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FA - Micro - Antimicrobials Flashcards

0
Q

Antimicrobials - DNA topoisomerases?

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

Antimicrobials - Folic acid synthesis (DNA methylation)?

A 
Sulfonamides:
1. Sulfamethoxazole
2. Sulfisoxazole
3. Sulfadiazine
\+ Trimethoprim.
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2
Q

Antimicrobials - Damages DNA?

A

Metronidazole

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3
Q

Antimicrobials - mRNA synthesis (RNA pol)?

A

Rifampin

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4
Q

Antimicrobials - Protein Synthesis - 50S subunit?

A
  1. Chloramphenicol
  2. Clindamycin
  3. Linezolid
    Macrolides:
  4. Azithromycin
  5. Clarithromycin
  6. Erythromycin
    Streptogramins
  7. Quinupristin
  8. Dalfopristin
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5
Q

Antimicrobials - Protein synthesis - 30S subunit?

A 
Aminoglycosides
1. Gentamicin
2. Neomycin
3. Amikacin
4. Tobramycin
5. Streptomycin 
Tetracyclines:
1. Tetracycline
2. Doxycycline 
3. Minocycline
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6
Q

Antimicrobials - Cell wall synthesis - Peptidoglycan synthesis - Glycopeptides?

A
  1. Vancomycin

2. Bacitracin

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7
Q

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

A
  1. Penicillins G, V
  2. Ampicillin
  3. Amoxicillin
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8
Q

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

A
  1. Oxacillin
  2. Nafcillin
  3. Dicloxacillin
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9
Q

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

A
  1. Ticarcillin

2. Piperacillin

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10
Q

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

A 
1st - Cephazolin
2nd - Cefoxitin
3rd - Ceftriaxone 
4th - Cefipime
5th - Ceftaroline
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11
Q

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

A
  1. Imipenem
  2. Meropenem
  3. Ertapenem
  4. Doripenem
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12
Q

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

A

Aztreonam

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13
Q

Penicillin G route?

A

IV, IM

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14
Q

Penicillin V route?

A

Oral

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15
Q

Penicillin G, V - Mechanism?

A
  1. Bind penicillin-binding proteins (transpeptidases)
  2. Block transpeptidase cross-linking of peptidoglycan.
  3. Activate autolytic enzymes.
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16
Q

Penicillin G, V - Clinical use?

A
  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.
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17
Q

Penicillin G,V - Toxicity?

A
  1. HSR

2. DIRECT COOMBS (+) Hemolytic anemia

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18
Q

Penicillin G, V - Resistance?

A

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

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19
Q

Ampicillin, amoxicillin - Mechanism?

A

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

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20
Q

Ampicillin vs Amoxicillin - Bioavailability?

A

Amoxil > Ampicillin

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21
Q

Ampicillin/Amoxicillin - Clinical use?

A

Extended-spectrum penicillin:

  1. H.influenza
  2. E.coli
  3. L.monocytogenes
  4. P.mirabilis
  5. Salmonella
  6. Shigella
  7. Enterococci
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22
Q

Ampicillin/Amoxicillin - Toxicity?

A
  1. HSR
  2. Rash
  3. Pseudomembranous colitis
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23
Q

Ampicillin/Amoxicillin - Mechanism of resistance?

A

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

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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.
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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.
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Ribavirin - Clinical use?
RSV (palivizumab preferred in children). | Chronic Hep C.
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Ribavirin - toxicity?
1. Hemolytic anemia | 2. Severe teratogen
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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.
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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.
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Valacyclovir?
Prodrug of acyclovir --> better ORAL bioavailability.
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Acyclovir/Famciclovir/Valacyclovir - Toxicity?
1. Obstructive crystalline nephropathy | 2. Acute renal failure if not adequately hydrated.
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Acyclovir/Famciclovir/Valacyclovir - Mechanism of resistance?
Mutated viral thymidine kinase.
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Ganciclovir - mechanism?
5-monophosphate formed by a CMV viral kinase --> Guanosine analog --> Triphosphate formed by cellular kinases --> Preferentially inhibits viral DNA poly.
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Ganciclovir - Clinical use?
CMV especially in immunocompromised.
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Valganciclovir?
Prodrug of ganciclovir - better ORAL bioavailability.
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Ganciclovir toxicity?
1. Leukopenia 2. Neutropenia 3. Thrombocytopenia 4. Renal toxicity 5. More toxic to host enzymes than acyclovir
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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.
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Foscarnet - clinical use?
1. CMV retinitis in immunocompromised when ganciclovir fails. 2. Acyclovir-resistant HSV.
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Foscarnet - toxicity?
1. Nephrotoxicity. 2. Electrolyte abnormalities = Hypo/hyperCALCEMIA + Hypo/hyperPHOSPHATEMIA + HYPOkalemia + HYPOmagnesemia --> Can lead to SEIZURES.
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Foscarnet mechanism of resistance?
Mutated DNA polymerase.
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Cidofovir - mechanism?
Preferentially inhibits viral DNA poly - does NOT require phosphorylation by viral kinase.
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Cidofovir - clinical use?
CMV retinitis in immunocompromised patients - acyclovir resistant HSV - Long half-life.
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Cidofvir - toxicity?
Nephrotoxicity --> Coadminister with probenecid and IV saline to decrease toxicity.
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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.
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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.
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Important about ritonavir?
Can "boost" other drug concentrations by inhibiting CYP450.
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PIs - toxicity?
1. Hyperglycemia 2. GI intolerance (nausea, diarrhea) 3. Lipodystrophy (Cushing-like syndrome) 4. Nephropathy (indinavir) 5. Hematuria (indinavir)
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NRTIs - Mechanism?
Competitively inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain (lack a 3-OH group).
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Important about tenofovir?
The only NRTI that is a nucleoTide - others are nucleoSides and need to be phosphorylated to be active.
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ZDV - clinical use?
It is used for general prophylaxis and during pregnancy to decr. risk of fetal transmission.
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NRTIs - Toxicity?
1. Bone marrow suppression (reversed with G-CSF, erythropoietin) 2. Peripheral neuropathy 3. Lactic acidosis (nucleosides) 4. Anemia (ZDV) 5. Pancreatitis (Didanosine)
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NNRTIs - mechanism?
Bind to reverse transcriptase at site different from NRTIs. | Do NOT require phosphorylation to be active or compete with nucleotides.
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NNRTIs toxicity?
1. Rash + hepatotoxicity --> Common to ALL NNRTIs. 2. Vivid dreams and CNS symptoms --> common to efavirenz. 3. Delavirdine + Efavirenz --> Contra in pregnancy.
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Raltegravir - mechanism?
Inhibits HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase.
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Raltegravir toxicity?
UP Creatine kinase.
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Efuvirtide - mechanism?
Binds gp41 - inhibiting viral entry.
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Maraviroc - mechanism?
Binds CCR5 on surface of T-cells/monocytes, inhibiting interaction with gp120.
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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.
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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
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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.
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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
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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.
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Ribavirin in pregnancy?
Teratogenic
213
Griseofulvin in pregnancy?
Teratogenic
214
Chloramphenicol in pregnancy?
"Gray baby"

Microbiology (46 decks)

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