Pharm 4 Exam 2 & 3 Flashcards
Components of fungi cell walls
- Chitin
- Egesterol
- Beta Glucans
- Structural Proteins
Ergosterol Pathway
The CP450 enzyme 14a-sterol demethlase converts lanosterol into ergoesterol
Subcutaneous and systemic Mycoses
- Azoles
- Echinocandins
- Polyenes
- Prymadine Antifungals
MOA for Azoles
Inhibition of CELL MEMBRANE BY Inhibiting ergoesterol synthesis by direct inhibition of 14a demythlase.
Side effects of Azoles
- Mild GI
- Hepatotoxicity (rarely)
Contraindications of Azoles
None
MOA of Echinocandins
Inhibition of fungal CELL WALL synthesis, which weakens the wall. By inhibition of beta 1-3 glucan synthase.
Contraindications of Echinocandins
None
Side Effects of Echinocandins
- Mild GI N/V
- Infusion reactions
MOA of Polyenes
Polyenes bind to ergosterol creating pores within the CELL MEMBRANE, causing an escape of H+ and K+ leading to cell death.
Contraindications of Polyenes
Renal dysfunction
Side Effects of Polyenes
- Nephrotoxicity
- Infusion reactions
- Electrolyte imbalances
Define the depletion theory of the interaction between Azoles an Polyenes.
Preexposure to Azoles depletes the fungal cells of ergosterol, leading to fewer targets for polyene, resulting in antagonism
Define the enhancement theory of the interaction between Azoles an Polyenes.
Preexposure to Polyene leads to the formation of pores that facilitate greater access for azoles to the intercellular space leading to an additive effect
Pyrimidine Antifungals MOA
It is taken up by cytosine permeases which are specific to fungal cells. It is converted to 5FU then 5FdUMP which inhibits Thymine synthase leading to termination of DNA synthesis and cell division.
Pyrimidine Contraindications
- Pregnancy
Side Effects of Pyrimidine Antifungals
- GI abd pain N/V
- Risk of infection
Agents used for cutaneous mycoses
- Griseofulvin
- Terbinafine
Griseofulvin MOA
- Deposited in keratin precursor cells in the skin
- It is then taken up by fungal cells and inhibits microtubule polymerization
- Inhibits mitosis
- New skin and hair is then resistant to infection
Griseofulvin contraindications
Pregnancy
Griseofulvin side effects
- CNS; headache, peripheral neuropathy
- Dermatologic; skin rashes
Terbinafine MOA
Inhibits the conversion of Squalene to Lanosterol via inhibition of squalene monoxidase. (Lanosterol is then converted to Ergosterol)
Terbinafine contraindications
Pregnancy
Terbinafine side effects
- Steven-Johnson syndrome
- Toxic epidermal necrolysis
- Liver failure
- Neutropenia and lymphopenia
Quinolones MOA
- Act to inhibit the stage in which merozoites are released from the liver back into the blood within the erythrocyte
Quinolones Side effects
- GI, Headache, Pruritus
- Retinopathy, Ototoxicity, Arrhythmia
Metronidazole MOA
Is a prodrug which is activated by ferredoxin. Reduction results ini toxic products and free radicals which damage DNA. Effective on anaerobic bacteria.
Metronidazole contraindications
- Ethanol (acetyldehyde)
- Pregnancy
Metronidazole side effects
- GI nausea
- Metalic Taste
- CNS toxicitiy (encephalopathy or seizure)
- Neutropenia
- Pancreatitis
- Peripheral neuropathy
- Hepatitis
Antiprotozoals (Diamidines) MOA
- Penertates through parasite specific pores
- Bind to ferriprotoporphyrin
- Inhibit DNA replication
- Inhibits topoisomerase II
Antiprotozoals (Diamidines) contraindications
Highly toxic but infections are life threatening
Anitprotozoals (diamidines)Side effects
- Hypotension
- Glucose abnormalities
- Renal dysfunction
- Hepatic dysfunction
