Antimicrobials - First Aid Flashcards
1
Q
Penicillin G and V (prototype Beta-lactams) MOA
A
Bind penicillin-binding proteins to block transpeptidase cross-linking of peptidoglycan.
They also activate autolytic enzymes.
2
Q
Penicillin G and V Use
A
- mostly for gram-positive organisms
- also for N. meningitidis and T. pallidum
3
Q
Penicillin G, V are bactericidal for…
A
gram-positive cocci and rods, gram-negative cocci and spirochetes.
4
Q
Toxicity of Penicillin G, V
A
HSRs and hemolytic anemia
5
Q
Resistance to Penicillin G, V
A
penicillinase in bacteria (a type of beta-lactamase) cleaves the beta-lactam ring
6
Q
Ampicillin/Amoxicillin MOA
A
same as penicillin
7
Q
Ampicillin/Amoxicillin Use
A
extended spectrum penicillins
- H. influenzae
- E. coli
- Listeria
- Proteus
- Salmonella
- Shigella
- enterococci
8
Q
Ampicillin/Amoxicillin Toxicity
A
- HSRs
- rash
- pseudomembranous colitis
9
Q
Ampicillin/Amoxicillin Resistance
A
-penicillinase
10
Q
Oxacillin, Nafcillin, Dicloxacillin MOA
A
same as penicillin; penicillinase resistant because bulky R group blocks access of beta-lactamase
11
Q
Oxacillin, Nafcillin, Dicloxacillin Use
A
S. aureus (narrow spectrum)
12
Q
Oxacillin, Nafcillin, Dicloxacillin Toxicity
A
HSRs, interstitial nephritis
13
Q
MRSA is resistant because of….
A
altered PBP target site.
14
Q
Ticarcillin, Piperacillin MOA
A
same as penicillin
15
Q
Ticarcillin, Piperacillin Use
A
extended spectrum; Pseudomonas and gram-negative rods
16
Q
Beta-lactamse inhibitors are often…
A
added to penicillin antibiotics to protect the antibiotic from destruction by beta-lactamase.
(Clavulanic Acid, Sulbactam, Tazobactam)
17
Q
Cephalosporins MOA
A
Beta-lactam drugs that inhibit cell wall synthesis but are less suceptible to penicillinases; bactericidal
18
Q
Organisms typically not covered by cephalosporins are…
A
LAME:
- Listeria
- Atypicals
- MRSA
- Enterococci
(Exception: ceftaroline covers MRSA)
19
Q
1st generation Cephalosporins Use
A
Cefazolin, Cephalexin
- gram positive cocci
- Proteus
- E. coli
- Klebsiella
20
Q
Cefazolin is used prior to…
A
surgery to prevent S. aureus wound infections.
21
Q
2nd generation Cephalosposrins Use
A
Cefoxitin, Cefaclor, Cefuroxime
- gram positive cocci
- H. influenza
- Enterobacter
- Neisseria
- Proteus
- E. coli
- Klebsiella
- Serratia
22
Q
3rd genreation Cephalosporins Use
A
Ceftriaxone, Cefotaxime, Ceftazidime
-serious gram negative infections resistant to other beta-lactams
(Ceftriaxone for Neisseria and Ceftazidime for Pseudomonas)
23
Q
4th generation Cephalosporins Use
A
Cefepime
-increased activity against pseudomonas and gram-positives
24
Q
5th generation Cephalosporins Use
A
Ceftaroline
- broad gram positive and negative coverage
- including MRSA
- does NOT cover pseudomonas
25
Cephalosporins toxicity
- HSRs
- vitamin K deficiency
- increased nephrotoxicity of aminoglycosides
26
Aztreonam MOA
a monobactam; resistant to beta-lactamases; prevents peptidoglycan cross-linking by binding to PBP3
27
Aztreonam Use
gram-negative rods only; for penicillin allergic pts and those with renal insufficiency who cannot tolerate aminoglycosides
28
Carbapenems (4)
1. Imipenem
2. Meropenem
3. Ertapenem
4. Doripenem
29
Carpabenem (Imipenem) MOA
broad-spectrum, beta-lactamase reistant; always admisistered with Cilastatin (inhibitor of renal dehydropeptidase I) to decrease inactivation of the drug in the renal tubules
30
Clinical use of carbapenems
- gram positive cocci
- gram negative rods
- anaerobes
31
Toxicity
GI distress, rash, CNS toxicity (seizures) - limits use
| Meropenem has decreased risk of seizures
32
Vancomycin MOA
inhibits cell wall peptidoglycan formation by binding D-ala-D-ala portion of cell wall precurors; bactericidal
33
Use of Vancomycin
gram positive only (serious, multidrug resistant organisms including MRSA, enterococci and C. diff)
34
Toxicity of Vancomycin
- Red Man Syndrome
- Nephrotoxicity
- Ototoxicity
- Thrombophlebitis
35
Mechanism of resistance to Vancomycin
-amino acid modification of D-ala-D-ala to D-ala-D-lac
36
Protein synthesis inhibitors specifically target...
the smaller bacterial ribosome (70S (30S+50S)) leaving the human ribosome (80S) unaffected.
37
30S Inhibitors
Aminoglycosides (bactericidal)
| Tetracyclines (bacteriostatic)
38
50S Inhibitors
Chloramphenicol, Clindamycin (bacteriostatic)
Erythromycin (macrolides - bacteriostatic)
Linezolid
39
Aminoglycosides (5)
1. Gentamicin
2. Neomycin
3. Amikacin
4. Tobramycin
5. Streptomycin
40
Aminoglycosides MOA
inhibit formation of initiation complex and cause misreading of mRNA; also block translocation
41
Aminoglycosides are ineffective against...
anaerobes bc they require O2 for uptake.
42
Aminoglycosides Use
- severe gram-negative rod infections
| - neomycin for bowel surgery
43
Aminoglycosides Toxicity
- Nephrotoxicity (esp. with cephalosporins)
- Neuromuscular blockade
- Ototoxicity (esp. with loop diuretics)
- Teratogen
44
Aminoglycosides resistance
bacterial transferase enyzmes inactivate the drug by acetylation, phosphorylation or adenylation
45
Tetracyclines (3)
1. Tetracycline
2. Doxycycline
3. Minocycline
46
MOA of Tetracyclines
bind to 30S and prevent attachment of aminoacyl-tRNA
47
Doxycycline is eliminated...
fecally and can be used in pts with renal failure.
48
Tetracyclines should not be taken with...
milk, antacids or iron-containing preps because divalent cations inhibit its absorption in the gut.
49
Clinical use of tetracyclines
- Borrelia
- M. pneumoniae
- Rickettsia and Chlamydia (bc it can accumulate intracellularly)
50
Toxicity of Tetracycline
- GI
- discoloration of teeth-
- inhibition of bone growth
- photosensitivity
(contraindicated in pregnancy)
51
Resistance to Tetracycline
decreased uptake or increased efflux out of bacterial cells by plasmid-encoded transport pumps
52
Macrolides (3)
1. Azithromycin
2. Clarithromycine
3. Erythromycine
53
Macrolides MOA
inhibit protein synthesis by blocking translocation; binds to the 23S rRNA of the 50S ribosomal subunit
54
Macrolides Use
- atypical pneumonias
- STDs (Chlamydia)
- gram-positive cocci (strep infxns in pts allergic to penicillin)
55
Toxicity of Macrolides
- GI motility issues
- Arrhythmia (prolonged QT)
- acute cholestatic hepatitis
- rash
- eosinophilia
56
Macrolides increase the concentration of...
theophyllines and oral anticoagulants.
57
Resistance to Macrolides
methylation of 23S rRNA binding site prevents binding of drug
58
Chloramphenicol Mechanism
blocks peptidyltransferase at 50S ribosomal subunit; bacteriostatic
59
Chloramphenicol Use
Meningitis
| Rocky Mountain Spotted Fever
60
Toxicity of Chloramphenicol
- anemia (dose dependent)
- aplastic anemia (dose independent)
- gray baby syndrome
61
Chloramphenicol causes gray baby syndrome in premature infants because...
they lack liver UDP-glucuronyl transferase.
62
Chloramphenicol resistance
plasmid-encoded acetyltransferase inactivates the drug
63
Clindamycin MOA
blocks peptide transfer (translocation) at 50S ribosomal subunit; bacteriostatic
64
Clindamycin Use
- anaerobic infxns (Bacteroides, C. perfringens) in aspiration pneumonia
- lung abscesses
- oral infxns
- Group A Strep
65
Clindamycin Toxicity
- pseudomembranous colitis
- fever
- diarrhea
66
Treat anaerobes above the diaphragm with...
Clindamycin and below the diaphragm with Metronidazole.
67
Sulfonamides (3)
1. Sulfamethoxazole (SMX)
2. Sulfisoxazole
3. Sulfadiazine
68
Sulfonamides MOA
- inhibits folate synthesis
| - para-aminobenzoic acid (PABA) antimetabolites inhibit dihydropteroate synthase; bacteriostatic
69
Sulfonamides Use
- gram positive
- gram negative
- Nocardia
- Chlamydia
- simple UTI
70
Toxicity of Sulfonamides
- HSRs
- hemolysis if G6PD deficient
- tubulointerstitial nephritis
- photosensitivity
- kernicterus in infants
- displaces other drugs from albumin (warfarin)
71
Resistance to Sulfonamides
- altered enzyme (bacterial dihydropteroate synthase)
- decreased uptake
- increased PABA synthesis
72
Trimethoprim MOA
inhibits bacterial dihydrofolate reductase; bacteriostatic
73
Trimethoprim Use
in combo with sulfonamides causing sequential block of folate synthesis; UTIs, Shigella, Salmonella, Pneumocystis jirovecii, pneumonia tx/prophylasis, toxoplasmosis prophylaxis
74
Trimethoprim Toxicity
- megaloblastic anemia
- leukopenia
- granulocytopenia
75
Fluoroquinolones (9)
1. Ciprofloxacin
2. Norofloxacin
3. Levofloxacin
4. Ofloxacin
5. Sparfloxacin
6. Moxifloxacin
7. Gemifloxacin
8. Enoxacin
10. Nalidixic Acid (a quinolone)
76
MOA of Fluoroquinolones
inhibit DNA gyrase (topoisomerase II) and topoisomerase IV; bactericidal
77
Use of Fluoroquinolones
gram-negative rods of urinary and GI tracts (including pseudomonas), Neisseria
78
Fluoroquinolones Toxicity
- superinfections
- tendonitis
- tendon rupture (in people over 60 and people taking prednisone)
- leg cramps
- QT prolonagation
79
Fluoroquinolones are contraindicated in...
pregnant women, nursing mothers, and children under 18 due to risk of cartilage defect.
80
Resistance to Fluoroquinolones
chromosome-encoded mutation in DNA gyrase, plasma-mediated reissitance, efflux pumps
81
Metronidazole MOA
forms free radical toxic metabolites in the bacterial cell taht damage DNA; bactericidal; antiprotozoal
82
Metronidazole Use
```
Giardia
Entamoeba
Trichomonas
Gardnerella
Anaerobes
H. pylori (w/ a proton pump inhibitor and clarithromycin)
```
83
Metronidazole Toxicity
Disulfiram like rxn (flushing, tachycardia, hyoptension)
84
Mycobacterium tuberculosis prophylaxis
Isoniazid
85
Mycobacterium tuberculosis treatment
Rifampin
Isoniazid
Pyrazinamide
Ethambutol
86
Mycobacterium avium-intracellulare prophylaxis
Azithromycin
| Rifabutin
87
Mycobacterium avium-intracellulare treatment
- more drug resistant than M. tuberculosis
| - Azithromycin or Clarithromycin + Ethambutol
88
Mycobacterium leprae treatment
long-term treatment with dapsone and rifampin for tuberculoid form; add clofazimine for lepromatous form
89
Isoniazid MOA
decreased synthesis of mycolic acids; bacterial catalase-peroxidase needed to convert INH to the active metabolite
90
Isoniazid Use
M. tuberculosis
91
Toxicity of Isoniazid
-neurotoxicity, hepatotoxicity
| B6 can prevent the neurotoxicity
92
Rifampin, Rifabutin MOA
inhibits DNA-dependent RNA polymerase
93
Use of Rifampin, Rifabutin Use
M. tuberculosis; delays resistance to dapsone when used for leprosy; used for meningococcal prophylaxis and prophylaxis in contacts of kids w/ Hib
94
Toxicity of Rifampin, Rifabutin
-orange body fluids
-hepatotoxicity/drug interaction
(Rifabutin favored in pts with HIV due to less CYP450 stimulation.)
95
Pyrazinamide MOA
thought to acidify intracellular environment via conversion to pyrazinoic acid; effective in acidic pH of phagolysosomes where TB engulfed by macrophages is found
96
Pyrazinamide Use
M. tuberculosis
97
Toxicity of Pyrazinamide
Hyperuricemia, hepatotoxicity
98
Ethambutol MOA
decreased carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase
99
Ethambutol Use
M. tuberculosis
100
Ethambutol toxicity
optic neuropathy (red-green color blindness)
101
Prophylaxis for endocarditis with surgical or dental procedures
Penicillins
102
Prophylaxis for gonorrhea
Ceftriaxone
103
Prophylaxis for recurrent UTIs
TMP-SMX
104
Prophylaxis for meningococcal infxn
Ciprofloxacin
| Rifampin for children
105
Prophylaxis for pregnant women carrying group B strep
Ampicillin
106
Prevention of gonococcal or chlamydial conjunctivitis in the newborn
erythromycin ointment
107
Prevention of postsurgical infxn due to S. aureus
Cefazolin
108
Prophylaxis of strep pharyngitis in a child with prior rheumatic fever
oral penicillin
109
Prophylaxis for syphilis
benzathine penicillin G
110
Prophylaxis of Pneumocystis pneumonia in HIV pts with CD4<200
TMP-SMX
111
Prophylaxis of Pneumocystis pneumonia and toxoplasmosis in HIV pts with CD4 < 100
TMP-SMX
112
Prophylaxis of M. avium in HIV pts with CD4 < 50
Azithromycin
113
MRSA treatments
- vancomycin
- daptomycin
- linezolid (can cause serotonin syndrome)
- tigecycline
- ceftaroline
114
VRE treatments
- linezolid
| - streptogramins (quinupristin/dalfopristin)
115
Amphotericin B MOA
binds ergosterol (unique to fungi); forms membrane pores that allows leakage of electrolytes
116
Amphotericin B Use
- Cryptococcus
- Blastomyces
- Coccidioides
- Histoplasma
- Candida
- Mucor
(give supplemental K+ and Mg2+ bc of altered renal tubule permeability)
117
Amphotericin B toxicity
- fevers/chills
- nephrotoxicity
- arrhythmias
- anemia
- IV phlebitis
118
Nystatin MOA
same as amphotericin B; topical form only!
119
Nystatin Use
"swish and swallow" for oral candidiasis; topical for diaper rash or vaginal candidiasis
120
Azoles (6)
1. Fluconazole
2. Ketoconazole
3. Clotrimazole
4. Miconazole
5. Itraconazole
6. Voriconazole
121
Azoles MOA
inhibit fungal sterol synthesis by inhibiting the CYP450 that converts lanosterol to ergosterol
122
Azoles Use
local/less serious systemic mycoses
- Fluconazole for chronic suppression of cryptococcal meningitis in AIDS pts and candidal infections of all types
- Itraconazole for Blasto, Cocci, and Histo
- Clotrimazole/Miconazole for topical fungal infxns
123
Azoles toxicity
-testosterone synthesis inhibition (gyencomastia, esp. w/ ketoconazole), liver dysfunction (inhibits CYP450)
124
Flucytosine MOA
inhibits DNA and RNA biosynthesis by conversion to 5-FU by cytosine deaminase
125
Use of Flucytosine
systemic funcgal infections (esp. meningitis caused by Crypto) in combo w/ amphotericin B
126
Toxicity of flucytosine
bone marrow suppression
127
Echinocandins (3)
1. Caspofungin
2. Micafungin
3. Anidulafungin
128
Echinocandins MOA
inhibits cell wall synthesis by inhibiting synthesis of beta-glucan
129
Use of Echinocandins
invasive aspergillosis, Candida
130
Terbinafine MOA
inhibits the fungal enzyme squalene epoxidase
131
Terbinafine Use
dermatophytoses (esp onychomycosis)
132
Griseofulvin MOA
interferes w/ microtubule fxn; disrupts mitosis; deposits keratin-containing tissues
133
Use of Griseofulvin
oral treatment of superficial infections; inhibits growth of dermatophytes (tinea, ringworm)
134
Griseofulvin toxicity
teratogenic, carcinogenic, confusion, headaches, increased P450 and warfarin metabolism
135
Toxoplasmosis tx
pyrimethamine
136
Trypanosoma brucei tx
Suramin and Meelarsoprol
137
T. cruzi tx
Nifurtimox
138
Leishmaniasis tx
Sodium Stibogluconate
139
Chloroquine MOA
blocks detoxification of heme into hemozoin; heme accumulates and is toxic to plasmodia
140
Chloroquine Use
treatment of plasmodial species other than P. falciparum (resistance to P. falciparum due to membrane pump that decreases intracellular concentration of the drug)
141
Treat P. falciparum with...
artemether/lumefantrine or atovaquone/proguanil.
142
For life-threatening malaria, use...
quinidine or artesunate.
143
Toxicity of chloroquine
retinopathy
| pruritis
144
Antihelminthic therapy (5)
1. Mebendazole
2. Pyrantel pamoate
3. Ivermectin
4. Diethylcarbamazine
5. Praziquantel
(immobilize helminths)
145
Treatment for flukes (trematodes) such as Schistosoma
Praziquantel
146
Zanamivir, Oseltamivir MOA
inhibit influenza neuraminidase leading to decreased release of progeny virus
147
Zanamivir, Oseltamivir Use
treatment/prevention of influenza A and B
148
Ribavirin MOA
inhibits synthesis of guanine nucleotides by competitively inhibiting inosine monophosphate dehydrogenase
149
Ribavirin Use
RSV, chronic hep C
150
Ribavirin toxicity
- hemolytic anemia
| - severe teratogen
151
Acyclovir, Famciclovir, Valacyclovir MOA
guanosine analog; triphosphate formed by cellular enzymes; preferentially inhibits DNA polymerase by chain termination
152
Acyclovir, Famciclovir and Valacyclovir have few adverse effects because...
they are monophosphorylated by HSV/VZV thymidine kinase and not phosphorylated in uninfected cells.
153
Use of Acyclovir, Famciclovir and Valacyclovir
HSV and VZV
-HSV induced mucocutaneous/genital lesions and encephalitis
-prophylaxis in immunocompromised
-
154
Acyclovir, Famciclovir and Valacyclovir have no effect on..
latent forms of HSV and VZV.
155
Toxicity of Acyclovir, Famciclovir and Valacyclovir
obstructive crystalline nephropathy and acute renal failure
156
Mechanism of resistance to Acyclovir, Famciclovir and Valacyclovir
mutated viral thymidine kinase
157
Ganciclovir MOA
5' monophosphate formed by a CMV viral kinase; guanosine analog; triphosphate formed by cellular kinases; preferentially inhibits viral DNA polymerase
158
Use of Ganciclovir
CMV, esp. in immunocompromised pts
159
Toxicity of Ganciclovir
leukopenia, neutropenia, thrombocytopenia, renal toxicity
160
Resistance to Ganciclovir
mutated CMV DNA polymerase or lack of viral kinase
161
Foscarnet MOA
viral DNA polymerase inhibitor that binds to the pyrophosphate-binding site of the enzyme; does not require activation by viral kinase
162
Foscarnet Use
CMV retinitis in immunocompromised pts when ganciclovir fails; acyclovir resistant HSV
163
Toxicity of Foscarnet
Nephrotoxicity
164
Resistance to Foscarnet
mutated DNA polymerase
165
Cidofovir MOA
preferentially inhibits viral DNA polymerase; does not require phosphorylation by viral kinase
166
Use of Cidofovir
CMV retinitis in immunocompromised pts; acyclovir-resistant HSV
167
Toxicity of Cidofovir
nephrotoxicity (administer with probenecid and IV saline to decrease toxicity)
168
Highly Active Antiretroviral Therapy (HAART) is initiated when...
pts present with an AIDs defining illness, low CD4 cell counts (<500), or a high viral load.
169
HAART regimen consists of..
3 drugs to preven resistance:
- 2 nucleoside reverse transcriptase inhibitors
- 1 non-nucleoside reverse transcriptase inhibitor OR 1 protease inhibitor OR 1 integrase inhibitor
170
Protease Inhibitors (7)
1. Atazanavir
2. Darunavir
3. Fosamprenavir
4. Indinavir
5. Lopinavir
6. Ritonavir
7. Saquinavir
(Navir tease a protease)
171
The assembly of HIV virions depends on...
HIV-1 protease (pol gene) which cleaves the polypeptide products of HIV mRNA into their functional parts. Thus, protease inhibitors prevent maturation of new viruses.
172
Ritonavir can boost...
other drug concentrations by inhibiting CYP450.
173
Toxicity of protease inhibitors
hyperglycemia, lipodystrophy, nephropathy, hematuria
174
NRTIs (nucleoside reverse transcriptase inhibitors) (7)
1. Abacavir
2. Didanosine
3. Emtricitabine
4. Lamivudine
5. Stavudine
6. Tenofovir
7. Zidovudine
(Have you dined (vudine) w/ my nuclear (nucleoside) family?)
175
NRTIs MOA
competitively inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain
176
NRTIs need to be...
phosphorylated to be active (except for tenofovir which is a nucleotide).
177
Zidovudine is used for...
general prophylaxis and during pregnancy to decrease risk of fetal transmission.
178
Toxicity of NRTIs
bone marrow suppression (give G-CSF and EPO), neuropathy, lactic acidosis, anemia (ZDV), pancreatitis (didanosine)
179
NNRTIs (non-nucleoside reverse transcriptase inhibitors) (3)
1. Efavirenz
2. Nevirapine
3. Delavirdine
180
NNRTIs MOA
bind to reverse transcriptase at a site different from NRTIs; do not require phosphorylation for activation
181
Toxicity of NNRTIs
- rash, hepatotoxicity
| - vivid dreams and CNS symptoms (Efavirenz)
182
Delavirdine and Efavirenz are contraindicated in...
pregnancy.
183
Raltegravir MOA
inhibits HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase
184
Raltegravir Toxicity
hypercholesterolemia
185
Fusion inhibitors
Enfuvirtide
| Maraviroc
186
Enfuvirtide MOA
binds gp41, inhibiting viral entry
187
Maraviroc MOA
binds CCR-5 on surface of T cells/monocytes inhibiting interaction with gp120
188
Interferons MOA
glycoproteins normally synthesized by virus-infected cells, exhibiting a wide range of antiviral and antitumoral properties
189
Use of INF-alpha
chronic Hep B/C, Kaposi sarcoma, hairy cell leukemia, condyloma acuminatum, RCC and malignant melanoma
190
Use of IFN-beta
MS
191
Use of IFN-gamma
CGD
192
Toxicity of interferons
neutropenia
| myopathy
193
Antibiotics to avoid in pregnancy
```
SAFe Children Take Really Good Care
Sulfonamides
Aminoglycosides
Fluoroquinolones
Clarithromycin
Tetracyclines
Ribavirin
Griseofulvin
Chloramphenicol
```
194
Sulfonamides teratogenecity
Kernicterus
195
Aminoglycosides teratogenecity
ototoxicity
196
Fluoroquinolones teratogenecity
cartilage damage
197
Clarithromycin teratogenecity
embryotoxic
198
Tetracyclines teratogenecity
discolored teeth, inhibition of bone growth
