Dr. Hall Flashcards
MoA of Echinocandins
- Inhibits beta glucan synthesis
- Fungicidal
- IV formulations only
- Penicillin of antifungals
MoA of Ployenes
- Binds to ergosterol to weaken the cell membrane
- Leading to a leaky membrane, then cell lyses
MoA of Azoles
- Inhibits the synthesis of ergosterol
- Inhibits 14 alpha demethylase
MoA of 5-flucytosine (5FC)
- Prodrug converted to 5FU
- Inhibits DNA synthesis
- FdUMP inhibits DNA synthesis
- FUTP inhibits RNA/ protein synthesis
Cancidas
- Caspofungin
- Echinocandin
Mycamine
- Micafungin
- Echinocandin
Eraxis
- Anidulafungin
- Echinocandin
Mechanism of resistance to echinocandins
- Mustations in FKS1 or FKS2
- Decreased sensitivity to echinocandins
- Biofilms
- Increased chitin synthase
- Upregulation of multidrug transporters
Nystop
- Nystatin
- Polyene
Mechanism of resistance to Polyenes
- Defective ERG2 or ERG3 genes
- Reduced ergosterol content
- Alterations in sterol to phospholipid ratio
- Reorientation/masking of ergosterol
Monistat
- Miconazole
- Topical Imidazole
Lotrimin AF
- Clotrimazole
- Topical Imidazole
Lotrisone
- Clotrimazole plus betamethasone
- Topical Imidazole
Jublia
- Efinaconazole
- Topical Triazole
Diflucan
- Fluconazole
- PO/IV Triazole
- Has the widest therapeutic index of the azoles
Sporonox
- Itraconazole
- DO NOT USE IN CHF pts
- PO/IV Triazole
Vfend
- Voriconazole
- PO/IV Triazole
- Can lead to visual disturbances
Noxafil
- Posaconazole
- PO/IV Triazole
- Take with food
- Avoid with statins (prolonged QT interval)
Cresemba
- Isavuconazonium
- PO/IV Triazole
- Prodrug of isavuconazole
Nizoral
- Ketoconazole
- Topical Imidazole
Mechanisms of resistance to Azoles
- Point mutation in ERG11 gene
- Over expression of ERG11
- Alteration in ERG3
- Increased efflux pumps
- Changes in composition of fungal cell membrane (decreased permeability)
Lamisil AT and Lotrimin Ultra MoA
- Terbinafine and Butenafine
- Non azole inhibitors of ergosterol synthesis
- Inhibit squalene epoxidase
- Fungicidal
Ancobon
- 5FC
- Bone marrow toxicity due to accumulation of 5FU
Mechanism of resistance to 5FC
- Loss of permease or deaminase activity
- Then prodrug is never activated
- Use in synergy with AmB to help decrease resistance rates
Characteristics of TB
- Slow growing
- Rod shapped
- aerobic bacteria
LTBI signs and symptoms
- No symptoms or physical findings of TB
- Smear and culture negative
Active TB signs and symptoms
- Fever, cough, weight loss, fatigue
- Positive culture OR smear
Initiation phase
- Bactericidal/ intensive phase
- 4 drug therapy
- 2 month duration
Continuation phase
- Sterilizing phase
- 2 drug therapy
- 4 to 7 month duration
MoA of Isoniazid (INH, H)
- Inhibits synthesis of mycolic acids
- Prodrug
- Activated by KatG
- Bactericidal
Mechanism of resistance to INH
-Mutations in KatG or inhA
INH toxicities
- More common in slow acetylators
- Peripheral neuropathy
- Hepititis
- Rashes
How to decrease the likely hood of neuropathy caused by INH
- Supplement with pyridoxine (B6)
- Helps to increase GABA levels
MoA of Ethambutol (Myambutol)
- Inhibits cell wall synthesis by inhibiting arabinosyl transferase
- Bacteriostatic
- Helps increase the activity of RIF
Most common side effects with Ethambutol (Myambutol)
- Optic neuritis
- leads to diminished visual acuity and loss of red/green discrimination
- Do eye exam BEFORE starting this drug
- Increased risk of gout too
MoA of Pyrazinamide
- Prodrug, activated by pcnA
- Can lead to liver injury
MoA of Rifampin (Rifadin)
- Inhibits mRNA and protein synthesis
- Bactericidal
TB retreatment cases
- Higher likely hood of resistance
- 5 to 6 drug treatment in initiation phase
- 3 drugs in continuation phase
Situro (Bedaquiline)
- 1st new TB drug in the last 40 years
- Approved for MDR/XDR TB
- Inhibits proton pump for ATP synthase
- T1/2 is 5.5 months!
Delaminid
- Experimental TB drug
- Approved for MDR TB in EU
- Blocks mycolic acid synthesis
- Prolongs QT interval
Treatment of MAC
1) Macrolide (Azithromycin or Clarithromycin)
2) Ethambutol
3) +/- Rifampin or Rifabutin
