Infectious diseases caused by fungi are called
mycoses, and they are often chronic in nature.
Fungal infectious occur due to :
1- Abuse of broad spectrum antibiotics
2- Decrease in the patient immunity
They have rigid cell walls composed
largely of a polymer of N-
acetylglucosamine rather than
peptidoglycan (a characteristic component
of most bacterial cell walls).
The fungal cell membrane contains
ergosterol rather than the cholesterol found
in mammalian membranes.
These chemical characteristics are useful in
targeting chemotherapeutic agents against
Types of fungal infections
1. Superficial : Affect skin – mucous
Dermatophytes : Fungi that affect
keratin layer of skin, hair, nail. e.g. tinea
pedis ,ring worm infection
Candidiasis : Yeast-like, oral thrush,
vulvo-vaginitis , nail infections.
2- Deep infections
Affect internal organs as : lung ,heart ,
brain leading to pneumonia ,
endocarditis , meningitis.
Classification of Antifungal Drugs
1- Antifungal Antibiotics :
Polyene macrolide : Amphotericin- B &
2- Synthetic :
A) Imidazoles : Ketoconazole , Miconazole
B) Triazoles : Fluconazole , Itraconazole
Classification According to Route of
Griseofulvin , Amphotericin- B , Ketoconazole ,
Fluconazole , Terbinafine.
In candidiasis :
Imidazoles : Ketoconazole , Miconazole.
Triazoles : Terconazole.
Polyene macrolides : Nystatin , Amphotericin-B
Gentian violet : Has antifungal & antibacterial.
In Dermatophytes :
Squalene epoxidase inhibitors : Terbinafine &
White field ointment : 11% Benzoic acid &
6% Salicylic acid .
Amphotericin A & B are antifungal
Amphotericin A is not used clinically.
It is a natural polyene macrolide
(polyene = many double bonds )
(macrolide = containing a large lactone ring )
Poorly absorbed orally , is effective for fungal
infection of gastrointestinal tract.
For systemic infections given as slow I.V.I.
Highly bound to plasma protein .
Poorly crossing BBB.
Metabolized in liver
Excreted slowly in urine over a period of
Half-life 16 days.
Mechanism of action
It is a selective fungicidal drug.
Disrupt fungal cell membrane by binding to
ergosterol , so alters the permeability of the
cell membrane leading to leakage of
intracellular ions & macromolecules (cell
Resistance to amphotericin B
If ergosterol binding is impaired either by :
Decreasing the membrane concentration of
Or by modifying the sterol target molecule.
1- Immediate reactions (Infusion –related toxicity).
Fever, muscle spasm, vomiting, headache, hypotension.
Can be avoided by:
A. Slowing the infusion
B. Decreasing the daily dose
C.Premedication with antipyretics, antihistamincs or
D. A test dose.
2- Slower toxicity
Most serious is renal toxicity (nearly in all
Impaired liver functions
Has a broad spectrum of activity & fungicidal action.
The drug of choice for life-threatening mycotic
For induction regimen for serious fungal infection.
Also, for chronic therapy & preventive therapy of
In cancer patients with neutropenia who remain
febrile on broad –spectrum antibiotics.
Routes of Administration
1- Slow I.V.I. For systemic fungal disease.
2- Intrathecal for fungal C.N.S. infections.
3- Topical drops & direct subconjunctival
injection for Mycotic corneal ulcers & keratitis.
3- Local injection into the joint in fungal arthritis.
4- Bladder irrigation in Candiduria.
Liposomal preparations of
Amphotericin B is packaged in a lipid-
associated delivery system to reduce binding to
human cell membrane , so reducing :
B. Infusion toxicity
Also, more effective
It is a polyene macrolide ,similar in structure
& mechanism to amphotericin B.
Too toxic for systemic use.
Used only topically.
It is available as creams, ointment ,
suppositories & other preparations.
Not significantly absorbed from skin, mucous
membrane, GIT .
Prevent or treat superficial candidiasis of
mouth, esophagus, intestinal tract.
Can be used in combination with antibacterial
agents & corticosteroids.
A group of synthetic fungistatic agents with a
broad spectrum of activity .
They have antibacterial , antiprotozoal
anthelminthic & antifungal activity .
Mechanism of Action
1-Inhibit the fungal cytochrome P450 enzyme, (α-
demethylase) which is responsible for converting
lanosterol to ergosterol ( the main sterol in fungal
cell membrane ).
2- Inhibition of mitochondrial cytochrome
oxidase leading to accumulation of peroxides that
cause autodigestion of the fungus.
3- Imidazoles may alter RNA& DNA metabolism.
They are classified into :
They lack selectivity ,they inhibit human
gonadal and steroid synthesis leading to
decrease testosterone & cortisol production.
Also, inhibit human P-450 hepatic enzyme.
Well absorbed orally .
Bioavailability is decreased with antacids, H2
blockers , proton pump inhibitors & food .
Cola drinks improve absorption in patients
Half-life increases with the dose , it is (7-8 hrs).
Inactivated in liver & excreted in bile (feces )
Does not cross BBB.
Used topically or systematic (oral route only )
to treat :
1- Oral & vaginal candidiasis.
3- Systemic mycoses.
Nausea, vomiting ,anorexia
Inhibits human P 450 enzymes
Inhibits adrenal & gonadal steroids leading to:
Loss of libido
Gynaecomastia in males
Contraindications & Drug interactions
Contraindicated in :
Prgnancy, lactation ,hepatic dysfunction
Interact with enzyme inhibitors , enzyme
H2 blockers & antacids decrease its absorption
They are :
Resistant to degradation
Causing less endocrine disturbance
Lacks endocrine side effects
Has a broad spectrum activity
Given orally & IV
Food increases its absorption
Metabolized in liver to active metabolite
Highly lipid soluble ,well distributed to bone,
sputum ,adipose tissues.
Can not cross BBB
Half-life 30-40 hours
Used orally in dermatophytosis & vulvo-
IV only in serious infections.
Effective in AIDS-associated histoplasmosis
Side effects :
Nausea, vomiting, hypokalemia, hypertension,
edema, inhibits the metabolism of many drugs
as oral anticoagulants.
Completely absorbed from GIT
Excellent bioavailability after oral
Bioavailability is not affected by food or
Concentrated in plasma is same by oral or IV
Has the least effect on hepatic microsomal
Drug interactions are less common
Penetrates well BBB so, it is the drug of choice
of cryptococcal meningitis
Safely given in patients receiving bone marrow
transplants (reducing fungal infections)
Excreted mainly through kidney
Half-life 25-30 hours
Resistance is not a problem
( is effective in all forms of mucocutaneous
Histoplasmosis, blastomycosis, , ring worm.
Not effective in aspergillosis
Nausea, vomiting, headache, skin rash ,
diarrhea, abdominal pain , reversible alopecia.
Hepatic failure may lead to death
Highly teratogenic ( as other azoles)
Inhibit P450 cytochrome
No endocrine side effects
A broad spectrum antifungal agent
Given orally or IV
High oral bioavailability
Penetrates tissues well including CSF
Used for the treatment of invasive aspergillosis
& serious infections.
Reversible visual disturbances
Synthetic pyrimidine antimetabolite (cytotoxic
drug ) often given in combination with
amphotericin B & itraconazole.
Mechanism of action
Converted within the fungal cell to 5-
fluorouracil (Not in human cell ), that inhibits
thymidylate synthetase enzyme that inhibits
(Amphotericin B increases cell permeability ,
allowing more 5-FC to penetrate the cell, they
Rapidly & well absorbed orally
Widely distributed including CSF.
Mainly excreted unchanged through kidney
Half-life 3-6 hours
Severe deep fungal infections as in meningitis
Generally given with amphotericin B
For cryptococcal meningitis in AIDS patients
Nausea, vomiting , diarrhea, severe
Reversible neutropenia, thrombocytopenia,
bone marrow depression
Elevation in hepatic enzymes
Inhibits the synthesis of fungal cell wall by
inhibiting the synthesis of β(1,3)-D-glucan,
leading to lysis & cell death.
Given by IV route only
Highly bound to plasma proteins
Half-life 9-11 hours
Slowly metabolized by hydrolysis & N-
Elimination is nearly equal between the
urinary & fecal routes.
Effective in aspergillus & candida infections.
Second line for those who have failed or
cannot tolerate amphotericin B or
Adverse effects :
Flushing (release of histamine from mast cells)
Fungistatic, has a narrow spectrum
Given orally (Absorption increases with fatty
Half-life 26 hours
Taken selectively by newly formed skin &
concentrated in the keratin.
Induces cytochrome P450 enzymes
Should be given for 2-6weeks for skin & hair
infections to allow replacement of infected
keratin by the resistant structure
Inhibits fungal mitosis by interfering with microtubule
Used to treat dermatophyte infections ( ring worm of
skin, hair, nails ).
Highly effective in athlete,s foot.
Not effective in subcutaneous or deep mycosis.
Adverse effects ;
Peripheral neuritis, mental confusion, fatigue, vertigo,
GIT upset, enzyme inducer, blurred vision.
Increases alcohol intoxication.
Effective in most cutaneous mycosis.
Ineffective against Candida.
Used in tinea pedis ( cure rate 80% ).
Used as cream, gel, powder, topical solution.
Applied twice daily.
Broad spectrum fungicidal .
Available as cream or gel.
Effective for treatment of tinea cruris.
Drug of choice for treating dermatophytes
Better tolerated ,needs shorter duration of
Inhibits fungal squalene epoxidase, decreases
The synthesis of ergosterol .(Accumulation of
squalene ,which is toxic to the organism
causing death of fungal cell).
Fungicidal ,its activity is limited to candida
albicans & dermatophytes.
Effective for treatment of onychomycoses
6 weeks for finger nail infection & 12 weeks
for toe nail infections .
Well absorbed orally , bioavailability
decreases due to first pass metabolism in liver.
Highly protein binding
Accumulates in skin , nails, fat.
Severely hepatotoxic, liver failure even death.
Accumulate in breast milk , should not be
given to nursing mother.
GIT upset (diarrhea, dyspepsia, nausea )
Taste & visual disturbance.