Amphotericin B

• Class
• MoA
• Static or Cidal?
• Covers
• Doesn't Cover
• AE's

• Class: Antifungal, polyenes (IV)
• MoA: Bind ergosterol in fungal cell membrane. Pores increase cation permeability causing cell death 
• CIDAL
• Covers: most yeast, molds (including Aspergillus & zygomycetes), dimorphic fungi
• Doesn't cover Scedosporium
• SE: nephrotoxicity, infusion reactions (fever, chills, rigors, tachypnea (not allergy)), hypokalemia, phlebitis, N&V, anorexia

Ketoconazole

• Class
• MoA
• Static or Cidal?
• Covers
• Doesn't Cover
• AE's

Fluconazole

• Class
• MoA
• Static or Cidal?
• Covers
• Doesn't Cover
• AE's

• Class: Antifungal, azoles, triazoles (IV, PO)
• MoA: inhibit 14-alpha demethylase -> depletion of ergosterol in the cell membrane + accumulation of toxic intermediate sterols -> membrane permeability. 
• STATIC
• Covers:  susceptible Candida spp. (all C. albicans), Cryptococcus, Coccidioides
• First line yeast infections, good CSF penetration
• Doesn't Cover: resistant Candida spp. (C. glabrata, C. krusei), molds  (Aspergillus, Zygomycetes)
• AE's: well-tolerated. rare alopecia (3%)

Itraconazole

• Class
• MoA
• Static or Cidal?
• Covers
• Doesn't Cover
• AEs

• Class: Antifungal, azoles, triazoles (PO)
• MoA:inhibit 14-alpha demethylase -> depletion of ergosterol in the cell membrane + accumulation of toxic intermediate sterols -> membrane permeability. 
• STATIC
• Covers: fluc spectrum + Aspergillus + dimorphics + dermatophytes
• Used for onychomycosis
• Doesn't Cover: some resistant Candida, Zygomycetes
• AEs:aldosterone-like activity. peripheral edema

Voriconazole

Posaconazole

• Class: Antifungals, Azoles, Triazoles (PO)
• MoA: inhibit 14-alpha demethylase -> depletion of ergosterol in the cell membrane + accumulation of toxic intermediate sterols -> membrane permeability. 
• CIDAL (molds), STATIC (yeasts)
• Covers:  itra spectrum + fluc-R Candida, better mold (Aspergillus), zygomycetes
• Doesn't Cover: every azole-R Candida
• AEs: nephrotoxic?

Terbinafine

• Class: Antifungal, allylamines (PO, topical)
• MoA:  inhibit squalene epoxidase -> ergosterol depletion 
• CIDAL
• Covers:  superficial infections (dermatophytes, Candida, Malassezia) 
• First line for dermatophytic infections, including onychomycosis
• Doesn't Cover:  everything else
• AEs: dysgeusia (abnormal taste), headache, nausea

Echinocandins

• Class: Antifungals, echinocandins (IV)
• MoA:  inhibit 1,3-beta-glucan synthase -> depletion of glucan polymers in cell wall ->  weak cell wall unable to withstand osmotic stress -> cell death
• Covers: Candida spp. (CIDAL), Aspergillus (STATIC)
• For invasive Candidiasis with fluc-R yeast, sometimes aspergillosis
• Doesn't Cover: Cryptococcus, Zygomycetes
• AEs: Well-tolerated

Flucytosine (5-FC)

• Class: Antifungal, antimetabolite (IV, PO) 
• MoA:  converted to 5-fluorouracil (incorporates into RNA to block protein synthesis), metabolized to 5-dUMP to interfere with DNA synthesis  
• (STATIC)
• Covers: most Candida, Cryptococcus, some molds
• Cryptococcus meningitis (with ampho B or fluc)
• AEs: GI - mucositis, diarrhea, nausea. Marrow suppression (leukopenia, thrombocytopenia)

Griseofulvin

• Class: Antifungal, mitotic spindle inhibitor (PO)
• MoA:  inhibition of mitotic spindle formation 
• STATIC
• Covers: dermatophytes
• Used for onychomycosis and tinea capitis. Primarily pediatric (itra- and terbinafine N/A)
• Doesn't Cover: everything else
• AEs: may precipitate SLE, porphyria, nausea, headache, rash, diarrhea

Azoles

• MoA
• AEs

1st generation cephalosporin

- Coverage

- Classification

- Drug names

- MoA

[image]

- Classification: Antibacterial, Beta-lactam

- Names: Cefazolin, cephalexin (po)

- MoA: Inhibits cross-linking of PG, activates autolytic enzymes

2nd generation cephalosporin

- Coverage

- Classification

- Drug names

- MoA

[image]

- Classification: Antibacterial, Beta-lactam

- Names: Cefuroxime, cefprozil

- MoA: Inhibits cross-linking of PG, activates autolytic enzymes

3rd generation cephalosporin (IV)

- Coverage

- Classification

- Drug names

- MoA

[image]

- Classification: Antibacterial, Beta-lactam

- Names: Cefotaxime, ceftazidime, ceftriaxone, cefixime (po)

- MoA: Inhibits cross-linking of PG, activates autolytic enzymes. Also, crosses the BBB 

4th generation cephalosporin

- Coverage

- Classification

- Drug names

- MoA

- Coverage: Good gram positive, the most gram negatives

- Classification: Antibacterial, Beta-lactam

- Names: Cefepime

- MoA: Inhibits cross-linking of PG, activates autolytic enzymes

Monobactams

- Coverage

- Classification

- Names

- MoA

[image]

- Classification: Antibacterial, beta-lactam

- Names: Aztreonam

- MoA: Inhibits cross-linking of PG, activates autolytic enzymes

Carbapenems

- Coverage

- Classification

- Names

- MoA

[image]

- Classification: Antibacterial, beta-lactam

- Names: Imipenem (aka gorillacillin), meropenem. (Note: meropenem used more commonly because it has less side effects)

- MoA: Inhibits cross-linking of PG, activates autolytic enzymes

Vancomycin

- Coverage

- Classification

- MoA

- AEs

[image]

- Classification: Antibacterial

- MoA: Early action of PG cell wall (before cross-linking)

- AEs: Toxicity to hearing and kidneys

Aminoglycosides

- Coverage

- Classification

- Names

- MoA

- Static or Cidal?

- AEs

[image]

(in the gut)

Can combine with penicillin or ampicillin for gram positive coverage.

- Classification: Antibacterial

- Names: Gentamicin, tobramycin

- MoA: Cidal. Enter the cell cytoplasm by passive diffusion and some active transport. Permanently bind to ribosomes, inhibit translation.

- AEs: Ears and kidneys

Macrolides

- Coverage

- Classification

- Names

- MoA

- AEs

[image]

- Classification: Antibacterial

- Names: Erythromycin, azithromycin, clarithromycin

- MoA: Static. Bind to ribosomes, inhibit translation.

- AEs: Abdominal upset

Clindamycin

- Coverage

- Uses

- Classification

- MoA

- AEs

[image]

- Uses: commonly used for dental and gynecological infections

- Classification: Antibacterial

- MoA: Static. Bind to ribosomes, inhibit translation.

- AEs: Antibiotic associated diarrhea and can lead to C. difficile colitis

Chloramphenicol

- Coverage

- Classification

- MoA

- AEs

[image]

- Classification: Antibacterial

- MoA: Static. Bind to ribosomes, inhibit translation.

- AEs: Rare but severe. Aplastic anemia, gray baby syndrome -- rarely used in Canada

Tetracycline & Doxycyline

- Coverage

- Classification

- MoA

- AEs

[image]

- Classification: Antibacterial

- MoA: Static. Bind to ribosomes, inhibit translation.

- AEs: Photosensitivity and stained teeth (do not use in pregnancy or with kids <8 y)

2nd Generation Quinolones

- Coverage

- Uses

- Classification

- Names

- MoA

- AEs

[image]

- Uses: UTIs, bacterial infections, bacterial diarrheal illnesses and Pseudomonas infections

- Classification: Antibacterial

- Name: Ciprofloxacin

- MoA: Inhibit DNA gyrase (supercoiling) and topoisomerase 1 (relaxes supercoils) to disrupt nucleic acid synthesis

- AEs: abdominal upset, photosensitivity, joint pain.

3rd Generation Quinolones

- Coverage

- Uses

- Classification

- Names

- MoA

- AEs

- 1st and 4th generation

[image]

- Uses: Community acquired pneumonias

- Classification: Antibacterial

- Name: Levofloxacin, gatifloxacin, moxifloxacin

- MoA: Inhibit DNA gyrase (supercoiling) and topoisomerase 1 (relaxes supercoils) to disrupt nucleic acid synthesis. (CIDAL)

- AEs: abdominal upset, photosensitivity, joint pain (all quinolones)

- 1st generation rarely used. 4th generation(trovafloxacin) rarely used because of severe liver toxicity.

Metronidazole

- Classification

- Activation

- MoA

- AEs

- Uses

- Classification: Antibacterial, antimetabolite

- Activation: converted to active form by anaerobic bacteria or parasites

- MoA: Incorporated into growing DNA, making it unstable

- AEs: may incorporate into human DNA (risk of cancer), GI, antabuse effect

- Uses: anaerobic infections, C. diff diarrhea, some parasitic infections

TMP/SMX

- Coverage

- Uses

- Classification

- MoA

- Static or Cidal?

- AEs

[image]

- Uses: Bacterial diarrhea, UTIs, parasite infections.

- Classification: Antibacterial, antimetabolite

- MoA: Disrupts DNA synthesis by inhibiting two main enzymes in the synthesis of folic acid from Paba (folate is a precursor for nucleic acids)

- Low dose is static, high dose is cidal 

- AEs: abdominal upset

- Primaquine (exo-erythrocytic)

- Chloroquine (erythrocytic phase)

- Quinine + doxycyclin, or

- Artesunate IV, or

- Malarone (atovaquone proguanil) PO