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Flashcards in Micro AntiMicrobials Deck (81):
1

Blocks cell wall synthesis by inhibiting peptidoglycan cross-linking

Penicillin, Methicillin, Ampicillin, Piperacillin, Cephalosporins, Aztreonam, Imipenem

2

Blocks peptidoglycan synthesis

Bacitracin, Vancomycin

3

Inhibits Folic Acid Synthesis (involved in methylation)

Sulfonamides, Trimethoprim

4

Blocks DNA topoisomerase

Fluoroquinolones

5

Blocks mRNA synthesis

Rifampin

6

Damages DNA

Metronidazole

7

Blocks protein synthesis at 50S ribosome

Chloramphenicol, Macrolides, Clindamycin, Streptogamins (Quinupristin, dalfopristin), Linezolid

8

Blocks protein synthesis at 30S ribosome

Aminoglycosides, Tetracycline

9

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

10

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

11

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

12

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

13

β-lactamase Inhibitors

"CAST"
Clavulanic Acid, Sulbactam, Tazobactam

14

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

15

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

16

2nd gen Cephalosporins
Names
Uses

Cefoxitin, Cefaclor, Cefuroxime
Gram+ cocci, Haemophilus, Enterobacter aerogenes, Neisseria, Proteus, E coli, Klebsiella, Serratia
"HEN PEcKS"

17

3rd gen Cephalosporins
Names
Uses

Ceftriaxone, Cefotaxime, Ceftazidime
Serous Gram- infections resistant to other β-lactam
Ceftriazone: Meningitis and Gonorrhea
Ceftazidime: Pseudomonas

18

4th gen Cephalosporins
Names
Uses

Cefepime
Pseudomonas and Gram+

19

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.

20

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)

21

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

22

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)

23

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

24

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

25

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

26

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

27

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)

28

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

29

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

30

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

31

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

32

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)

33

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)

34

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

35

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)

36

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

37

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

38

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

39

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

40

Pyrazinamide
MoA
Use
Tox

Acidifies intracellular environment
TB
Hyperuricemia, Hepatotoxic

41

Ethambutol
MoA
Use
Tox

↓ carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltranferase
TB
Optic neuropathy (Red-Green Color Blindess)

42

Meningococcal infection prophylaxis

Ciprofloxacin or Rifampin (for children)

43

Gonorrhea prophylaxis

Ceftriaxone

44

Syphilis prophylaxis

Benzathine Penicillin G

45

History of recurrent UTI prophylaxis

TMP-SMX

46

Endocarditis with surgical or dental procedures prophylaxis

Penicillins

47

Pregnant woman carrying GBS prophylaxis

Ampicillin

48

Strep Pharyngitis in child with prior RF prophylaxis

Oral penicillin

49

Post-surgical infection due to S aureus prophylaxis

Cefazolin

50

Gonococcal or Chlamydial conjunctivitis in newborns prophylaxis

Erythromycin ointment

51

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

52

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

53

HIV prophylaxis for CD4 less than 50

Azithromycin for Mycobacterium avium complex

54

Treatment of MRSA and VRE (enterococci)?

MRSA: Vancomycin
VRE: Linezolid and Streptogramins (quinupristin/dafopristin)

55

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

56

Nystatin
MoA
Use

Binds ergosterol forming pores in membrane
"Swish and swallow" for oral candidiasis (thrush). Topical for diaper rash or vaginal candidiasis

57

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

58

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

59

Caspofungin, Micafungin
MoA
Use
Tox

Inhibits cell wall synthesis by inhibiting β-glucan
Invasive aspergillosis, Candida
GI upset, Flushing (by histamine release)

60

Terbinafine
MoA
Use
Tox

Inhibits fungal enzyme Squalene Epoxide
Dermatophytoses (onychomycosis)
LFTs, visual disturbances

61

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)

62

Antiprotozoan Therapy

Pyrimethamine (toxoplasmosis), Suramin and Melarsoprol (Trypanosoma brucei), Nifurtimox (T cruzi), Sodium Stibogluconate (Leishmaniasis)

63

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

64

Treatment for Plasmodia falciparum

Artemether/lumifantrine or Atovaquone/Proguanil

65

Treatment for life-threatenting malaria

Quinidine (in US), Quinine (Elsewhere), Artisunate

66

Anti-Helminthic Therapy
Names
MoA

Mebendazole, Pyrantel Pamoate, Ivermectin, Diethylcarbamazine, Praziquantel (for flukes like Schistosoma)
Imobilizes helminths

67

Zanamivir, Oseltamivir
MoA
Use

Inhibits Influenza Neuraminidase decreasing release of progeny
Treatment and Prevention of Influenza A and B

68

Ribavirin
MoA
Use
Tox

Inhibits synthesis of Guanine by competitively inhibiting IMP dehydrogenase
RSV, HCV (chronic)
Hemolytic anemia, Teratogen

69

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

70

Treatment for Herpes Zoster (Shingles)

Famciclovir

71

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

72

Foscarnet
MoA
Use
Tox
Resistance

Pyrophosphate analog. Viral DNA pol inhibitor
CMV retinitis (when ganciclovir fails), HSV (when acyclovir fails)
Nephrotoxic
Mutated DNApol

73

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

74

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

75

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

76

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)

77

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)

78

Integrase Inhibitors
Names
MoA
Tox

Raltegravir
Inhibits HIV genome integration into host cell chromosome
Hypercholesterolemia

79

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

80

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)

81

Killed Influenza Vaccine

Generates Abs to H preventing entry of viral particles into the cells