Microbe drugs Flashcards
1
Q
Penicillin G, V (mechanism and resistance)
A
Beta-lactam antibiotics (penicillinase-sensitive) -> bactericidal
Structural analog of D-Ala-D-Ala -> binds PBP (penicillin-binding proteins) -> covalently binds transpeptidase -> blocks X-linking of peptidoglycan -> blocks cell wall synthesis
Resistance: structural changes in PBP
2
Q
Penicillin G, V (3 uses)
A
G+ orgs (S pneumoniae, S. pyogenes, Actinomyces)
G- cocci (incld N. meningitidis)
Spirochetes (incl T. pallidum)
3
Q
Penicillin G, V (3 side effects)
A
Hypersensitivity
Hemolytic anemia
Resistance in bacteria w/ beta-lactamase (MRSA)
4
Q
Ampicillin, amoxicillin (mechanism)
A
Beta-lactam antibiotics (aminopenicillines, still penicillinase-sensitive so used w. clavulanic acid) -> bactericidal Binds PBP (penicillin-binding proteins; transpeptidases) -> blocks X-linking of peptidoglycan -> blocks cell wall synthesis
5
Q
Ampicillin, amoxicillin (uses)
A
Added spectrum from normal penicillins -> HELPSS enterococci (H. influenzae, E. coli, L. monocytogenes, P. mirabilis, Salmonella, Shigella)
Nornal penicillin spectrum:
G+ orgs (S pneumoniae, S. pyogenes, Actinomyces)
G- cocci (incld N. meningitidis)
Spirochetes (incl T. pallidum)
6
Q
Ampicillin, amoxicillin (3 side effects)
A
Pseudomembranous colitis
Hypersensitivity, rash
Resistance in bacteria w/ beta-lactamase (MRSA)
7
Q
Oxacillin, nafcillin, dicloxacillin (mechanism)
A
Beta-lactam antibiotics (penicillinase-resistant - bulky R group blocks access of beta lactamase) -> bactericidal
Binds PBP (penicillin-binding proteins; transpeptidases) -> blocks X-linking of peptidoglycan -> blocks cell wall synthesis
This means any resistance is from ALTERED PBP, NOT beta lactamase
8
Q
Oxacillin, nafcillin, dicloxacillin (use)
A
Nafcillin for MSSA
9
Q
Oxacillin, nafcillin, dicloxacillin (2 side effects)
A
Interstitial nephritis
Hypersensitivity
10
Q
Ticarcillin, piperacillin (mechanism)
A
Beta-lactam antibiotics (anti-pseudomonals, still penicillinase-sensitive so used w. clavulanic acid) -> bactericidal Binds PBP (penicillin-binding proteins; transpeptidases) -> blocks X-linking of peptidoglycan -> blocks cell wall synthesis
11
Q
Ticarcillin, piperacillin (2 uses)
A
Pseudomonas
G- rods, including ANAEROBES (so good for bacterioids)
12
Q
Ticarcillin, piperacillin (side effect)
A
Hypersensitivity
13
Q
Clavulanic acid (mechanism and use)
A
Beta lactamase inhibitor
Added to penicillinase-sensitive penicillin antibiotics
14
Q
Sulbactam (mechanism and use)
A
Beta lactamase inhibitor
Added to penicillinase-sensitive penicillin antibiotics
15
Q
Tazobactam (mechanism and use)
A
Beta lactamase inhibitor
Added to penicillinase-sensitive penicillin antibiotics
16
Q
Cephalosporins (mechanism and resistance)
A
Beta-lactam antibiotics (but less susceptible to penicillinases) -> bactericidal Binds PBP (penicillin-binding proteins; transpeptidases) -> blocks X-linking of peptidoglycan -> blocks cell wall synthesis Resistance: structural changes in PBP
17
Q
1st gen cephalosporins (2 names and 3 uses)
A
“Jeremy LIN drives LEX” -> cefazoLIN, cephaLEXin
G+ cocci
PEcK: P. mirabilis, E. coli, Klebsiella pneumoniae
Cefazolin used pre-op to prevent S. aureus wound infections
18
Q
List orgs not covered by cephalosporins
A
“LAME” -> Listeria, Atypicals (Chlamydia, Mycoplasma), MRSA (except ceftaroline), Enterococci
19
Q
2nd gen cephalosporins (3 names and 2 uses)
A
“Two make her happy, buy some Fake Fox Fur” -> ceFOXitin, ceFAClor, ceFURoxime
G+ cocci
HEN PEcKs: H. influenzae, Enterobacter aerogenes, Neisseria spp, P. mirabilis, E. coli, Klebsiella pneumoniae, Serratia marcescens
20
Q
3rd gen cephalosporins (3 names and 3 uses)
A
“Tri, Tax, Taz” -> cefTRIaxone, cefoTAXime, cefTAZidime
Serious G– infections resistant to other beta lactams
Ceftrixone - meningitis and gonorrhea
Ceftaxidime - pseudomonas
21
Q
4th gen cephalosporin (1 name and 2 uses)
A
Cefepime
Increased activity against Pseudomonas & G+
22
Q
5th gen cephalosporin (1 name and 2 uses)
A
Ceftaroline
Broad G+ (incl MRSA - the only one of cephalosporins that does this)
Broad G-
Does NOT cover Pseudomonas tho
23
Q
Cephalosporin (3 side effects)
A
Vit K deficiency
Increases nephrotoxicity of amonoglycocides
Hypersensitivity (cross-reactivity w/ penicillins)
24
Q
Aztreonam (mechanism)
A
Monobactam (resistant to beta lactamases)
Binds to PBP3 -> prevents peptidoglycan X-linking -> inhibits cell wall synthesis
Synergistic w/ aminoglycoside
25
Aztreonam (use)
G- rods only, for penicillin-allergic and those w/ renal insufficiency (can't tolerate aminoglycosides)
Can't use for G+ or anaerobes
26
Aztreonam (side effect)
GI upset, but usually non-toxic (don't even have cross-allergenicity w/ penicillins)
27
"-penems" (mechanism)
Carbapenems: imipenem, meropenem, ertapenem, doripenem
Peptidoglycan X-linking inhibitor -> inhibits cell wall synthesis
Use imipenem w/ cilastatin (competitively inhibits renal dehydropeptidase I -> inhibits inactivation of drug in renal tubules)
Meropenem is stable to renal dehydropeptidase I
28
"-penems" (3 uses)
Wide spectrum but only for life-threatening infections (significant side effects)
G+ cocci
G- rods
Anaerobes
29
"-penems" (3 side effects)
Seizures (meropenem has lower risk)
Skin rash
GI distress
30
Vancomycin (mechanism)
Binds D-ala D-ala portion of cell wall precursors -> inhibits cell wall peptidoglycan formation (prevents transpeptidation)
Bactericidal
Resistance thru plasmid/transposon-mediated modification of D-ala D-ala to D-ala D-lac
31
Vancomycin (3 uses)
G+ only -> serious, multidrug-resistant orgs -> MRSA, enterococci, Clostridium difficile (oral for pseudomembranous colitis)
32
Vancomycin (side effects)
```
Well-tolerated in general but can have:
Nephrotoxicity
Ototoxicity
Thrombophlebitis
Red man syndrome (diffuse flushing, prevented by pretreatment w/ antihistamines and slow infusion rate -> this is mediated by histamines NOT IgE like penicillins or prostaglandins like niacin!)
```
33
Aminoglycosides (mechanism)
```
GNATS: Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin -> don't confuse suffix w/ macrolides
30S inhibitor (bacterial ribosome) -> inhibits protein synthesis (causes misreading of mRNA, blocks translocation)
Bactericidal
```
34
Aminoglycosides (2 uses)
GNATS: Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin
Severe G- rods (synergistic w/ beta-lactam antibiotics)
Neomycin for bowel surgery
Requires O2 for uptake so ineffective against anaerobes
35
Aminoglycosides (side effects)
GNATS: Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin
NNOT: Nephrotoxicity (esp w/ cephalosporins; ATN), Neuromuscular blockade (flaccid paralysis), Ototoxicity (esp w/ loop diuretics), Teratogen
36
Aminoglycosides (resistance)
GNATS: Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin
Plasmids/transposons encode bacterial transferase enzymes inactivate drug by acetylation, phosphorylation, or adenylation
37
"-cycline" (mechanism)
```
Tetracycline, doxycycline, minocycline
30S inhibitor (bacterial ribosome) -> inhibits protein synthesis (prevents attachment of aminoacyl-tRNA)
Bacteriostatic
Limited CNS penetration
```
38
"-cycline" (4 uses)
Borrelia burgdorferi
M. pneumoniae
Acne
Intracellular bac: Rickettsia, Chlamydia
39
"-cycline" (side effects)
Pseudotumor cerebri in teens using tetracycline for acne
Teeth discoloration
GI distress
Inhibits bone growth in children
Photosensitivity
Can't use in pregnancy
Don't take w/ milk, antacids, or iron-containing stuff b/c divalent cations inhibit absorption in gut
Can use doxycycline w/ renal failure (fecally eliminated)
40
"-cycline" (resistance)
Plasmid-encoded transport pumps decrease uptake and increase efflux
41
Macrolides (mechanism)
```
Azithromycin, clarithromycin, erythromycin -> don't confuse suffix w/ aminoglycosides
50S inhibitor (bacterial ribosome) -> inhibits protein synthesis (blocking translocation)
Bacteriostatic
```
42
Macrolides (4 uses)
Azithromycin, clarithromycin, erythromycin
Atypical pneumonias (Mycoplasma, Chlamydia, Legionella)
M. avium-intracellulare (used prophylactically when CD4 < 50 cells/mm3 in HIV)
STDs (erythromycin ointment used to prevent conjunctivitis in newborn)
G+ cocci (strep infections in pts allergic to penicillin)
43
Macrolides (side effects)
Azithromycin, clarithromycin, erythromycin
MACRO: gi Motility issues, Arrhythmia caused by prolonged qt, acute Cholestatic hepatitis, Rash, eOsinophilia
Increases serum conc of theophyllines and oral anticoagulants
44
Macrolides (resistance)
Methylation of 23S rRNA-binding site
| Transmembrane efflux pumps
45
Chloramphenicol (mechanism)
```
50S inhibitor (bacterial ribosome) -> inhibits protein synthesis (blocks peptidyltransferase)
Bacteriostatic
```
46
Chloramphenicol (2 uses)
Limited b/c of toxicities but used in developing countries b/c of low cost
Meningitis (H. influenzae, Neisseria, Strep pneumoniae)
Rocky mountain spotted fever
47
Chloramphenicol (side effects)
Anemia, aplastic anemia
| Gray baby syndrome in premies (lacking liver UDP-glucuronyl transferase)
48
Chloramphenicol (resistance)
Plasmid-encoded acetyltransferase inactivates drug
49
Clindamycin (mechanism)
```
50S inhibitor (bacterial ribosome) on 23S site (same as macrolides) -> inhibits protein synthesis (blocks translocation/peptide transfer)
Bacteriostatic
```
50
Clindamycin (2 uses)
Anaerobic infections ABOVE diaphragm (Bacteroides, C. perfringens) - aspiration pneumonia, lung abscesses, oral infections (below diaphragm use metronidazole)
Group A strep
51
Clindamycin (3 side effects)
Pseudomembranous colitis
Fever
Diarrhea
52
Sulfonamides (mechanism and resistance)
Sulfamethoxazole (SMX), sulfisoxazole, sulfadiazine
Inhibits bacterial dihydropteroate synthase -> inhibits folate synthesis (can't go from PABA to DHF)
Bacteriostatic
Resistance - altered enzyme
53
Sulfonamides (5 uses)
```
Sulfamethoxazole (SMX), sulfisoxazole, sulfadiazine
G+
G-
Nocardia
Chlamydia
Simple UTI (triple sulfas or SMX)
```
54
Sulfonamides (6 side effects)
G6PD hemolysis
Nephrotoxicity (tubulointerstitial nephritis)
Photosensitivity
Hypersensitivity
Kernicterus in infants
Displaces other drugs from albumin (like warfarin)
55
Trimethoprim, Pyrimethamine (mechanism and resistance)
Inhibits bacterial dihydrofolate reductase -> inhibits folate synthesis (can't go from DHF to THF, basically one step after sulfonamides)
Bacteriostatic
Resistance: salvage metabolic pathway
56
Trimethoprim, Pyrimethamine (5 uses)
```
TMP-SMX combo for
UTIs
Shigella, Salmonella
Pneumocystis jirovecii (AIDs prophylaxis when CD4 < 200 cells/mm3)
Malaria
Pneumonia tx and prophylaxis
Toxoplasmosis prophylaxis
```
57
Trimethoprim, Pyrimethamine (3 side effects)
TMP = Treats Marrow Poorly (allevaited w/ supplemental folinic acid)
Megaloblastic anemia
Leukopenia
Granulocytopenia
58
"-oxacin" (mechanism)
Fluoroquinolones
Inhibits DNA gyrase (topoisomerase II) and topoisomerase IV
Bactericidal
59
"-oxacin" (4 uses)
G- rods of urinary and GI tracts (ciprofloxacin and levofloxacin food for Pseudomonas)
Neisseria
Some G+
Moxifloxacin mainly for infections that cause exacerbation of COPD, sinusitis, CAP (poor anti-pseudomonal)
INEFFECTIVE against anaerobes
60
"-oxacin" (4 side effects)
Can't take w/ antacids
SBJ stuff: tendonitis, rupture (esp elderly or taking prednisone), leg cramps, myalgia
QT prolongation in some
CI in pregnant, nursing mothers, and children (damage to cartilage)
61
"-oxacin" (3 resistance mechanisms)
Chr-encoded mutation in DNA gyrase
Plasmid-mediated resistance
Efflux pumps
62
Linezolid (mechanism)
Inhibits 50S bacterial ribosome -> prevents formation of initiation complex -> inhibits protein synthesis
63
Metronidazole (mechanism)
Forms free radical toxic metabolites that damage bacterial DNA
Bactericidal
64
Metronidazole (6 uses)
Antiprotozoal & antibacterial
GET GAP -> Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis, Anaerobes (below diaphragm, as opposed to clindamycin which treats above diaphragm), Pylori (part of triple therapy w/ PPI and chlarithromycin)
65
Metronidazole (3 side effects)
Disulfiran-like rxn w/ alcohol (severe flushing, tachycardia, hypotension)
Headache
Metallic taste
66
Isoniazid (INH) (mechanism)
Decreases synthesis of mycolic acids -> so LOSES ACID-FASTNESS
Need bacterial catalase-peroxidase (encoded by KatG) to convert to active metabolite
Chemically related to pyridoxine (B6)
67
Isoniazid (INH) (use)
TB (as part of RIPE tx w/ Rifampin, INH, Pyrazinamide, Ethambutol)
68
Isoniazid (INH) (side effects)
Diff HL bet. fast and slow acetylators
Neurotoxicity (prevented w/ pyrdoxine/B6)
Hepatotoxicity
Acquired sideroblastic anemia (depleting B6 which is required in the rate-limiting step of heme synthesis - ALA synthetase)
69
Nalidixic acid (mechanism)
Quinolone
Inhibits DNA gyrase (topoisomerase II) and topoisomerase IV
Bactericidal
70
Nalidixic acid (3 uses)
G- rods of urinary and GI tracts (incl Pseudomonas)
Neisseria
Some G+
71
Nalidixic acid (4 side effects)
Can't take w/ antacids
SBJ stuff: tendonitis, rupture (esp elderly or taking prednisone), leg cramps, myalgia
QT prolongation in some
CI in pregnant, nursing mothers, and children (damage to cartilage)
72
Nalidixic acid (3 resistance mechanisms)
Chr-encoded mutation in DNA gyrase
Plasmid-mediated resistance
Efflux pumps
73
Rifamycins (mechanism)
Rifampin, rifabutin
| Inhibits DNA-dependent RNA polymerase
74
Rifamycins (3 uses)
Rifampin, rifabutin
TB (as part of RIPE tx w/ Rifampin, INH, Pyrazinamide, Ethambutol)
Leprosy (delays resistance to dapsone for tuberculoid form; adds in clofazimine for lepromatous form)
M. avium-intracellulare (rifabutin)
Meningococcal prophylaxis in contacts of children w. HiB
75
Rifamycins (side effects)
Rifampin, rifabutin
Drug interactions (rifampin is an inducer of P450, so use rifabutin in HIV pts)
Orange body fluids! (stains contact lenses)
Minor hepatotoxicity
76
Pyrazinamide (mechanism)
Acidify intracellular environment via conversion to pyrazinoic acid (TB engulfed by macrophages are found in acidic phagolysosomes) -> so only one of TB drugs that works best against intracellular TB
Need BACTERIAL ENZYME pyrazinamidase for this conversion!
77
Pyrazinamide (use)
TB (as part of RIPE tx w/ Rifampin, INH, Pyrazinamide, Ethambutol) -> pyrazinamide good against INTRACELLULAR TB (unlike other ones listed which are good for extracellular TB)
78
Pyrazinamide (2 side effects)
Hyperuricemia
| Hepatotoxicity
79
Ethambutol (mechanism)
Blocks arabinosyltransferase -> decreases carbohydrate polymerization of mycobacterium cell wall
80
Ethambutol (use)
TB (as part of RIPE tx w/ Rifampin, INH, Pyrazinamide, Ethambutol)
81
Ethambutol (side effect)
Red-green color blindness
82
Linezolid (3 side effects)
Serotonin syndrome
Thrombocytopenia
Optic neuritis
83
Linezolid (2 uses)
MRSA (along w/ vancomycin and daptomycin), VRE
84
"-pristin" (mechanism and use)
Streptogramins: quinupristin, dalfopristin
50S inhibitor -> inhibits protein synthesis
Used for VRE
85
Isoniazid (INH) (resistance)
Decreased activity of bacterial catalase peroxidase (can't activate the drug)
86
Amphotericin B (mechanism and resistance)
```
Binds ergosterol (unique to fungi) to form membrane pores -> leakage of electrolytes
Resistance from decreased incorporation of ergosterol into cell membrane
```
87
Amphotericin B (6 uses)
```
Serious systemic mycoses:
Cryptococcus (w/ or w/out flucytosine for meningitis)
Bastomyces
Coccidioides
Histoplasma
Candida
Mucor
```
88
Amphotericin B (5 side effects)
Infusion-related rxns (prevent w/ antipyretics and antihistamines: shake and bake (fever/chills), hypotension
Nephrotoxicity (prevented by hydration and supplement K+ and Mg2+ b/c of altered renal tubule permeability -> ALWAYS TRACK THESE 2 IONS)
Arrhythmias (from kidney messing up -> lower K+)
Anemia (from suppression of EPO)
IV phlebitis
Liposomal amphotericin reduces toxicity
89
Nystatin (mechanism and resistance)
```
Binds ergosterol (unique to fungi) to form membrane pores -> leakage of electrolytes
Topical only (too toxic for systemic)
Resistance from decreased incorporation of ergosterol into cell membrane
```
90
Nystatin (2 uses)
Topical for
Candidiasis: oral (swish and swallow) or vaginal -> 1st line for oral candidiasis in pts WITHOUT advanced immunodeficiency
Diaper rash
91
"-nazole" or "-mazole" (mechanism)
Fluconazole, ketoconazole, clotrimazole, miconazole, itraconazole, voriconazole
Inhibits lanosterol 14a-demethylase (P450 enzyme) that converts lanosterol to ergosterol -> so inhibits ergosterol synthesis -> inhibits cell membrane synthesis
92
"-nazole" or "-mazole" (3 uses)
For less serious systemic mycoses
Fluconazole: HIV-assc cryptococcal meningitis, candidal infections of all types
Itraconazole for Blastomyces, Coccidioides, Hitoplasma
Clotrimazole and miconazole for topical fungal infections (oral thrush)
93
"-nazole" or "-mazole" (side effects)
```
Gynecomastia esp w/ ketoconazole bc it inhibits testosterone synthesis
Liver dysfx (bc it inhibits cytochrome P450)
```
94
Flucytosine (mechanism)
Converted by cytosine deaminase to 5-fluorouracil
| Interferes w/ thymidylate synthetase -> inhibits DNA and RNA synthesis
95
Flucytosine (2 uses)
Systemic fungal infections
| Combo w/ amphotericin B to treat meningitis caused by Cryptococcus
96
Flucytosine (side effects)
Bone marrow suppression (CI in HIV pts)
97
"-fungin" (mechanism)
Echinocandins: caspofungin, micafungin, anidulafungin
| Inhibits beta glucan synthesis -> inhibits fungal cell wall synthesis
98
"-fungin" (2 uses)
Invasive aspergillosis
| Candida
99
"-fungin" (2 side effects)
GI upset
| Flushing (by histamine release)
100
Terbinafine (mechanism)
Inhibits fungal enzyme squalene epoxidase -> so inhibits lanosterol synthesis (precursor to ergosterol) -> inhibits cell membrane synthesis
101
Terbinafine (use)
Dermatophytoses (esp onychomycosis, tinea corporis)
102
Terbinafine (4 side effects)
GI upset
Headaches
Hepatotoxicity
Taste disturbance
103
Griseofulvin (mechanism)
Interferes w/ microtubule fx -> disrupts fungal mitosis -> concentrated in keratin-containing tissues (nails, stratum corneum)
104
Griseofulvin (2 uses)
Oral for superficial fungal infections
| Dermatophytes (tinea, ringworm)
105
Griseofulvin (4 side effects)
Teratogenic
Carcinogenic
Confusion/headaches
Induces P450 and warfarin metab
106
Pyrimethamine (use)
Toxoplasmosis
107
Suramin (use)
Trypanosoma brucei
108
Melarsoprol (use)
Trypanosoma brucei
109
Nifurtimox (use)
T. cruzi
110
Sodium stibogluconate (use)
Leishmaniasis
111
Chloroquine (mechanism)
Blocks Plasmodium heme polymerase -> blocks detox of heme into hemozoin -> heme accumulates and becomes toxic to plasmodia
112
Chloroquine (use)
For erythrocytic forms (like mefloquine)
| Plasmodial species other than P. falciparum (high resistance -> from membrane pump that decrease intracel conc of drug)
113
Chloroquine (2 side effects)
Retinopathy!
| Pruritus (esp in dark-skinned individuals)
114
Artemether/lumefantrine (use)
P. falciparum
115
Atovaquone/proguanil (use)
P. falciparum
| Atovaquone + azithromycin for Babesia
116
Quinidine (use)
Life-threatening malaria
| Use quinine in other countries
117
Artesunate (use)
Life-threatening malaria
118
Praziquantel (mechanism and 2 uses)
Immobilize helminths
For
Flukes (trematodes): all of them -> Schistosoma, Clonorchis sinensis
Tapeworms (cestodes): all of them except for Echinococcus -> so Taenia solium (but use albendazole for neurocysticercosis), diphyllobothrium latum (fish)
119
"-bendazole" (mechanism and 3 uses)
Immobilize helminths (acts on microtubules)
For
Intestinal roundworms (nematodes): all of them except for Strongyloides -> so enterobius vermicularis (pinworm), ascaris lumbricoides (giant roundworm), strongyloides stercoralis (threadworm), ancylostoma duodenale & necator americanus (hookworms), trichuris trichulura (whipworm)
Tissue roundworms (nematodes): toxocara canis
Tapeworms (cestodes): echinococcus granulosus, taenia solium (for neurocysticercosis)
120
Pyrantel pamoate (mechanism and use)
Immobilize helminths, for pregnant (second line after bendazoles)
For intestinal roundworms (nematodes): all of them except for Strongyloides -> so enterobius vermicularis (pinworm), ascaris lumbricoides (giant roundworm), ancylostoma duodenale & necator americanus (hookworms)
121
Ivermectin (mechanism and 2 uses)
```
Immobilize helminths
For
Intestinal roundworms (nematodes): strongyloides stercoralis (threadworm)
Tissue roundworms (nematodes): onochocerca volvulus (river blindness)
```
122
Diethylcarbamazine (mechanism and uses)
```
Immobilize helminths
For
Tissue roundwormds (nematodes): loa loa (fly), wuchereria bancrofti
```
123
Interferons (uses)
IFN-a: HBV, HCV, Karposi's sarcoma, Condyloma acuminatum, Hairy cell leukemia
IFN-b: MS
IFN-g (increases expression of MHC class I & II and improves Ag presentation): chronic granulomatous disease
124
"-mivir" (mechanism and use)
Zanamivir, oseltamivir
Inhibits influenza neuraminidase -> decreases viral progeny release
For tx and prevention of influenza A and B
125
Ribavirin (mechanism)
Competitively inhibits inosine monophosphate DH -> inhibits synthesis of guanine nucleotide
Direct inhibition of HCV RNA polymase (by ribavirin triphosphate)
Induces defective 5'-cap formation on viral mRNA transcript -> inefficient translation
Enhances Th1-mediated immunity while inhibiting Th2
126
Ribavirin (2 uses)
RSV, chronic HCV
127
Ribavirin (2 side effects)
Hemolytic anemia
| Severe teratogen
128
Acyclovir, famciclovir, valacyclovir (mechanism)
Guanosine analog
HSV/VZV thymidine kinase (infected cells only) monophosphorylates it -> cellular enzyme triphosphorylates it -> preferentially inhibits viral DNA polymerase by chain termination
Valacyclovir is a prodrug of acyclovir and has better oral bioavailability
129
Acyclovir, famciclovir, valacyclovir (3 uses)
Prophylaxis in immunocompromised pts
HSV: mucocutaneous and genital lesions, encephalitis
VZV: use famciclovir for herpes zoster
No effect on latent form
Weak/no activity against EBV and CMV (because they don't produce the same thymidine kinsae)
130
Acyclovir, famciclovir, valacyclovir (side effects)
Obstructive crystalline nephropathy -> renal failure
| Prevented/tx by aggressive IV hydration
131
Acyclovir, famciclovir, valacyclovir (mechanism of resistance)
Mutated viral thymidine kinase
132
Ganciclovir, valganciclovir (mechanism)
Guanosine analog
CMV viral kinase 5'-monophosphates it -> cellular kinase triphosphates it -> preferentially inhibits viral DNA polymerase
Valganciclovir is a prodrug of gangiclovir and has better oral bioavailability
133
Ganciclovir, valganciclovir (use)
CMV (esp in immunocompromised) -> but don't use if already on zidovudine b/c neutropenia will be made worse
134
Ganciclovir, valganciclovir (side effects)
Leukopenia (NEUTROPENIA especially), thrombocytopenia
Renal toxicity
More toxic to host enzymes than acyclovir
135
Ganciclovir, valganciclovir (2 mechanisms of resistance)
Mutated CMV DNA polymerase
| Lack of viral kinase
136
Foscarnet (mechanism)
Viral DNA polymerase inhibitor (pyrophosphate analog)
Also binds HCV reverse transcriptase
Does NOT require activation by viral kinase (like acyclovir, famciclovir, valacyclovir, ganciclovir, valganciclovir)
137
Foscarnet (2 uses)
CMV retinitis in immunocompromised (when ganciclovir fails)
| Acyclovir-resistant HSV
138
Foscarnet (side effects)
Nephrotoxic
| Seizures (from Ca2+ chelation & renal wasting of magnesium)
139
Foscarnet (mechanism of resistance)
Mutated DNA polymerase
140
Cidofovir (mechanism)
Preferentially inhibits viral DNA polymerase
Does NOT require phosphorylation by viral kinase
Long HL
141
Cidofovir (2 uses)
CMV retinitis in immunocompromised
| Acyclovir-resistant HSV
142
Cidofovir (side effect)
Nephrotoxicity -> coadminister w/ probenecid and IV saline to prevent this
143
HAART therapy combination?
- 2 NRTIs
| - 1 NNRTI OR 1 protease inhibitor OR 1 integrase inhibitor
144
"-navir" (mechanism and use)
Protease inhibitor -> prevents maturation of new viruses
Ritonavir can inhibit P450 -> boosts other drug conc
Part of HIV HAART
145
"-navir" (side effects)
Hyperglycemia
GI intolerance (nausea/diarrhea)
Lipodystrophy (fat redistribution, hyperTG)
Indinavir: nephropathy (crystallization), hematuria
146
"-dine", "-bine", "-sine", Tenofovir, Abacavir (mechanism)
EXCEPT delavirdine (that's NNRTI)
NRTIs (blocks RNA -> DNA)
Competitively inhibits nucleotide binding to reverse transcriptase -> terminates DNA chain (lacks 3'OH group)
Tenofovir is nucleotide (so doesn't need thymidine kinase like other ones which are nucleoside)
147
"-dine", "-bine", "-sine", Tenofovir, Abacavir (use)
```
EXCEPT delavirdine (that's NNRTI)
NRTIs, part of HIV HAART
Zidovudine: general prophylaxis and during pregnancy -> reduces vertical transmission
```
148
"-dine", "-bine", "-sine", Tenofovir, Abacavir (side effects)
```
EXCEPT delavirdine (that's NNRTI)
Bone marrow suppression (reversed w/ G-CSF, erythropoietin)
Peripheral neuropathy
Lactic acidosis (nucleosides only)
Rash (non-nucleosides)
Anemia (zidovudine)
Pancreatitis (didanosine)
```
149
Efavirenz, nevirapine, delavirdine (mechanism and use)
```
"vir" in the middle
NNRTIs (blocks RNA -> DNA)
Binds reverse transcriptase (at a site diff from NRTIs)
Don't require phosphorylation
Part of HIV HAART
```
150
Efavirenz, nevirapine, delavirdine (side effects)
"vir" in the middle
Rash (can be severe like Stevens-Johnson and TEN)
Hepatotoxicity (life-threatening hepatic failure w/ encephalopathy)
Efavirenz: vivid dreams and CNS sx
Efavirenz and delavirdine CI in pregnancy
151
Raltegravir (mechanism and use)
```
Integrase inhibitor (blocks DNA -> mRNA)
Reversibly inhibits HIV integrase
Part of HIV HAART
```
152
Raltegravir (side effects)
Hypercholesterolemia
153
Enfuvirtide (mechanism, use, and side effect)
Fusion inhibitor
Binds gp41 and inhibits viral PENETRATION
Part of HIV HAART
Skin rxn at injection site
154
Maraviroc (mechanism, use, and side effect)
Prevents ATTACHMENT -> binds CCR-5 on surface T cells/monocytes -> inhibits interaction w/ gp120
Part of HIV HAART
Skin rxn at injection site
155
Interferons (2 side effects)
Neutropenia, myopathy
156
Groups of antibiotics that bind 30S and 50S?
"buy AT 30, CCEL (sell) at 50"
30S: Aminoglycosides, Tetracyclines
50S: Chloramphenicol, Clindamycin, Erythromycin (macrolides), Linezolid
157
Daptomycin (mechanism and use)
Depolarize cellular membrane
For MRSA (along w/ vancomycin and linezolid)
Not effective against G-, and inactivated by pulm surfactant (so can't use for lung infection/pneumonia)
158
Daptomycin (side effect)
Myopathy (CPK elevation)
159
Interferons a and b (mechanism)
Paracrine signaling -> stimulate neibouring cells to synthesize antiviral proteins that degrade intracellular mRNA and impair protein synthesis (both of host and virus!)
160
Fidaxomicin (mechanism and use)
Impairs RNA polymerase -> impairs protein synthesis -> bacteriocidal
Oral w/ minimal systemic absorption
For recurrent C. diff refractory to metronidazole and oral vancomycin
161
Primaquine (use)
For P. vivax and P. ovale LIVER schizonts (mefloquine/chloroquine takes care of erythrocytic phase only)
162
Puromycin (mechanism)
Analog of aminocyl-tRNA -> causes premature release of unfinished peptide chain
