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Flashcards in Microbe drugs Deck (162):
1

Penicillin G, V (mechanism and resistance)

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

Penicillin G, V (3 uses)

G+ orgs (S pneumoniae, S. pyogenes, Actinomyces)
G- cocci (incld N. meningitidis)
Spirochetes (incl T. pallidum)

3

Penicillin G, V (3 side effects)

Hypersensitivity
Hemolytic anemia
Resistance in bacteria w/ beta-lactamase (MRSA)

4

Ampicillin, amoxicillin (mechanism)

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

Ampicillin, amoxicillin (uses)

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

Ampicillin, amoxicillin (3 side effects)

Pseudomembranous colitis
Hypersensitivity, rash
Resistance in bacteria w/ beta-lactamase (MRSA)

7

Oxacillin, nafcillin, dicloxacillin (mechanism)

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

Oxacillin, nafcillin, dicloxacillin (use)

Nafcillin for MSSA

9

Oxacillin, nafcillin, dicloxacillin (2 side effects)

Interstitial nephritis
Hypersensitivity

10

Ticarcillin, piperacillin (mechanism)

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

Ticarcillin, piperacillin (2 uses)

Pseudomonas
G- rods, including ANAEROBES (so good for bacterioids)

12

Ticarcillin, piperacillin (side effect)

Hypersensitivity

13

Clavulanic acid (mechanism and use)

Beta lactamase inhibitor
Added to penicillinase-sensitive penicillin antibiotics

14

Sulbactam (mechanism and use)

Beta lactamase inhibitor
Added to penicillinase-sensitive penicillin antibiotics

15

Tazobactam (mechanism and use)

Beta lactamase inhibitor
Added to penicillinase-sensitive penicillin antibiotics

16

Cephalosporins (mechanism and resistance)

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

1st gen cephalosporins (2 names and 3 uses)

"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

List orgs not covered by cephalosporins

"LAME" -> Listeria, Atypicals (Chlamydia, Mycoplasma), MRSA (except ceftaroline), Enterococci

19

2nd gen cephalosporins (3 names and 2 uses)

"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

3rd gen cephalosporins (3 names and 3 uses)

"Tri, Tax, Taz" -> cefTRIaxone, cefoTAXime, cefTAZidime
Serious G-- infections resistant to other beta lactams
Ceftrixone - meningitis and gonorrhea
Ceftaxidime - pseudomonas

21

4th gen cephalosporin (1 name and 2 uses)

Cefepime
Increased activity against Pseudomonas & G+

22

5th gen cephalosporin (1 name and 2 uses)

Ceftaroline
Broad G+ (incl MRSA - the only one of cephalosporins that does this)
Broad G-
Does NOT cover Pseudomonas tho

23

Cephalosporin (3 side effects)

Vit K deficiency
Increases nephrotoxicity of amonoglycocides
Hypersensitivity (cross-reactivity w/ penicillins)

24

Aztreonam (mechanism)

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