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65 Cards in this Set
- Front
- Back
What do the majority of Bacterial protein synthesis inhibits target? Which do not?
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Most target 50S ribosome except tetracyclines
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What are the broad, immediate, and narrow spectrum bacterial protein synthesis inhibitors?
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Broad = Chloramphenicol, Tetracyclines
Intermediate = Macrolides, Ketolides Narrow spectrum = Lincosamides, Streptogramins, Linezolid |
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What mode of action do tetracyclines have?
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Reversible binding to 30S ribosome subunit blocks amnoacyl-tRNA access to acceptor site.
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Would you use a Beta lactam for treating mycoplasma?
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NO, do not have PG so ineffective
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What organisms are susceptible to protein synthesis targeting antibacterials?
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Many G+ and G- bacteria including Anaerobes, rickettsiae, chlamydiae, mycoplasmae
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What protein synthesis drug will act against protozoa?
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Doxycycline is effective against Entamoeba and Plasmodium falciparum
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How do protein synthesis inhibitors get into bacteria?
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Both active and passive transport
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What are the methods in which Resistance to tetracyclines occurs?
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1) Upregulaton of efflux pump
Resistance depends on whether pump binds drug Pseudomaonas and Proteus (resistant to all tetracyclines) Staph. aureus efflux pump doesn't bind doxycycline and minocycline 2)Production of proteins interfering with ribosomal binding. 3) Can sometimes find impaired uptake via active process and enzymatic inactivation of the drug. |
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What is the normal functon of the 50s ribosome?
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Transpeptidation
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How are Tetracyclines given?
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Orally except for Tigecycline that must be given i.v.
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What can interfere with the absorption of tetracyclins?
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Food uptake, divalent cations (Ca++, Mg++), antancids, dairy products.
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What percentage of tetracyclins in the blood are bound to plasma proteins?
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40-80%
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Where does tetracyclin diffuse in the body?
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Enters all body fluids well except CSF.
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How is Tetracyclin excreted?
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In bile and then into feces
Also urine (except doxycycline and tigecycline) |
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What are the concerns about using tetracyclin in pregnant women?
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Crosses placenta and enters breast milk
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Why should tetracyclins not be used in growing children?
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Chelate with calcium and cause binding to growing bones and teeth which caues damage.
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What color are teeth that have deposits of tetracyclin?
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Yellowish or brownish grey. Discoloration becomes more brownish after exposure to light.
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Do the tetracyclins enter the CSF?
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NO
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What are the adverse reactions of tetracyclins?
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Irritation of GI tract (diarrhea, vomiting, nausea)
GI effects due to microbial flora change Teeth/bone effects Liver toxicity High doses cause vestibular toxicity Significant urinary excrretion of most drugs means higher toxicity in those with impaired kidney function. Hypersensitivity is uncommon |
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What is the spectrum of Tigecycline? What is it not effective against?
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Very broad spectrum
Not effective against Pseudomonas or Proteus where the efflux pump is effective causing intrinsic resistance. |
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How is Tigecycline adminstered and excreted? What side effects does it have in addition to other normal tetracycline side effects?
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Administered I.V. (very poorly absorbed orally)
Excreted mainly via bile like doxycyclin (no renal adjustment) Has nausea in addition to most tetracycline class side effects |
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What function do macrolides block?
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Transpeptidation of the 50s ribosome.
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What organisms are susceptible to macrolides?
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G+ and G- organisms including Neisseria
Some mycobactria Intracellular bacteria, spirochetes (Treponema), mycoplasmae, legionella, Listeria, Helicobacter |
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How is Erythromycin resistance found in bacteria? How does it occur?
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Plasmid encoded
Reduces intracellular concentration (reducing permeability or increasing efflux) Hydrolysis by esterases Methylation of the binding site in the 50s ribosome Methylation can be induced by the presence of a macrolide |
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What will methylation of the binding site in 50s ribosome result in resistance to? How about MLSb resistance?
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methylation = All macrolides and clindamycin and streptogramin B.
MLSb resistance = macrolide, licosamide and streptogramin B |
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What are the macrolides with a lactone ring with deoxy sugars attached?
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Erythromycin
Clarithromycin Azithromycin Kelotides |
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How is erythromycin absorbed and excreted?
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Given orally but must use enteric coating as is acid sensitive.
Esters and salts can also provide acid resistance. Food interferes with its uptake. I.V. preparations also used Majority excreted in bile |
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What is Erythromycin used to treat?
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Corynebacterium (erythrasma and diptheria as well)
Chlamydial infections Community acquired pneumonia (gets both Strep. Pneumoniae and Legionella) Used for susceptible Staph and Strep infections with penicillin allergic persons |
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What are the adverse reactions of Erythromycin?
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Nausea, anorexia, diarrhea
Gi intolerance causing increased gut motility Liver toxicity Allergy |
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What drug/enzyme interactions does erythromycin have?
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Increases bioavailibilty of oral digoxin and inhibits cytochrome P450 enzymes.
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What are the additional organisms that clarithromycin is effective against?
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Corynebacterium
Chlamydia Strep. Pneumo Legionella Staph and Strep All like erythromycin Also Works on Mycobacterium avium, M. leprae, Toxoplasma gondii |
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What organisms is azithromycin effective against? How is it different from the other macrolides and what is it used for mostly in particular?
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Used for
Corynebacterium Strep. pneumo Legionella Staph and Strep infections in penicillin allergic Mycobacterium avium, M. leprae, Toxoplasma gondii Very active against Chlamydia Penetrates tissues to high concentration with slow release Very useful for STDs Does NOT interact with P450s |
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What organisms are ketolides (telithromycin used for)?
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Used for macrolide resistant strains where efflux pumps give resistance.
doesnt work with resistance due to to methylated target in ribosome Useful for community acquired pneumonias (mycoplasma, chlamydia, Legionella, Strep. pneumonia) DOES interact with P450 3A4 |
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What type of drug is Clindamycin? What is its mechanism of action? What is its major target?
What is the major danger with its use? What is it mostly used to treat? |
It is a lincosamide and it acts on Ribosomoal 50s.
Enterococci and gram- aerobes are resistant Most anaerobes are susceptible High risk of inducing C. diff colitis Mainly used for treating acne and in a combination for treating and preventing mixed anaerobe infections (abdominal wounds, dental procedures, pelvic abscess and septic abortion) |
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How does chloramphenicol work?
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binds 50s subunit and blocks transpeptidation
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How is chloramphenicol delivered?
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Orally or with succinate salt for i.v.
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Where does chlorampheincol distribute to?
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CNS and all body fluids
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Where is chloramphenicol inactivated?
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Liver
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How is chlormapheiincol excreted?
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Urine
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What organisms are chormphenicol effective against?
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Aerobic and anaerobic G+ and G- bacteria, Rickettsiae
NOT chlamydiae |
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What is chloramphenicol resistance due to?
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Plasmid encoded acetyltranferase which inactivates the drug.
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Where is chloramphenicol metabolised? What considerations must one take due to this?
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Metabolised in the liver via conjugation with glucuronic acid and exceted in the urine.
Dose must be reduced if liver dysfunciton. |
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What are the serious reactions that can occur with chloramphenicol?
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Suprression of RBCs leading to aplastic anemia
Is bacteriostatics so may slow beta lactams Inhibits liver metabolism of other drugs. |
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What considerations must there b when giving a newborn chloramphenicol?
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Newborn infants have poor glucuronic acid conjugation and develop grey baby syndrome= gray color, flaccidity, hypothermia, shock
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What diseases is chloramphenicol used to treat?
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Serious rickettsial infections
Bacterial meningits when beta lactams cannot be used And topical use in eye infections (not chlamydia) |
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What is Quinupristin-dalfopristin?
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A combination of a streptogramin A with a streptogramin B.
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How does Quinupristin-dalfopristin work?
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Act on bacterial 50S ribosomal subunit to prevent protein formation (act on different sites)
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What is Quinupristin dalfoprisin used to treat?
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VRSA
MRSA Vanocomycin resistant Enterococcus faecium |
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What are the adverse reactions of Quinuprisitin-dalfopristin?
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Minor
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What is Linezolid used for?
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G+ including anaerobes
MRSA VRSA enterococci (both faecium and faecalis) |
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How does linezolid work?
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Binds at 50s subuinit inhibiting protein synthesis
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What adverse effects does Linezolid cause?
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mild thrombocytopenia and bone marrow supression
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What are Aminoglycosides mainly used for?
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G- enteric bacteria (bacteremia and sepsis)
In combination with vancomycin or beta lactam (endocarditis) Tuberculosis |
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What are the broad spectrum aminoglycosides?
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Gentamicin
Amikacin Tobramycin Netilmicin |
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What are the narrow spectrum aminoglycosides?
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Streptomycin
Neomycin Kanamycin |
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Do aminoglycosides cure disease?
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No! Do not work alone on serious infections by enterococci or streptococci but can increase antimicrobial activity of other drugs when used in combination.
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How does gentamicin work?
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Binds ribosomal 30s subunit, distorts it and causes misreading of codons.
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How do bacteria acquire resistance to aminoglycosides?
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Impair uptake of drug
Drug modification -adenylation -acetylation -phosphorylation Target modification/deletion -30S ribosome |
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What are some of the useful antibacterial features of aminoglycosides?
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Action independent of bacterial concentration (differs from most beta lactams) thus useful for intrabdominal infections with massive bacterial numbers
Persistent suppression of microbial growth after non lethal exposure |
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How is Aminoglycoside absorbed/delivered? Excreted? Distribution?
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highly charged so not absorbed well. Must be given IV or IM.
Highly water soluble with little binding to plasma protiens Plasma concentration = interstitial concentration Concentration in bile Poor penetration into CSF Eliminated in urine but some readsorption in proximal tubule |
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What is the peak dose for Aminoglycoside?
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12X MIC once a day.
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What is aminoglycoside toxicity dependent on?
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Amount of time the drug remains above a toxic concentration
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What are the adverse reactions of Aminoglycosides?
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Neuromoscular blockade (bind calcium in presynapse) (reversible)
Nephrotoxicity (Interfere with tubular function, increased toxicity in combination with vancomycin, amphotericin B, diuretics, others) Ototoxicity (NOT reversible, accumulate in perilymph of inner ear and kill sensory cells in organ of Corti, hair cells) also vestibular damage. Loss of hearing at high frequencies |
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Besides bacterial treatment what can aminoglycosides be used for?
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Treating genetic disease in humans caused by premature stop codon.
Alter ribosome and allow some normal read through. |
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What is Spectomycin used to treat? What is its target?
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Treats Neisseria gonorrhoeae
Target is 30S ribosome |