicillium: penicillin
Synthetic:
manufactured from nonnatural products
-sulfonamides, trimethoprim
Semisynthetic
Chemical modification of natural antibiotics
- penicillin derivatives: ampicillin, carbenicillin, methicillin
5 mechs of Antimicrobial action:
Protein synthesis
Nucleic acid
Cell wall
Cell membrane
Metabolic reactions
Protein synthesis drugs
aminoglycosides
chloramphenicol
tetracyclines
erythromycin
clindamycin
spectinomycin
Nucleic acid drugs
rifampin
nalidixic acid
metronidazole
Cell wall drugs
penicillin
cephalosporins
vancomycin
bacitracin
cefoxitin
Cell membrane drugs
polymyxins
only one
Metabolic reaction drugs
sulfa drugs
isoniazid
trimethoprim
Polymyxin B
cell membrane disruption- binds cell membrane components
Natural: bacillus
Effective against: G- (pseudomonas aeruginosa)
Triple Antibiotic Ointment w/ neomycin (broad spectrum) and bacitracin (g+)
if ingested: can cause numbness in extremities,kidney damage, respiratory arrest
low selective toxicity
Sulfonamides
Synthetic
- Sulfanilimide is analog of PABA (p-aminobenzoic acid)
-inhibits folic acid production b/c competes with PABA for active site DIHYDROPTERATE SYNTHETASE
- bacterias make folic acid not humans
-high therapeutic index, but 5% allergic
Examples of sulfonamides: (2)
sulfamethoxazole
sulfisoxazole
Inhibition of DNA synthesis are due to:
Quinolones - Nalidixic acid
Nalidixic acid selectively inhibits DNA gyrase (enzyme req'd for dna replication)
-effective against certain urinary infections
- bad for kids, pregnant women b/c affects cartilage
- therefore made FLUOROQUINOLONES
improvment over nalidixic acid
penetrate tissue better
more broad spectrum
Ms. Doan
Examples of Fluroquinolones and what do fluoroquinolones do?
Ciprofloxacin, norfloxacin
they inhibit DNA synthesis by messing with DNA gyrase (enzyme needed for DNA replication)
Inhibition of RNA synthesis
what is used, the origin, used for what, side effects
-Rifampin inhibits DNA dependent RNA polymerase in bacteria
-semi-synthetic
- for: tuberculosis, leprosy, protectin again meningitis
- side effect: turn body secretions red/orange
Penicillins
what do they do, origin, problems, what is common in all of them
-inhibit transpeptidation -->cell wall synthesis; results in osmotic lysis
- semi synthetic dervatives: ampicillin- more acid stable
- problem: allergic reactions/ growing resistance
- Beta lactam nucleus is common in all of them
Cephalosporins
what do they do?, examples, origin
cell wall synthesis inhibitor has beta lactam ring like penicillin
- cephalein (Keflex), cephalothin
- useful alternative to penicillin (allergy and resistance)
Bacitracin
what does it do?
interferes with bactoprenol- carrier that transports peptidoglycan subunits to cell wall
Drugs used for inhibition of protein synthesis (4)
tetracyclines
aminoglycosides
macrolides
chloramphenicol
Tetracyclines
origin, use, problems, used for?
- broad spectrum, semi-synthetic, from streptomyces
- four benzene rings
- inhibit protein synthesis by binding 30S ribosomal unit - inhibits binding of tRNA to ribosome
- problem for kids and pregnant women with bone formation - yellow teeth
- used for rickettsial, chlamydial diseases
Examples of Tetracyclines:
2 natural
4 semisynthetic
from streptomyces:
- chlortetracycline
- oxytetracycline
semisynthetic:
- doxycycline
- tetracycline
- methacycline
- minocycline
Aminoglycosides
origin (2), what do they do, problems
- amino groups bound to glycosides (carbs)
- origin: Streptomyces and Micromonospora purpurea
- prevent reading of mRNA by irreversibly binding to ribosome
- TOXIC: deafness, renal damage, loss of balance
Examples of aminoglycosides
3 from Streptomyces
1 from Micromonospora purpurea
strept: streptomycin, kanamycin, neomycin
micro: gentamicin
Macrolides
what does it do, used for, examples
-Broad spectrum: g+/-
-12-22 carbon lactone ring
- inhibits peptide chain elongation
- used to treat Legionnaire's disease: legonella pneumophilla
- erythromycin, clindamycin, azithromycin
Chloramphenicol
last resort drug
- binds ribosome and blocks peptide bond formation to inhibit protein synthesis
- natural: streptomyces
- broad spectrum (bact, small bact, fungi)
- low therapeutic index; cause aplastic anemia by preventing hemoglobin being incorporated into RBC, Gray syndrome: toxic reactino, breakdown of cardiovascular system
Mechanisms of Resistance for Microorganisms (3 ways)
1. prevent entrance of drug
2. pump drug out of cell
3. inactivation of drug
Example of Preventing entrance of drug
-Mycobacterium has mycolic acid in cell wall which is impermeable to most drugs
- use of isoniazid (isonicotinic acid hydrazide) inhibits production of mycolic acid
mycolic acid
Inactivation of drug through chemical modification
- use penicillinase to inactivate beta lactam ring
- type of resistance can be encoded by PLASMIDS and transferred via conjugation and transformation
2 reasons why microbial drug resistance is increasing
1. indiscriminate use of chemotherapeutics
2. transmission of R factors between microbes (r factors transferred b/n unrelated strains through conjugation and transformation)