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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
Rifampin Uses
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
26
Clindamycin MOA
inhibition of protein synthesis; binds to 50S ribosomal subunit
27
Clindamycin Resistance
occurs slowly in stepwise manner; decreased affinity of drug from ribosome - methylation by erm-encoded genes provides resistance
28
Clindamycin Uses
effective for anaerobes, G+, G-, peptostreptococcus, bacteroides fragilis, MRSA, GAS
29
Clindamycin Absorption
rapid and near complete oral absorption, rate but not extent of absorption delayed by food; acid stable
30
Clindamycin Distribution
widely distributed, penetrates bone and abscesses, does not penetrate CSF or intracellular; does cross placenta and is found in breast milk
31
Clindamycin Metabolism and Excretion
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
32
Clindamycin Adverse Effects
pseudomembranous colitis from C. diff; GI disturbances - diarrhea; hypersensitivity rashes
33
Clindamycin Uses
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
34
Mupirocin MOA
Inhibits protein and RNA synthesis by binding reversibly to staphylococcal isoleucyl tRNA synthetase; static or cidal depending on conc.; used for G+
35
Mupirocin Pharm
Little systemic absorption with topical use; quickly inactivated upon absorption; ointment is in polyethylene glycol which can cause renal failure
36
Mupirocin Uses
Topically for Impetigo; can be used to eliminate MRSA carriage by patients or healthcare workers
37
Bacitracin MOA
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
38
Bacitracin Uses
gram+ cocci and bacilli
39
Bacitracin Application and Toxicity
Used topically usually in ointment with neomycin and polymyxin B; severe nephrotoxicity with parenteral use
40
Therapy for widespread tinea infection
Oral: TERBINAFINE, itraconazole, fluconazole, griseofulvin,
41
Therapy for localized tinea infection
Topical: AZOLES, terbinafine, nafitifine, Ciclopirox
42
Oral therapy for Onchomychosis
TERBINAFINE, griseofulvin, itraconazole, fluconazole
43
Topical therapy for Onchomychosis
Ciclopirox, Amorolfine
44
Flucytosine MOA
works intracellularly (nucleus); blocks DNA, RNA synthesis
45
Griseofulvin MOA
works intracellularly (nucleus); blocks DNA/RNA synthesis
46
Ciclopirox MOA
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
Terbinafine MOA
blocks squalene to squalene epoxide pathway
48
Naftifine MOA
blocks squalene 2,3 epixodase (blocking squalene epoxide to lanosterol) (cell wall)
49
Azoles MOA
blocks Lanosterol to Ergosterol (cell wall)
50
Amphotericin B, Nystatin MOA
increases cell wall degradation?
51
Caspofungin MOA
blocks beta-glucan synthase (cell wall)
52
Ketoconazole adverse effects
primarily due to hormones; impotence, menstrual irregularity, gynecomastia, male breast pain, hot flashes
53
Ketoconazole CYP interactions
inhibition: 2C19, 3A4 | Substrate for: 3A4
54
Fluconazole CYP interactions
Inhibition: 2C19, 2C9, 3A4 | Substrate for: 3A4
55
Itraconazole CYP interactions
Inhibition: 2C9, 3A4 | Substrate for: 3A4
56
Posaconazole CYP interactions
Inhibition: 3A4
57
Voriconazole CYP interactions
Inhibition: 2C19, 2C9, 3A4 | Substrate for: 2C19, 2C9, 3A4
58
Azoles eliminated hepatically
Keto, Itra, Posa, Vori
59
Azoles with Renal elimination
Fluconazole
60
Azoles and pregnancy
all teratogenic
61
Azoles that enter CSF
Fluconazole (high), Keto (low), Vori (low), Itra (v. low)
62
Azoles that cause QT prolongation
Flu, Posa, Vori
63
Griseofulvin Pharm
oral only; extensive hepatic metabolism; elimination is renal, hepatic, and perspiration
64
Griseofulvin Interactions
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
Griseofulvin Contraindications
Pregnancy (teratogen), Hepatotoxic, Interferes with porphyrin metabolism
66
Griseofulvin Adverse Effects
Photosensitivity, Neurological issues
67
Terbinafine pharm
Hepatic metabolism, Renal elimination; can be given topically or orally
68
Terbinafine Adverse Effects
generally well tolerated (esp. topically), transient lymphopenia/neutropenia (oral), can be used during pregnancy
69
Naftifine Uses
locally bactericidal (G+/-), anti inflammatory properties via inhibition of mediators (PGs, LTs, Hist.), topical agent
70
Naftifine Pharm
hepatic metabolism, renal elimination
71
Nftifine Contras
hypersensitivity to drug, no significant systemic drug interactions; same pathway as azoles so don't use together
72
Ciclopirox
topical drug with limited absorption; avoid if allergy; may irritate if applied to skin abrasions
73
Amorolfine
inhibits ergosterol synthesis; topical only with limited absorption; avoid if allergy and on skin abrasions.
74
Acyclovir Uses
Varicella Zoster, Varicella chicken pox
75
Cidofovir Uses
Pox virus family, HHV-6,7,8
76
Famciclovir Uses
Varicella Zoster, HHV-8
77
Forscarnet Uses
HHV-6
78
Ganciclovir Uses
HHV-6, 8 (FDA for 8)
79
Valacyclovir Uses
Varicella Zoster, Varicella Chicken Pox, HHV-8
80
Valganciclovir Uses
HHV-6, HHV-8 (FDA for 8)
81
Penciclovir Use
Herpes Labialis (pen is a metabolite of Famciclovir)
82
MOA of -Clovir drugs
competitively inhibits viral DNA polymerase; competes with deoxyguanosine triphosphate for incorporation into viral DNA
83
Cidofovir MOA
Competitively inhibits viral DNA polymerase; competes with deoxycystine triphosphate for incorporation into viral DNA
84
Forscarnet MOA
selectively inhibits the viral-specific DNA polymerases and reverse trascriptases at pyrophosphate-binding site; blocks chain elongation
85
Drugs that retain efficacy against kinase-deficient viral strains
Cidofovir, Forscarnet
86
Antivirals with cross-hyper-sensitivity
all those ending in -Clovir
87
Acyclovir toxicity
neurotoxicity including seizures
88
Cidofovir toxicity
nephrotoxicity - monitor creatinine and urinary protein (give probenecid to minimize potential for renal issues with normal saline)
89
Famciclovir toxicity
No significant issues
90
Forscarnet toxicity
electrolyte imbalance - chelates Ca2+ ions
91
Ganciclovir toxicity
anermia, leukopenia, neutropenia, pancytopenia, thrombocytopenia; teratogen
92
Valacyclovir toxicity
neurotoxicity including seizures
93
Valganciclovir toxicity
anermia, leukopenia, neutropenia, pancytopenia, thrombocytopenia; teratogen

Dermatological Block (6 decks)

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