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Secective toxicity
drug that kills pathogen withough damaging the host
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Antibiotic
- substance made by a microbe that inhibits growth of another microbe
- (sulfa drugs are not technically antibiotics but are usually included)
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chemotherapy
the use of drugs to treat a disease
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Penicillin
- Discovered in 1928
- Used clinically in 1940 for the 1st time
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3 sources of antibiotics
1. bacteria - 50% of all antibiotis are from streptomyres
2. fugus - penicillin, cephalosporins
3. synthetic - sulfa drugs
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1. Why are gram (-) bacteria harder to kill than gram (+)?
2. Are mycobacteria hard to kill?
3. Are fungi hard to kill?
4. Are viruses hard to kill?
1. Gram(-) have outer membrane with porins that only let small molecules in
2. Mycobacteria have mycolic acid in their cell wall - drugs cant penetrate it
3. Fungi are a eukaryotic pathogen - same cell type as host - may damage host
4. Viruses live inside host cell - hard to kill w/o damaging host
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Broad spectrum antibiotics
affects a wide range of microbes - Gram (+) & Gram (-)
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Superinfection
results from antibiotic killing off normal flora - bacterial overgrowth of a pathogen
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bacteriocidal
bacteriostatic
bactericidal - antibiotic that KILLS bacteria - requires bacterial growth to work
bacteriostatic - antibiotic that prevents (or limits) bacterial growth - allows hosts immune system to work - requires that the host's immune system is competent
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5 ways that antibiotics work
1. inhibit cell wall synthesis - bacteria - penicillin blocks peptidoglycan cross links - cell lysis
2. inhibit protein synthesis -bacteria -block normal function of 70S ribosome - could cause problem because mitochondria bacuse they ahve 70 S ribosomes
3. Injure cell membrane - bacteria/ fungus - alter selective permeability (binds to sterols on fungus)
4. Inhibit DNA/ RNA synthesis - blocks DNA replication or RNA transcription
5. Inhibit synthesis of essential metabolites - blocks folic acid synthsis - can't make nitrogenous bases
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What is the difference between prokaryotic and eukaryotic ribosomes?
- Prokaryotic cells = 70S ribosomes
- 50 + 30 = 70 S (Svedberg)
Eukaryotic cells = 80S ribosomes
Svedberg unit is based on rate of sedimentation in a high-speed centerfuge
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List 5 ways antibiotics work and give examples of drugs
- 1. Cell wall disruption
- - peninillin
- - cephalosporins
- - bacitracin
- - vancomycin
- - anti TB drugs - INH and Ethambutol (block mycolic acid synthesis)
- 2. Protein synthesis disruption
- - chloramphenicol
- - aminoglycosides
- - tetracyclines
- - macrolides (erythromycin)
- 3. Cell membrane disruption
- - polymyxin
- - antifungals : amphotericin, ketoconozole
- 4. DNA/ RNA synthesis disruption
- - rifampin - DNA replication
- - quinolones (cipro) - RNA transcription
- 5. Vital Metabolite synthesis disruption
- - sulfonamides (sulfa) - bactrim
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Characteristics of Penicillins (Pcn)
- CELL WALL DISRUPTION
- Penicillin - has a "nucleus" = all penicillins have a Beta lactam ring structure with different R goups attached
Works by preventing peptidoglycan cross bridges from forming - most work best on Gram (+)
- Penicillinase - enzyme made my some bacteria that inactivate PCN by cleaving the Beta lactam ring

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Penicillins -PCN or pen
- CELL WALL DISRUPTION
- Work by messing with peptidoglycan
- Natural penicillins:
- a. Pen G = IV (narrow)
- b. Pen V = (PO) - stable in stomach acid
- c. procaine Pcn - lasts longer - given deep IM in a suspension w/ local anesthetic
- Semisynthetic penicillins:
- narrow spectrum - Gram (+)
- 1. methicillin - penicillinase resistant penicillin - can cause MRSA (no longer used much)
- MRSA = methacillin resistant staph aureus
- 2. oxacillin - penicillinase resistant pcn
- Broad spectrum - polar group added so it can penetrate outer membrane on Gram (-)
- 1. ampicillin
- 2. amoxicillin
- 3. ticarcillin
Augmentin - amoxicillin + penicillinase inhibitor
Primaxin - last generation - very powerful - kills 98% of hospital microbes
Monobactam - newer selective killer - pseudomonas, E. coli
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Cephalosporins
- CELL WALL DISRUPTION
- -Penicillin- like structure - beta lactam ring- all are penecillinase resistant
- - kill by messing with peptidoglycan
- - made from a fungu
- - many are semi-synthetic
- - each generation is more effective against Gram (-) and has a broader spectrum of activity
- 1st generation:
- 1. Ancef (IV)- cetazolin
- 2. Keflex - po - cetatexin
- 2nd gen:
- 3. Cettin - cefuroxime
- 4. Zinacef
- 3rd gen:
- 5. Rocephin
- 6. Claforan
- 4th gen - broadest spectrum
- 7. Maxipime
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Polypeptide antibiotics (small proteins)
- CELL WALL DISRUPTION
- 1. Bacitracin - bacillus from Tracy's wound
- - narrow spectrum -Gram (+) topical ointment
- - Block pepdidoglycan synthesis
- 2. Vancomycin - to vanquish
- - very narrow but KILLS MRSA
- - but VRE not exists - no Rx for some VRE
- - - VRE = Vancomycin Resistant Enterocicci
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Antimycobacterial antibiotics
- CELL WALL DISRUPTION
- inhibit mycolic acid in cell wall
- 1. Isoniazid (INH) - Rx for M. tuberculosis
- - 1st line treatment for TB - 1 year Tx
- - Can cause drug hepatitis
- - effect mycobacteria only
- - penetrates macrophages & walled off tissue
- 2. Ethambutol - Rx for TB
- - inhibits incorporation of mycolic acid in cell wall
- - 2nd line drug for TB
- - effects mycobacteria only
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Chloramphenicol (CAM)
- INHIBITS PROTEIN SYNTHESIS
- 70S ribosome inhibitors (50S + 30S)
- Broad Spectrum -
- *bacteriostatic - binds to 50S & stops peptide bond formation
- - inexpensive
- - toxic - can cause aplactic anemia (no blood cell production - rare)
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Aminoglycosides
- INHIBITS PROTEIN SYNTHESIS
- - best for Gram (-)
- - - bind to 30S & stop peptide bond formation
- - - Toxic - ototoxic (auditory nerve) & nephrotoxic (renal failure) - must monitor blood levels
- Streptomycin
- Neomycin
- Gentamycin (IV)
- Tobramycin (IV)
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Tetracyclines
- INHIBITS PROTEIN SYNTHESIS
- *Broad spectrum - bacteriostatic
- *Interferes with tRNA attachment to mRNA on ribosome 30S
- *Excellent penetrating properties- effective against intercellular Chlamydia & Rickettsia
- *Used for UTIs, STDs, walking pneumonia (mycoplasma)
- *Can cause superinfection - kills normal flora
- *Can stain developing teeth
- *Eyedrops for neonates
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Macrolides
- INHIBITS PROTEIN SYNTHESIS
- * Better for Gram (+) infections (dont penetrate outer cell membrane very well)
- * Sits in tunnel between 30S & 50S subunits - inhibits protein systhesis
- * Used for ppl with PCN allergies
- * Bacteriostatic
- Erythromycin
- Zithromax (broad spectrum)
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Lincosamides
- INHIBITS PROTEIN SYNTHESIS
- * Broad spectrum - bacteriostatic
- * Used for MRSA, anerobic bacteria, protists
- * Semi-synthetis
- * Can cause C. difficile overgrowth - causes pseudomembranous colitis
Clindamycin
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Polymyxin B
- INJURY TO PLASMA MEMBRANE
- *plasma membrane looses its selective permeability
- * can kill Gram (-) (pseudomonas)
- * combined with neomycin or bacitracin in antibiotic ointment
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Rifamycins
- DNA/ RNA SYNTHESIS INHIBITOR
- *Block transcription of DNA (no mRNA, no protein)
- * Anti TB drug - combined with INH to reduce chance of resistant stratins
- * Able to penetrate macrophages (TB), abscesses, CSF
Rifampicin - Rifampin
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Quinolones
- DNA/ RNA SYNTHESIS INHIBITOR
- *inhibit DNA gyrase - DNA cant unwind
- * Broad stectrum - synthetic
- * UTIs - IV drug for urosepsis
- * not for children - affects cartilage growth and can cause spontaneous tendon rupture
- Ciprofloxacin = Cipro
- Levofloxacin = Levaquin
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Sulfonamides - Sulfa drugs
- COMPETITIVE INHIBITOR
- * Competitive inhibitor of PABA (para-aminobenzoic acid) - blocks folic acid synthesis from PABA - folic acid is necessary for nucleotide synthesis for DNA replication
- * Broad spectrum - bacteriostatic
1. Bactrim = TMP (trimethoprim) + SMZ (sulfamethoxazole) - synergistic
- 2. Silvadene = silver + sulfadiazine
- - used for burns - silver (heavy metal toxicity to bacteria -denatures proteins)
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How do antifungals work?
Fungi are eukaryotes - hard to make durgs with "selective toxicity"
- 1. affect sterols (ergosterol) in plasma membrane
- 2. affect cell wall
- 3. affect DNA/ RNA synthesis
- 4. other
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Antifungals that affect ergosterol (a sterol) in the cell membrane
- ANTIFUNGALS THAT EFFECT STEROLS
- * effect ergosterol and effect seletive permeability
- 1. Amphotericin B - (IV) for systemic fungal infections
- - PO for oral thrush
- - nephrotixic (kidney)
- 2. Ketoconozole
- - PO for systemic fungal infections
- - used topically for athletes foot, ringwork, 2% prescrition shampoos
- - hepatotoxic (liver)
- 3. Miconazole = eg Monistat 7
- - topical for candida vaginitis, athletes foot, ringworm
- - used to prevent fungal growth on camera film
- 4. Terbinafine - Lamisil
- - treatment for dermatophytes (nail fungus)
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Other antifungal drugs:
- Griseofulvin - Fulvicin
- - PO for dermatophytes in/on skin, hair, nails
- - block microtubole assembly in the mitotic spindle - cell not able to divide
- - must bind to keratin to work
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How do anti-viral drugs work?
- 60% of all infectious disease is caused by viruses
- selective toxicity is difficult - virus lives in host cell
- 1. Stop DNA replication - nucleotide analogues (fake nucleotides) block DNA polymerase function
- 2. Reverse transcriptase inhibitors - AZT
- 3. Protease inhibitors - blocks assembly
- 4. Integrase inhibition - blocks provirus formation
- 5. Fusion inhibition - blocks viral entry into cell
- 6. Inhibits viral uncoating
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Viral Nucleotide Analogues
Fake nucleotides - block DNA replication
- 1. acyclovir = Zovirax - PO & ointment
- - herpes simplex I & II, varicella (chicken pox, shingles), epstein barr virus (mono)
2. lamivudine - for Hep B & HIV (also blocks reverse transcriptase)
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Reverse Transcriptase Inhibitors
- AZT - zidubvidine - for HIV
- - blocks reverse transcriptase - cant make DNA
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Drugs that Inhibit viral uncoating
Stops virus from uncoating one inside the cell
- 1. amantadine - for Influenza
- *used to treat influenza, not prevent it - keeps virus from replicating
- 2. Interferon - made by infected cells & prevents spread of virus to uninfected cells (keep virus from replication in uninfected cells)
- - used to treat hep B & C, MS, viral cancers, infulenza
- - can be toxic- liver, heart, kidney
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Antiprotazoal Drugs
- 1. Chloroquine - quinine derivative
- - #1 drug for malaria (plamodium infection)
- - drug enters microbe with Host RBC & prevents microbe form detoxifying here → parasite death
- 2. Metronidazole = Flagyl
- *Damages DNA (disrupts double helix shape)
- Rx Giardia - beaver fever - protazoa
- Rx Trichomonas vaginalis
- Also
- Rx Chlamydia vaginitis -obligate intercellular bacteria
- Rx anerobic bacteria - used for GI pre-op prophylaxis
- & bowel perforations
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