Anti fungal drugs targeting membrane disruption

Question 1

what is a polyene macrolide antibiotic that targets ergosterol binding thus disrupting fungi membranes

Answer 1

Amphotericin B (fungizone)

Question 2

how is amphotericin B made and describe its solubility and is it subject to photooxidation?

Answer 2

Amphotericin B is made by Streptomyces nodosus

POOR solubility and IS subject to photooxidation

Question 3

Amphotericin B MoA?

CIdal or static?

Answer 3

Amphotericin B is fungiCIDAL!
affects membrane ergosterols causing pores to form and alteration of membrane fluidity also causes loss of selective membrane permeability and inhibition of AA uptake

Question 4

what is the selectivity for Amphotericin B due to?

Ampho B is not active against bacteria, what is the one exception and why?

Answer 4

Amphotericin B selectivity is due to the 100x fold lower binding affinity for human cholesterol
Ampho B is active against mycoplasma bc mycoplasma has sterols in there membranes

Question 5

what is Amphotericin B used to treat?

aka what types of fungi (6)

Answer 5

systemic fungal infections

aspergillus, cryptococcus, Candidiasis, histoplasmosis, blastomycosis, coccidiomycosis

Question 6

what can Ampho B be used with to treat cryptococcal meningitis?

Answer 6

flucytosine (5-FC)

Question 7

Amphotericin B
solubility? Route of admin and why?
CNS affect?
what happens to it in the body concerning the release of the drug?

Answer 7

Ampho B is poor orally so given IV over several hours to avoid arrhythmias
also given topically
poor distribution in CNS
rapidly sequestered in tissues and slowly released giving it a long half life

Question 8

describe the metabolism of Amphotericin B and the excretion

Answer 8

Ampho B is NOT metabolized, 90% is bound to proteins

slow renal excretion, majority is extra renal

Question 9

Describe the toxicity of Amphotericin B

What is Ampho B toxicity called?

Answer 9

Ampho B is DOSE related reversible!!
causes nephrotoxicity (renal impairment)
hypokalemia, hypomagnesemia, tubular acidosis
fevers, chills (shake and bake),
Headaches, NVD, reversible anemia
Thrombophlebitis
Hypersensitivity rxns- anaphylaxis, pain, seizures,

Question 10

The nephrotoxicity of Ampho B is a high concern. What is the action of Amphotericin called?
What can it cause concerning the kidneys?
What should one monitor and then use if renal flow if impaired?

Answer 10

Amphotericin B is DOSE RELATED REVERSIBLE, total dose irreversible
Follow BUNM, creatinine levels, interrupt tx if renal impairment Infuse w mannitol to maintain urine flow.
can cause renal tube degeneration, glomerular damage- hyalinization

Question 11

What is a classic toxicity symptom of Amphotericin B? How do you treat this side effect?

Answer 11

SHAKE AND BAKE (fever and chills)

Tx w antipyretics like aspirin, acetaminophen, and hydrocortisone)

Question 12

Ampho B causes vein necrosis what is this called? How do you minimize this?

Answer 12

Thrombophlebitis

Infuse slowly with heparin, and/or hydrocortisone

Question 13

Describe 3 drug interactions of Amphotericin B

1. Rifampin + ampho B
2. 5-FC + ampho B
3. Ampho B + triazoles

Answer 13

1. Rifampin +Ampho B= Ampho B INC the toxicity of rifampin to fungi allowing rifampin to enter
2. use Ampho B + 5-FC to treat cyrptococcal meningitis
3. Amph B + triazoles= SYNGERISM/. Additivity

Question 14

Describe the drug resistance of Amphotericin B

Answer 14

Ampho B resistance is rare, but due to altered sterol content or change in sterol composition so less binding of Ampho B

Question 15

Describe the 3 Drug Delivery systems of Amphotericin B:

1. Fungizone
2. ABLC and Liposomal Ampho B
3. Sterol Complex + Ampho B

Answer 15

1. Fungizone- Ampho B bile salt for better dissolution
2. ABLC and Liposomal Ampho B:allow for INC concentrations in SPECIFIC organs, DEC toxicity and dec time required for TX
3. Sterol Complex + Ampho B: DEC vein necrosis at site of injection

Question 16

what is Ampho B given with to DEC thrombophlebitis? (DEC vein necrosis)

Answer 16

DEC vein necrosis at site of injection by giving Ampho B with sterol complex

Question 17

Basic summary of Amphotericin B

Answer 17

WIDE Spectrum of activity

BUT Amphotericin B has very undesirable pharmacokinetics compared to 5FC

Question 18

What is a polyene antibiotic from Streptomyces noursei that is similar in structure and function to Amphotericin B

Answer 18

NyStatin

Question 19

What is Nystatin used for? what fungi?

Answer 19

topical tx for candiasis: thrush, esophaginitis, vaginitis

Question 20

Nystatin
absorption:
Distribution:
Metabolism/ excretion:
Toxicity:

Answer 20

Nystatin
Absorption: poor oral, rapid breakdown, restricted to GI distribution
No metabolism, little kidney excretion
Minimal toxicity