Antimicrobials Flashcards
Beta-lactams
Mechanism
Block cell wall synthesis
Inhibit peptidoglycan cross-linking
(penicillin, methicillin, ampicillin, piperacillin, cephalosporins, aztreonam, imipenem)
Bacitracin, vancomycin
Mechanism
Block peptidoglycan synthesis
TMP, sulfonamides
Mechanism
Block nucleotide synthesis-
Inhibit folic acid synthesis
Fluoroquinolones
Mechanism
Block DNA topoisomerases
Rifampin
Mechanism
Block mRNA synthesis
Metronidazole
Mechanism
Damage DNA
Chloramphenicol, macrolides, clindamycin, streptogramins, linezolid
Mechanism
50S ribosomal subunit inhibitor
Chloramphenicol, macrolides, clindamycin, streptogramins (quinupristin, dalfopristin), linezolid
Aminoglycosides, tetracyclines
Mechanism
30S ribosomal subunit inhibitor
Bind transpeptidases
Gram-positives, gram-neg cocci, spirochetes
Hypersensitivity, hemolytic anemia
Beta-lactamases for resistance
Penicillin G (IV,IM)
Penicillin V (oral)
Penicillinase susceptible
Penicillinase resistant
S. aureus
Hypersensitivity, interstitial nephritis
Oxacillin, nafcillin, dicloxacillin
(naf for staph)
bulky -R group
blocks beta-lactamase access to b-lactam ring
MRSA
Mechanism of resistance
Altered penicillin-binding protein target site
HELPSS kill enterococci
Hypersensitivity, rash, pseudomembranous colitis
Combined with clavulanic acid
Aminopenicillins
Ampicillin, amoxiciliin
amoxi > bioavailability
penicillinase susceptible (add clavulate)
HELPSS:
Haemophilus, E. coli, Listeria, Proteus, Salmonella, Shigella
Gram-neg rods, Pseudomonas
Combined with clavulanate
Hypersensitivity
Antipseudomonals
Ticarcillin, piperacillin
Susceptible to penicillinase
Beta-lactamase inhibitors
CAST
Clavulanic acid, sulbactam, tazobactam
Covers everything but LAME
(Listeria, Atypicals (Chlamydia, Mycoplasma), MRSA, Enterococci)
Cephalosporins
except ceftaroline covers MRSA
Can cause
Hypersensitivity, Vit K deficiency, increased nephrotoxicity of aminoglycosides
Cephalosporins
Gram-pos cocci
PEcK
(Proteus, E. coli, Klebsiella)
1st gen cephalosporins
Cefazolin, Cephalexin
Cefazolin - prior to surgery to prevent
S. aureus wound infections
Gram-pos cocci
HEN PEcKS
(Haemophilus, Enterobacter aerogenes, Neisseria, Proteus, E. coli, Klebsiella, Serratia marcescens)
2nd gen cephalosporins
Cefoxitin, Cefaclor, Cefuroxime
Serious gram-neg infections
(meningitis, gonorrhea)
resistant to other beta-lactams
3rd gen cephalosporins
Ceftriaxone- meningitis, gonorrhea
Ceftazidime- Pseudomonas
Gram-neg rods only
monobactam (resistant to beta-lactamases)
No penicillin cross-allergenicity
Binds PBP3
Aztreonam
Binding to PBP3 prevents peptidoglycan cross-linking
Syngeristic with aminoglycosides
Beta-lactamase resistant
Inactivation in renal tubules prevented by cilastatin
Wide spectrum- serious infections
GI distress, seizures, rash
Imipenem/cilastatin
meropenem
Binds D-ala portion of cell wall precursors
Gram-pos only
Red man syndrome
Vancomycin
Red man syndrome:
Nephrotoxicity, ototoxicity, thrombophlebitis,
diffuse flushing
(pretreat w/ antihistamine, do slow infusion)
Result of
D-ala D-ala
change to
D-ala D-lac
in cell wall precursor
Vancomycin resistance
Inhibits intiation complex formation
Ineffective against anaerobes
Nephrotoxic, ototoxic, teratogen, neuromuscular block
Inactivated by acetylation, phosphorylation, adenylation
Aminoglycosides
(gentamicin, neomycin, amikacin, tobramycin, streptomycin)
Cause misreading of mRNA
Requires O2 for uptake
Resistance: transferase enzymes
Prevents aminoacyl-tRNA attachment to 30S
Divalent cations inhibit absorption in gut
GI distress, discoloration of teeth, inhibits bone growth in children, photosensitivity. Contraindication: pregnancy
Resistance: plasmid-encoded transport pumps
Tetracyclines
(tetracycline, doxycycline, demeclocycline, minocycline)
Intracellular accumulation- effective against:
B. burgdorferi, M.pneumoniae, Rickettsia, Chlamydia
Divalent cations in milk, antacids, iron-preps
Demeclocycline- ADH antagonist. SIADH- first line
Blocks translocation by binding 23S subunit (of 50S)
Atypical pneumonias, Chlamydia, gram-pos cocci
Motility issues, long QT arrythmia, acute cholestatic hepatitis, rash, eosinophilia
Resistance: methylation of 23S binding site
Macrolides
Azithromycin, clarithromycin, erythromycin
Blocks peptidyltransferase at 50S
Meningitis (3rd world)
Anemia, gray baby syndrome
Chloramphenicol
Blocks peptide transfer at 50S
Anaerobic infections- aspiration pneumonia, oral infections
Pseudomembranous colitis, fever, diarrhea
Clindamycin
Clindamycin- anaerobes above diaphragm
Metronidazole- anaerobes below diaphragm
Inhibit dihydropteroate synthase
Nocardia, Chlamydia, UTIs
Hypersensitivity, hemolysis, nephrotoxicity, kernicterus
Sulfonamides
Sulfamethoxazole (SMX), sulfisoxazole, sulfadiazine
PABA antimetabolites inhibit enzyme
Hemolysis in G6PD deficiency
Inhibit dihydrofolate reductase
UTI, Shigella, Salmonella, Pneumocystis jirovecii
Megaloblastic anemia, leukopenia, granulocytopenia
Trimethoprim
Leucovorin reverses folate deficiency due to TMP
Reverses side-effects of Trimethoprim
Leucovorin
(Supplemental folinic acid)
Inhibit DNA gyrase (topo II) and topo IV
Gram-neg rods in urinary, GI. Neisseria, Pseudomonas.
Rarely tendon rupture, leg cramps, myalgias.
Contra: pregnant, children (cartilage damage)
Fluoroquinolones
(ciprofloxacin, norfloxacin, levofloxacin, ofloxacin, sprafloxacin, moxifloxacin, gatifloxacin, enoxacin, nalidixic acid)
No antacids
Free radical metabolites damage DNA
Anaerobes, protozoa (Giardia, Entamoeba, Trichomonas, Gardernella)
Reacts with EtOH, metallic taste
Metronidazole
Treats anerobes below the diaphragm
Mycobacterium tuberculosis
RIPE
Rifampin, isoniazid, pyrazinamide, ethambutol
Prophylaxis: Isoniazid
Mycobacterium avium-intracellulare
ARES
Azithromycin, rifampin, ethambutol, streptomycin
Prophylaxis: Azithromycin
Mycobacterium leprae
Tuberculoid- dapsone, rifampin
Lepromatous- dapsone, rifampin, clofazimine
No prophylaxis
Active metabolite decreases sythesis of mycolic acids
Bacterial catalase-peroxidase (KatG) creates metabolite
Solo prophylaxis against TB
Neurotoxicity, hepatotoxicity, lupus.
Isoniazid
INH- Injures Neurons and Hepatocytes
pyridoxine (B6) can prevent neurotoxicity
Inhibits DNA-dependent RNA Pol
TB, leprosy, meningococcal prophylaxis
Activates P450, orange body fluids
Rifampin
Meningococcal prophylaxis in contacts of children with Haemophilus influenzae B
Delays resistance to dapsone in leprosy.
Uncertain mechanism
Active in pH of phagolysosome
TB
Hyperuricemia, hepatotoxicity
Pyrazinamide
Blocks arabinosyltransferase
Decreased carbohydrate polymerization in cell wall
TB
Optic neuropathy (red-green colorblindness)
Ethambutol
HIV prophylaxis
CD4 < 200
CD4 < 100
CD4 < 50
TMP-SMX (Pneumocystis)
TMP-SMX (Pneumocystis and toxoplasmosis)
Azithromycin (M. avium complex)
Vancomycin resistant enterococcus (VRE)
Linezolid
Streptogramins (quinupristin, dalfopristin)
Binds ergosterol
Forms membrane pores
(2)
Amphotericin B
Nystatin
Inhibits fungal ergosterol synthesis
-azoles
Fluconazole, itraconazole, voriconazole
Inhibits synthesis of beta-glucan
Inhibits fungal cell wall synthesis
Caspofungin
Inhibits squalene epoxidase
Disrupts lanosterol synthesis
Terbinafine, Naftifine
Inhibits fungal DNA and RNA biosynthesis
5-Flucytosine
By conversion to 5-fluorouracil
by cytosine deaminase
Bind ergosterol
Systemic mycoses: Cryptococcus, Blastomyces, Coccidioides, Histoplasma, Candida, Mucor, meningitis
Fever/chills, nephrotoxic, arrhytmias, IV phlebitis, anemia
Amphotericin B
Supplement K+ and Mg2+
(altered renal tubule permeability)
Hydration reduces nephrotoxicity
Liposomal reduces toxicity
Binds ergosterol
Topical
Oral candidiasis, diaper rash, vaginal candidiasis
Nystatin
Blocks conversion of lanosterol to ergosterol
(inhibits P450)
AIDS- cryptococcal meningitis suppression, candida
Blastomyces, Coccidioides, Histoplasma
Testosterone synth inhibition, liver dysfunction
Fluconazole
Itraconazole
Gynecomastia- ketoconazole
Inhibits DNA, RNA biosynthesis
Systemic infections, Cyptoccal meningitis
Bone marrow suppression
Flucytosine
Active metabolite: 5-fluorouracil
by cytosine deaminase
Inhibits fungal cell wall synthesis
(beta-glucan)
Invasive aspergillosis, candida
GI upset, flushing (histamine)
Caspofungin, micafungin
Inhibits squalene epoxidase
Dermtophytoses (i.e. onychomycosis)
Abnormal liver function tests, visual disturbances
Terbinafine
Disrupts microtubule formation, mitosis
Deposits in keratin-containing tissues (nails)
Oral Tx of superficial infections (tinea, ringworm)
Teratogen, carcinogen, increases P450
Griseofulvin
Blocks detox of heme to hemozoin
Plasmodium (other than falciparum)
Retinopathy
Resistance: membrane pump
Chloroquine
Heme accumulates, is toxic to Plasmodia.
Life-threatening malaria in US: quinidine
Flukes- such as Schistosoma
Praziquantel
Pyrimethamine
Suramin and melarsoprol
Nifurtimox
Sodium stibogluconate
Antiprotozoans
Pyrimethamine- toxoplasmosis
Suramin and melarsoprol- Trypanosoma brucei
Nifurtimox- Trypanosoma cruzi
Sodium stibogluconate- Leishmaniasis
Mebendazole
Pyrantel pamoate
Ivermectin
Diethylcarbamazepine
Praziquantel
Antihelminthic
Inhibits neuraminidase
Influenza A and B
Oseltamivir, Zanamivir
Inhibits synthesis of guanine nucleotides
(competitive IMP dehydrogenase inhibition)
Respiratory synctial virus, chronic HCV
Hemolytic anemia, severe teratogen
Ribavirin
Guanosine analog
Monophosphorylation by viral thymidine kinase
DNA Pol chain termination
Herpes simplex virus, Varicella zoster virus
Acyclovir
Prophylaxis in immunocompromised
Valacyclovir (prodrug) better bioavailability
For herpes zoster- famiciclovir
Guanosine analog
Converted to monophosphate by viral kinase
Inhibits viral DNA Pol
Cytomegalovirus
Leukopenia, neutropenia, thrombocytopenia, renal toxicity
Ganciclovir
Valganciclovir (prodrug)- better oral bioavailability
Inhibits viral DNA Pol
by binding pyrophosphate binding site
No activation by viral kinase
CMV retinitis in immunocompromised
(when ganciclovir fails)
Acyclovir-resistant HSV
Nephrotoxicity
Foscarnet
Pyrophosphate analog
Inhibits viral DNA Pol
No activation by viral kinase
CMV retinitis in immunocompromised
Acyclovir-resistant HSV
Long half-life
Nephrotoxicity
Cidofovir
Codminister with probenecid and IV saline
to reduce toxicity
HIV therapy
2 nucleoside reverse transcriptase inhibitors (NRTIs)
+
1 non-NRTI
or
1 protease inhibitor
or
1 integrase inhibitor
Prevent cleavage of HIV proteins into functional parts
Hyperglycemia, GI intolerance, lipodystrophy
Protease inhibitors
Lopinavir, atazanavir, darunavir, fosamprenavir, saquinavir, ritonavir, indinavir
-navir tease a protease
Protease inhibitor
Nephropathy, hematuria
Indinavir
Competitive inhibition of nucleotide binding to RT
DNA chain termination
(lack 3’ OH group)
Most need to be phosphorylated
Bone marrow suppression, peripheral neuropathy, lactic acidosis, rash, anemia
Nucleoside reverse transcriptase inhibitors
Tenofovir, emtricitabine, abacavir, lamivudine, zidovudine, didanosine, stavudine
Tenofovir- doesnt need phosphylation
(a nucleo_tide)_
Zidovudine- prophylaxis during pregnancy
Competitive inhibition of nucleotide binding to RT
No phosphorylation
Bone marrow suppression, peripheral neuropathy, lactic acidosis, rash, anemia
Non-nucleoside reverse transcriptase inhibitors
Nevirapine, efavirenz, delavirdine
Inhibits HIV genome integration into host cell
Reversible inhibition
Hypercholesterolemia
Integrase inhibitors
Raltegravir
Reversible inhibition of HIV integrase
Block both DNA, RNA viral replication
Glycoproteins synthesized by infected cells
Chronic HBV, HCV, Kaposi’s sarcoma
Multiple sclerosis
NADPH oxidase deficiency
Neutropenia, myopathy
Interferons
IFN-alpha
IFN-beta
IFN-gamma
