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Dermatological Block > Antibiotics, Antifungals, Antivirals > Flashcards

Antibiotics, Antifungals, Antivirals Flashcards

1
Q

Daptomycin MOA

A

rapidly disrupts bacterial cell membranes; results in depolarization and loss of membrane potential and K+ efflux

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2
Q

Daptomycin Resistance

A

No known mechanism of resistance has been identified and no known transferable genetic elements for resistance

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3
Q

Daptomycin Administration, metabolism and elimination

A

IV infusion once daily, administered after hemodialysis; primarily bound to serum albumin; renal elimination requiring dose adjustment with renal deficiency

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4
Q

Daptomycin Adverse Effects

A

Muscle pain or weakness; monitor for development due to serum creatine phosphokinase elevations; direct muscle toxicity precludes IM injection

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5
Q

Daptomycin Drug interactions

A

None with CYPs; use caution with co-administration of statins

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6
Q

Daptomycin Uses

A

Aerobic gram positive bacteria; multi-drug resistant staph, strep, and enterococcus; complicated skin and soft tissue infections; MSSA/MRSA bacteremia including right sided endocarditis; does not work for pneumonia

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7
Q

Linezolid MOA

A

inhibits protein synthesis - binds to 23S RNA on 50 ribosomal subunit; bacteriostatic for staph and entero; bacteriocidal for strep

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8
Q

Linezolid Resistance

A

point mutation in 23S RNA; no cross resistance with other classes; emerging resistance observed in enteroco and staph aureus strains

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9
Q

Indications for Linezolid

A

MRSA, penicillin resistant staph, enterococcus faecium and faecalis, serious VRE infections

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10
Q

Linezolid pharm features

A

oral and parenteral use; 100% absorption orally; metabolized by non-enzymatic oxidation; eliminated renal and non renal so no dose adjustment for AKI/CKI; no CYP interactions; supplemental dose needed post hemodialysis

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11
Q

Linezolid Adverse Effects

A

generally well tolerated; n/v/d (possible Psuedomembrane colitis), HA, myelosuppression with therapy >2wks; contains aspartame (patients with phenylketonuria need to be aware)

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12
Q

Linezolid Drug Interactions

A

non selective inhibitor of monoamine oxidase; caution with co-administration of drug metabolized by MOA (pseudoephedrine, phenylpropanolamine, SSRIs); HTN from decreased breakdown of tyramine absorbed in diet

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13
Q

Streptogramins

A

Dalfopristin-Quinupristin; remotely related to macrolides, but no cross sensitivity

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14
Q

Streptogramins MOA

A

Protein synthesis inhibition - bind to ribosome peptidyltransferase domain, tRNA synthetase is inhibited, AA addition to peptide chain is blocked; synergistic bactericidal combo (alone each is static)

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15
Q

Streptogramins Resistance

A

Due to changes in 23S ribosomal target site; constitutive expression of erm gene encoding MLSb phenotype

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16
Q

Streptogramins Pharm

A

IV only (best via central venous cath); hepatic metabolism via conjugation via CYP3A4 - metabolites have activity; biliary excretion; increase dosing interval if unable to tolerate drug.

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17
Q

Streptogramins Adverse Effects

A

Thrombophlebitis and pain at the infusion site; increase in conjugated bilirubin; increase in liver enzymes that is reversible; myalgia and arthralgia (usually in pts with chronic liver disease)

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18
Q

Streptogramins Interactions

A

Inhibits CYP3A4; increases conc. for cyclosporine, midazolam, some statins, HIV protease inhibitors, etc; does not inhibit other CYPs

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19
Q

Streptogramins Indications

A

Gram positive organisms other than enterococcus faecalis; VRE; skin and skin structure infections from MRSA or GAS; bone infections due to VRE and MRSA

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20
Q

Tigecycline MOA

A

inhibits protein translation - binds to 30S subunit (bacteriostatic), expanded broad spectrum compared to structurally similar tetracyclines

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21
Q

Tigecycline Resistance

A

overcomes key mechanism of resistance to tetracyclines by having high affinity binding at additional ribosomal sites and not being expelled for cell by efflux pumps

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22
Q

Tigecycline pharm features

A

administered via slow IV infusion (lower dose with impaired liver function, no adjust for renal issues); distributed extensively beyond plasma to tissues; very little metabolism (t1/2 = 27hr), excreted biliary/fecal and renal

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23
Q

Tigecycline Adverse Effects

A

d/n/v, pain at injection site, swelling, irritation; possible hepatic/pancreatic toxicity; affects teeth/bones, photosensitivity, possible superinfections

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24
Q

Tigecycline Uses

A

broad spectrum; gram + bacteria, Gram -, anaerobes, MRSA, skin and soft tissue infections, intra abdominal infections; no activity against pseudomonas or proteus; not for use under 18yo

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25
Q

Rifampin Uses

A

First line for MTB; also used for MRSA/MRSE, prophylaxis for family members of meningitis pt caused by meningococcus or H. flu; eradication of staph in nasal carriers; anti-leprosy drugs

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26
Q

Clindamycin MOA

A

inhibition of protein synthesis; binds to 50S ribosomal subunit

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27
Q

Clindamycin Resistance

A

occurs slowly in stepwise manner; decreased affinity of drug from ribosome - methylation by erm-encoded genes provides resistance

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28
Q

Clindamycin Uses

A

effective for anaerobes, G+, G-, peptostreptococcus, bacteroides fragilis, MRSA, GAS

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29
Q

Clindamycin Absorption

A

rapid and near complete oral absorption, rate but not extent of absorption delayed by food; acid stable

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30
Q

Clindamycin Distribution

A

widely distributed, penetrates bone and abscesses, does not penetrate CSF or intracellular; does cross placenta and is found in breast milk

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31
Q

Clindamycin Metabolism and Excretion

A

Metabolized in liver to inactive forms; dose adjustment needed for patients with liver disease; excreted in bile and urine, no dose change for renal issues, not removed by hemodialysis

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32
Q

Clindamycin Adverse Effects

A

pseudomembranous colitis from C. diff; GI disturbances - diarrhea; hypersensitivity rashes

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33
Q

Clindamycin Uses

A

Bacteroides fragilis (outside CSF), prophylaxis when pt is allergic to pen; MSSE/MRSA, toxoplasmosis in patients with AIDS (w/ pyrimethamine), PJP (w/ primaquine), oral infections

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34
Q

Mupirocin MOA

A

Inhibits protein and RNA synthesis by binding reversibly to staphylococcal isoleucyl tRNA synthetase; static or cidal depending on conc.; used for G+

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35
Q

Mupirocin Pharm

A

Little systemic absorption with topical use; quickly inactivated upon absorption; ointment is in polyethylene glycol which can cause renal failure

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36
Q

Mupirocin Uses

A

Topically for Impetigo; can be used to eliminate MRSA carriage by patients or healthcare workers

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37
Q

Bacitracin MOA

A

inhibits bacterial cell wall synthesis by inhibiting movement of peptidoglycan building blocks of cell wall from inside to outside the cell membrane by inhibiting dephosphorylation of the isoprenyl pyrophosphate carrier protein

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38
Q

Bacitracin Uses

A

gram+ cocci and bacilli

39
Q

Bacitracin Application and Toxicity

A

Used topically usually in ointment with neomycin and polymyxin B; severe nephrotoxicity with parenteral use

40
Q

Therapy for widespread tinea infection

A

Oral: TERBINAFINE, itraconazole, fluconazole, griseofulvin,

41
Q

Therapy for localized tinea infection

A

Topical: AZOLES, terbinafine, nafitifine, Ciclopirox

42
Q

Oral therapy for Onchomychosis

A

TERBINAFINE, griseofulvin, itraconazole, fluconazole

43
Q

Topical therapy for Onchomychosis

A

Ciclopirox, Amorolfine

44
Q

Flucytosine MOA

A

works intracellularly (nucleus); blocks DNA, RNA synthesis

45
Q

Griseofulvin MOA

A

works intracellularly (nucleus); blocks DNA/RNA synthesis

46
Q

Ciclopirox MOA

A

blocks fungal transmembrane transport, depleting essential substrates and interfering with RNA/DNA synthesis; at high concentrations it permits leakage of intracellular material; works intracellularly (nucleus)

47
Q

Terbinafine MOA

A

blocks squalene to squalene epoxide pathway

48
Q

Naftifine MOA

A

blocks squalene 2,3 epixodase (blocking squalene epoxide to lanosterol) (cell wall)

49
Q

Azoles MOA

A

blocks Lanosterol to Ergosterol (cell wall)

50
Q

Amphotericin B, Nystatin MOA

A

increases cell wall degradation?

51
Q

Caspofungin MOA

A

blocks beta-glucan synthase (cell wall)

52
Q

Ketoconazole adverse effects

A

primarily due to hormones; impotence, menstrual irregularity, gynecomastia, male breast pain, hot flashes

53
Q

Ketoconazole CYP interactions

A

inhibition: 2C19, 3A4

Substrate for: 3A4

54
Q

Fluconazole CYP interactions

A

Inhibition: 2C19, 2C9, 3A4

Substrate for: 3A4

55
Q

Itraconazole CYP interactions

A

Inhibition: 2C9, 3A4

Substrate for: 3A4

56
Q

Posaconazole CYP interactions

A

Inhibition: 3A4

57
Q

Voriconazole CYP interactions

A

Inhibition: 2C19, 2C9, 3A4

Substrate for: 2C19, 2C9, 3A4

58
Q

Azoles eliminated hepatically

A

Keto, Itra, Posa, Vori

59
Q

Azoles with Renal elimination

A

Fluconazole

60
Q

Azoles and pregnancy

A

all teratogenic

61
Q

Azoles that enter CSF

A

Fluconazole (high), Keto (low), Vori (low), Itra (v. low)

62
Q

Azoles that cause QT prolongation

A

Flu, Posa, Vori

63
Q

Griseofulvin Pharm

A

oral only; extensive hepatic metabolism; elimination is renal, hepatic, and perspiration

64
Q

Griseofulvin Interactions

A

Similar structure to Penicillin so cross-sensitivity; CYP3A4 inducer - decreased anticoagulant with Warfarin, decrease effect with OC, decreased cyclosporine levels, increased ethanol effects (tachycardia, diaphoresis, flushing)

65
Q

Griseofulvin Contraindications

A

Pregnancy (teratogen), Hepatotoxic, Interferes with porphyrin metabolism

66
Q

Griseofulvin Adverse Effects

A

Photosensitivity, Neurological issues

67
Q

Terbinafine pharm

A

Hepatic metabolism, Renal elimination; can be given topically or orally

68
Q

Terbinafine Adverse Effects

A

generally well tolerated (esp. topically), transient lymphopenia/neutropenia (oral), can be used during pregnancy

69
Q

Naftifine Uses

A

locally bactericidal (G+/-), anti inflammatory properties via inhibition of mediators (PGs, LTs, Hist.), topical agent

70
Q

Naftifine Pharm

A

hepatic metabolism, renal elimination

71
Q

Nftifine Contras

A

hypersensitivity to drug, no significant systemic drug interactions; same pathway as azoles so don’t use together

72
Q

Ciclopirox

A

topical drug with limited absorption; avoid if allergy; may irritate if applied to skin abrasions

73
Q

Amorolfine

A

inhibits ergosterol synthesis; topical only with limited absorption; avoid if allergy and on skin abrasions.

74
Q

Acyclovir Uses

A

Varicella Zoster, Varicella chicken pox

75
Q

Cidofovir Uses

A

Pox virus family, HHV-6,7,8

76
Q

Famciclovir Uses

A

Varicella Zoster, HHV-8

77
Q

Forscarnet Uses

A

HHV-6

78
Q

Ganciclovir Uses

A

HHV-6, 8 (FDA for 8)

79
Q

Valacyclovir Uses

A

Varicella Zoster, Varicella Chicken Pox, HHV-8

80
Q

Valganciclovir Uses

A

HHV-6, HHV-8 (FDA for 8)

81
Q

Penciclovir Use

A

Herpes Labialis (pen is a metabolite of Famciclovir)

82
Q

MOA of -Clovir drugs

A

competitively inhibits viral DNA polymerase; competes with deoxyguanosine triphosphate for incorporation into viral DNA

83
Q

Cidofovir MOA

A

Competitively inhibits viral DNA polymerase; competes with deoxycystine triphosphate for incorporation into viral DNA

84
Q

Forscarnet MOA

A

selectively inhibits the viral-specific DNA polymerases and reverse trascriptases at pyrophosphate-binding site; blocks chain elongation

85
Q

Drugs that retain efficacy against kinase-deficient viral strains

A

Cidofovir, Forscarnet

86
Q

Antivirals with cross-hyper-sensitivity

A

all those ending in -Clovir

87
Q

Acyclovir toxicity

A

neurotoxicity including seizures

88
Q

Cidofovir toxicity

A

nephrotoxicity - monitor creatinine and urinary protein (give probenecid to minimize potential for renal issues with normal saline)

89
Q

Famciclovir toxicity

A

No significant issues

90
Q

Forscarnet toxicity

A

electrolyte imbalance - chelates Ca2+ ions

91
Q

Ganciclovir toxicity

A

anermia, leukopenia, neutropenia, pancytopenia, thrombocytopenia; teratogen

92
Q

Valacyclovir toxicity

A

neurotoxicity including seizures

93
Q

Valganciclovir toxicity

A

anermia, leukopenia, neutropenia, pancytopenia, thrombocytopenia; teratogen

Dermatological Block (6 decks)

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