Micro AntiMicrobials Flashcards
Blocks cell wall synthesis by inhibiting peptidoglycan cross-linking
Penicillin, Methicillin, Ampicillin, Piperacillin, Cephalosporins, Aztreonam, Imipenem
Blocks peptidoglycan synthesis
Bacitracin, Vancomycin
Inhibits Folic Acid Synthesis (involved in methylation)
Sulfonamides, Trimethoprim
Blocks DNA topoisomerase
Fluoroquinolones
Blocks mRNA synthesis
Rifampin
Damages DNA
Metronidazole
Blocks protein synthesis at 50S ribosome
Chloramphenicol, Macrolides, Clindamycin, Streptogamins (Quinupristin, dalfopristin), Linezolid
Blocks protein synthesis at 30S ribosome
Aminoglycosides, Tetracycline
Penicillin Names? Class? MoA Use? Bactericidal for... Tox Resistance
G (IV and IM), V (oral). β-lactam Antibiotic
Binds PBP (transpeptidiases) and blocks its cross-linking of peptidoglycan
Gram+, N meningitidis, T pallidum, Syphilis
Bactericidal for Gram+ cocci, Gram+ rods, Gram- cocci, Spirochetes
Hypersensitivity rxn, Hemolytic anemia
β-lactamase cleaves β-lactam ring
Penicillinase-Resistent Penicillins Names Spectrum MoA Use Tox
Oxacillin, Nafcillin, Dicloxacillin
Narrow spectrum
Same as penicillin but bulk R group blocks β-lactamase access
S aureus (except MRSA)
Hypersensitivity reaction. Interstitial nephritis
Aminopenicillins Names? Spectrum? MoA Availability Use Tox Resistance
Ampicillin and Amoxicillin. Wide spectrum
Same as penicillin.
AmOxicillin has greater Oral availability
“HELPSS kill Enterococci “
H influenzae, E coli, Listeria, Proteus, Salmonella, Shigella, Enterococci
Hypersensitivity rxn, Ampicillin rash, Pseudomembranous colitis
Penicillinase sensitive. Combine w/ Clavulanic acid to protect against β-lactamase
Antipseudomonals Names MoA? Spectrum? Use Tox Resistance
Ticarcillin and Peperacillin Same as penicillin. Extended spectrum Pseudomonas and Gram- rods Hypersensitivity rxn Penicillinase. Use with Clavulanic acid
β-lactamase Inhibitors
“CAST”
Clavulanic Acid, Sulbactam, Tazobactam
Cephalosporins MoA Resistance What does it do to bacteria What bacteria can in kill? Tox
β-lactam
Less susceptible to penicillinase
Does not kill “LAME” bugs
Listeria, Atypicals (chlamydia, Mycoplasma, MRSA, Enterococci
Ceftaroline covers MRSA
Hypersensitivity, VitK deficiency. ↑ nephrotoxicity of aminoglycosides
1st gen Cephalosporins
Names
Uses
Cefazolin, Cephalexin
Gram+ cocci, Proteus, E coli, Klebsiella
“PEcK”
Cefazolin used prior to surgery to prevent S aureus wound infection
2nd gen Cephalosporins
Names
Uses
Cefoxitin, Cefaclor, Cefuroxime
Gram+ cocci, Haemophilus, Enterobacter aerogenes, Neisseria, Proteus, E coli, Klebsiella, Serratia
“HEN PEcKS”
3rd gen Cephalosporins
Names
Uses
Ceftriaxone, Cefotaxime, Ceftazidime
Serous Gram- infections resistant to other β-lactam
Ceftriazone: Meningitis and Gonorrhea
Ceftazidime: Pseudomonas
4th gen Cephalosporins
Names
Uses
Cefepime
Pseudomonas and Gram+
Aztreonam MoA Resistance Use Tox
Monobactam. Prevents peptidoglycan cross-linking by binding PBP3
Resistant to β-lactamase
Gram- rods only. No activity against Gram+ or anaerobes (pseudomonas)
Used for penicillin allergy pts and those with renal insufficiency who cannot tolerate aminoglycosides
Generally nontoxic. Possible GI upset.
Carbapenems Names MoA Co-administration w/... Resistance Use Tox
Imipenem, Meropenem, Ertapenem, Doripenem
Broad spectrum β-lactam.
I is coadministered w/ Cilastatin (inhibitor of renal dehydropeptidase I) to ↓ inactivation of drug in renal tubules. M resistent to inactivation
Resistent to β-lactamase
Gram+ cocci, Gram- rods, and anaerobes
Only used when all else fails or life threatening
GI distress, Skin rash, CNS tox (seizures)
Vancomycin MoA What does it do to bacteria? Use Tox Resistance
Inhibits cell wall peptidoglycan formation by binding D-ala D-ala portion of cell wall precursors
Bactericidal
Gram+ only. Multi-drug resistant organisms: MRSA, enterococci, C diff
“NOT so bad”
Nephrotoxic, Ototoxic, Thrombophlebitis (inflammation of a vein caused by a blood clot), Diffuse flushing - Red Man Syndrome (prevented by pretreatment with antihistamines and slow infusion rate)
Mutation of 2nd D-ala to D-lac
Protein Synthesis inhibitors
“Buy AT 30, CCEL (sell) at 50”
30S inhibitors:
Aminoglycosides (bactericidal), Tetracyclines (bacteristatic)
50S inhibitors (bacteristatic):
Chloramphenicol, Clindamycin, Erythromycin (macrolides), Linezolid (variable)
Aminoglycosides Names What does it do to bacteria? MoA Uptake
“Mean GNATS caNNOT kill Anaerobes”
Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin
Bactericidal
Inhibits formation of initiation complex and causes misreading. Blocks translocation
Needs O2 for uptake thus ineffective against anaerobes
Aminoglycosides
Use
Tox
Resistance
“Mean GNATS caNNOT kill Anaerobes”
Severe Gram- rods. Synergistic w/ β-lactams. N for bowel surgery
Nephrotoxic (esp w/ cephalosporins), Neuromuscular blockade, Ototoxic (esp w/ loops diuretics), Teratogen
Transferase enzyme that inactivates the drug by acetylation, phosphorylation or adenylation
Tetracylcines Names What does it do to bacteria? MoA Elimination Do not take w/
Tetracycline, Doxycycline, Demeclocycline, Minocycline
Bacteriostatic
Binds 30S and prevents attachment of aminoacyl-tRNA
Demeclocycline is an ADH antagonist used to treat SIADH
Doxycycline fecally eliminated so it can be given to pts with renal failure
Do not take with milk, antaacids, iron b. divalent cations inhibit gut absorption
Tetracylcines Use Tox Contraindications Resistance
Borrelia burgdorferi, M pneumoniae, Rickettsia, and Chlamydia (accumulates in cells so good at killing last 2)
GI distress, discoloration of teeth and inhibition of bone growth in children. Photosensitivity
Pregnancy
↓ Uptake or ↑ efflux by plasmid encoded pump
Macrolides Names What does it do to bacteria MoA Use
Azithromycin, Clarithromycin, Erythromycin
Bacteriostatic
Blocks translocation ("macroSLIDES"). Binds 23S rRNA of 50S ribosome
Atypical pneumonia (Mycoplasma, Chlamydia, Legionella), STDs (Chlamydia), Gram+ cocci (strep in pts allergic to penicillin)Macrolides
Tox
Resistance
“MACRO”
Motility issues, Arrhythmia (long QT), acute Cholestatic hepatitis, Rash, eOsinophilia. Increased serum concentration of theophyllines and oral anticoagulants
Methylation of 23S rRNA binding site
Chloramphenicol What does it do to bacteria? MoA Use Tox Resistance
Bacteriostatic. Blocks peptidyltransferase at 50S
Meningitis (Haemophilus, N meningitidis, Strep pneumoniae)
Anemia, Aplastic anemia, Gray baby syndrome (in premies b/c lack of UDP glucuronyl transferase)
Plasmid encoded acetyltransferase inactivates drug
Clindamycin What does it do to bacteria? MoA Use Tox
Bacteriostatic. Blocks peptide transfer (transpeptidation) at 50S ribosomal subunit
Anaerobes (Bacteroides fragilis, C perfringens) in aspiration pneumonia or lung abscesses. Oral infections with mouth anaerobes
“Anaerobes above the diaphragm”
Pseudomembranous colitis (C diff overgrowth), Fever, Diarrhea
Sulfonamides Names What does it do to bacteria? MoA Use Tox Resistance
Sulfamethoxazole (SMX), Sulfisoxazole, Sulfadiazine
Bacteriostatic
PABA antimetabolite inhibits dihydropteroate syntahse
Gram+, Gram-, Nocardia, Chlamydia, UTIs
Hypersensitivity, Hemolysis (G6PD deficiency), Nephrotoxic (tubulointerstitial nephritis), Photosensitivity, Kernicterus (infants), Displace other drugs from albumin (warfarin)
Altered dihydropteronate synthase, ↓ uptake, ↑ PABA synthesis
Bacterial DNA, RNA, and Protein Synthesis
PABA + Pteridine –> [Dihydropteroate Synthase] –> Dihydropteroic acid –> Dihydrofolic acid –> [Dihydrofolate reductase] –> THF –> N methylene THF –> Purines (DNA and RNA), Thymidine (DNA), and Methionine (proteins)
Trimethoprim What does it do to bacteria? MoA Used w/ Use Tox
Bacteriostatic
Inhibits bacterial DHF reductase
Combined with SMX
UTIs, Shigella, Salmonella, Pneumocystis jirovecii pneumonia (treatment and prophylaxis)
“TMP: Treats Marrow Poorly”
Megaloblastic anemia, Leukopenia, Granulocytopenia. May alleviate w/ supplemental folic acid (Leucovorin rescue)
Fluoroquinolones Names What does it do to bacteria Co-administration MoA Resistance
Ciprofloxacin, Norfloxacin, Levofloxacin, Olfoxacin, Sparfloxacin, Moxifloxacin, Gatifloxacin, Enoxacin. Nalidixic acid (quinolone)
Bactericidal. Do not take with antacids
Inhibits DNA gyrase (topoisomerase II) and topoisomerase IV
Chromosome-encoded mutation in DNA gyrase, Plasmid-mediated resistance, efflux pumps
Fluoroquinolones
Use
Tox
Contraindications
Gram- rods of Urinary and GI tracts (including Pseudomonas), Neisseria, Some Gram+ organisms
“LONES hurt your BONE attachments”
GI upset, Super-infections, Skin rashes, Headache, Dizziness. Tendonitis, Tendon rupture, Leg cramps, Myalgias, Long QT
Pregnant women, Children (damage to cartilage)
Metronidazole What does it do to pathogens? MoA Use Tox
Bactericidal. Antiprotozoal
Free radicals
“GET GAP on the METRO”
Giardia, Entamoeba, Trichomanas, Gardnerella vaginalis, Anaerobes below the diaphragm (Bacteroides, C diff), H pylori (w/ PPI and Clarithromycin)
Disulfiram-like reaction w/ EtOH, Headache, Metallic taste
Antimycobacterial Drugs
Tuberculosis
Prophylaxis: Isoniazid. Treatment: “RIPE” Rifampin, Isoniazid, Pyrazinamide, Ethambutol
M avium-intracellulare
Prophylaxis: Azithromycin. Treatment: Azithromycin, Rifampin, Ethambutol, Streptomycin
Leprae
Treatment: Tuberculoid form w/ Dapsone and Rifampin. Add Clofazimine for Lepromatous form
Isoniazid Activation MoA Use Tox
Bacterial catalase-peroxidase (KatG) converts INH into active metabolite ↓ synthesis of mycolic acids TB Neurotoxicity and Hepatotoxicity. Lupus VitB6 prevents neurotoxicity
Rifampin
MoA
Use
Tox
“4Rs” RNA pol, Revs up P450, Red/Orange fluid, Rapid resistance if used alone
Inhibits DNA-dependent RNA pol
TB. Delays resistance to dapsone in leprosy. Meningococcal prophylaxis and chemoprophylaxis in contacts of children with Haemophilus influenzae type B
Hepatotoxic. Drug interactions (↑ P450). Orange body fluid
Pyrazinamide
MoA
Use
Tox
Acidifies intracellular environment
TB
Hyperuricemia, Hepatotoxic
Ethambutol
MoA
Use
Tox
↓ carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltranferase
TB
Optic neuropathy (Red-Green Color Blindess)
Meningococcal infection prophylaxis
Ciprofloxacin or Rifampin (for children)
Gonorrhea prophylaxis
Ceftriaxone
Syphilis prophylaxis
Benzathine Penicillin G
History of recurrent UTI prophylaxis
TMP-SMX
Endocarditis with surgical or dental procedures prophylaxis
Penicillins
Pregnant woman carrying GBS prophylaxis
Ampicillin
Strep Pharyngitis in child with prior RF prophylaxis
Oral penicillin
Post-surgical infection due to S aureus prophylaxis
Cefazolin
Gonococcal or Chlamydial conjunctivitis in newborns prophylaxis
Erythromycin ointment
HIV prophylaxis for CD4 less than 200
TMP-SMX for Pneumocystis pneumonia
Aerosolized pentamidine used if pt cannot tolerate TMP-SMX but this may not prevent toxoplasmosis
HIV prophylaxis for CD4 less than 100
TMP-SMX for Pneumocystis pneumonia and Toxoplasmosis
Aerosolized pentamidine used if pt cannot tolerate TMP-SMX but this may not prevent toxoplasmosis
HIV prophylaxis for CD4 less than 50
Azithromycin for Mycobacterium avium complex
Treatment of MRSA and VRE (enterococci)?
MRSA: Vancomycin
VRE: Linezolid and Streptogramins (quinupristin/dafopristin)
Amphotericin B MoA Use Route Supplement Tox How to reduce tox?
Binds ergosterol forming pores in membrane
Cryptococcus (w/ or w/o Flucytosine), Blastomyces, Coccidioides, Histoplasma, Candida, Mucor
Intrathecally for fungal meningitis
K and Mg to change renal tubule permeability
Fever/Chills (“shake and bake”), Hypotension, Nephrotoxic, Arrhythmias, Anemia, IV phlebitis
Hydration (for kidneys) and Liposomal form reduces tox
Nystatin
MoA
Use
Binds ergosterol forming pores in membrane
“Swish and swallow” for oral candidiasis (thrush). Topical for diaper rash or vaginal candidiasis
Azoles Names MoA Use Tox
Fluconazole, Ketoconazole, Clotimazole, Miconazole, Itraconazole, Voriconazole
Inhibits fungal sterol (ergosterol) synthesis by inhibiting P450 that converts Lanosterol to Ergosterol
F for chronic suppression of Crytococcal meningitis in AIDS and Candidal infection of all types
I for Blastomyces, Coccidioides, Histoplasma
C and M for topical fungal infections
Inhibits Testosterone synthesis (gynecomastia), Liver dysfunction
Flucytosine
MoA
Use
Tox
Inhibits DNA and RNA synthesis by conversion to 5FU by cytosine daminase
Systemic fungal infections (esp miningitis by Cryptococcus) w/ Amphotericin B
Bone marrow suppression
Caspofungin, Micafungin
MoA
Use
Tox
Inhibits cell wall synthesis by inhibiting β-glucan
Invasive aspergillosis, Candida
GI upset, Flushing (by histamine release)
Terbinafine
MoA
Use
Tox
Inhibits fungal enzyme Squalene Epoxide
Dermatophytoses (onychomycosis)
LFTs, visual disturbances
Griseofulvin MoA Where does it accumulate? Use Tox
Interferes to MT function disrupting mitosis
Oral treatment for superficial infection.
Deposits in keratin containing tissues (nails)
Inhibits growth of dermatophytes (tinea, ringworm)
Teratogenic, Carcinogenic, Confusion, Headaches, ↑ P450 (warfarin metabolism)
Antiprotozoan Therapy
Pyrimethamine (toxoplasmosis), Suramin and Melarsoprol (Trypanosoma brucei), Nifurtimox (T cruzi), Sodium Stibogluconate (Leishmaniasis)
Chloroquine MoA Resistance Use Tox
Blocks detoxification of Heme into Hemozoin. Heme accumulates and is toxic to Plasmodia
Plasmodial species other than P falciparum
Membrane pump that ↓ intracellular concentration
Retinopathy
Treatment for Plasmodia falciparum
Artemether/lumifantrine or Atovaquone/Proguanil
Treatment for life-threatenting malaria
Quinidine (in US), Quinine (Elsewhere), Artisunate
Anti-Helminthic Therapy
Names
MoA
Mebendazole, Pyrantel Pamoate, Ivermectin, Diethylcarbamazine, Praziquantel (for flukes like Schistosoma)
Imobilizes helminths
Zanamivir, Oseltamivir
MoA
Use
Inhibits Influenza Neuraminidase decreasing release of progeny
Treatment and Prevention of Influenza A and B
Ribavirin
MoA
Use
Tox
Inhibits synthesis of Guanine by competitively inhibiting IMP dehydrogenase
RSV, HCV (chronic)
Hemolytic anemia, Teratogen
Acyclovir MoA Use Better version? Tox Resistance
Guanosine analog that inhibits viral DNA pol by chain termination
HSV and VZV. Weak activity against EBV
HSV induced mucocutaneous or genital lesions and encephalitis. Prophylaxis for immunocompromised pts
No effect on latent HSV or VZV
Vanacyclovir has better bioavailability
Few toxicities
Mutated viral Thymidine kinase
Treatment for Herpes Zoster (Shingles)
Famciclovir
Ganciclovir MoA Use Better version? Tox Resistance
Guanosine analog that inhibits viral DNA pol
CMV
Valganiciclovir is a prodrug with better bioavailability
Leukopenia, Neutropenia, Thrombocytopenia, Renal toxicity
Mutated CMV DNA pol or lack of viral kinase
Foscarnet MoA Use Tox Resistance
Pyrophosphate analog. Viral DNA pol inhibitor
CMV retinitis (when ganciclovir fails), HSV (when acyclovir fails)
Nephrotoxic
Mutated DNApol
Cidofovir MoA Use Half life Tox Co-administration
Inhibits viral DNA pol
CMV retinitis, HSV (when acyclovir fails)
Long half-life
Nephrtoxic
Probenecid and IV saline to reduce toxicity
HAART
When is it initiated?
Regimen
AIDS-defining illness, low CD4 (below 500), High vial load
2 nucleoside RT inhibitors + 1 non-nucleoside RT inhibitor OR Protease inhibitor OR Integrase inhibitor
Protease inhibitors
Names
MoA
Tox
“Navir tease a protease”
-navir (Lopi, Ataza, Daru, Fosampre, Saqui, Rito, Indi)
Protease cleaves products of HIV mRNA into functional parts
Ritonavir can boost other [drug] by inhibiting P450
Hyperglycemia, GI intolerance (nausea, diarrhea), Lipodystrophy
Indinavir: Nephropathy and Hematuria
NRTI Names MoA Activation Uses Tox
“Have you DINED with my NUCLEAR family”
Tenofovir (TDF), Emtricitabine (FTC), Abacavir (ABC), Lamivudine (3TC), Zidovudine (ZDV, AZT), Didanosine (ddl), Stavudine (d4T)
Competitive NT that gets used by RT but has not 3’ OH –> early chain termination
TDF does not need activation. The rest need to phosphorylated
ZDV used as prophylaxis during pregnancy
Bone marrow suppression (reversible w/ G-CSF and EPO), Peripheral neuropathy, Lactic Acidosis, Anemia (ZDV)
NNRTIs Names MoA Activation Tox
Nevirapine, Efaverenz, Delavirdine
Inhibits RT
Does not require phosphorylation
Bone marrow suppression (reversible w/ G-CSF and EPO), Peripheral neuropathy, Rash, Anemia (ZDV)
Integrase Inhibitors
Names
MoA
Tox
Raltegravir
Inhibits HIV genome integration into host cell chromosome
Hypercholesterolemia
Interferons What is it? What produces it? MoA Use Tox
Glycoprotein synthesized by virus-infected cells.
Blocks replication of both RNA and DNA viruses
IFNα: chronic HBV or HCV, Kaposi sarcoma
IFNβ: MS
IFNγ: NADPH oxidase deficiency
Neutropenia, Myopathy
Antibiotics to avoid during pregnancy
“SAFe Children Take Really Good Care”
Sulfonamides (Kernicterus), Aminoglycosides (Ototoxic), Fluoroquinolones (Cartilage damage), Clarithromycin (Embryotoxic), Tetrocycline (Discolored teeth, inhibition of bone growth), Ribavirin (teratogenic), Griseofulvin (Teratogenic), Chloramphenicol (gray baby)
Killed Influenza Vaccine
Generates Abs to H preventing entry of viral particles into the cells
