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Flashcards in FA - Micro - Antimicrobials Deck (215):
0

Antimicrobials - Folic acid synthesis (DNA methylation)?

Sulfonamides:
1. Sulfamethoxazole
2. Sulfisoxazole
3. Sulfadiazine
+ Trimethoprim.

1

Antimicrobials - DNA topoisomerases?

Fluoroquinolones:
1. Ciprofloxacin
2. Levofloxacin
Quinolone
1. Nalidixic acid

2

Antimicrobials - Damages DNA?

Metronidazole

3

Antimicrobials - mRNA synthesis (RNA pol)?

Rifampin

4

Antimicrobials - Protein Synthesis - 50S subunit?

1. Chloramphenicol
2. Clindamycin
3. Linezolid
Macrolides:
1. Azithromycin
2. Clarithromycin
3. Erythromycin
Streptogramins
1. Quinupristin
2. Dalfopristin

5

Antimicrobials - Protein synthesis - 30S subunit?

Aminoglycosides
1. Gentamicin
2. Neomycin
3. Amikacin
4. Tobramycin
5. Streptomycin
Tetracyclines:
1. Tetracycline
2. Doxycycline
3. Minocycline

6

Antimicrobials - Cell wall synthesis - Peptidoglycan synthesis - Glycopeptides?

1. Vancomycin
2. Bacitracin

7

Antimicrobials - Peptidoglycan cross-linking - Penicillinase-sensitive penicillins?

1. Penicillins G, V
2. Ampicillin
3. Amoxicillin

8

Antimicrobials - Cell wall synthesis - Peptidoglycan cross-linking - Penicillinase-resistant penicillins?

1. Oxacillin
2. Nafcillin
3. Dicloxacillin

9

Antimicrobials - Cell wall synthesis - Peptidoglycan cross linking - Antipseudomonals?

1. Ticarcillin
2. Piperacillin

10

Antimicrobials - Cell wall synthesis - peptidoglycan cross-linking Cephalosporins?

1st - Cephazolin
2nd - Cefoxitin
3rd - Ceftriaxone
4th - Cefipime
5th - Ceftaroline

11

Antimicrobials - Cell wall synthesis - Peptidoglycan cross-linking Carbapenems?

1. Imipenem
2. Meropenem
3. Ertapenem
4. Doripenem

12

Antimicrobials - Cell wall synthesis - Peptidoglycan cross-linking - monobactams?

Aztreonam

13

Penicillin G route?

IV, IM

14

Penicillin V route?

Oral

15

Penicillin G, V - Mechanism?

1. Bind penicillin-binding proteins (transpeptidases)
2. Block transpeptidase cross-linking of peptidoglycan.
3. Activate autolytic enzymes.

16

Penicillin G, V - Clinical use?

1. Mostly for Gram(+) - S.pneumoniae, S.pyogenes, Actinomyces.
2. Also for N.meningitidis, T.pallidum.
3. Bactericidal for gram(+) cocci, gram(+) rods, gram(-) cocci, spirochetes.
4. Penicillinase sensitive.

17

Penicillin G,V - Toxicity?

1. HSR
2. DIRECT COOMBS (+) Hemolytic anemia

18

Penicillin G, V - Resistance?

Penicillinase in bacteria (a type of beta-lactamase) cleaves beta-lactam ring.

19

Ampicillin, amoxicillin - Mechanism?

Same as penicillin. Wider spectrum + Penicillinase SENSITIVE.
--> Combine with clavulanic acid to protect against beta-lactamase.

20

Ampicillin vs Amoxicillin - Bioavailability?

Amoxil > Ampicillin

21

Ampicillin/Amoxicillin - Clinical use?

Extended-spectrum penicillin:
1. H.influenza
2. E.coli
3. L.monocytogenes
4. P.mirabilis
5. Salmonella
6. Shigella
7. Enterococci

22

Ampicillin/Amoxicillin - Toxicity?

1. HSR
2. Rash
3. Pseudomembranous colitis

23

Ampicillin/Amoxicillin - Mechanism of resistance?

Penicillinase in bacteria (a type of beta-lactamase) cleaves beta-lactam ring.

24

Oxacillin/Nafcillin/Dicloxacillin - Mechanism?

Same as penicillin. Narrow spectrum - Penicillinase-RESISTANT because bulky R group blocks access of beta-lactamase to beta-lactam ring.

25

Oxacillin/Nafcillin/Dicloxacillin - Clinical use?

S.aureus - except MRSA - resistant because of altered penicillin-binding protein target site.

26

Oxacillin/Nafcillin/Dicloxacillin - Toxicity?

1. HSR
2. Interstitial nephritis

27

Ticarcillin/Piperacillin (antipseudomonals) - Mechanism?

Same as penicillin. Extended spectrum.

28

Ticarcillin/Piperacillin (antipseudomonals) - Clinical use?

1. Pseudomonas spp.
2. Gram(-) rods
3. Susceptible to penicillinase
4. Use with beta-lactamase inhibitors

29

Ticarcillin/Piperacillin (antipseudomonals) - Tox?

HSR

30

Mention beta-lactamase inhibitors?

1. Clavulanic acid
2. Sulbactam
3. Tazobactam

31

Cephalosporins - Mechanism?

1. Beta-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases.
2. Bactericidal.

32

Organisms typically NOT covered by cephalosporins?

LAME:

Listeria
Atypicals (Chlamydia, Mycoplasma)
MRSA
Enterococci

Exception: Ceftaroline covers MRSA.

33

1st Gen cephalosporins - Clinical use?

Cefazolin, cephalexin.
1. Gram(+) cocci
2. P.mirabilis
3. E.coli
4. K.pneumoniae
5. Cefazolin used prior to surgery to prevent S.aureus wound infections.

34

2nd gen cephalosporins - Clinical use?

Cefoxitin, cefaclor, cefuroxime:
1. Gram(+) cocci
2. H.influenza
3. Enterobacter aerogenes
4. Neisseria spp.
5. P.mirabilis
6. E.coli
7. K.pneumoniae
8. S.marcescens

35

3rd gen cephalosporins - Clinical use?

Ceftriaxone, cefotaxime, ceftazidime.
Serious gram(-) infections resistants to other beta-lactams.
Ceftriaxone --> Meningitis + Gonorrhoeae + Disseminated LYME.
Ceftazidime --> Pseudomonas.

36

4th gen cephalosporins - clinical use?

Cefepime.
Incr. activity against pseudomonas + gram(+) organisms.

37

5th gen cephalosporins - clinical use?

Ceftaroline.
Broad gram(+) and gram(-) organism coverage, incl. MRSA.
Does NOT cover Pseudomonas.

38

Cephalosporins toxicity?

1. HSR.
2. Autoimmune hemolytic anemia.
3. Disulfiram-like reaction.
4. VitK def.
5. Low cross-reactivity with penicillins.
6. Increase nephrotoxicity of aminoglycosides.

39

Aztreonam - Mechanism?

1. Monobactam - resistant to beta-lactamases.
2. Prevents peptidoglycan cross-linking by binding to penicillin-binding protein 3.
3. Synergistic with aminoglycosides.
4. No cross-allergenicity with penicillins.

40

Aztreonam - Clinical use?

1. Gram(-) rods only.
2. No activity against gram(+) or anaerobes.
3. For penicillin allergic patients and those with renal insufficiency who cannot tolerate aminoglycosides.

41

Aztreonam - toxicity?

Usually nontoxic - occasional GI upset.

42

Aminoglycosides - Mechanism?

1. Bactericidal
2. Inhibit formation of initiation complex and cause misreading of mRNA.
3. Also block translocation.
4. Require O2 for uptake - therefore ineffective against anaerobes.

43

Aminoglycosides - Clinical use?

1. Severe gram(-) rods.
2. Synergistic with beta-lactams
3. Neomycin for bowel surgery.

44

Aminoglycosides toxicity?

1. Nephrotoxicity (especially when used with cephalosporins)
2. Neuromuscular blockade
3. Ototoxicity (especially when used with loop diuretics)
4. Teratogen

45

Aminoglycosides - Mechanism of resistance?

Bacterial transferase enzymes inactivate the drug by acetylation, phosphorylation, or adenylation.

46

Tetracyclines - mechanism?

1. Bacteriostatic
2. Bind to 30S and prevent attachment of aminoacyl-tRNA.
3. Limited CNS penetration.
4. Doxycycline is fecally eliminated and can be used in patients with renal failure.
5. Do NOT take with milk (Ca), antacids (Ca, Mg), or iron-containing preparations because divalent cations inhibit its absorption in the gut.

47

Tetracyclines - Clinical use?

1. Borrelia burgdorferi
2. M.pneumoniae
3. Drug's ability to accumulate intracellularly makes it very effective against Rickettsia/Chlamydia.
4. Also used to treat acne.

48

Tetracyclines - Toxicity?

1. GI distress
2. Discoloration of teeth and inhibition of bone growth in children
3. Photosensitivity
4. Contraindicated in pregnancy

49

Tetracyclines - Mechanism of resistance?

1. Decr. UPTAKE
2. Incr. EFFLUX out of bacterial cells by plasmid-encoded transport pumps.

50

Macrolides - Mechanism?

1. Inhibits protein synthesis by blocking TRANSLOCATION (macroslides).
2. Bind to the 23S rRNA of the 50S subunit.
3. Bacteriostatic.

51

Macrolides - Clinical use?

1. Atypical pneumonias
2. STDs (Chlamydia)
3. Gram(+) cocci (strep infections in patients allergic to penicillin).

52

Macrolides - toxicity?

1. GI motility issues
2. Arrhythmia caused by prolonged QT
3. Acute cholestatic hepatitis
4. Rash
5. Eosinophilia
6. Incr. serum concentration of theophyllines + Oral anticoagulants.
7. Erythro + Clarithro INHIBIT CYP450.

53

Macrolides - mechanism of resistance?

Methylation of 23S rRNA-binding site prevents binding of drug.

54

Chloramphenicol - Mechanism?

Blocks peptidyltransferase at 50S ribosomal subunit - Bacteriostatic.

55

Chloramphenicol - Clinical use?

1. Meningitis (H.influenza, N.meningitidis, S.pneumoniae).
2. RM spotted fever - R.rickettsii
3. Limited use due to toxicity but often still in developing countries because of low cost.

56

Chloramphenicol - Toxicity?

1. Anemia - DOSE-dependent.
2. Aplastic anemia - DOSE-dependent.
3. Gray baby syndrome - in premature infants because they lack liver UDP-glucuronyl transferase.

57

Chloramphenicol - Mechanism of resistance?

Plasmid-encoded acetyltransferase inactivates the drug.

58

Clindamycin - Mechanism?

Blocks peptide transfer (translocation) at 50S - Bacteriostatic.

59

Clindamycin - Clinical use?

1. Anaerobic infections (e.g., Bacteroides spp., C.perfringens) in aspiration pneumonia, lung abscesses, oral infections.
2. Also effective against invasive Group A strep infection.

60

Clindamycin vs Metronidazole?

Treats anaerobes ABOVE the diaphragm.

61

Clindamycin - toxicity?

1. Pseudomembranous colitis (C.difficile overgrowth)
2. Fever
3. Diarrhea

62

Sulfonamides - Mechanism?

1. Inhibit folate synthesis.
2. Para-aminobenzoic acid (PABA)
3. Antimetabolites inhibit dihydropteroate synthase.
4. Bacteriostatic

63

Sulfonamides - Clinical use?

1. Gram(+)
2. Gram(-)
3. Nocardia
4. Chlamydia
5. Triple sulfas or SMX for simple UTI

64

Sulfonamides - Toxicity?

1. HSR
2. Hemolysis if G6PD deficient
3. Nephrotoxicity (tubulointerstitial nephritis)
4. Photosensitivity
5. Kernicterus in infants
6. Displace other drugs from albumin (e.g., warfarin)

65

Mechanism of resistance - Sulfonamides?

1. Altered enzyme (bacterial dihydropteroate synthase)
2. Decr. UPTAKE
3. Incr. PABA synthesis

66

Trimethoprim - mechanism?

Inhibits bacterial dihydrofolate REDUCTASE - Bacteriostatic.

67

Trimethoprim - Clinical use?

1. Used in combination with sulfonamides (TMP-SMX)
2. Cause sequential block of folate synthesis.
3. Combination used for UTIs, Shigella, Salmonella, Pneumocystis jirovecii pneumonia treatment and prophylaxis.
4. Toxo prophylaxis.

68

Trimethoprim - Toxicity?

1. Megaloblastic anemia
2. Leukopenia
3. Granulocytopenia
May alleviate with supplemental folinic acid.

69

Fluoroquinolones - mechanism?

1. Inhibits DNA gyrase (topoiso II) + topoiso IV.
2. Bactericidal.
3. Must not be taken with antacids.

70

Fluoroquinolones - Clinical use?

Gram(-) rods of urinary and GI tracts (including Pseudomonas), Neisseria, some gram(+) organisms.

71

Fluoroquinolones - Toxicity?

1. GI upset
2. Superinfections
3. Skin rashes
4. Headaches
5. Dizziness

72

Fluoroquinolones - Less common toxicity?

1. Tendonitis
2. Tendon rupture
3. Leg cramps
4. Myalgias
5. Contra in pregnancy, nursing mothers , and children under 18yrs due to possible damage to cartilage.
6. May prolong QT syndrome
7. May cause tendon rupture in people >60 and in patients taking prednisone.

73

Fluoroquinolones - Mechanism of resistance?

Chromosome-encoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps.

74

Metronidazole - mechanism?

Forms free radical toxic metabolites in the bacterial cell that damages DNA. Bactericidal, antiprotozoal.

75

Metronidazole - Clinical use?

1. Giardia
2. Entamoeba
3. Trichomonas
4. G.vaginalis
5. Anaerobes (bacteroides, C.difficile)
6. H.pylori + clarithromycin + PPI

76

Metronidazole - Disulfiram-like toxicity?

1. Disulfiram-like reaction - severe flushing, tachycardia, hypotension with alcohol.
2. Headache
3. Metallic taste

77

M.tuberculosis - prophylaxis?

Isoniazid

78

M.tuberculosis - Treatment?

1. Rifampin
2. Isoniazid
3. Pyrazinamide
4. Ethambutol (RIPE for treatment)

79

M.avium-intracellulare - Prophylaxis?

1. Azithromycin
2. Rifabutin

80

M.avium-intracellulare - treatment?

1. More drug resistant than M.tuberculosis.
2. Azithromycin or clarithromycin + ethambutol
3. Can add rifabutin or ciprofloxacin.

81

M.leprae - prophylaxis?

No prophylaxis.

82

M.leprae - Treatment?

1. Long-term treatment with dapsone + rifampin for TUBERCULOID FORM.
2. Add clofazimine for LEPROMATOUS form.

83

Isoniazid - Mechanism?

1. Decr. synthesis of mycolic acids.
2. Bacterial catalase-peroxidase (encoded by katG) needed to convert INH to active metabolite.

84

Isoniazid - Clinical use?

M.tuberculosis - the ONLY agent used as solo prophylaxis against TB.

85

Isoniazid - fast vs slow acetylators?

Different half-lives.

86

Isoniazid - toxicity?

1. Neurotoxicity
2. Hepatotoxicity
3. Pyridoxin (B6) can prevent neurotoxicity, lupus

87

Rifamycins (Rifampin, rifabutin) - mechanism?

Inhibits DNA-dependent RNA polymerase.

88

Rifamycins - clinical use?

1. M.tuberculosis.
2. Delays resistance to dapsone when used for leprosy.
3. Used for meningococcal prophylaxis and chemoprophylaxis in contacts of children with H.influenza B.

89

Rifamycins - Toxicity?

1. Minor hepatotoxicity and drug interactions (Incr. P-450).
2. Orange body fluids (non hazardous side effect).
3. Rifabutin favored over rifampin in patients with HIV infection due to less CYP450 stimulation.

90

Rifampin's 4 R's?

RNA polymerase inhibitor
Ramps up microsomal CYP450
Red/orange body fluids
Rapid resistance if used alone
Rifampin ramps up CYP450, but rifabutin does not.

91

Pyrazinamide - mechanism?

1. Uncertain
2. Thought to acidify intracellular environment via conversion to pyrazinoic acid.
3. Effective in acidic pH of phagolysosomes, where TB engulfed by macrophages is found.

92

Pyrazinamide - clinical use?

M.tuberculosis

93

Pyrazinamide - Tox?

1. HYPERURICEMIA
2. Hepatotoxicity

94

Ethambutol - mechanism?

DECREASED carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase.

95

Ethambutol - Clinical use?

M.tuberculosis.

96

Ethambutol - toxicity?

Optic neuropathy - red/green color blindness.

97

High risk for endocarditis and undergoing surgical or dental procedures - Prophylaxis?

Amoxicillin.

98

Gonorrhea - Prophylaxis?

Ceftriaxone

99

History of recurrent UTIs - proph?

TMP-SMX

100

Exposure to meningococcal infection - proph?

1. Ceftriaxone.
2. Ciprofloxacin.
3. Rifampin.

101

Pregnant women carrying GBS - Proph?

1. Intrapartum penicillin G.
2. Ampicillin.

102

Prevention of gonococcal or chlamydial conjunctivitis in newborn?

Erythromycin ointment on eyes.

103

Prevention of postsurgical infection due to S.aureus?

Cefazolin

104

Prophylaxis of strep pharyngitis in child with prior RF?

1. Benzathine penicillin G.
2. Oral penicillin V.

105

Syphilis proph?

Benzathine penicillin G.

106

Proph in HIV - CD4<200?

TMP-SMX --> Pneumocystis pneumonia.

107

Proph in HIV - CD4<100?

TMP-SMX --> Pneumocystis pneumonia and toxoplasmosis.

108

Proph in HIV patients - CD4

Azithromycin or Clarithromycin --> MAC complex.

109

Treatment of MRSA?

1. Vancomycin
2. Daptomycin
3. Linezolid (can cause serotonin syndrome)
4. Tigecycline
5. Ceftaroline

110

Treatment of VRE?

1. Linezolid
2. Streptogramins (quinupristin/dalfopristin)

111

Antifungal therapy - Lanosterol synthesis?

Terbinafine

112

Antifungal therapy - Cell wall synthesis?

Echinocandins:
1. Caspofungin
2. Micafungin
3. Anidulafungin

113

Antifungal therapy - Forms membrane pores?

Polyenes:
1. Amphotericin B
2. Nystatin

114

Antifungal therapy - Nucleic acid synthesis?

5-flucytosine

115

Antifungal therapy - Ergosterol synthesis?

Azoles:
1. Fluconazoles
2. Ketoconazole
3. Clotrimazole
4. Miconazole
5. Itraconazole
6. Voriconazole

116

Amphotericin B - mechanism?

1. Binds ergosterol (unique to fungi)
2. Forms membrane pores that allow leakage of electrolytes

117

Amphotericin B - Clinical use?

1. Serious, systemic mycoses.
2. Cryptococcus - ampho B +/- flucytosine for cryptococcal meningitis.
3. Blastomyces
4. Coccidioides
5. Histoplasma
6. Candida
7. Mucor

118

Amphotericin B - route for fungal meningitis?

Intrathecally

119

Amphotericin B - Supplements?

K and Mg because of altered renal tubule permeability.

120

Amphotericin B - toxicity?

1. Fever/chills (shake and bake)
2. Hypotension
3. Nephrotoxicity
4. Arrhythmias
5. Anemia
6. IV phlebitis

121

Amphotericin B - what to reduce toxicity?

1. Hydration reduces nephrotoxicity.
2. Liposomal amphotericin decreases toxicity.

122

Nystatin - Mechanism?

Same as amphotericin B.

123

Nystatin - route?

Topical form because too toxic for systemic use.

124

Nystatin - clinical use?

1. "Swish and shallow" for oral candidiasis.
2. Topical for diaper rash or vaginal candidiasis.

125

Azoles - mechanism?

Inhibit fungal sterol (ergosterol) synthesis, by inhibiting CYP450 that converts lanosterol to ergosterol.

126

Azoles - Clinical use?

1. Local and less serious systemic mycoses.
2. FLUCONAZOLE for chronic suppression of cryptococcal meningitis in AIDS patients and candidal infections of all types.
3. ITRACONAZOLE --> Blasto + Coccidioides + Histoplasma.
4. CLOTRIMAZOLE/MICONAZOLE --> Topical fungal infections.

127

Azoles - Toxicity?

1. Testosterone synthesis inhibition --> gynecomastia esp. with ketoconazole.
2. Liver dysfunction (inhibits CYP450).

128

Flucytosine - Mechanism?

Inhibits DNA/RNA biosynthesis by conversion to 5-fluorouracil by cytosine deaminase.

129

Flucytosine - clinical use?

Systemic fungal infections (esp.meningitis caused by Cryptococcus) in combination with amphotericin B.

130

Flucytosine - toxicity?

Bone marrow suppression.

131

Echinocandins - mechanism?

Inhibit cell wall synthesis by inhibiting synthesis of β-glucan.

132

Echinocandins - clinical use?

1. Invasive aspergillosis
2. Candida

133

Echinocandins - toxicity?

1. GI upset
2. Flushing (histamine release)

134

Terbinafine - mechanism?

Inhibits the fungal enzyme squalene epoxidase.

135

Terbinafine - clinical use?

Dermatophytoses (especially onychomycosis - fungal infection of finger or toe nails).

136

Terbinafine - toxicity?

1. GI upset
2. Headaches
3. Hepatotoxicity
4. Taste disturbance

137

Griseofulvin - Mechanism?

1. Interferes with microtubule function - Disrupts mitosis.
2. Deposits in keratin-containing tissues (e.g. nails).

138

Griseofulvin - clinical use?

1. Oral treatment of superficial infections.
2. Inhibits growth of dermatophytes (tinea, ,ringworm).

139

Griseofulvin - Toxicity?

1. Teratogenic
2. Carcinogenic
3. Confusion
4. Headaches
5. Incr. P450 + warfarin metabolism

140

Antiprotozoan therapy - Toxoplasmosis?

Pyrimethamine

141

Antiprotozoan therapy - T.bruceii?

Suramin and melarsoprol.

142

Antiprotozoan therapy - T.cruzi?

Nifurtimox

143

Antiprotozoan therapy - Leishmaniasis?

Sodium stibogluconate.

144

Chloroquine - mechanism?

Blocks detoxification of heme into hemozoin --> Heme accumulates and is toxic to plasmodia.

145

Chloroquine - Clinical use?

Treatment of plasmodial species other than P.falciparum - frequeency of resistance in P.falciparum is too high.

146

P.falciparum - mechanism of resistance to chloroquine?

Resistance due to membrane pump that decreases intracellular concentration of drug.

147

How to treat P.falciparum?

Artemether/Lumefantrine or atorvaquone/proguanil.

148

What to give for life-threatening malaria?

Use quinidine in US (quinine elsewhere) or artesunate.

149

Chloroquine toxicity?

1. Retinopathy
2. Pruritus - esp. in dark skinned.

150

Antihelminthic therapy - main agents?

1. Mebendazole
2. Pyrantel pamoate
3. Ivermectin
4. Diethylcarbamazine
5. Praziquantel
immobilize helminths.

151

Praziquantel - clinical use?

Against flukes (trematodes) such as Schistosoma.

152

Antiviral therapy - HIV - Fusion?

Attachment --> Maraviroc
Penetration --> Enfuvirtide

153

Antiviral therapy - HIV - Integrase inhibitors?

1. Raltegravir.
2. Dolutegravir.
3. Elvitegravir.

154

Antiviral therapy - HIV antiviral therapy - reverse transcriptase inhibitors - NRTIs?

1. Tenofovir (TDF)
2. Emtricitabine (FTC)
3. Abacavir (ABC)
4. Lamivudine (3TC)
5. Zidovudine (ZDV, formerly AZT)
6. Didanosine (ddl)
7. Stavudine (d4T)

155

Antiviral therapy - HIV - RTI - NNRTIs?

1. Nevirapine
2. Efavirenz
3. Delavirdine

156

Antiviral therapy - HIV - PIs?

1. Lopinavir
2. Atazanavir
3. Darunavir
4. Fosamprenavir
5. Saquinavir
6. Ritonavir
7. Indinavir

157

Other antiviral therapy - protein synthesis?

IFN-α (HBV, HCV).

158

Other antiviral therapy - Uncoating?

1. Amantadine
2. Rimantadine
no longer useful for influenza due to incr. resistance.

159

Antiviral therapy - Nucleic acid synthesis - Guanine nucleotide synthesis?

Ribavirin --> RSV, HCV.

160

Antiviral therapy - Nucleic acid synthesis - Viral DNA polymerase inhibitors?

1. Foscarnet
2. Cidofovir
--> CMV, HSV (acyclovir-resistant)

161

Antiviral therapy - Guanosine analogs?

1. Acyclovir --> HSV, VZV.
2. Ganciclovir --> CMV.

162

Antiviral therapy - release of progeny virus?

Neuraminidase inhibitors:
1. Zanamivir
2. Oseltamivir
influenza A, B.

163

Zanamivir/Oseltamivir - mechanism?

Inhibit influenza neuraminidase --> Decr. RELEASE of progeny virus.

164

Zanamivir/Oseltamivir - Clinical use?

Treatment and prevention of both influenza A and B.

165

Ribavirin - Mechanism?

Inhibits synthesis of guanine nucleotides by competitively inhibiting inosine monophosphate dehydrogenase.

166

Ribavirin - Clinical use?

RSV (palivizumab preferred in children).
Chronic Hep C.

167

Ribavirin - toxicity?

1. Hemolytic anemia
2. Severe teratogen

168

Acyclovir/Famciclovir/Valacyclovir - mechanism?

1. Monophosphorylated by HSV/VZV thymidine kinase and NOT phosphorylated in uninfected cells --> Few adverse effects.
2. Guanosine anagog
3. Triphosphate formed by cellular enzymes.
4. Preferentially inhibits viral DNA polymerase by chain termination.

169

Acyclovir/Famciclovir/Valacyclovir - clinical use?

1. HSV/VZV
2. Weak activity against EBV.
3. No activity against CMV.
4. Used for HSV-induced mucocutaneous and genital lesions as well as for encephalitis.
5. Prophylaxis in immunocompromised patients.
6. No effect on LATENR forms of HSV, VZV.
7. For herpes zoster use Famciclovir.

170

Valacyclovir?

Prodrug of acyclovir --> better ORAL bioavailability.

171

Acyclovir/Famciclovir/Valacyclovir - Toxicity?

1. Obstructive crystalline nephropathy
2. Acute renal failure if not adequately hydrated.

172

Acyclovir/Famciclovir/Valacyclovir - Mechanism of resistance?

Mutated viral thymidine kinase.

173

Ganciclovir - mechanism?

5-monophosphate formed by a CMV viral kinase --> Guanosine analog --> Triphosphate formed by cellular kinases --> Preferentially inhibits viral DNA poly.

174

Ganciclovir - Clinical use?

CMV especially in immunocompromised.

175

Valganciclovir?

Prodrug of ganciclovir - better ORAL bioavailability.

176

Ganciclovir toxicity?

1. Leukopenia
2. Neutropenia
3. Thrombocytopenia
4. Renal toxicity
5. More toxic to host enzymes than acyclovir

177

Ganciclovir - mechanism of resistance?

Mutated viral kinase.

178

Foscarnet - mechanism?

Viral DNA polymerase inhibitor that binds to the pyrophosphate-binding site of the enzyme.
Does NOT require activation by viral kinase.

179

Foscarnet - clinical use?

1. CMV retinitis in immunocompromised when ganciclovir fails.
2. Acyclovir-resistant HSV.

180

Foscarnet - toxicity?

1. Nephrotoxicity.
2. Electrolyte abnormalities = Hypo/hyperCALCEMIA + Hypo/hyperPHOSPHATEMIA + HYPOkalemia + HYPOmagnesemia --> Can lead to SEIZURES.

181

Foscarnet mechanism of resistance?

Mutated DNA polymerase.

182

Cidofovir - mechanism?

Preferentially inhibits viral DNA poly - does NOT require phosphorylation by viral kinase.

183

Cidofovir - clinical use?

CMV retinitis in immunocompromised patients - acyclovir resistant HSV - Long half-life.

184

Cidofvir - toxicity?

Nephrotoxicity --> Coadminister with probenecid and IV saline to decrease toxicity.

185

HAART - when to initiate?

Often initiated AT THE TIME OF DIAGNOSIS - When patients present with AIDS-defining illness --> Low CD4 cell counts (

186

HAART regimen?

3 drugs to prevent resistance:
2 NRTIs + preferrably an integrase inhibitor.

187

PIs - mechanism?

Assembly of virions depends on HIV-1 protease (pol gene), which cleaves the polypeptide products of HIV mRNA into their functional parts.
--> PIs prevent MATURATION of new viruses.

188

Important about ritonavir?

Can "boost" other drug concentrations by inhibiting CYP450.

189

PIs - toxicity?

1. Hyperglycemia
2. GI intolerance (nausea, diarrhea)
3. Lipodystrophy (Cushing-like syndrome)
4. Nephropathy (indinavir)
5. Hematuria (indinavir)

190

NRTIs - Mechanism?

Competitively inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain (lack a 3-OH group).

191

Important about tenofovir?

The only NRTI that is a nucleoTide - others are nucleoSides and need to be phosphorylated to be active.

192

ZDV - clinical use?

It is used for general prophylaxis and during pregnancy to decr. risk of fetal transmission.

193

NRTIs - Toxicity?

1. Bone marrow suppression (reversed with G-CSF, erythropoietin)
2. Peripheral neuropathy
3. Lactic acidosis (nucleosides)
4. Anemia (ZDV)
5. Pancreatitis (Didanosine)

194

NNRTIs - mechanism?

Bind to reverse transcriptase at site different from NRTIs.
Do NOT require phosphorylation to be active or compete with nucleotides.

195

NNRTIs toxicity?

1. Rash + hepatotoxicity --> Common to ALL NNRTIs.
2. Vivid dreams and CNS symptoms --> common to efavirenz.
3. Delavirdine + Efavirenz --> Contra in pregnancy.

196

Raltegravir - mechanism?

Inhibits HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase.

197

Raltegravir toxicity?

UP Creatine kinase.

198

Efuvirtide - mechanism?

Binds gp41 - inhibiting viral entry.

199

Maraviroc - mechanism?

Binds CCR5 on surface of T-cells/monocytes, inhibiting interaction with gp120.

200

Enfuvirtide - toxicity?

Skin reaction at injection sites.

201

Interferons - mechanism?

Glycoproteins normally synthesized by virus-infected cells, exhibiting a wide range of antiviral and antitumoral properties.

202

Interferons - IFN-alpha - clinical use?

1. Chronic hep B/C
2. Kaposi sarcoma
3. Hairy cell leukemia
4. Condyloma acuminatum
5. Renal cell carcinoma
6. Melanoma

203

IFN-beta - clinical use?

MS

204

IFN-gamma - clinical use?

Chronic granulomatous disease.

205

Interferons - Toxicity?

1. Neutropenia.
2. Myopathy.
3. Flu-like symptoms.
4. Depression.

206

Antibiotics to AVOID IN PREGNANCY:

1. Sulfonamides
2. Aminoglycosides
3. Fluoroquinolones
4. Clarithromycin
5. Tetracyclines
6. Ribavirin
7. Griseofulvin
8. Chloramphenicol

SAFe Children Take Really Good Care

207

Sulfonamides in pregnancy?

Kernicterus

208

Aminoglycosides in pregnancy?

Ototoxicity

209

Fluoroquinolones in pregnancy?

Cartilage damage

210

Clarithromycin in pregnancy?

Embryotoxic

211

Tetracyclines in pregnancy?

Discolored teeth + inhibition of bone growth.

212

Ribavirin in pregnancy?

Teratogenic

213

Griseofulvin in pregnancy?

Teratogenic

214

Chloramphenicol in pregnancy?

"Gray baby"