Pharmacology Ii - Anti-Fungals

Front 1

What is a mycoses?
What are the three main types?

Back 1

A fungal infection
Superficial, Subcutaneous and Systemic

Front 2

What is a superficial mycoses?
What are two examples?

Back 2

A generally contagious infection of the skin, hair and nails by saprophytic molds that unusually digest skin keratin.
Ringworm or "tinea" - infection of the skin by a dermatophyte such as trycophyton, microsporum or epidermophyton
Candidiasis - the yeast candida albicans can infect the mouth or vagina during times of impaired immunity or treatment with antibiotics that alter the balance of normal flora.

Front 3

What is subcutaneous mycoses?
What is an example?

Back 3

Confined infection of the dermis, subcutaneous tissue or adjacent surroundings
Sporotrichosis caused by sporothrix schendckii

Front 4

What is a systemic mycoses?

Back 4

Invasive infection of internal organs after organisms gain entry via the lungs, GIT or IV lines.

Front 5

Name the anti-fungal mechanisms.

Back 5

Inhibition of cell wall synthesis
Disruption of cell membrane stability
Inhibition of mitosis
Inhibition of fungal nucleic acid synthesis
Inhibition of Ergosterol synthesis

Front 6

What is the drug class that inhibits cell wall synthesis?
Name the 3 drugs

Back 6

Echinocandins:
Anidulafungin
Caspofungin
Micofungin

Front 7

What is the mechanism of cell wall synthesis inhibition?

Back 7

Inhibition of the enzyme 1,3 - beta glucan synthase
Glucan polymers leads to defective and weak cell wall

Front 8

Echinocandins are fungicidal against candida species, and fungistatic against aspergillus species. They are well tolerated but exhibit these 5 adverse effects.

Back 8

Hypersensitivity
Abnormal liver function tests
Headaches
Fever
Rarely Hemolysis

Front 9

What drug class disrupts membrane stability?

Back 9

Polyenes

Front 10

Name 6 polyenes

Back 10

Nystatin
Amphotericin B
Natamycin
Rimocidin
Filipin
Pimaricin

Front 11

What is the mechanism of membrane de-stability?

Back 11

Target of the ergosterol synthesis
Ergosterols are used similarly to animal cholesterol as a stiffening agent in the cell membrane.
This causes leakage of essential nutrients, eventually leading to cell death.

Front 12

When is Amphotericin B preferred treatment?

Back 12

The treatment of life threatening fungal infections such as Coccidioides and Histoplasma

Front 13

When is Nystatin preferred treatment?

Back 13

It is not absorbed systemically, and hence is used for topical treamtment of Candida infections of the skin and oral or vaginal mucosa

Front 14

What are the adverse effects of Amphotericin B?

Back 14

Host immune cell stimulation causing release of inflammatory cytokines resulting in fever, chills, rigor, nausea, vomiting, myalgia, arthralgia, and headache during intravenous infusions.
At high doses, it can bind cholesterol and become toxic to organs, specifically nephrotoxic

Front 15

There are 4 enzymes involved in the biosynthesis of ergosterol targeted by anti-fungal drugs. Name the enzymes.

Back 15

squalene epoxidase
Demethylase
Reductase
Isomerase

Front 16

Name the two classes of drug that inhibit Squalene epoxidase.
Name the two drugs under each of these class of drug.

Back 16

Allylamines - Naftifine, Terbinafine

Benzylamines - Butenafine, Tolnaftate

Front 17

What are these drugs effective against?

Back 17

Superficial Dermatophytes

Front 18

Demethylase is the same enzyme used in mammilian cholesterol synthesis. It requires a much higher concentration in mammals to be inhibited however. How does demethylase function What drug class inhibits demethylase?

Back 18

Converts lanosterol to ergosterol

Azole antifungals

Front 19

What situations are these agents useful in?

Back 19

Superficial and Systemic mycoses

They are broad spectrum anti-fungals

Front 20

The two subgroups of Azole anti-fungals include Imidazoles and Triazoles. What is the difference?

Back 20

Triazoles are newer, less toxic and more effective

Front 21

What is Ketoconazole used for?

Back 21

Systemic mycoses: Systemic candidiasis, coccidiomycosis, blastomycosis

Front 22

What are the drawbacks of Ketoconazole?

Back 22

Inhibits human demethylase to the extent that it causes a decrease in serum testosterone and corticosterone

Inhibits cyt p 450s in humans and is involved in many drug drug interactions with drugs such as cyclosporin, phenytoin, and terfenadine.

Front 23

What are Clotrimazole and Butoconazole used in?

Back 23

Clotrimazole - Tinea and candidiasis

Butoconazole - vaginal candidiasis

Front 24

What are Econazole and Miconazole used in? What is notable about Miconazole

Back 24

Econazole - Tinea and Candidiasis

Miconazole - Severe systemic mycosis: coccidiomycosis
It is very broad spectrum

Front 25

What is Amorolfine?
What is it effective in?

Back 25

Mixed acting agent - inhibits both reductase and isomerase

The treatment of dermatophytoses (fungal infection of the skin)

Front 26

What is the fungal DNA synthesis inhibitor?
How does it work?

Back 26

Flucytosine - Inhibits fungal thymidylate synthase which is required for dTMP synthesis

Front 27

What is the fungal Mitosis Inhibitor?
How does it work?

Back 27

Griseofulvin - Binds to polymerized microtubules and inhibits fungal mitosis.

Must be continued until new skin, nails, or hair emerge to completely replace the affected tissue.