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136 Cards in this Set
- Front
- Back
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what acts as the target for Protein Synthesis Inhibitors?
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Bacterial Ribosome
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What are the 4 drug classes that inhibit protein synthesis?
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Aminoglycosides
Tetracyclines Macrolides Chloramphenicol |
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What are the Drug classes that act on the 30S subunit?
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AGs
Tetracyclines |
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What are the drug classes that act on the 50S subunit?
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Chloramphenicol
Macrolides Lincosamides Strptogramins Oxazolidinones Daptomycin |
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what is the MOA by which AGs act on Bacterial ribosomes?
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IRREVERSIBLY binds to 30S (b-cidal)
1.Interferes with Initiation complex formation 2. causes misreading of mRNA 3. restricts polysome formation |
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Why are AGs usage LIMITED?
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Ags are ToXiC (like B. Spears)
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AG spectrum of activity?
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Aerobic G (-) Bacilli
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What are/is AGs used as DOC?
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Pseudomonas (in combo w B-lactam)
Francisella Tularenis |
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What are AGs used for most frequently?
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Empiric Tx for SERIOUS Ixs
Septicemic Nosocomial RTI Complicated UTIs and IntraABD Ixs Osteomyelitis |
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What Protein Synthesis I- is used against AEROBIC G(-) Bacilli?
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AGs
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What is DOC for Francisella Tularensis?
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Aminoglycosides.
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What protein synthesis I- drug glass has the UNIQUE action of Long PAE?
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AGs
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What 5 drugs are Aminoglycosides?
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Gentamicin Streptomucin
Amikacin Tobramyin Neomycin "STANG" |
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Why are AGs only active against Gram Neg?
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Bc AGs diffuse across porin channels which G(+) dont have.
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What are some ways that bugs become RESISTANT to AGs? Most Common Mech?
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Inactivation of drug via enzymes (MOST COMMON MECH)
Failure to permeate bacteria Ribosomal Mutation (altered drug binding site--> big for Streptomycin) |
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What is the most common mechanism of Resistance to AGs?
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Inactivation of drug via microbial enzymes.
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Do AGs cross BBB? Why or Why not?
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NO!!
AGs are very POLAR! (water soluble= poorly absorbed) |
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How are AGs administered to pt?
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Paraenterally
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In prescribing AGs it is of utmost IMPORTANCE to do what 1st?
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Check renal function, bc AGs are eliminated via GF.
Must adjust does relative to creatine clearance!!! |
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Why are AGs given as a SINGLE DAILY DOSE?
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- they have long PAE
- less toxic bc of threshold effect (less drug accum (inner ear/kidney) |
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When is consolidation dosing not preferred with AGs?
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Pregos
osteomyelitis Ix endocarditis pt recieving ototoxins (furosemide) organ txplant |
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What are the adverse effects of AGs?
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Narrow Therapeutic Index
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What toxicities are assoc with AGs?
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Nephro-
Oto- (irreversible!!! :( )` Neuromuscular blockade |
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Nephrotoxicity and Ototoxicity are the major limiting factor for which Drug class?
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AGs!!!
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Pt is at greater risk of Nephro and ototoxicity if....
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Tx >5d
eldely renal dysfunction |
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There is a linear relationship b/t plasma creatinine conc and drug half life with which drug class?
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AGs
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Is nephrotoxicity from AGs reversible or irreversible?
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REVERSIBLE
Toxicity is time and conc- dependent!! |
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How does AGs cz Nephrotoxicity?
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AGs accum in Proximal tubule--> impairs renal conc. ability-->proteinuria-->granular and hyaline casts--> GFR decreases several days later
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Is OTOTOXICITY from AGs reversible or irreversible?
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IRREVERSIBLE!!!
Can occur even after drug is discont. |
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How do AGs cz OTOTOXICITY?
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AGs accum in perilumpg and endolymph of inner ear--> progressibe destruction of Vestibular or cochlear sensory cells
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Pt comes in with tinnitus and high frequency hearing loss... your 1st thoughts are?!
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AGs OTOTOXICITY
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Pt comes in with Vertigo, Ataxia, and loss of balance.... your 1st thoughts are SE from...
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AGs OTOTOXICITY!!!
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OTOTOXICITY from AGs can enhanced if pt is also taking....?
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LOOP DIURETICS!!! **Know This**
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Pt comes in G(-) Ix...has myasthenia gravis or any neuromusc disorder you immediately eliminate which drug class?
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AGs!!! Bc they have adverse effects of Neuromuscular blockade!
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When is STREPTOMYCIN DOC?
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Used alone in Tx against Tularemia and Plague
In combo to Tx: TB Brucellosis (w Doxycycline) Endocarditis (w a PCN) |
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When is GENTOMYCIN a DOC?
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One of the most freq used AGs
in combo w PCN DOC= Pseudomonas Enterococcal **KNOW THIS** |
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When is AMIKAN a DOC?
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Pseudomonas
and other serious Ix czd by organisms resistant to other AGs!! |
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which AG has broadest spectrum?
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AMIKAN
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Which AG is used when all other AGs fail?
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AMIKAN
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When is NEOMYCIN DOC?
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to Sterilize the gut
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Which AG is used to sterilize the gut?
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NEOMYCIN
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Which AG is most Toxic?
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NEOMYCIN
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How is NEOMYCIN administered to pt?
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ORALLY!!
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which AG is 1st choice above other AGs?
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Gentamycin>Tobramycin, AMIKACIN
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What 4 drugs are TETRACYCLINES?
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Tetracycline
Doxycycline Minocycline Tigecycline |
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What is the spectrum of action for TETRACYLINES?
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Aerobic and Anaerobic G(-) and G (+) bacteria
Intracel bacteria (chlamydia, rickettsia, mycoplasma m.) Plasmodium (protazoa) |
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Which TETRACYLINE is used in pts with poor renal function?
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DOXYCYCLINE
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which TETRACYLINE enters CSF in therapeutic amts?
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MINOCYCLINE!!
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TETRACYCLINES are DOC or Alternative for...?
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Bacillus Anthracis (cipro=DOC too)
Mycoplasma p., Chlamydia, Rickettsiae, Lyme Dz Plague, Tularemia, Brucellosis, Malaria prophylaxis (DOXYcycline) |
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Which TETRACYCLINE is used prophylactically for Malaria?
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DOXYCYLINE
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Are TETRACYCLINES bacteristatic or cidal?
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BACTERIOSTATIC!!!
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TETRACYCLINES MOA? reversible?
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Bind 30S subunit; reversible
Prevents tRNA binding to acceptor site and AA from adding to growing peptide They enter cell bia passive diffusion (porin) or active transport (plasma mem) |
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Which ABX should NOT be combined with PCN?!?!
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TETRACYCLINES,
combo w PCN is antagonistic!!! |
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What are the primary mechanisms bugs utilize for RESISTANCE against TETRACYCLINES?
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1. efflux pumps
2. RIBOSOME PROTECTION= bug produces proteins that have very high affinity for binding site and interfere w tetra binding. these proteins can straight DISLODGE TETRA from site or binding site is altered is also a form of rib. protexn. |
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Which ABX from stable chelates with anions?
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TETRACYCLINES
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what foods should be avoided prior to taking a TETRACYCLINE?
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Milk, antacids, peptobismol... bc they are chelators and will bind to these ions and be prevented from being absorbed
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Why can you NOT use TETRA in KIDS?
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Bc tetras are CHELATORS, they will concentrate in bones and teeth. With kids their teeth are still developing and will result in permanent staining.
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How are most TETRAS eliminated?
Which TETRAS differ? |
KIDNEY
MINO and DOXYcycline are less dependent on kidneys for elimination and can be excreted via BILE... (NO DOSAGE ADJUSTMENT if pt has dec renal function!!) |
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Which Tetras are excreted via BILE?
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MINO and DOXCYCLINE which are also 2 of the most commonly prescribe ABX.
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adverse rxn of TIGECYCLINES
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GI, Boney structures/teetch, HEPATOTOXIC, local tissue toxicity, PHOTOSENSITIZATION
VESTIBULAR RXNS |
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How is TIGECYCLINE administered?
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IV... poor oral absorption
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How is TIGECYCLINE eliminated?
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BILIARY Secretion
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Can you use TIGECYCLINE for UTIs?
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No, bc it is excreted via BILIARY
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Which TETRAs can cause LIVER TOXICITY?
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Tetracycline
minocycline Tigecycline less often with Doxycycline |
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Which ABX should be avoided during pregnanacy and childhood?
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TETRACYCLINE NO if <8yrs old
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If a Pt is on an ABX and comes in with sever sunburns on areas of exposed skin... your 1st thought is...
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TETRACYCLINES --> Photosensitivity
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When do you use Tetracyclines?
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only for SERIOUS INFECTIONS!! LAST RESORT!!
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What could happen if a pt takes an expired dose of Tetracyclin?
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FACONI SYNDROM
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What is FACONI SYNDROME and how do you get it?
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Get it from outdated drugs (like Tetracycline)
--> NV and renal Tox: proximal tubular fxn is impaired--> proteinuria, acidosis, glycosuria, aminoaciduria |
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When do you use Chloramphenicol?
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RARELY!!!
--> Reserved for LIFE-THREATENING Ixs!! due to resistance or allergies to safer drugs -rickettsia, miningitis, anaerobic Ixs |
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CHLORAMPHENICOL binds to which part of ribosome?
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50Ssubunit
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CHLORAMPHENICOL is bacteri______?
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STATIC= reversibly binds
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is CHLORAMPHENICOL broad spectrum?
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yes
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Adverse Effects of CHLOAMPHENICOL?
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1.HEMATOLOGICAL TOX: anemia, leukemia, t-cyto-penia
a. Bone Marrow Suppression (rev, dose-dep) b. idiosyncratic response: Fatal blood dyscrasias (aplastic anemia) 2. GRAY SYNDROME (newborns) gray color, chock, hypOthermia, flaccidity 40%mortality rate |
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Which 50S subunit Inhibitor can cause HEMATOLOGICAL TOX?
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CHLORAMPHENICOL
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Which 50S subunit Inhibitor can cause BONEMARROW SUPPRESION?
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CHLORAMPHENICOL: result of its hematological tox adverse effects
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What is GRAY SYNDROME? What causes it?
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CHLORAMPHENICOL czs it
- MOA: lack of GLUCRUONYL TXFERASE ACTIVITY - SnS: gray, hypOThermia, vomitting, flaccid, shock.... NEWBORNS |
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What are the 3 macrolides?
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Erythromycin
Clarithromycin Azithromyin |
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If pt is PCN resistant... whats a good protein synthesis inhibitor that could substitute?
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MACROLIDES, baby!!!
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which 2 MACROLIDES have enhanced G(-) activity?
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Clarithro and Axithromycin!!!
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What G(-)s are AZITHRO and CLARITHROMYCIN DOC for?
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Campylobacter jejuni
H. Pylori Shigella |
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Generally MACROLIDES are DOC for....
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Children and Pregos
Pts. allergic to PCN Preferred for OUTPATIENT CAP (other URIs) |
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Which Protein synthesis Inhibitor is Preferred for OUTPATION CAP?
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MACROLIDES
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MOA for MACROLIDES?
Bacteri_____? |
BacterioSTATIC= Reversibly bind to 50S
Inhibits Peptide chain elongation Inhibits Txlocation of peptidyl tRNA from A to P site |
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What is the Primary Mech of RESISTANCE to MACROLIDES? other mechs?
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1= Active efflux pump
2= Ribosome modification (methylation of RNA (not mutated) changing binding site |
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Which MACROLIDE has the longest Half life?
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AZITHROMYCIN.. Once a day dosing
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Which Macrolide is once a day dosing?
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AZITHROMYCIN
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What are some drug interactions of MACROLIDES
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Inhibit CYP3A4 (not azithro tho)
P450 Inhibition bases for interactions with: Theophylline Oral anticoags CS Digoxin Carbamazipine |
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Macrolide Toxicity....?
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GI:
a. Epigastric distress (DIRECTLY STIM GI MOTILITY, not so much w CLARITHRO!!!), anorexia, NVD b. CHOLESTATIC HEPATITIS a. fever, jaundice, imparied liver fxn. Primarily seen w erythromycin estolate. |
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what is the primary reason for STOPPING ERYTHROMYCIN?
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Epigastric distress: over stim of GI motility.
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What ABX can cz CHOLESTATIC Hepatitis?
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MACROLIDES... primaryily with erthromycin estolate
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what ABX can directly stimulate gut motility?
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MACROLIDES... primarilt ERYTHROMYCIN
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Lincosamides=
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CLINDAMYCIN
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Spectrum of CLINDAMYCIN?
DOC? |
Anaerobic and Strep and Staph Ix (skin/soft tissue)
DOC for: C. Perfringins |
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What is DOC for C. Perfringens?
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CLINDAMYCIN
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CLINDAMYCIN is NOT useful agains what 3 bugs?
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Enterococci, H. Influenza, N. Meninitidis
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Aerobic G(-) bacillar are intrinically resistant to which ABX?
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CLINDAMYCIN
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Which ABX is good for ANAEROBIC bacteria?
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CLINDAMYCIN
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CLINDAMYCIN MOA?
Bacteri___? |
BacterioSTATIC- Reversibly bind to 50S subunit
Binds close to Erythomycin and Chloamphicol binding sites... SO DONT USE IN COMBO Inhibits Peptide formation |
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Erythromycin, Chloramphenicol, and Clindamyin all share what?
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They all share similar binding sites... so cant use in COMBO, even thought here is not indications fro combined use
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CLINDAMYCIN resistance?
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Alteration of binding site via METHYLATION **know**
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Clindmycin can cz CROSS RESISTANCE with what other ABX?
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ERYTHROMYCIN
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Does Clindamycin cross BBB?
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NO
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Where does Clindamycin penetrate well?
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Bone amd PMN Leukocytes= good penetrationinto ABSCESSES
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What ABX can penetrate will into ABSCESSES?
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CLINDAMYCIN
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Adverse Effects of CLINDAMYCIN
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Severe Diarrhea (fun)
Pseudomembranous Colitis |
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What 3 Protein synthesis Inhibitors can cz Pseudomembranous colitis?
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CLINDAMYCIN
TETRACYCLINES DAPTOMYCIN |
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Macrolides are DOC for?
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Mycoplasma p.
Chlamydia Bordetella p. Cmpylobacter (enteritis) |
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Streptogramins=
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Quinupristin+dalfoporistin
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What is the spectrum of activity for Quinupristin+Dalfopristin?
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GRAM POSITIVES!!!!
- Alt for MRSA and staph resistant to Vancomycin and quinolones - Alt for S. Pneumo resistant to PCCNS - DOC for Vancomycin resistant Enterococcus Faecium (VRE) |
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What is DOC for Vancomycin resistant Enterococcus Faecium?
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Quinupristin+Dalfopristin
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Which ABX is used for Gram Positive Cocci Ix?
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Quinupristin+Dalfopristin
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Quinupristin+Dalfopristin MOA?
Bactri______? |
They bind close to eachother czing a synergistic effect
BacteriCIDAL due to the synergy |
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What other protein synthesis Inhibitor should not be used in combo with Quinupristin+Dalfopristin?
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Macrolides!!! they bind at same site.
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Quinipristin and Dalfoprisitin RESISTANCE?
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Quinipristine: Binding site modified by Methylase and Enzymatic inactivation
Falfopristin: enzymatic inactivation and efflux pump |
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Quinipristin and Dalfoprisitin frug interactions?
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POTENT CYP3A4 Inhibitor... (same as macrolides)... so should be careful with drugs that have Narrow TI
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Quinipristin and Dalfoprisitin ADVERSE EFFECTS
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Pain at infusion site (central line access can prevent this)
Severe Arthralgias and myalgias EXPENSIVE |
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OXASOLIDINONES=?
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LINEZOLID
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Spectrum of LINEZOLID?
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similar to Quinipristin and Dalfoprisitin... G+ plus E. Faecalis
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LINESOLID is DOC for?
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Hospital and CAP
MRSA, Strep Pneumo (DOC if PCN Resistant) VRE Faecium and FAECALIS |
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What ABX can be used as DOC for both VRE Faecium and Faecalis?
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LINEZOLID
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LINEZOLID MOA?
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Binds to 50S to block formation of initiation complex
BacterioSTATIC (cidal for strep) |
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Primary Mech of Resistance to LINEZOLID?
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Mutation of rRNA binding site
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Whose Primary Mech of Resistance is Mutation of rRNA binding site?
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LINEZOLID
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What ABX is a Monoamine oxidase (MOA) Inhibitor?
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LINEZOLID
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What ABX should avoid use with adrenergic of serotonergic drugs (SSRIs)?
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LINEZOLID
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Adverse effects of LINEZOLID
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Generally mild:
a. Myelosuppression b. Thrombocytopenia (MOST COMMON) c. anemia, leukopenia |
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Which to protein synthesis Inhibitors can cause Thrombocytopenia?
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CHLORAMPHENICOL
LINEZOLID |
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DAPTOMYCIN Spectrum?
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Similar to Vancomycin--> All G(+)!!!!
Enterococcus Faecalis and Faecium +VRE Staph + MRSA |
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What 2 protein synthesis INhibitors are active against both Enterococcus Faecalis and Faecium +VRE?
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LINEZOLID and DAPTOMYCIN
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Clinical use for DAPTOMYCIN?
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Complicated skin and skin structure IX.
Bacteremia, endocarditis, other sever Ix cased by MRSA of VRE |
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DAPTOMYCIN MOA?
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UNIQUE!!!!!! B-CIDAL!!
Binds to Bacterial membranes--> apid depolarization--> loss of mem potential--> cell death (czs loss of K potential, pokes holes in bac mem) ultimately I- DNA, RNA, and Protein Synthesis |
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How is DAPTOMYCIN eliminated?
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Renal (adj dose if renally impaired)
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What are the Drug-Drug interactions of DAPTOMYCIN?
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THERE ARENT ANY!!!!
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Can you used Daptomycin in Tx for Pneumonia?
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NOPE. Not effective.
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Adverse effects of Daptomycin?
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Skeletal Muscle damage (Myopathy)
a. look for CPK elevations b. careful if pt. is on other drugs that can cz myopathy (HMG Co-A reductase I-) SuperInfection and/or Pseudomem colitis. |
