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Chapter 12 List of Antifungal Antimicrobials

 


I. Antifungal Drugs

 

A. Topical antifungal drugs

1. Nystatin (MycostatinR)

2. Cuprimyxin

3. Tolnaftate (Tinactin)

4. Candicidin

5. Haloprogin (component of HalotexR)

6. Iodochlorohydroxyquin (VioformR)

7. Clotrimazole (LotriminR, MycelexR)

 

8. Organic acids

a. Undecylenic acid

b. Proprionic acid and caprylic acid

c. Benzoic acid

d. Salicylic acid

B. Enteric antifungal drugs

1. Nystatin (MycostatinR)

C. Systemic antifungal drugs

1. Griseofulvin

2. Amphotericin B (FungizoneR)

3. Ketoconazole (NizoralR)

4. Miconazole

 

 

A. Topical antifungal drugs

1. For superficial fungal infections

a. Dermatophytes of skin, hair, and nails generally Trichophyton and Microsporum spp.

b. Dermatophytes of mucus membranes of the G.I. tract such as Candida spp. (Note: genus Candida use to be called Monilia.)

2. Adjunct drugs in combination with antifungal agents

a. Keratolytic drugs

b. Astringents

3. Cuprimixin (UnitopR)

a. Description

 

1) Dark green crystalline material

2) After application, myxin released from copper complex

and color changes to pink

 

b. Mechanism of action

1) Inhibits bacterial DNA and RNA synthesis

c. Spectrum of activity

1) Broad spectrum antibacterial activity against gram-

positive and gram-negative bacteria

2) Antifungal activity against Candida, Microsporum, and Trichophyton

 

3) Inhibits growth of a yeast Pityrosporum canis in ears

d. Can stain clothing and household furnishings

4. Tolnaftate (Tinactin)

a. Active against Epidermophyton, Microsporum, Trichophyton

 

b. Not active against Candida or against bacteria

c. Used in 1% concentration

 

5. Candicidin

 

a. Fungistatic and fungicidal antibiotic

b. Especially active against Candida albicans, more effective than amphotericin-B

c. Effective against superficial dermatomycoses (ringworm)

6. Haloprogin (component of HalotexR)

a. Synthetic antifungal

 

b. Used as 1% cream

c. Effective against Microsporum canis, Trichophyton spp, and Candida

7. Iodochlorohydroxyquin (VioformR)

a. Antifungal, antibacterial, and antiyeast activity

b. 3% cream, ointment, or powder

c. Avoid contact with eyes

7. Clotrimazole (LotriminR, MycelexR)

a. Chemically related to miconazole

b. Broad spectrum antifungal activity effective against Epidermophyton, Microsporum, Trichophyton, and Candida albicans

c. 1% cream or solution

d. Adverse effects include erythema, blistering, edema, pruritus, urticaria

9. Nystatin (MycostatinR)

a. Description

 

1) Antifungal antibiotic from Streptomyces nouresi

2) Pale yellow and insoluble in water

b. Mechanism of action

1) Disturbs permeability of the fungal membrane

2) Intracellular cations are lost

c. Spectrum of activity and resistance

1) Especially effective against Candida spp

2) Also effective against Aspergillus, Rhizopus, and Mucor fungal infections of poultry

d. Pharmacokinetics

1) Oral administration

a) Poorly absorbed from GI tract

b) Antifungal action limited to GI tract

2) Not given parentally - too toxic

e. Toxicity

1) Too toxic for system use

2) Little absorbed from GI tract hence little toxicity

f. Clinical use

1) Used primarily for Candida infections of skin, mucous

membranes, and GI tract

2) Available for oral and topical use

10. Organic acids

a. Used for treating superficial mycoses

b. Mechanism of action is unknown

c. Undecylenic acid

 

1) Yellow liquid with sharp odor

 

2) Available as 10% alcoholic solution or powder

3) Potent fungistatic against superficial fungal infections

4) Often combined with zinc undecylenate and salicylanilide

d. Propionic acid and caprylic acid

 

1) Propionic acid at concentrations above 3ug/mL in feed is fungicidal against Aspergillus parasiticus

e. Benzoic acid

1) In Whitfield's ointment (6% benzoate + 3% salicylate)

f. Salicylic acid

 

1) Slight fungistatic activity

2) Good keratolytic activity in presence of water

B. Systemic antifungal drugs

1) Most are antibiotics (though they may or may not be antibacterial

agents)

a. Note: the antibacterials neomycin and the tetracyclines

enhance Candida growth in keratitis

2) Clinical uses

a. For systemic fungal infections

b. For gastrointestinal fungal infections

c. For systemic treatment of fungal infections of the skin

3) Griseofulvin

a. Description

1) Colorless and slightly bitter fungistatic antibiotic

2) Metabolic product of Penicillium griseofulvin

b. Mechanism of action

1) Probably interferes with nucleic acid biosynthesis

c. Spectrum of activity and Resistance

1) Effective against various species of Trichophyton,

Microsporum, and Epidermophyton

2) Not effective against Candida and bacteria

d. Pharmacokinetics

1) Oral administration

 

a) Absorbed from GI tract

b) High dietary fat intake increases absorption

 

c) Deposited in new epithelial cells of skin, hair, claws, and nails

d) Concentration of griseofulvin in new cells is

fungistatic and prevents invasion of new tissue

e) Half life in canine plasma is 47 min.

f) Demethylated and conjugated with glucuronide

2) Topical application in DMSO

a) DMSO (dimethyl sulfoxide) allows drug to penetrate keratin layer

e. Toxicity

 

1) Definitely teratogenic in cats - avoid use in pregnant cats

2) May also interfere with spermatogenesis

3) Low toxicity otherwise

f. Clinical use

1) For dermatophyte infections in small animals

a) Treat for at least one week after disappearance of clinical signs

b) For fungal infections of skin and hair, treat for 3 - 4 weeks

c) For fungal infections of nails or claws, treat for about 4 months

2) For ringworm in calves

3) Has been used in horses and cattle for dermatomycoses

4. Amphotericin B (FungizoneR)

a. Description

1) Antibiotic antifungal isolated from Streptomyces nodosus

2) Has no antibacterial action

3) Yellow powder with low solubility

b. Mechanism of action

1) Combines with ergosterol in cell membrane of susceptible fungi creating pores which allow molecules to leak out.

2) Combines with cholesterol of mammalian membranes less readily than with ergosterol but enough to cause toxicity problems

3) Bacterial membranes do NOT have sterols

c. Spectrum of activity and resistance

1) Broad spectrum of antifungal activity

2) Effective against histoplasmosis, blastomycosis, coccidioidomycosis, cryptococcossis, candidiasis, mucormycosis, phycomycosis, aspergillosis, and sporotrichosis

3) NOT effective against bacteria

d. Pharmacokinetics

1) Oral absorption is poor thus use orally only for fungal infections of GI tract

2) Sodium deoxycholate added to make colloidal suspension

3) Colloidal suspension available for intravenous injection

4) Blood concentrations persist for 18-24 hours

5) Slow excretion in urine

e. Toxicity

1) Nephrotoxicity

a) Do not exceed dose of 2 mg/kg

b) Monitor blood urea nitrogen (BUN) and stop treatment if it increases to 2 times normal

2) Other adverse effects include nausea, emesis, fever, phlebitis, and hemolytic anemia

f. Clinical use

1) Use for treating systemic mycoses due to sensitive fungi

2) Use various treatment regimens to avoid toxicity e.g. treat for 7 days, stop treatment for 7 days, then treat again for 7 days

3) Use topically for treating Candidiasis

5. Ketoconazole (NizoralR)

a. Description

1) Synthetic imidazole compound

b. Mechanism of action

1) Interferes with synthesis of ergosterol increasing permeability in fungal membrane

2) Increased permeability allows drug to penetrate into cell where it inhibits precursors of nucleic acid synthesis

c. Spectrum of activity and resistance

1) Effective against fungi causing candidiasis, coccidioidomycoses, blastomycoses, and spirotrichosis

2) Not effective against aspergillus or phycomycetes

d. Pharmacokinetics

1) Well absorbed from GI tract

2) Give with food because gastric acid is necessary to dissolve tablets

3) Well distributed throughout body but does not cross BBB

4) Extensively metabolized by o-dealkylation and aromatic hydroxylation

5) Primary biliary excretion

e. Toxicity

1) Reversibly inhibits synthesis of corticosteroids in adrenal gland which causes abnormal ACTH challenge test

6. Miconazole

a. Spectrum limited to fungi causing coccidioidomycoses, candidiasis, and cryptococcosis

b. Given IV for systemic fungal infections

c. Is largely being replaced by ketoconazole, which can be given orally and is less toxic

 

TOPICAL ANTIFUNGAL DRUGS

 

 

Antifungal Drugs Susceptible Organisms

Candicidin Candida, Dermatophytes

Clotrimazole Dermatophytes, Candida, Aspergillus

Cuprimyxin Pityrosporum canis*, Candida, and Dermatophytes

Haloprogin Dermatophytes, Candida

Iodochlorohydroxyquin Dermatophytes

Nystatin Candida, Dermatophytes, Aspergillus (variable)

Tolnaftate Dermatophytes

Undecylenic acid Dermatophytes

 

 

 

ENTERIC ANTIFUNGAL DRUGS

Nystatin Candida infections of GI tract

 

 

 

SYSTEMIC ANTIFUNGAL DRUGS

Amphotericin B Blastomyces, Histoplasma, Cryptococcus, Candida, Coccidioides, etc. (IV or topical)

Griseofulvin Dermatophytes, Sporothrix schenckii (PO)

Miconazole Coccidioides, Candida, Histoplasma, Cryptococcus, Aspergillus, Blastomyces (IV)

Ketoconazole Candida, Coccidioides, Histoplasma, Blastomyces, Crytococcus, Sporothrix, Aspergillus, Dermatophytes (PO)