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anti-microbials > Anti-Fungal & Anti-Protozoal Agents > Flashcards

Anti-Fungal & Anti-Protozoal Agents Flashcards

1
Q

Classes of anti-fungals & anti-protozoals & examples

A
  1. Polyenes (Amphotericin B, Nystatin)
  2. Imidazoles (Clotrimazole, Miconazole, Ketoconazole)
  3. Triazoles (Itraconazole, Fluconazole, Voriconazole)
  4. Echinocandins (Caspofungin)
  5. Pyrimidine Analogues (Flucytosine)
  6. Topical - Terbinafine
  7. Metronidazole
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2
Q

Mechanism of action of polyenes

A
  1. Strong affinity for ergosterol - binds & disrupts fungal cell membrane
  2. Allows for leakage of intracellular ions & macromolecules - fungal cell death
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3
Q

Spectrum of activity & uses of polyenes (3+1)

A

Broadest antifungal spectrum including candida, histoplasma, aspergillus

Amphotericin B (oral, IV, topical - eyedrops, intra-articular)

  1. Invasive aspergillosis
  2. Histoplasmosis
  3. Systemic candidiasis

Nystatin (pessary)
1. Vaginal candidiasis

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4
Q

Toxicity of polyenes + Contraindications (4+1)

A
  1. Infusion reaction (shake & bake syndrome - chills & fever)
  2. Thrombophlebitis
  3. Nephrotoxicity
  4. Bone marrow suppression
  5. Nephrotoxic agents eg aminoglycosides, vancomycin, NSAIDs, cyclosporine - increases nephrotoxic potential
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5
Q

Mechanism of action of imidazoles

A

Topical

  • Clotrimazole - cream, lotion, powder, pessary
  • Miconazole - cream, powder, oral gel

Inhibits ergosterol synthesis by inhibiting α-demethylase - affects cell membrane synthesis

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6
Q

Spectrum of activity & uses of imidazoles (2)

A

Epidermophyton, microsporum, trichophyton, candida

  1. Clotrimazole - skin & vulvovaginal infections
  2. Miconazole - tineal infections & vulvovaginal candidiasis, oral gel fo thrush (alt to nystatin)
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7
Q

Mechanism of action of triazoles

A

Inhibits ergosterol synthesis by inhibiting lanosterol 14α-demethylase

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8
Q

PK of triazoles

A
  • Itraconazole - oral only, best absorbed with food
  • Fluconazole, voriconazole - oral, IV
  • CSF penetration: itraconazole - poor entry, fluconazole & voriconazole - good entry
  • Itraconazole & voriconazole extensively metab by liver, fluconazole not
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9
Q

Spectrum of activity & uses of triazoles (5)

A

I: Trichophyton, Histoplasma
F: Cryptococcus, Candida
V: Candida, Aspergillus

  1. Trichophyton infection (I)
  2. Histoplasmosis (I)
  3. Cryptococcosis (F)
  4. Candidiasis (AIDS, vaginal) (F), Candidemia (V)
  5. Invasive aspergillosis (alt to amphotericin) (V)
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10
Q

Toxicity of triazoles (8)

A
  1. GIT disturbance
  2. Mild rash
  3. SJ syndrome
  4. Headache (I)
  5. Cardiac suppression (I)
  6. Hepatotoxicity (I), Hepatitis (V)
  7. Visual disturbances (V)
  8. Infusion associated w chest tightness, dyspnea, faintness, flushing (V) - infuse slowly, dilute
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11
Q

Drug interactions of triazoles

A
  1. Hepatic CYP450 enzyme inhibitor - can cause toxicity in warfarin, digoxin, absorbtion decreased by PPI, antacids, H2 blockers (I, F, V)
  2. Substrate of CYP450 (V) - should avoid potent CYP450 inducers eg carbamazepine & inhibitors eg erythromycin
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12
Q

Mechanism of action & PK of caspofungin

A

IV only

Inhibits synthesis of 1,3-β-glucan - disrupts fungal cell wall

  • Limited CSF penetration (HMW, water solubility, high protein binding)
  • Gradual metab over time - excreted in bile & urine
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13
Q

Spectrum of activity & uses of caspofungin (2)

A

Narrow spectrum, only candida & aspergillus

  1. Mucocutaneous candidiasis & candidemia (immunocompromised)
  2. Salvage therapy in invasive aspergillosis (failed response to amphotericin B)
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14
Q

Toxicity of caspofungin & Drug interactions (5+2)

A
  1. Fever
  2. GIT related
  3. Histamine-like facial flushing
  4. Rash, pruritus
  5. Thrombophlebitis
  6. CYP450 inducers eg rifampicin - reduce plasma levels of caspofungin, req higher dose
  7. Avoid use with cyclosporine - increased risk of hepatotoxicity
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15
Q

Mechanism of action of flucytosine

A
  1. Converted to 5-fluorouracil by cytosine deaminase found in fungal cells
    (A) Converted to 5-fluoro dUMP - inhibits thymidylate synthase - inhibits DNA synthesis
    (B) Converted to 5-fluoro dUTP - inhibits RNA processing & translation
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16
Q

Spectrum of activity & uses of flucytosine (2)

A

Narrow spectrum, candida & cryptococcus

  1. Systemic candidiasis
  2. Cryptococcal meningitis
    - combined w amphotericin B
17
Q

Toxicity of flucytosine & Drug interactions (2+2)

A
  1. Bone marrow suppression
  2. Hepatotoxicity
  3. Inhibitory effect on CYP450 enzymes
  4. With quinidine - dysrhythmia
18
Q

Mechanism of action of terbinafine

A

Topical, oral (uncommon)

Inhibits squalene epoxidase - affects ergosterol synthesis + squalene accumulates in cell - fungicidal

19
Q

Uses & toxicity of terbinafine (1+2)

A
  1. Dermatophytic infection of skin & nails
  2. Erythema
  3. Dry skin
20
Q

Mechanism of action of metronidazole

A

Enzyme nitroreductase reduces nitro group in metronidazole to cytotoxic metabolites - bind to DNA - strand breakage & loss of helical structure - inhibits nucleic acid synthesis

21
Q

Spectrum of activity & uses of metronidazole (3+6)

A
  1. Protozoa - Entameba histolytica, Trichomonas vaginalis, Giardia lamblia
  2. Anaerobes - C. diff, Bacteroides fragilis
  3. H. pylori
  4. Amoebiasis
  5. Treatment & prophylaxis of anaerobic infections
  6. 1st line for CDAD
  7. Vaginitis (Trichomonas)
  8. Giardiasis
  9. Triple therapy for H. pylori infection
22
Q

Toxicity of metronidazole + Contraindications (4+1)

A
  1. Bitter metallic taste, dry mouth, nausea, headache
  2. GIT
  3. CNS
  4. Ataxia, convulsions, peripheral neuropathy
  5. Pregnancy

anti-microbials (6 decks)

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