Antimicrobials Flashcards

Question

# [](http://) Flucystosine (ANTIMETABOLITE)

Answer 1

**MOA:** Pyrimidine analog; penetrates fungal cells and converted to fluorouracil that competes with uracil --> intereferes with fungal RNA/protein synthesis **Spectrum:** "Cryptococcal meningitis + Candida (resistance develops rapidly) * 4x daily (short half-life) * TDM monitoring (70-80 mcg/mL)" **PK:** * Dose adjustment w renal dysfunction **Side Effects/AEs:** "* GI * Leukopenia/thrombocytopenia * Hepatotoxic * Aplastic anemia * Photosensitivity * increased risk of bone marrow suppression with other immunosuppressive agents" **Extra Notes:** **Resistance:** | Antifungals

Answer 2

**MOA:** Inhibits fungal CYP450 (lanosterol 14-alpha-demethlase) -> decreased ergosterol synthesis -> inhibition of cell membrane formation **Spectrum:** Candida albicans (NOT crucii), Coccidioides, Cryptococcus **PK:** * PO = excellent bioavailability **Side Effects/AEs:** "* LFT elevations (long term use > 1 wk) * QTc prolongation * GI upset * DDIs (CYP3A4 inhibitor -> higher levels of substrates such as immunosuppressants, warfarin, statins, etc.)" **Extra Notes:** **Resistance:** | Antifungals - Azoles ## Footnote PO + IV

Answer 3

**MOA:** Inhibits fungal CYP450 (lanosterol 14-alpha-demethlase) -> decreased ergosterol synthesis -> inhibition of cell membrane formation **Spectrum:** Candida albicans (NOT crucii), Coccidioides, Cryptococcus, Aspergillus, Histoplasmosis, Blastomycosis **PK:** "* Poor CNS penetration * Capsules taken w acidic beverage * Susp taken at any time" **Side Effects/AEs:** "* LFT elevations (long term use > 1 wk) * QTc prolongation * GI upset * DDIs (CYP3A4 inhibitor -> higher levels of substrates such as immunosuppressants, warfarin, statins, etc.)" **Extra Notes:** **Resistance:** | Antifungals - Azoles ## Footnote PO + IV

Answer 4

**MOA:** Inhibits fungal CYP450 (lanosterol 14-alpha-demethlase) -> decreased ergosterol synthesis -> inhibition of cell membrane formation **Spectrum:** Candida, Aspergillus, Fusarium, Cryptococcus, Blastomyces, Coccidioides, Histoplasma, Sporothrix **PK:** "* Poor CNS penetration * CNS toxicity (hallucinations) * Requires TDM (2-5 mcg/mL) * IV w renal dysfunction --> cyclodextrin (what its made with) accumulation" **Side Effects/AEs:** visual disturbances "* LFT elevations (long term use > 1 wk) * QTc prolongation * GI upset * DDIs (CYP3A4 inhibitor -> higher levels of substrates such as immunosuppressants, warfarin, statins, etc.)" **Extra Notes:** **Resistance:** | Antifungals - Azoles ## Footnote PO + IV

Answer 5

**MOA:** Inhibits fungal CYP450 (lanosterol 14-alpha-demethlase) -> decreased ergosterol synthesis -> inhibition of cell membrane formation **Spectrum:** Candida, Aspergillus, Fusarium, Cryptococcus, Blastomyces, Coccidioides, Histoplasma, Mucormycosis **PK:** "* Susp taken w acidic beverage * Tablets at any time * Requries TDM (> 0.7-1 mcg/mL)" **Side Effects/AEs:** "* LFT elevations (long term use > 1 wk) * QTc prolongation * GI upset * DDIs (CYP3A4 inhibitor -> higher levels of substrates such as immunosuppressants, warfarin, statins, etc.)" **Extra Notes:** **Resistance:** | Antifungals - Azoles ## Footnote PO + IV

Answer 6

**MOA:** Inhibits fungal CYP450 (lanosterol 14-alpha-demethlase) -> decreased ergosterol synthesis -> inhibition of cell membrane formation **Spectrum:** Candida (NOT IDEAL), Aspergillus, Fusarium, Cryptococcus, Blastomyces, Coccidioides, Histoplasma, Mucormycosis, Sporothrix **PK:** * No TDM required **Side Effects/AEs:** "* LFT elevations (long term use > 1 wk) * NO QTc prolongation (all other azoles do) may be QTc shortening even * GI upset * DDIs (CYP3A4 inhibitor -> higher levels of substrates such as immunosuppressants, warfarin, statins, etc.)" **Extra Notes:** **Resistance:** | Antifungals - Azoles ## Footnote PO + IV

Answer 7

**MOA:** Inhibits synthesis of b-(1,3)-D-glucan --> reduced formation of polysaccharide in cell walls --> osmotic instability & cell lysis **Spectrum:** "* Candida & salvage therapy for Aspergillus * All IV only (No PO forms) * Works well against biofilms * Fungicidal against Candida" **PK:** "* NO CNS penetration * High protein binding (daily dosing)" LD + daily dosing, **no LD for micafungin** **Side Effects/AEs:** "* LFT elevation * Mild infusion site rxn" DDI w immunosuppressants **Extra Notes:** **Resistance:** | Antifungals - ECHINOCANDINS

Answer 8

**MOA:** Inhibits NA preventing release of virions from plasma membranes **Spectrum:** **PK:** PO (cap or susp) BID for 5 days, daily for 10 days if ppx, renal dose adjustments **Side Effects/AEs:** "* GI disturbance * Insomnia * Vertigo * Neuropsychiatric events" **Extra Notes:** "* Resistance possible, but NOT tested * Tx started within 48 hr of symptoms for benefit" **Resistance:** | Antivirals - Influenza

Answer 9

**MOA:** Inhibits NA preventing release of virions from plasma membranes **Spectrum:** **PK:** Inhaled BID for 5 days, daily for 10 days if ppx **Side Effects/AEs:** "* GI disturbance * Insomnia * Vertigo * Neuropsychiatric events" * Bronchospasm (inhaled) **Extra Notes:** "* Resistance possible, but NOT tested * Tx started within 48 hr of symptoms for benefit" **Resistance:** | Antifungals

Answer 10

**MOA:** Inhibits NA preventing release of virions from plasma membranes **Spectrum:** IV, very expensive, only for use in critically ill, once daily **PK:** renal dose adjustments **Side Effects/AEs:** "* Hyperglycemia * LFT/CPK elevations * SJS" **Extra Notes:** "* Resistance possible, but NOT tested * Tx started within 48 hr of symptoms for benefit" **Resistance:** | Antivirals - Influenza

Answer 11

**MOA:** Prodrug hydrolyzed to baloxavir --> inhibits replication by interfering w "cap snatching" in which virus hijacks host mRNA transcription system) & inhibits endonuclease activity of selective pol acidic protein required for viral gene transcription **Spectrum:** **PK:** Tablets or susp once daily **Side Effects/AEs:** **Extra Notes:** **Resistance:** | Antivirals - Influenza

Answer 12

**MOA:** **Spectrum:** Influ A only **PK:** **Side Effects/AEs:** **Extra Notes:** **Resistance:** | Antivirals - Influenza

Answer 13

**MOA:** Converted to acyclovir-triP by viral TK then host enzymes --> inhibits viral DNA synthesis by competing with deoxyguanoside triP for incorporation into viral DNA --> termination of viral replication **Spectrum:** (VZV/HSV) **PK:** IV + PO (poor bioavailability) 3-5x daily, renal dose adjustments (weight based) **Side Effects/AEs:** "* GI upset * Neurotoxic * LFT elevations (longer term > 1 wk) * Avoid in pts with AKI (crystalluria)" **Extra Notes:** **Resistance:** Resistance due to viral mutants deficient in TK or reduced affinity of TK for acyclovir-triP | Antivirals - Herpesviridae (HSV, VZV)

Answer 14

**MOA:** Prodrug --> acyclovir **Spectrum:**(VZV/HSV) **PK:** PO (better bioavailability) 2-3x daily --> preferred over acyclovir! renal dose adjustments (weight based) **Side Effects/AEs:** "* GI upset * Neurotoxic * LFT elevations (longer term > 1 wk) * Avoid in pts with AKI (crystalluria)" **Extra Notes:** * Resistance due to viral mutants deficient in TK or reduced affinity of TK for acyclovir-triP **Resistance:** | Antivirals - Herpesviridae (HSV, VZV)

Answer 15

**MOA:** Viral TK then host enzymes phosphorylate drug --> triphosphate form that competes with deoxyguanosine triphosphate --> inhibition of DNA pol --> termination of viral replication **Spectrum:** (HSV only) **PK:** Topical (poor PO bioavailability), q2h for 4 days **Side Effects/AEs:** "* Headache * GI upset" **Extra Notes:** **Resistance:** | Antivirals - Herpesviridae (HSV, VZV)

Answer 16

**MOA:** Prodrug --> penciclovir **Spectrum:** (VZV/HSV) **PK:** PO only (better bioavailability), 2-3x daily **Side Effects/AEs:** "* Headache * GI upset" **Extra Notes:** **Resistance:** | Antivirals - Herpesviridae (HSV, VZV)

Answer 17

**MOA:** Activated through triphosphorylation by host UL97 + kinases --> incorporated into host DNA (guanine analog) **Spectrum:** (CMV & some HSV activity if worried about both) **PK:** IV only (PO poor bioavailability) * Induction period of 2-3 wk to lower VL, then lower MD (less toxicity) **Side Effects/AEs:** "* Cytopenias (granulocytopenia) * GI upset (more with oral) * rash * increased LFT * neurotoxicity * Bone marrow suppression --> cytopenia (granulocytopenia)" **Extra Notes:** **Resistance:** * Resistance due to mutation in UL97 (encodes DNA Pol) | Antivirals - Herpesviridae (CMV)

Answer 18

**MOA:** Prodrug --> ganciclovir **Spectrum:** (CMV) **PK:** PO only (great bioavailability) * Induction period of 2-3 wk to lower VL, then lower MD (less toxicity) **Side Effects/AEs:** "* Cytopenias (granulocytopenia) * GI upset (more with oral) * rash * increased LFT * neurotoxicity * Bone marrow suppression --> cytopenia (granulocytopenia)" **Extra Notes:** **Resistance:** * Resistance due to mutation in UL97 (encodes DNA Pol) | Antivirals - Herpesviridae (CMV)

Answer 19

**MOA:** Inhibits pyrophosphate binding on DNA pol --> inhibits DNA chain elongation (greater affinity for viral DNA Pol > host cell); does NOT require TK/intracellular activation **Spectrum:** CMV **PK:** "* Confusing dose adjustments * Induction period of 2-3 wk to lower VL, then lower MD" **Side Effects/AEs:** "* Nephrotoxic * Myelosuppression (anemia) * Hypocalcemia, -kalemia, -phsophatemia, - magnesemia (hydration/electrolytes) " **Extra Notes:** **Resistance:** * Resistance due to UL54 mutations | Antivirals - Herpesviridae (CMV)

Answer 20

**MOA:** Nucleotide analong that is converted to cidofovir diP by host enzymes --> incorporated into viral DNA --> inhibition of DNA Pol **Spectrum:** (CMV) **PK:** "* Short half-life --> prolonged when administered with probenecid (reduces renal excretion) * Induction period of 2-3 wk to lower VL, then lower MD" **Side Effects/AEs:** "* Nephrotoxic * Myelosuppression * Ocular hypotony, uveitis, iritis" **Extra Notes:** **Resistance:** | Antivirals - Herpesviridae (CMV)

Answer 21

**MOA:** Inhibits CMV terminase complex --> No functional CMV DNA **Spectrum:** (CMV ppx) **PK:** "* Used in HSCT * IV/PO daily 100 days" **Side Effects/AEs:** "* GI upset * Headache * Peripheral edema * DDIs" **Extra Notes:** * Active against UL97 mutations **Resistance:** | Antivirals - Herpesviridae (CMV)

Answer 22

**MOA:** Inhibits mycolic acid/cell wall synthesis (active against actively replicating organisms in all tissues) **Spectrum:** "Oral TB & LTBI (alone or w RIF)" **PK:** * Hepatic (few DDIs) **Side Effects/AEs:** "* Heptatitis (age, alcohol) * Peripheral neuropathy (Vit B6 helps) * Rash * Lupus-like * CNS effects (alt mental status, seizures)" **Extra Notes:** KatG, inh **Resistance:** | TB drugs

Answer 23

**MOA:** Inhibits protein synthesis (bactericidal for actively replicating, active at all sites) **Spectrum:** "Oral & IV TB & LTBI (alone or w INH)" **PK:** * Hepatic **Side Effects/AEs:** "* Orange staining (urine, tears, etc.) * Rash, itchy * Flu-like syndrome * Hepatitis (less common than in INH & PZA) * Thrombocytopenia * CYP450 inducer --> dec conc of drugs" **Extra Notes:** **Resistance:** | TB drugs

Answer 24

**MOA:** Not understood (shortens tx course) **Spectrum:** Oral **PK:** * Hepatic/renal **Side Effects/AEs:** "* Hepatitis (increased risk w INH/RIF) * Uric acid/gout * GI symptoms * Photosensitivity" **Extra Notes:** pnc, BCG resistant **Resistance:** | TB drugs

Answer 25

**MOA:** Inhibits cell wall synthesis (bacteriostatic) **Spectrum:** Oral (poor CNS penetration) **PK:** * Renal **Side Effects/AEs:** "* Retrobulbar/optic neuritis (dose dep) * Rare rash * rare peripheral neuropathy" **Extra Notes:** embB gene cluster **Resistance:** | TB drugs

Antimicrobials Flashcards

(50 cards)