Antimicrobials Flashcards
Block cell wall synthesis by in inhibition of peptidoglycan cross linking
Penicillin, methicillin, ampicillin, piperacillin, cephalosporins, aztreonam, imipenem
Block peptidoglycan synthesis
Bacitracin, vancomycin
Block nucleotide synthesis by inhibiting folic acid synthesis
Sulfonamides, trimethroprim
Block DNA topoisomerase
Fluoroquinolones
Block mRNA synthesis
Rifampin
Damage DNA
Metronidazole
Block protein synthesis at 50s ribosomal subunit
Chloramphenicol, macrolides, clindamycin, streptogramins (quinupristin, dalfopristin), linezolid
Block protein synthesis at 30s ribosomal subunit
Aminoglycosides, tetracyclines
Penicillin
G = IV and IM
V = oral
Bind to transpeptidases to prevent cross-linking of peptidoglycan. Use mostly for gram positive bacteria, N. meningitides, T. pallidum.
Resistance = beta lactamase cleaves beta lactam ring.
Penicillinase resistant penicillins
Oxacilin, nafcillin, dicloxacillin
Same MOA as penicillin. Resistant to beta lactamase b/c bulky R group blocks access of beta lactamase to beta lactam ring. USE: Staph aureus (except MRSA)
Aminopenicillins
Ampicillin, amoxicillin. Same MOA penicillin. Beta lactamase sensitive. Combine with clavulanic acid to protect against beta lactamase. Amoxicillin has greater oral bioavailability than ampicillin. Haemophilus influenzae, E. coli, Listeria monocytogenes, Proteus, Salmonella, Shigella, Enterococci. HELPSS kill enterococci.
Antipseuomonals
Same MOA as penicillin. Ticarcillin and piperacillin. Use for Pseudomonas and gram negative rods. susceptible to beta lactamase so use clavulanic acid.
beta lactamase inhibitors
CAST
Clavulanic Acid, Sulabactam, Tazobactam. Can add to penicillin antibiotics.
Cephalosporins and 1st gen
B lactam drugs that inhibit cell wall synthesis but less susceptible to penicillinases. 1st generation (Cefazolin, Cephalexin): gram positive cocci and PEcK - proteus, E coli, Klebsiella. Cefazolin before surgery to prevent S. Aureus wound infections.
2nd gen cephalosporins
Cefoxitin, cefaclor, Cefuroxime.
gram positive cocci + HEN PEcKS
H. influenzae, Enterobacter, Neisseria, Proteus, E coli, Klebsiella, Serratia
Aztreonam
Prevents peptidoglycan cross linking by binding to PBP3. Synergistic with aminoglycosides. Only for gram negative rods. For penicillin allergic pts and pts with renal insufficiency that cannot tolerate aminoglycosides.
Imipenem/cilastin, meropenem
Imipenem is a beta lactamase resistant carbapenem. Always with cilastatin (Inhibitor of renal dehydropeptidase I) to decrease inactivation of drug in renal tubules. Meropenem is stable to dehydropeptidase I and reduced risk of seizures.
SE - Can cause seizures.
Vancomycin
Inhibits cell wall peptidoglycan formation by binding D-ala D-ala portion of cell wall precursors. For gram positive only. For MRSA, enterococci, and C. Dif (pseudomembrane colitis - oral dose). SE: NOT many probs. Nephrotoxicity, Ototoxicity, Thrombophlebitis. Diffuse flushing - red man syndrome - prevent with antihistamines and slow infusion rate. Resistance = Dala D ala to D ala D lac.
Protein synthesis inhibitors
Target smaller bacterial ribosome (70s, made of 30s and 50s subunits), leaving 80s (human) unaffected. 30s inhibitors = Aminoglycosides and Tetracyclines. 50s = Choramphenicol, Clindamycin, Erythromycin, and Linezolid. So…buy AT 30, CCEL at 50.
Aminoglycosides
Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin. MOA: inhibit formation of initiation complex cause misreading of mRNA and block translocation. Require O2 for uptake…so ineffective against anaerobes. USE: gram negative rod infections. Synergistic with beta lactams. Neomycin for bowel surgery. SE: Nephrotoxicity, Neuromuscular blockade, Ototoxicity, Teratogen. SO….Mean (aminoglycoside) GNATS caNNOT kill anaerobes.
Tetracyclines
Tetracycline, doxycycline, demeclocycline, and minocycline. Demeclocycline is ADH antagonist that can be used as diuretic for SIADH. Binds to 30s and prevents attachment of aminoacyl - tRNA. Doxycycline is fecally eliminated so can be used in pts with renal failure. Divalent cations prevent absorption in gut so do not take with milk, antacids or iron preps. Use - borrelia, M pneumonia. Drug accumulates intracellular so can use against Rickettsia and Chlamydia. SE - Dicoloration of teeth and inhibit bone growth in children. CI in pregnancy. Resistance - efflux pumps or decrease uptake.
Macrolides
Azithromycin, Clarithromycin, Erythromycin
Block translocation to inhibit protein synthesis. Bind to 23S rRNA of 50S ribosome. USE: atypical pneumonia (mycoplasma, chlamydia, legionella), STDs(chlamydia) and gram positive cocci (step infections in pt allergic to penicillin). SE: MACRO: Motility issues, Arrhythmia by prolong QT, acute Cholestatic hepatitis, Rash, eosinophilia. Resistance - methylate 23s rRNA site.
Chloramphenicol
Block peptidyltransferase at 50S. USE: meningitis (H flue, N menigitidis, Strep pneumo) Toxicity: anemia, gray baby syndrome - premature baby has no liver UDP - glucuronyl transferase
Clindamycin
Block peptide transfer (transpeptidation) at 50s. for Anaerobic infections (Bacteroides, C perfringens) in aspiration pneumonia. oral infections with anaerobes. SE - pseudomembranous colitis (c dif overgrowth). tx anaerobes above the diaphragm vs metronidazole (anaerobic infections below the diaphragm).
Sulfonamides
SMX (sulfamethoxazole), sulfisoxazole, sulfadiazine.
MOA: PABA antimetabolites inhibit dihydropteroate synthase. For gram positive, gram negative, Nocardia, Chlamydia. SE: hemolysis if G6PD deficient, kernicterus in infants, displace other drugs from albumin (like warfarin)
Trimethoprim
Inhibit dihydrofolate reductase. Use with sulfonamides to cause blockage of folate synthesis. Combo for UTI, Shigella, Salmonella, pneumocystis jirovecii pneumonia. SE : TMP: treats marrow poorly….megaloblastic anemia, leukopenia, granulocytopenia.
Fluoroquinolones
End with floxacin. MOA: inhibit DNA gyrase (topoisomerase II) and topoisomerase IV. Do not take with antacids. USE: Gram negative rods of urinary and GI tract. SE: tendon rupture.
Metronidazole
Forms free radical toxic metabolites in bacteria that damage DNA. Tx: GET GAP on METRO. for Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis, Anaerobes (Bacteroides, C Dif). will take care of anaerobes below the diaphragm. Use with PPI and clarithromycin for triple therapy against H pylori.
SE: Disulfiram like reaction with ETOH and metallic taste.
M. tuberculosis
Prophylaxis - isoniazid Tx - Rifampin, Isoniazid, Pyrazinamide, Ethambutol (RIPE)
M. avium
Azithromycin, rifampin, ethambutol, streptomycin
M. leprae
Long term tx with dapsone and rifampin for tuberculoid form. Add clofazimine for lepromatous form.
Isoniazid
Decrease synthesis of mycolic acid. Bacterial catalase peroxidase need to convert to active metabolite. For M tuberculosis. proph against TB. INH - injures neurons and hepatocytes
Rifampin
Inhibits DNA dependent RNA polymerase. USE - TB. Delays resistance to dapsone when used for leprosy. Prophylaxis for meningococcal and children in contact with H influenza type B. Increases P-450 activity. Orange body fluids. Rifampin 4 Rs: RNA polymerase inhibitor, Revs P450, red/orange body fluids, Rapid resistance if used alone.
Pyrazinamide
For TB. Effective in acidic pH of phagolysosomes. SE - hyperuricemia, hepatotoxicity.
Ethambutol
Decrease polymerizatiom of mycobacterium cell wall by blocking arabinosyltransferase. For TB. Can cause red-green color blindness.
N. meningitidis proph
Ciprofloxacin in adults
Rifampin in kids.
Gonorrhea proph
ceftriaxone.
Syphilis proph
Benzathine penicillin G
Hx of recurrent UTIs proph
TMP-SMX
proph for endocarditis with surgical or dental
Penicillin
Preg woman with group b strep
Ampicillin
Proph of strep in child with prior rheumatic fever
oral penicillin
Prevent postsurgical infection due to staph aureus
Cefazolin
Prevent gonococcal or chlamydia conjunctivitis in newborn
erythromycin ointment
HIV proph
CD4<50 Azithromycin for MAC
Amphotericin B
Binds ergosterol to form membrane pores. Ampho “tears” holes in membrane. Supplement with K and Mg b/c altered renal tubule permeability. SE - IV phlebitis
Nystatin
Same MOA as ampho B. Topical use only b/c too toxic for systemic use. use for thrush (candida)
Azoles
Inhibits ergosterol synthesis. SE: inhibits testosterone synthesis …gynecomastia. Inhibits CYP450.
Flucytosine
Inhibits DNA and RNA synthesis by conversion to 5-fluorouracil by cytosine deaminase. SE - bone marrow suppression. Tx - used in combo with ampho B. esp for meningitis caused by Cryptococcus.
Caspofungin, micafungin
Inhibit cell wall synthesis by inhibiting synthesis of beta glucan. For aspergillosis and candida. SE - flushing b/c histamine release.
Terbinafine
Inhibits the fungal enzyme squalene epoxidase. used for dermatophytoses (especially onchomycosis - fungal infection of finger or toe nail). SE - abnormal LFTs, visual change.
Griseofulvin
Interferes with microtubules to disrupt mitosis. Deposits in keratin like nails. Txs superficial infections of fungi. SE - teratogenic
Antiprotozoan tx
Toxoplasma - pyrimethamine
T brucei - suramin and melarsoprol
T cruzi - nifurtimox
Leishmaniasis - sodium stibogluconate
Chloroquine
Blocks detox of heme into hemozoin. Heme accumulates and is toxic. Tx for plasmodium other than falciparum (resistance). SE - retinopathy
Zanamivir, Oseltamivir
Inhibit influenza neuraminidase, decrease release of virus. Tx influenza A and B.
Ribavarin
Inhibit synthesis of guanine nucleotides .
Tx: RSV and chronic hep C.
SE: hemolytic anemia and teratogen.
Acyclovir
Monophosphorylated by HSV/VZV thymidine kinase. gaunosine analog. Inhibits viral DNA polymerase. Tx HSV and VZV.
Ganciclovir
5 monophosphate formed by CMV viral kinase. Guanosine analog. Inhibits viral DNA polymerase. Tx - CMV
Foscarnet
Viral DNA polymerase inhibitor. Does not require activation by viral kinase. It is a pyrophosphate analog. SE: nephrotoxicity.
Cidofovir
Inhibitis viral DNA polymerase. No phosphorylation by viral kinase. For CMV. SE: nephrotoxicity. Administer with probenecid and IV saline to reduce toxicity.
HAART Therapy?
Initiate when pt has less than 500 CD4 T cells. 3 drugs to prevent resistance. 2NRTIs + 1 NNRTI or 1 protease inhibitor or 1 integrase inhibitor.
Protease Inhibitors
End with -navir. Navir (never) tease a protease. HIV-1 protease (pol gene) cleaves the polypeptide products of HIV mRNA into their functional parts. SE: Ritonavir can increase the concentration of other drugs by inhibiting CYP 450. Hyperglycemia, lipodystrophy
NRTIs
Competitely inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain (lack a 3’OH group). Zidovudine is for prophylaxis and during pregnancy to reduce the risk of fetal transmission. SE: Bone marrow suppression
NNRTIS bind to reverse transcriptase at different site from NRTIS
Integrase Inhibitors
Raltegravir. Inhibit HIV integration into host chromosome. SE : high cholesterol
Interferons
Block replication of RNA and DNA viruses.
IFNalpha: chronic hepB and C, Kaposi Sarcoma
IFNbeta: MS
IFNgamma: NADPH oxidase deficiency
Sulfonamides in preg
kernicterus
Aminoglycosides in preg
Ototoxicity
Fluoroquinolones in preg
cartilage damage
Tetracyclines in preg
Discolored teeth, inhibit bone growth
Griseofulvin and Ribavirin in Preg
teratogenic
Chloramphenicol in preg
gray baby