Renal 16 Antibiotics Word Scramble
|
Embed Code - If you would like this activity on your web page, copy the script below and paste it into your web page.
Normal Size Small Size show me how
Normal Size Small Size show me how
Question | Answer |
Inhibit bacterial cell wall synthesis | Beta-lactams Vancomycin Bacitracin |
Anti-metabolic activity | Sulfonamides Trimethoprim |
Inhibition of bacterial protein synthesis. | Aminoglycosides Tetracyclins Chloramphenicol Macrolides |
Inhibit bacterial nucleic acid syntheses | Fluoroquinolones |
Which drug classes target the bacterial ribosome? | Aminoglycosides Tetracyclins Macrolides Chloramphenicol |
This class is of protein synthesis inhibitors are bacteriocidal | Aminoglycosides |
Classes that work on the 50s unit | Macrolides Streptogramins Chloramphenicol Lincosamides Oxazolidinones |
Classes that work on the 30s unit | Aminoglycosides Tetracyclins |
Animoglycoside that is topically OTC | Neomycin |
Aminoglycosides are frequently used in | Serious infxn from aerobic G- |
Use is limited due to | Toxicity |
Used in combination with... | Beta-lactams Vancomycin |
Why does it work best in aerobics G-? | Uptake of the drug requires O2 dependent transport system |
Frequently used for infxns due to... | PEPS Pseudomonas (DoC) Enterobacter Proteus Serratia |
Can also be used to treat | Invasive enterococcal infxn Serious staph. infxn Y. pestis and Francisella tularenis |
Clinical applications of aminoglycosides | -Serious infxns- Septicemia Nosocomial RTI Complicated UTI Osteomyelitis |
When are aminoglycosides discontinued? | Once the organism is identified and susceptibility is known |
Aminoglycoside MoA | Irreversibly binds to 30s ribosome 1. interferes with initiation complex formation 2. Causes misreading of mRNA 3. Restricts polysome formation |
What contributes to the bacteriocidal nature? | Concentration-dependent killing Long PAE |
AG uptake into G- | Diffuse across the outer membrane via porin channels Cross the inner membrance via O2 dependent active transport Inner membrane potential drives transport |
What can block the transport of AG? | Anaerobic environment Low extracellular pH |
Aminoglycoside resistance | Inactivation of drug by microbial enzymes (aminoglycoside modifying enzymes) |
Aminoglycoside kinetics | Very polar compounds Don't cross the membrane well |
Aminoglycoside pharmacokinetics | Concentrated in the proximal tubular cells Largely eliminated by GF |
What must you do in renal compromised pts? | Adjust the dose/dosing frequency Blood levels are very important Must adjust dose relative to creatintine clearance |
Advantages of consolidated therapy | Comparable efficacy Decreased nephrotoxicity Long PAE |
Toxicity is dependent on | Concentration and time above threshold |
Consolidation therapy is not recommended for what situations? | Pregnant pts Osteomyelitis Infective endocarditis Pts recieving concurrent ototoxins Pts undergoing solid organ transplantation |
Aminoglycosides therapeutic index | Narrow |
Primary toxicities of aminoglycosides | Nephrotoxicity Ototoxicity Neuromuscular blockade |
Which of these are reversible/irreversible? | -Reversible- Nephrotoxicity Neuromuscular blockade -Irreversible- Ototoxicity |
Makes nephrotoxicity and ototoxicity more likely | Therapy > 5 days In elderly pts In pts with renal dysfunction Tox incidence related to drug concentration |
Nephrotoxicity | Reversible Involves an acute tubular necrosis |
The most important result of nephrotoxicity | Decreased AG excretion -Increased AG plasma levels -Predisposes to ototoxicity |
AGs accumulate and are retained in.. | Proximal tubular cells |
Results of AG accumulation | Impairs renal concentrating ability Mild proteinuria Appearance of hyalin and granular casts GFR decreases |
2 drugs that are nephrotoxic | Amphotericin B Cyclosporine |
Why is ototoxicity is difficult to determine? | May occur after drug is stopped |
Where do AGs accumulate in the ear? | Perilymph and endolymph in the inner ear |
Ototoxicity manifestations | Tinnitus High freq. hearing loss Vestibular damage |
What is special about ototoxicity? | Irreversible Damage accumulates with repeat courses |
This class of drugs may enhance ototoxicity. | Loop diuretics |
Absolute contraindication for AG use | Pts with Myasthenia gravis |
What may be seen with neuromuscular blockade? | Acute respiratory paralysis May enhance effects skeletal muscle relaxants |
Mechanism of NM blockade | May inhibit prejunctional relase of acetylcholine Reduce postsynaptic sensitivity |
Streptomycin use | Limited by resistance and advent of newer AGs |
Streptomycin used alone to treat... | Tularemia and plague (DoC) |
Streptomycin used in combination to treat | Tuberculosis Brucellosis (DoC with doxy) Endocarditis (w/ cillin) |
Gentamycin | One of the most frequently used Generally chosen first |
Gentamycin used in combination for... | (used with cillin) Pseudomonas (DoC) Enterococcal (DoC) |
Amakacin primarily used for | Pseudomonas Other serious infxns caused by *organisms resistant to other AGs* |
Amikacin has | The broadest spectrum Resistance to inactivating enzymes |
What makes amikacin more effective than other AGs? | There is only one site susceptible to enzyme anabolism |
Neomycin is... | Not used systemically Used topically The most toxic AG |
Only time Neomycin is used orally/systemically | To sterilize the gut When organisms are resistant to other agents |
Tetracycline (class) spectrum | G+, G-, aerobic, anaerobic Intracellular bacteria -Chlamydia, Rickettsia, Mycoplasm p.) |
Doxycycline and minocycline | 2 of the most widely prescribed drugs |
Doxycycline | One of the most active and clinically used Preferred in pts with poor renal fxn |
Minocycline | Meningococcal carrier state Crosses the blood-brain-barrier |
Tetracyclines are Docs or alternatives for | Mycoplasma p Chlamydia Rickettsiae Lyme Dz Plague, tularemia, brucellosis, malaria prophylaxis |
Tetracycline (group) MoA | Reversibly binds to 30s Prevents tRNA binding to acceptor site Prevents addition of amino acids to growing peptide |
How does it get into the cell? | Passive diffusion (porin Om in G-) Active transport (plasma membrane) |
Why are tetracyclins and penicillina antagonistic? | Tetra's stop bacterial growth Penicillions need bacterial growth |
Primary mechanism of resistance to tetras | Efflux pumps *Ribosome protection* -Proteins interfere with binding and dislodge drug form ribosome |
This provides a cross-resistance among tetracyclines except for | Tigrecyclin |
Tetracycline pharmacokinetics | GI absorption is variable For stable chelates with cations |
DD interactions | Milk Antacids Pepto-Bismol |
Tetracycline that gets into the CSF | Minocycline |
Chelates with Ca effecting | Bones and teeth |
Don't give to which patient population? | Pregnant women |
Tetracycline elimination | Eliminated by the kidneys |
Which 3 tetras are less dependent on the kidneys for excretion? | Doxy, mino, and Tige Excreted by the bile |
Tigecycline spectrum of action | Very broad spectrum antibiotic Effective in resistant organisms (MRSA, Staph epi, PRSP, VRE) |
What makes tigecycline so useful? | Not susceptible to efflux pumps and ribosome protection |
Tigecyclin route of administration and excretion | IV Poor oral absorption Biliary excretion |
Tigecycline uses | Complicated skin and skin structure infxn Intraabdominal infxn Community-acquired pneumonia |
Tetracycline adverse effects | GI Boney structures and teeth Liver tox Local Tissus Tox Photosensitivity Vestibular reactions |
Tetracycline AE: GI | Oral dosing can cause GI distress NVD |
Tetracycline AE: Bone | Bind Ca, esp. in newly formed bone of young kids Kids may develop permanent brown discoloration |
What increases the risk of permanent brown discoloration? | Use in the last half of pregnancy and up to 8 y/o Crosses the placenta and accumulates in fetus |
Tetracycline AE: Liver Tox | Rare but fatal Occurs more commonly with tetra and mino |
Tetracycline AE: Local tissue tox | Directly irritating to tissues IV: thromboplebitis IM: painful |
Tetracycline AE: Photosensitivity | Fair skin pts ate major risk |
Tetracycline AE: Vestibular Rxn | May be produced by Mino Ataxia Dizziness NV |
Tetracycline AE: Superinfections | Pseudomembranous colitis |
Precautions with Tetracyclines | Don't give to: Pregnant pts kids <8 Discard unused drugs as it may cause Fanconi syndrome |
Drug classes that act on the 50s | Chloramphenicol Macrolides Lincosamides Streptogramins Oxazolidinones |
Chloramphenicol | Rarely used Serious toxicity limits use Reserved for life-threatening infxn due to resistance or allergies to safer drugs |
Chloramphenicol occasionally used for | Rickettsial infxn Menengitis Anaerobic infxn |
Chloramphenicol spectrum and MoA | Broad spectrum -Aerobic, anaerobic, G+, G- Reversibly binds to inhibit peptidyl transferase (Peptide bond formation) |
Chloramphenicol Toxicity | Hematological Toxicity Bone marrow suppression -anemia, leukocytopenia, thrombocytopenia Dose dependent and reversible |
Chloramphenicol: Idiosyncratic response | Serious and fatal Aplastic anemia-> fatal pancytopenia Rare; does NOT containdicate |
Chloramphenicol: Idiosyncratic drug reaction | Abnormal Rare and unpredictable Occurs sporadically Not related to dose |
Chloramphenicol: Adverse Effects | Gray syndrome/gray baby syndrome -Gray color, shock, hypothermia, vomiting, flaccidity Can be fatal in 2 days |
Gray baby syndrome: Mechanism | Lack of glucuronyl transferare activity |
Macrolides | Good substitute for penicillins G+ activity |
Clarithromycin and Azrithromycin: Spectrum | G+ and some G- Camylobacter jejuni H. pylori Shingella spp E. Coli Meisseria gonorrhoeae |
Macrolides are DoC for | Kids and pregnant women Pts allergic to penicillin Preferred for community-acquired RTIs |
Restrictions for macrolide use in CAP | Uncomplicated pneumonia not requiring hospitalization No sig. comorbidities No ABx use in past 3 mo. No sig. macrolide-resistant strains locally |
Macrolides also DoC for... | Mycoplasma p Chlamydia Bordetella Campylobacter Mycobacterium avian complex (MAC) |
Macrolides: Mechanism of Action | Bacteriostatic Inhibits peptide chain elongation (translocation or peptidyl tRNA from A to P site is inhibited |
Macrolides: Resistance | Efflux pumps Ribosome modification -Alters macrolide binding site on the bacterial ribosome |
Macrolides: Pharmacokinetics | New macrolides are more acid-stable Clarithro: less freq dosing Azithro has 1/2 life ~70hrs |
Macrolides: Drug interactions | **Inhibit CYP3A4** P450 inhibition |
Macrolides: Toxicity (Primarily seen with Erythromycin) | GI -Anorexia, NVD -Epigastric distress Cholestatic hepatitis -Fever, jaundice, impaired liver fxn |
Lincosamides Clindamycin: Spectrum and Clinical use | Anaerobic, strept, staph infxns DoC for C. perfringens Aerobic G- bacilli are intrinsically resistant |
Lincosamides Clindamycin: Mechanism of Action | Binds close to erythromycin and chloramphenicol binding sites Inhibits peptide bond formation |
Lincosamides Clindamycin: Resistance | Alterations of ribosomal binding site -Cross resistance with erythro Metabolism of drug G- intrinsic resistance |
Lincosamides Clindamycin: Pharmacokinetics | Does not cross BBB Penetrates into bone (high levels) Actively transported into PMN leukocytes and macrophages (high levels) |
Lincosamides Clindamycin: Adverse effects | Severe diarrhea -May cause antibiotic associated diarrhea |
Lincosamides Clindamycin and pseudomembranous colitis | Clindamycin classically assoc. with this disorder |
Streptogramins Quinupristin + Dalfopristin: Spectrum | G+ bacteria -Staph resistant to: Methacillin, quinolones, vanc -Strept. pneumonia resistant to Pens Vanc-resistant E. farcium |
Streptogramins Quinupristin + Dalfopristin: Principle Clinical Use | Drug resistant G+ cocci infxn -Skin and soft tissue Serious or life-threatening VRE Complicated skin infxn -MSSA and S. pyrogenes |
Streptogramins Quinupristin + Dalfopristin: Mechanism of Action | Q: binds same site as macrolides D: directly interferes with polypeptide chain formation Binds near Q, enhances binding of Q Bactericidal |
Streptogramins Quinupristin + Dalfopristin: Resistance | D: enzymatic inactivation, efflux pumps Q: binding site mods by methylase, enzymatic inactivation |
Streptogramins Quinupristin + Dalfopristin: Drug Interactions | **POTENT CYP3A4 inhibitor** |
Streptogramins Quinupristin + Dalfopristin: Adverse Effects | Pain and phlebitis at infusion site Severe arthalgias and myalgias |
Oxazolidinones Linezolid: Spectrum | Similar to quinupristin+dalfopristin (G+) plus e. faecalis Should be reserved for MDR G+ |
Oxazolidinones Linezolid: Clinical Use | Hospital and community AP -Strep pneumoniae Tx of skin and soft tissue -Complicated/uncomplicated -MRSA & MSSA VR enterococcus |
Oxazolidinones Linezolid: Mechanism of Action | Block formation of initiation complex Mostly bacteriostatic -Cidal to strep. |
Oxazolidinones Linezolid: Resistance and Pharmacokinetics | R: mutation or rRNA binding site P: MAO inhibitor Weak, reversible Tyramine rich foods can cause sudden and severe high BP |
Oxazolidinones Linezolid: Adverse Effects | Myelosuppression -Thrombocytopenia (most common effect) Anemia, Leukopenia |
Created by:
bcriss
Popular Medical sets