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ANTIFUNGAL AGENTS
By: Mrs. Kalaivani Sathish M. Pharm
Assistant Professor,
PIMS - PANIPAT
Dr Mrs Borkar 1
• Fungi are eukaryotic, heterotrophic organisms that
live as saprobes or parasites.
• Complex organisms in comparison to bacteria .
• Have nucleus and well defined nuclear membrane,
and chromosomes.
• Have rigid cell wall composed of chitin (bacterial
cell wall is composed of peptidoglycan)
• Fungal cell membrane contains ergosterol , human
cell mebmrane is composed of cholesterol
• Antibacterial agents are not effective against fungi.
• Fungal infections are also called as mycoses
ANTIFUNGAL AGENTS
Introduction
2Dr Mrs Borkar
ANTIFUNGAL AGENTS
• Systemic fungal infections are a major cause of death
in patients whose immune system is compromised
– cancer or its chemotherapy,
– organ transplantation
– HIV-1 infection.
• Superficial infections of the skin and other soft tissue
structures.
• Antifungal agents target
– distinctive components of the fungal cell membrane
– others alter cell wall synthesis
– nucleic acid synthesis
Introduction
3Dr Mrs Borkar
• Superficial : Affect skin – mucous membrane
– Tinea versicolor
– Dermatophytes : affect keratin layer of skin, hair, nail.
e.g.tinea pedis, ring worm infection
– Candidiasis : Yeast-like, oral thrush, vulvo-vaginitis , nail
infections.
• Deep Infections :
– Affect internal organs as : lung ,heart , brain leading to
pneumonia , endocarditis , meningitis.
ANTIFUNGAL AGENTS
Types of Fungal Infections
4Dr Mrs Borkar
• Disrupt fungal cell membrane
– Polyenes – amphotericin, Nystatin
– Azoles
• Imidazole – Ketoconazole, Miconazole, Clotrimazole
• Triazole – Fluconazole, Itraconazole
– Allylamines - Terbinafin
– Echinocandins - Capsofungin
• Inhibit mitosis - Gresiofulvin
• Inhibit DNA synthesis - Flucytosine
• Miscellaneous
– Tolnaftate
– Cyclopirox
ANTIFUNGAL AGENTS
Mechanism of action of Antifungal agents
5Dr Mrs Borkar
Membrane function
Amphotericin B
Cell Wall Synthesis
Capsofungin
Nucleic acid
synthesis
Flucytosine
Ergosterol synthesis
Azoles
Lanosterol synthesis
Terbinafine 6Dr Mrs Borkar
• Antifungal agent with the broadest spectrum of activity
• Produced by Streptomyces nodosus.
• Natural, Amphoteric polyene macrolide –
– Amphoteric = can react as an acid as well as a base
– polyene = many double bonds
– macrolide = containing a large lactone ring
• Heptaene macrolide - large lactone ring with multiple ketone and
hydroxyl group)
• Drug of choice for the vast majority of life-threatening systemic
fungal infections
• Interacts with ergosterols, forms pores that increase membrane
permeability and allow leakage of intracellular ions &
macromolecules from fungal cell ( cell death ).
ANTIFUNGAL AGENTS
Amphotericin B
7Dr Mrs Borkar
• Broad range of pathogenic fungi
• Protozoa, Leishmania braziliensis and
Naegleria fowleri
• No antibacterial activity
• Amphotericin A & B are antifungal antibiotics.
• Amphotericin A is not used clinically.
ANTIFUNGAL AGENTS
Amphotericin B
8Dr Mrs Borkar
Mechanism of
action of
Amphotericin
9Dr Mrs Borkar
• Poorly absorbed orally, useful for fungal infection of
gastrointestinal tract.
• For systemic infections given as slow I/V infusion.
• Locally used in corneal ulcers, arthritis and candidial
bladder irrigation
• Highly protein bound - > 90%
• Penetration through BBB is poor but increases in inflamed
meninges.
• Excreted slowly via kidneys, traces found in urine for
months after cessation of drugs.
• Half life 15 days
ANTIFUNGAL AGENTS
Amphotericin - ADME
10Dr Mrs Borkar
Amphotericin
ADME
11Dr Mrs Borkar
1. Slow IV infusion for systemic fungal disease.
2. Intrathecal for fungal CNS infections.
3. Topical drops & direct subconjunctival
injection for Mycotic corneal ulcers &
keratitis.
4. Local injection into the joints in fungal
arthritis.
5. Bladder irrigation in Candiduria.
ANTIFUNGAL AGENTS
Routes of Administration
12Dr Mrs Borkar
• Packaged in a lipid- associated delivery system
which acts as a reservoir
• Large doses can be administered – 5 times
• Reduces binding to human cell membrane
• Clinically have more efficacy , less nephrotoxicity
• More expensive
ANTIFUNGAL AGENTS
Amphotericin – Liposomal Preparations
13Dr Mrs Borkar
Liposomal preparations of Amphotericin
14Dr Mrs Borkar
• Usual dose is 0.5–0.6 mg/kg, administered in 5% glucose over 4
hours
• Candida esophagitis, Rapidly progressive mucormycosis or invasive
aspergillosis .
• Coccidioides meningitis: Intrathecal infusion ; started with twice
weekly schedule , increased to thrice weekly and continued on twice-
weekly schedule.
• Treatment of cryptococcal meningitis, Severe or rapidly progressing
histoplasmosis, blastomycosis, coccidioidomycosis, penicilliosis
marneffei, invasive aspergillosis, extracutaneous sporotrichosis,
fusariosis, alternariosis, and trichosporonosis.
• Given once weekly to prevent relapse in patients with AIDS who have
been treated successfully for cryptococcosis or histoplasmosis.
ANTIFUNGAL AGENTS
Amphotericin B - Therapeutic Uses and Dosage
15Dr Mrs Borkar
• Major acute reaction to intravenous is fever and chills, which
typically end spontaneously in ~30 minutes and often abate with
subsequent infusions.
• Tachypnea and modest hypotension may occur, but true
bronchospasm or anaphylaxis is rare.
• Hypotension and hypoxia in preexisting cardiac or lung disease
• Prophylactic use of IV glucocorticoids decreases reaction
• Transient azotemia occurs in 80% of patients
• Kidney function may be affected if other nephrotoxic agents like
aminoglycoside are used concurrently.
• Administration of 1 L of NS IV prior to amphotericin B administration
is recommended for adults who can tolerate the Na+ load.
• Azotemia occurs less frequently with lipid preparations of
amphotericin, and saline loading is not needed.
ANTIFUNGAL AGENTS
Amphotericin B - Adverse effects
16Dr Mrs Borkar
• Hypochromic, normocytic anemia is usual and reverses
slowly following cessation of therapy.
• It is due decreased production of erythropoietin and often
responds to erythropoietin.
• Headache, nausea, vomiting, malaise, weight loss, and
phlebitis at peripheral infusion sites are common.
• Arachnoiditis, manifested by fever and headache, can
occur with intrathecal injection; it may be decreased by
intrathecal administration of 10–15 mg of hydrocortisone.
• Local injections of amphotericin B into a joint or peritoneal
dialysate fluid commonly produce irritation and pain.
ANTIFUNGAL AGENTS
Amphotericin B - Adverse effects
17Dr Mrs Borkar
Immediate reactions ( Infusion –related toxicity ).
• Fever, muscle spasm, vomiting ,headache, hypotension.
• Can be avoided by :
– Slowing the infusion
– Decreasing the daily dose
– Premedication with antipyretics, antihistamincs or corticosteroids.
– test dose.
Slower Reactions:
• Most serious is renal toxicity (nearly in all patients ).
• Hypokalemia
• Hypomagnesaemia
• Impaired liver functions
• Anemia, Thrombocytopenia
ANTIFUNGAL AGENTS
Amphotericin B - Adverse effects
18Dr Mrs Borkar
19Dr Mrs Borkar
• Synthetic, water soluble, fluorinated pyrimidine analog
• Often used in combination with amphotericin B and
Itraconazole
• Spectrum of antigungal activity is considerably less than
that of amphotericin B.
• Amphotericin B increases cell permeability , allowing more
5-FC to penetrate the cell, they are synergistic
• Fungistatic
• Has useful activity against Candida and Cryptococcus.
• Acts by inhibiting synthesis of fungal DNA
ANTIFUNGAL AGENTS
Flucytosine
20Dr Mrs Borkar
• Absorbed rapidly and well from the GI tract, widely
distributed
• Minimally bound to plasma proteins.
• Penetrates well into CSF.
• Mainly excreted unchanged through kidney
• Half life drug normally is 3–6 hours but may reach
200 hours in renal failure.
• Dose modification is necessary in renal dysfunction
plasma concentrations should be measured
periodically
• Flucytosine is cleared by hemodialysis and
peritoneal dialysis
ANTIFUNGAL AGENTS
Flucytosine - ADME
21Dr Mrs Borkar
• Given orally at 100 mg/kg/day, in 4 divided doses
and is used predominantly in combination with
amphotericin B.
• Severe deep fungal infections as in meningitis
• Cryptococcal meningitis: begin with
amphotericin B plus flucytosine and change to
fluconazole after the patient has improved.
• There is the risk of amphotericin induecd
azotemia and flucytocine dose has to be reduced
in this situation otherwise the combination will
cause bone marrow suppression or colitis
ANTIFUNGAL AGENTS
Flucytosine – Uses
22Dr Mrs Borkar
• Hematologic : Leukopenia, thrombocytopenia,
bone marrow depression
• Allergic: Rash, nausea, vomiting, diarrhea, and
enterocolitis
• Hepatic: Elevation in hepatic transaminases but
this reverses when therapy is stopped.
• Toxicity is more frequent in patients with AIDS or
azotemia.
• Alopecia
ANTIFUNGAL AGENTS
Flucytosine – Adverse effects
23Dr Mrs Borkar
• Bacterial origin.
• Isolated from Streptomyces noursei in 1950
by Elizabeth Lee Hazen and Rachel Fuller
Brown,.
• Polyene macrolide ,similar in structure &
mechanism to amphotericin B.
• Too toxic for systemic use.
• Used only topically - available as creams,
ointment , suppositories & other
preparations.
ANTIFUNGAL AGENTS
Nystatin/Nysfungin
24Dr Mrs Borkar
• Prevent or treat superficial candidiasis of mouth,
esophagus, intestinal tract.
• Oral suspension of 100,000 U/ml 4 times a day and
tablets 500,000 U are used to decrease GIT
colonization with Candida
• Vaginal candidiasis - pessaries used for 2 weeks
• Can be used in combination with antibacterial
agents & corticosteroids
• In Cutaneous infection available in cream, ointment
or powder form and applied 2-3 times a day
ANTIFUNGAL AGENTS
Nystatin/Nysfungin – Clinical uses
25Dr Mrs Borkar
• Bivalent chemical group composed of five-membered
organic rings
• Broad spectrum of activity - Antibacterial, antiprotozoal,
anthelminthic and antifungal.
• Group of synthetic fungistatic agents
• Classification: according to the number of nitrogen atoms
attached to the ring
– Imidazoles (2 nitrogen atoms): Ketoconazole,
Miconazole, Econazole, Clotrimazole, Bifonazole
– Triazoles (3 nitrogen atoms): Itraconazole, Fluconazol,
Vorionazole → systemic treatment
ANTIFUNGAL AGENTS
Azole Antifungals
26Dr Mrs Borkar
• Cryptococci, Blastomyces, Histoplasma
capsulatum, Coccidioides , Paracoccidioides
brasiliensis, and dermatophytes.
• Aspergillus spp., Scedosporium,
apiospermum (Pseudallescheria boydii),
Fusarium, and Sporothrix schenckii are
intermediate in susceptibility.
• C. krusei and the agents of mucormycosis are
resistant.
ANTIFUNGAL AGENTS
Azole - antifungal activity
27Dr Mrs Borkar
• Inhibit the fungal cytochrome
P450 enzyme
• Responsible for converting
lanosterol to ergosterol ( the
main sterol in fungal cell
membrane ).
ANTIFUNGAL AGENTS
Azole Antifungals- Mechanism of Action
28Dr Mrs Borkar
• Contain 2 Nitrogen atoms attached to the ring
• Reduce the formation of ergosterol in the cell
membrae which become permeable to cellular
constituents.
• They lack selectivity, and also inhibits human
gonadal and steroid synthesis leading to decreased
testosterone and cortisol production
• Ketoconazole,
• miconazole,
• clotrimazole,
• isoconazole ,
• Tioconazole
ANTIFUNGAL AGENTS
Azole Antifungals- Imidazoles
29Dr Mrs Borkar
Mechanism of
action
Ketoconazole
30Dr Mrs Borkar
• Well absorbed orally as acidic environment favors its
dissolution.
• Bioavailability is impaired with food.
• Cola drinks improve its absorption in patients with
achlorhydria.
• Metabolized extensively in liver and inactive products
appear in the feces.
• Moderate hepatic dysfunction has no effect on drug
concentration.
• 84 % is bound to plasma proteins.
• Half life increases with dose
• It does not enter CSF.
ANTIFUNGAL AGENTS
Imidazole – Ketoconazole- ADME
31Dr Mrs Borkar
• Inhibits adrenal and gonadal steroids which leads to
menstrual irregularities, loss of libido, impotency and
gynaecomastia in males.
• Efficacy is poor in immunosuppressed patients and
in meningitis.
• Hepatotoxic - rare but may prove fatal.
• Dose dependant nausea, anorexia ,vomiting
• Hair loss
• Fluid retention and hypertension.
• Not used in Pregnancy, lactation ,hepatic dysfunction
ANTIFUNGAL AGENTS
Imidazole – Ketoconazole – Adverse Effects
32Dr Mrs Borkar
Decrease in the
ergosterol in the
fungal membrane
By ketoconazle
reduces
the fungicidal
action of
amphotericin
33Dr Mrs Borkar
Used topically or systematic (oral route only ) to treat
1. Oral & vaginal candidiasis.
2. Dermatophytosis.
3. Systemic mycoses & mucocutaneous candidiasis.
ANTIFUNGAL AGENTS
Imidazole – Ketoconazole – Clinical uses
34Dr Mrs Borkar
Ketoconazole is
not useful for
fungal infections of
UT
as level of parent
drug in urine is
very low
35Dr Mrs Borkar
• Bioavailability is low by taking orally.
• Used topically.
• Absorption less than 0.5 % from intact skin, 3-10 %
from vagina
• Activity in vagina remains for 3 days.
• Stigma, erythema, edema, vesication, pruritus,
urticaria mild vaginal burning sensation may occour.
• Cure dermatophytes, cutaneous candidiasis and
vulvovaginal candidiasis
ANTIFUNGAL AGENTS
Imidazole – Clotrimazole
36Dr Mrs Borkar
• Damage the fungal cell membrane by inhibiting
enzyme desmethylase
• They are selective
• Penetrate to CNS
• Resistant to degradation
• Cause less endocrine disturbance.
• Fluconazole,
• itraconazole,
• voriconazole
ANTIFUNGAL AGENTS
Azole Antifungals- Triazoles
37Dr Mrs Borkar
• It is a synthetic triazole, new drug
• Lacks endocrine side effects of ketoconazole.
• Broad spectrum activity
• Administered orally as well as I/V.
• Food increases its absorption
• Metabolized in liver to active metabolite
• Highly lipid soluble ,well distributed to bone, sputum,
adipose tissues.
• Can not cross BBB
ANTIFUNGAL AGENTS
Azole antifungals – Itraconazole
38Dr Mrs Borkar
• Food increases its absorption
• Metabolized in liver extensively
• It is highly lipid soluble and well distributed to
bone, sputum and adipose tissue.
• Highly bound to plasma protein
• Half life is 30-40 hours
• Does not penetrate CSF adequately
• The capsule is better absorbed with food, but the
oral solution is better absorbed in the fasting
state
ANTIFUNGAL AGENTS
Itraconazole- ADME
39Dr Mrs Borkar
ANTIFUNGAL AGENTS
Azole antifungals – Itraconazole - Therapeutic Uses
• Available as a capsule and solutions for oral or intravenous
administration
• Oral solution is 60% more bioavailable than the capsules
• IV only in serious infections.
• Dose – Cap 200 to 400 mg/day
• doses exceeding 200 mg/day are given in 2 divided doses
• Loading dose: 200 mg 3 times daily can be given for the first 3
days
• The only agent with significant activity against aspergillus species
• It can safely be administered prophylactically in patients receiving
bone marrow transplants
40Dr Mrs Borkar
• Dermatophytoses and onychomycosis.
• Onychomycosis - 200 mg daily after food for 3 months
• For deep mycoses, loading dose of 200 mg three times
daily for 3 days. Thereafter, two 100-mg capsules are given
twice daily with food.
• Histoplasmosis : AIDS-associated histoplasmosis
maintainance therapy - 200 mg once daily
• It easily penetrate CSF and is a drug of choice in
cryptococcal meningitis and coccido mycosis
• Cryptococcosis: 400 mg daily for 8 weeks in meningitis, In
AIDS 200 mg for life.
ANTIFUNGAL AGENTS
Azole antifungals – Itraconazole - Therapeutic Uses
41Dr Mrs Borkar
• Itraconazole solution - for oropharyngeal and esophageal
candidiasis.
• Taken fasting in a dose of 100 mg once daily and swished
vigorously in the mouth before swallowing to optimize topical
effect.
• 100 mg of the solution twice a day for 2–4 weeks.
• Candidiasis: 200 mg on 1st day then 100 mg daily for 2 weeks.
• Not effective in aspergillosis.
• Used orally in dermatophytosis & vulvo-vaginal candidiasis.
ANTIFUNGAL AGENTS
Azole antifungals – Itraconazole - Therapeutic Uses
42Dr Mrs Borkar
• Interact with many drugs
• Interactions can cause serious toxicity
• Fatal cardiac arrhythmias.
• Congestive heart failure in patients with impaired
ventricular function.
• Hepatic failure and death. If symptoms of hepatotoxicity
occur, the drug should be discontinued and liver function
assessed.
• Anaphylaxis and severe rash have rarely occurred.
ANTIFUNGAL AGENTS
Itraconazole – Adverse Effects
43Dr Mrs Borkar
• Relative to capsules, the oral solution of
itraconazole more frequently causes diarrhea,
abdominal cramps, anorexia, and nausea.
• Intravenous itraconazole has all the adverse
effects of capsules but generally is well tolerated.
• Chemical phlebitis: dedicated catheter port is
required,
• Infusion durations >1 hour are recommended.
• Intravenous formulation is contraindicated in
patients with a creatinine clearance <30 mL/min.
ANTIFUNGAL AGENTS
Itraconazole – Adverse Effects
44Dr Mrs Borkar
• The adverse effects are related to dose and duration of use
• In the absence of interacting drugs, itraconazole capsules
are well tolerated at 200 mg daily.
• GI distress occurs with use of 300 mg/day or more
• In patients receiving 50–400 mg/day, nausea and vomiting,
hypertriglyceridemia, hypokalemia, elevated serum
aminotransferases, and rash occurred in few patients
• Doses of 300 mg twice daily have led to adrenal
insufficiency, lower limb edema, hypertension, and
rhabdomyolysis
• Doses above 400 mg/day are not recommended for long-
term use
ANTIFUNGAL AGENTS
Itraconazole – Adverse Effects
45Dr Mrs Borkar
• It is fluorinated bistriazole.
• The widest therapeutic index of the azoles.
• Excellent bioavailability by oral route.
• Bioavailability not altered by food or gastric acidity
• Not hepatotoxic
• It can safely be administered prophylactically in patients
receiving bone marrow transplants.
• Maximum excretion by kidney
• Half life is 25-30 hours.
ANTIFUNGAL AGENTS
Fluconazole - ADME
47Dr Mrs Borkar
• Fluconazole is almost completely absorbed
from the GI tract irrespective of food or gastric
acidity.
• Concentration in plasma is same by oral or I/v
route.
• Only 10% of drug in circulation is protein
bound.
• Readily diffuses into body fluids, including
breast milk, sputum, saliva, and CSF.
ANTIFUNGAL AGENTS
Fluconazole - ADME
48Dr Mrs Borkar
• Tablets for oral administration
• Powder for oral suspension
• Intravenous solutions containing 2 mg/mL.
• Dosage is 50–800 mg once daily for oral or
intravenous administration.
• Children are treated with 3–6 mg/kg once
daily
ANTIFUNGAL AGENTS
Fluconazole - Dosage
49Dr Mrs Borkar
• Candidiasis - 200 mg on the first day and then 100 mg daily
for at least 2 weeks, in oropharyngeal candidiasis.
• single dose of 150 mg is effective in uncomplicated vaginal
candidiasis.
• 400 mg daily in deep candidiasis in allogeneic bone marrow
transplant recipients
• Systemic fungal infections
– 400-800 mg q24h
– > 800 mg q24h in unstable patient
• Maintenance for cryptococcal meningitis - 400 mg/day, for
the initial 8 weeks in the treatment in AIDS after the
patient has been stabilized with intravenous amphotericin
ANTIFUNGAL AGENTS
Fluconazole - Uses
50Dr Mrs Borkar
• Nausea and vomiting at doses >200 mg/day
• Headache, skin rash, abdominal pain, and diarrhea
• Reversible alopecia may occur with prolonged
therapy
• Rare deaths due to hepatic failure or Stevens-
Johnson syndrome have occurred.
• Highly teratogenic: Associated with skeletal and
cardiac deformities in infants born to women taking
high doses during pregnancy and should be avoided
during pregnancy
ANTIFUNGAL AGENTS
Fluconazole – Adverse effects
51Dr Mrs Borkar
• Fungistatic in vitro for various species of
dermatophytes.
• Inhibits fungal mitosis
52Dr Mrs Borkar
ANTIFUNGAL AGENTS
Griseofulvin
• Entirely local action, no systemic absorption
• Micronized and ultramicronized powders are used to
facilitate dissolution
• Half life in plasma of ~1 day.
• Deposited in keratin precursor cells and persists in keratin
to provide prolonged resistance to fungi.
• The new growth of hair or nails is the first to become free
of disease.
• As the fungus-containing keratin is shed, it is replaced by
normal tissue.
• Griseofulvin is detectable in the stratum corneum within 4–
8 hours of oral administration.
53Dr Mrs Borkar
ANTIFUNGAL AGENTS
Griseofulvin - ADME
• Mycotic infections of the hair (tinea capitis)
• Tinea of the hands and beard
• “Athlete’s foot” or epidermophytosis involving
the skin and nails
• Not effective in treatment of subcutaneous or
deep mycoses
54Dr Mrs Borkar
ANTIFUNGAL AGENTS
Griseofulvin - Uses
• 5–15 mg/kg for children
• 0.5–1 g for adults in 4 divided doses
• Severe infections: 1.5–2 g daily for short periods
• Best results are obtained
• Treatment must be continued until infected tissue is
replaced by normal hair, skin, or nails, which
requires 1 month for scalp and hair ringworm, 6–9
months for fingernails, and at least a year for
toenails.
55Dr Mrs Borkar
ANTIFUNGAL AGENTS
Griseofulvin - Dosage
• Headache, GI symptoms (e.g., nausea, vomiting,
diarrhea, heartburn, flatulence), and rash.
• More serious reactions include hepatotoxicity,
serum sickness reaction, angioedema, and
hematologic effects (e.g., leukopenia, neutropenia,
punctate basophilia, and monocytosis).
• Blood should be checked weekly during treatment.
• Estrogen-like effects have been observed in
children.
56Dr Mrs Borkar
ANTIFUNGAL AGENTS
Griseofulvin – adverse effects
• Topical treatment is useful in superficial fungal infections
confined to the stratum corneum, squamous mucosa, or
cornea, including dermatophytosis (ringworm), candidiasis,
tinea versicolor, piedra, tinea nigra, and fungal keratitis.
• Unsuccessful for mycoses of the nails (onychomycosis) and
hair (tinea capitis)
• No place in subcutaneous mycoses, such as sporotrichosis
and chromoblastomycosis.
• Efficacy of topical agents depends not only on the type of
lesion and the mechanism of drug action, but also on the
viscosity, hydrophobicity, and acidity of the formulation.
57Dr Mrs Borkar
ANTIFUNGAL AGENTS
Topical Antifungal Agents
• Regardless of formulation, penetration of topical
drugs into hyperkeratotic lesions often is poor.
• Removal of thick, infected keratin may be a useful
adjunct to therapy.
• Preferred formulations are
– Creams
– Solutions
– Powders, whether applied by shake containers or
aerosols, largely are used for the feet and moist
lesions of the groin and other intertriginous areas
58Dr Mrs Borkar
ANTIFUNGAL AGENTS
Topical Antifungal Agents
1. Topical azole derivatives
2. Nystatin& Amphotericin
3. Terbinafine
4. Tolnaftate
5. Naftifine
6. Griseofulvin
59Dr Mrs Borkar
ANTIFUNGAL AGENTS
Topical Antifungal Agents
• Used in superficial fungal infections:
– Dermatophytosis ( ring worm)
– Candidiasis
– Fungal keratitis.
• Not effective in mycoses of the nails & hair or
subcutaneous mycoses.
• Preferred formulation for cutaneous application
is cream or solution.
60Dr Mrs Borkar
ANTIFUNGAL AGENTS
Topical Antifungal Agents
• Indications for topical use include
– tinea corporis
– tinea pedis
– tinea cruris
– tinea versicolor
– cutaneous candidiasis.
• Agents for topical use should be selected based on cost
and availability.
• They are applied twice daily for 3–6 weeks.
• Preparations for cutaneous use are effective for
61Dr Mrs Borkar
ANTIFUNGAL AGENTS
Topical Antifungal Agents - Azoles
• Creams, suppositories, and tablets for vaginal candidiasis
• 5 gm, Used once daily for 1–7 days, preferably at bedtime to
facilitate retention.
• Three vaginal formulations—
– clotrimazole tablets,
– miconazole suppositories,
– Terconazole cream
• Come in both low- and high-dose preparations.
• Shorter duration of therapy is recommended for the higher
doses.
• The action is local and only little is absorbed
• Most common side effect is vaginal burning or itching.
• A male sexual partner may experience mild penile irritation.62Dr Mrs Borkar
ANTIFUNGAL AGENTS
Topical Antifungal Agents – Vaginal Applications

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Anti fungal agents

  • 1. ANTIFUNGAL AGENTS By: Mrs. Kalaivani Sathish M. Pharm Assistant Professor, PIMS - PANIPAT Dr Mrs Borkar 1
  • 2. • Fungi are eukaryotic, heterotrophic organisms that live as saprobes or parasites. • Complex organisms in comparison to bacteria . • Have nucleus and well defined nuclear membrane, and chromosomes. • Have rigid cell wall composed of chitin (bacterial cell wall is composed of peptidoglycan) • Fungal cell membrane contains ergosterol , human cell mebmrane is composed of cholesterol • Antibacterial agents are not effective against fungi. • Fungal infections are also called as mycoses ANTIFUNGAL AGENTS Introduction 2Dr Mrs Borkar
  • 3. ANTIFUNGAL AGENTS • Systemic fungal infections are a major cause of death in patients whose immune system is compromised – cancer or its chemotherapy, – organ transplantation – HIV-1 infection. • Superficial infections of the skin and other soft tissue structures. • Antifungal agents target – distinctive components of the fungal cell membrane – others alter cell wall synthesis – nucleic acid synthesis Introduction 3Dr Mrs Borkar
  • 4. • Superficial : Affect skin – mucous membrane – Tinea versicolor – Dermatophytes : affect keratin layer of skin, hair, nail. e.g.tinea pedis, ring worm infection – Candidiasis : Yeast-like, oral thrush, vulvo-vaginitis , nail infections. • Deep Infections : – Affect internal organs as : lung ,heart , brain leading to pneumonia , endocarditis , meningitis. ANTIFUNGAL AGENTS Types of Fungal Infections 4Dr Mrs Borkar
  • 5. • Disrupt fungal cell membrane – Polyenes – amphotericin, Nystatin – Azoles • Imidazole – Ketoconazole, Miconazole, Clotrimazole • Triazole – Fluconazole, Itraconazole – Allylamines - Terbinafin – Echinocandins - Capsofungin • Inhibit mitosis - Gresiofulvin • Inhibit DNA synthesis - Flucytosine • Miscellaneous – Tolnaftate – Cyclopirox ANTIFUNGAL AGENTS Mechanism of action of Antifungal agents 5Dr Mrs Borkar
  • 6. Membrane function Amphotericin B Cell Wall Synthesis Capsofungin Nucleic acid synthesis Flucytosine Ergosterol synthesis Azoles Lanosterol synthesis Terbinafine 6Dr Mrs Borkar
  • 7. • Antifungal agent with the broadest spectrum of activity • Produced by Streptomyces nodosus. • Natural, Amphoteric polyene macrolide – – Amphoteric = can react as an acid as well as a base – polyene = many double bonds – macrolide = containing a large lactone ring • Heptaene macrolide - large lactone ring with multiple ketone and hydroxyl group) • Drug of choice for the vast majority of life-threatening systemic fungal infections • Interacts with ergosterols, forms pores that increase membrane permeability and allow leakage of intracellular ions & macromolecules from fungal cell ( cell death ). ANTIFUNGAL AGENTS Amphotericin B 7Dr Mrs Borkar
  • 8. • Broad range of pathogenic fungi • Protozoa, Leishmania braziliensis and Naegleria fowleri • No antibacterial activity • Amphotericin A & B are antifungal antibiotics. • Amphotericin A is not used clinically. ANTIFUNGAL AGENTS Amphotericin B 8Dr Mrs Borkar
  • 10. • Poorly absorbed orally, useful for fungal infection of gastrointestinal tract. • For systemic infections given as slow I/V infusion. • Locally used in corneal ulcers, arthritis and candidial bladder irrigation • Highly protein bound - > 90% • Penetration through BBB is poor but increases in inflamed meninges. • Excreted slowly via kidneys, traces found in urine for months after cessation of drugs. • Half life 15 days ANTIFUNGAL AGENTS Amphotericin - ADME 10Dr Mrs Borkar
  • 12. 1. Slow IV infusion for systemic fungal disease. 2. Intrathecal for fungal CNS infections. 3. Topical drops & direct subconjunctival injection for Mycotic corneal ulcers & keratitis. 4. Local injection into the joints in fungal arthritis. 5. Bladder irrigation in Candiduria. ANTIFUNGAL AGENTS Routes of Administration 12Dr Mrs Borkar
  • 13. • Packaged in a lipid- associated delivery system which acts as a reservoir • Large doses can be administered – 5 times • Reduces binding to human cell membrane • Clinically have more efficacy , less nephrotoxicity • More expensive ANTIFUNGAL AGENTS Amphotericin – Liposomal Preparations 13Dr Mrs Borkar
  • 14. Liposomal preparations of Amphotericin 14Dr Mrs Borkar
  • 15. • Usual dose is 0.5–0.6 mg/kg, administered in 5% glucose over 4 hours • Candida esophagitis, Rapidly progressive mucormycosis or invasive aspergillosis . • Coccidioides meningitis: Intrathecal infusion ; started with twice weekly schedule , increased to thrice weekly and continued on twice- weekly schedule. • Treatment of cryptococcal meningitis, Severe or rapidly progressing histoplasmosis, blastomycosis, coccidioidomycosis, penicilliosis marneffei, invasive aspergillosis, extracutaneous sporotrichosis, fusariosis, alternariosis, and trichosporonosis. • Given once weekly to prevent relapse in patients with AIDS who have been treated successfully for cryptococcosis or histoplasmosis. ANTIFUNGAL AGENTS Amphotericin B - Therapeutic Uses and Dosage 15Dr Mrs Borkar
  • 16. • Major acute reaction to intravenous is fever and chills, which typically end spontaneously in ~30 minutes and often abate with subsequent infusions. • Tachypnea and modest hypotension may occur, but true bronchospasm or anaphylaxis is rare. • Hypotension and hypoxia in preexisting cardiac or lung disease • Prophylactic use of IV glucocorticoids decreases reaction • Transient azotemia occurs in 80% of patients • Kidney function may be affected if other nephrotoxic agents like aminoglycoside are used concurrently. • Administration of 1 L of NS IV prior to amphotericin B administration is recommended for adults who can tolerate the Na+ load. • Azotemia occurs less frequently with lipid preparations of amphotericin, and saline loading is not needed. ANTIFUNGAL AGENTS Amphotericin B - Adverse effects 16Dr Mrs Borkar
  • 17. • Hypochromic, normocytic anemia is usual and reverses slowly following cessation of therapy. • It is due decreased production of erythropoietin and often responds to erythropoietin. • Headache, nausea, vomiting, malaise, weight loss, and phlebitis at peripheral infusion sites are common. • Arachnoiditis, manifested by fever and headache, can occur with intrathecal injection; it may be decreased by intrathecal administration of 10–15 mg of hydrocortisone. • Local injections of amphotericin B into a joint or peritoneal dialysate fluid commonly produce irritation and pain. ANTIFUNGAL AGENTS Amphotericin B - Adverse effects 17Dr Mrs Borkar
  • 18. Immediate reactions ( Infusion –related toxicity ). • Fever, muscle spasm, vomiting ,headache, hypotension. • Can be avoided by : – Slowing the infusion – Decreasing the daily dose – Premedication with antipyretics, antihistamincs or corticosteroids. – test dose. Slower Reactions: • Most serious is renal toxicity (nearly in all patients ). • Hypokalemia • Hypomagnesaemia • Impaired liver functions • Anemia, Thrombocytopenia ANTIFUNGAL AGENTS Amphotericin B - Adverse effects 18Dr Mrs Borkar
  • 20. • Synthetic, water soluble, fluorinated pyrimidine analog • Often used in combination with amphotericin B and Itraconazole • Spectrum of antigungal activity is considerably less than that of amphotericin B. • Amphotericin B increases cell permeability , allowing more 5-FC to penetrate the cell, they are synergistic • Fungistatic • Has useful activity against Candida and Cryptococcus. • Acts by inhibiting synthesis of fungal DNA ANTIFUNGAL AGENTS Flucytosine 20Dr Mrs Borkar
  • 21. • Absorbed rapidly and well from the GI tract, widely distributed • Minimally bound to plasma proteins. • Penetrates well into CSF. • Mainly excreted unchanged through kidney • Half life drug normally is 3–6 hours but may reach 200 hours in renal failure. • Dose modification is necessary in renal dysfunction plasma concentrations should be measured periodically • Flucytosine is cleared by hemodialysis and peritoneal dialysis ANTIFUNGAL AGENTS Flucytosine - ADME 21Dr Mrs Borkar
  • 22. • Given orally at 100 mg/kg/day, in 4 divided doses and is used predominantly in combination with amphotericin B. • Severe deep fungal infections as in meningitis • Cryptococcal meningitis: begin with amphotericin B plus flucytosine and change to fluconazole after the patient has improved. • There is the risk of amphotericin induecd azotemia and flucytocine dose has to be reduced in this situation otherwise the combination will cause bone marrow suppression or colitis ANTIFUNGAL AGENTS Flucytosine – Uses 22Dr Mrs Borkar
  • 23. • Hematologic : Leukopenia, thrombocytopenia, bone marrow depression • Allergic: Rash, nausea, vomiting, diarrhea, and enterocolitis • Hepatic: Elevation in hepatic transaminases but this reverses when therapy is stopped. • Toxicity is more frequent in patients with AIDS or azotemia. • Alopecia ANTIFUNGAL AGENTS Flucytosine – Adverse effects 23Dr Mrs Borkar
  • 24. • Bacterial origin. • Isolated from Streptomyces noursei in 1950 by Elizabeth Lee Hazen and Rachel Fuller Brown,. • Polyene macrolide ,similar in structure & mechanism to amphotericin B. • Too toxic for systemic use. • Used only topically - available as creams, ointment , suppositories & other preparations. ANTIFUNGAL AGENTS Nystatin/Nysfungin 24Dr Mrs Borkar
  • 25. • Prevent or treat superficial candidiasis of mouth, esophagus, intestinal tract. • Oral suspension of 100,000 U/ml 4 times a day and tablets 500,000 U are used to decrease GIT colonization with Candida • Vaginal candidiasis - pessaries used for 2 weeks • Can be used in combination with antibacterial agents & corticosteroids • In Cutaneous infection available in cream, ointment or powder form and applied 2-3 times a day ANTIFUNGAL AGENTS Nystatin/Nysfungin – Clinical uses 25Dr Mrs Borkar
  • 26. • Bivalent chemical group composed of five-membered organic rings • Broad spectrum of activity - Antibacterial, antiprotozoal, anthelminthic and antifungal. • Group of synthetic fungistatic agents • Classification: according to the number of nitrogen atoms attached to the ring – Imidazoles (2 nitrogen atoms): Ketoconazole, Miconazole, Econazole, Clotrimazole, Bifonazole – Triazoles (3 nitrogen atoms): Itraconazole, Fluconazol, Vorionazole → systemic treatment ANTIFUNGAL AGENTS Azole Antifungals 26Dr Mrs Borkar
  • 27. • Cryptococci, Blastomyces, Histoplasma capsulatum, Coccidioides , Paracoccidioides brasiliensis, and dermatophytes. • Aspergillus spp., Scedosporium, apiospermum (Pseudallescheria boydii), Fusarium, and Sporothrix schenckii are intermediate in susceptibility. • C. krusei and the agents of mucormycosis are resistant. ANTIFUNGAL AGENTS Azole - antifungal activity 27Dr Mrs Borkar
  • 28. • Inhibit the fungal cytochrome P450 enzyme • Responsible for converting lanosterol to ergosterol ( the main sterol in fungal cell membrane ). ANTIFUNGAL AGENTS Azole Antifungals- Mechanism of Action 28Dr Mrs Borkar
  • 29. • Contain 2 Nitrogen atoms attached to the ring • Reduce the formation of ergosterol in the cell membrae which become permeable to cellular constituents. • They lack selectivity, and also inhibits human gonadal and steroid synthesis leading to decreased testosterone and cortisol production • Ketoconazole, • miconazole, • clotrimazole, • isoconazole , • Tioconazole ANTIFUNGAL AGENTS Azole Antifungals- Imidazoles 29Dr Mrs Borkar
  • 31. • Well absorbed orally as acidic environment favors its dissolution. • Bioavailability is impaired with food. • Cola drinks improve its absorption in patients with achlorhydria. • Metabolized extensively in liver and inactive products appear in the feces. • Moderate hepatic dysfunction has no effect on drug concentration. • 84 % is bound to plasma proteins. • Half life increases with dose • It does not enter CSF. ANTIFUNGAL AGENTS Imidazole – Ketoconazole- ADME 31Dr Mrs Borkar
  • 32. • Inhibits adrenal and gonadal steroids which leads to menstrual irregularities, loss of libido, impotency and gynaecomastia in males. • Efficacy is poor in immunosuppressed patients and in meningitis. • Hepatotoxic - rare but may prove fatal. • Dose dependant nausea, anorexia ,vomiting • Hair loss • Fluid retention and hypertension. • Not used in Pregnancy, lactation ,hepatic dysfunction ANTIFUNGAL AGENTS Imidazole – Ketoconazole – Adverse Effects 32Dr Mrs Borkar
  • 33. Decrease in the ergosterol in the fungal membrane By ketoconazle reduces the fungicidal action of amphotericin 33Dr Mrs Borkar
  • 34. Used topically or systematic (oral route only ) to treat 1. Oral & vaginal candidiasis. 2. Dermatophytosis. 3. Systemic mycoses & mucocutaneous candidiasis. ANTIFUNGAL AGENTS Imidazole – Ketoconazole – Clinical uses 34Dr Mrs Borkar
  • 35. Ketoconazole is not useful for fungal infections of UT as level of parent drug in urine is very low 35Dr Mrs Borkar
  • 36. • Bioavailability is low by taking orally. • Used topically. • Absorption less than 0.5 % from intact skin, 3-10 % from vagina • Activity in vagina remains for 3 days. • Stigma, erythema, edema, vesication, pruritus, urticaria mild vaginal burning sensation may occour. • Cure dermatophytes, cutaneous candidiasis and vulvovaginal candidiasis ANTIFUNGAL AGENTS Imidazole – Clotrimazole 36Dr Mrs Borkar
  • 37. • Damage the fungal cell membrane by inhibiting enzyme desmethylase • They are selective • Penetrate to CNS • Resistant to degradation • Cause less endocrine disturbance. • Fluconazole, • itraconazole, • voriconazole ANTIFUNGAL AGENTS Azole Antifungals- Triazoles 37Dr Mrs Borkar
  • 38. • It is a synthetic triazole, new drug • Lacks endocrine side effects of ketoconazole. • Broad spectrum activity • Administered orally as well as I/V. • Food increases its absorption • Metabolized in liver to active metabolite • Highly lipid soluble ,well distributed to bone, sputum, adipose tissues. • Can not cross BBB ANTIFUNGAL AGENTS Azole antifungals – Itraconazole 38Dr Mrs Borkar
  • 39. • Food increases its absorption • Metabolized in liver extensively • It is highly lipid soluble and well distributed to bone, sputum and adipose tissue. • Highly bound to plasma protein • Half life is 30-40 hours • Does not penetrate CSF adequately • The capsule is better absorbed with food, but the oral solution is better absorbed in the fasting state ANTIFUNGAL AGENTS Itraconazole- ADME 39Dr Mrs Borkar
  • 40. ANTIFUNGAL AGENTS Azole antifungals – Itraconazole - Therapeutic Uses • Available as a capsule and solutions for oral or intravenous administration • Oral solution is 60% more bioavailable than the capsules • IV only in serious infections. • Dose – Cap 200 to 400 mg/day • doses exceeding 200 mg/day are given in 2 divided doses • Loading dose: 200 mg 3 times daily can be given for the first 3 days • The only agent with significant activity against aspergillus species • It can safely be administered prophylactically in patients receiving bone marrow transplants 40Dr Mrs Borkar
  • 41. • Dermatophytoses and onychomycosis. • Onychomycosis - 200 mg daily after food for 3 months • For deep mycoses, loading dose of 200 mg three times daily for 3 days. Thereafter, two 100-mg capsules are given twice daily with food. • Histoplasmosis : AIDS-associated histoplasmosis maintainance therapy - 200 mg once daily • It easily penetrate CSF and is a drug of choice in cryptococcal meningitis and coccido mycosis • Cryptococcosis: 400 mg daily for 8 weeks in meningitis, In AIDS 200 mg for life. ANTIFUNGAL AGENTS Azole antifungals – Itraconazole - Therapeutic Uses 41Dr Mrs Borkar
  • 42. • Itraconazole solution - for oropharyngeal and esophageal candidiasis. • Taken fasting in a dose of 100 mg once daily and swished vigorously in the mouth before swallowing to optimize topical effect. • 100 mg of the solution twice a day for 2–4 weeks. • Candidiasis: 200 mg on 1st day then 100 mg daily for 2 weeks. • Not effective in aspergillosis. • Used orally in dermatophytosis & vulvo-vaginal candidiasis. ANTIFUNGAL AGENTS Azole antifungals – Itraconazole - Therapeutic Uses 42Dr Mrs Borkar
  • 43. • Interact with many drugs • Interactions can cause serious toxicity • Fatal cardiac arrhythmias. • Congestive heart failure in patients with impaired ventricular function. • Hepatic failure and death. If symptoms of hepatotoxicity occur, the drug should be discontinued and liver function assessed. • Anaphylaxis and severe rash have rarely occurred. ANTIFUNGAL AGENTS Itraconazole – Adverse Effects 43Dr Mrs Borkar
  • 44. • Relative to capsules, the oral solution of itraconazole more frequently causes diarrhea, abdominal cramps, anorexia, and nausea. • Intravenous itraconazole has all the adverse effects of capsules but generally is well tolerated. • Chemical phlebitis: dedicated catheter port is required, • Infusion durations >1 hour are recommended. • Intravenous formulation is contraindicated in patients with a creatinine clearance <30 mL/min. ANTIFUNGAL AGENTS Itraconazole – Adverse Effects 44Dr Mrs Borkar
  • 45. • The adverse effects are related to dose and duration of use • In the absence of interacting drugs, itraconazole capsules are well tolerated at 200 mg daily. • GI distress occurs with use of 300 mg/day or more • In patients receiving 50–400 mg/day, nausea and vomiting, hypertriglyceridemia, hypokalemia, elevated serum aminotransferases, and rash occurred in few patients • Doses of 300 mg twice daily have led to adrenal insufficiency, lower limb edema, hypertension, and rhabdomyolysis • Doses above 400 mg/day are not recommended for long- term use ANTIFUNGAL AGENTS Itraconazole – Adverse Effects 45Dr Mrs Borkar
  • 46. • It is fluorinated bistriazole. • The widest therapeutic index of the azoles. • Excellent bioavailability by oral route. • Bioavailability not altered by food or gastric acidity • Not hepatotoxic • It can safely be administered prophylactically in patients receiving bone marrow transplants. • Maximum excretion by kidney • Half life is 25-30 hours. ANTIFUNGAL AGENTS Fluconazole - ADME 47Dr Mrs Borkar
  • 47. • Fluconazole is almost completely absorbed from the GI tract irrespective of food or gastric acidity. • Concentration in plasma is same by oral or I/v route. • Only 10% of drug in circulation is protein bound. • Readily diffuses into body fluids, including breast milk, sputum, saliva, and CSF. ANTIFUNGAL AGENTS Fluconazole - ADME 48Dr Mrs Borkar
  • 48. • Tablets for oral administration • Powder for oral suspension • Intravenous solutions containing 2 mg/mL. • Dosage is 50–800 mg once daily for oral or intravenous administration. • Children are treated with 3–6 mg/kg once daily ANTIFUNGAL AGENTS Fluconazole - Dosage 49Dr Mrs Borkar
  • 49. • Candidiasis - 200 mg on the first day and then 100 mg daily for at least 2 weeks, in oropharyngeal candidiasis. • single dose of 150 mg is effective in uncomplicated vaginal candidiasis. • 400 mg daily in deep candidiasis in allogeneic bone marrow transplant recipients • Systemic fungal infections – 400-800 mg q24h – > 800 mg q24h in unstable patient • Maintenance for cryptococcal meningitis - 400 mg/day, for the initial 8 weeks in the treatment in AIDS after the patient has been stabilized with intravenous amphotericin ANTIFUNGAL AGENTS Fluconazole - Uses 50Dr Mrs Borkar
  • 50. • Nausea and vomiting at doses >200 mg/day • Headache, skin rash, abdominal pain, and diarrhea • Reversible alopecia may occur with prolonged therapy • Rare deaths due to hepatic failure or Stevens- Johnson syndrome have occurred. • Highly teratogenic: Associated with skeletal and cardiac deformities in infants born to women taking high doses during pregnancy and should be avoided during pregnancy ANTIFUNGAL AGENTS Fluconazole – Adverse effects 51Dr Mrs Borkar
  • 51. • Fungistatic in vitro for various species of dermatophytes. • Inhibits fungal mitosis 52Dr Mrs Borkar ANTIFUNGAL AGENTS Griseofulvin
  • 52. • Entirely local action, no systemic absorption • Micronized and ultramicronized powders are used to facilitate dissolution • Half life in plasma of ~1 day. • Deposited in keratin precursor cells and persists in keratin to provide prolonged resistance to fungi. • The new growth of hair or nails is the first to become free of disease. • As the fungus-containing keratin is shed, it is replaced by normal tissue. • Griseofulvin is detectable in the stratum corneum within 4– 8 hours of oral administration. 53Dr Mrs Borkar ANTIFUNGAL AGENTS Griseofulvin - ADME
  • 53. • Mycotic infections of the hair (tinea capitis) • Tinea of the hands and beard • “Athlete’s foot” or epidermophytosis involving the skin and nails • Not effective in treatment of subcutaneous or deep mycoses 54Dr Mrs Borkar ANTIFUNGAL AGENTS Griseofulvin - Uses
  • 54. • 5–15 mg/kg for children • 0.5–1 g for adults in 4 divided doses • Severe infections: 1.5–2 g daily for short periods • Best results are obtained • Treatment must be continued until infected tissue is replaced by normal hair, skin, or nails, which requires 1 month for scalp and hair ringworm, 6–9 months for fingernails, and at least a year for toenails. 55Dr Mrs Borkar ANTIFUNGAL AGENTS Griseofulvin - Dosage
  • 55. • Headache, GI symptoms (e.g., nausea, vomiting, diarrhea, heartburn, flatulence), and rash. • More serious reactions include hepatotoxicity, serum sickness reaction, angioedema, and hematologic effects (e.g., leukopenia, neutropenia, punctate basophilia, and monocytosis). • Blood should be checked weekly during treatment. • Estrogen-like effects have been observed in children. 56Dr Mrs Borkar ANTIFUNGAL AGENTS Griseofulvin – adverse effects
  • 56. • Topical treatment is useful in superficial fungal infections confined to the stratum corneum, squamous mucosa, or cornea, including dermatophytosis (ringworm), candidiasis, tinea versicolor, piedra, tinea nigra, and fungal keratitis. • Unsuccessful for mycoses of the nails (onychomycosis) and hair (tinea capitis) • No place in subcutaneous mycoses, such as sporotrichosis and chromoblastomycosis. • Efficacy of topical agents depends not only on the type of lesion and the mechanism of drug action, but also on the viscosity, hydrophobicity, and acidity of the formulation. 57Dr Mrs Borkar ANTIFUNGAL AGENTS Topical Antifungal Agents
  • 57. • Regardless of formulation, penetration of topical drugs into hyperkeratotic lesions often is poor. • Removal of thick, infected keratin may be a useful adjunct to therapy. • Preferred formulations are – Creams – Solutions – Powders, whether applied by shake containers or aerosols, largely are used for the feet and moist lesions of the groin and other intertriginous areas 58Dr Mrs Borkar ANTIFUNGAL AGENTS Topical Antifungal Agents
  • 58. 1. Topical azole derivatives 2. Nystatin& Amphotericin 3. Terbinafine 4. Tolnaftate 5. Naftifine 6. Griseofulvin 59Dr Mrs Borkar ANTIFUNGAL AGENTS Topical Antifungal Agents
  • 59. • Used in superficial fungal infections: – Dermatophytosis ( ring worm) – Candidiasis – Fungal keratitis. • Not effective in mycoses of the nails & hair or subcutaneous mycoses. • Preferred formulation for cutaneous application is cream or solution. 60Dr Mrs Borkar ANTIFUNGAL AGENTS Topical Antifungal Agents
  • 60. • Indications for topical use include – tinea corporis – tinea pedis – tinea cruris – tinea versicolor – cutaneous candidiasis. • Agents for topical use should be selected based on cost and availability. • They are applied twice daily for 3–6 weeks. • Preparations for cutaneous use are effective for 61Dr Mrs Borkar ANTIFUNGAL AGENTS Topical Antifungal Agents - Azoles
  • 61. • Creams, suppositories, and tablets for vaginal candidiasis • 5 gm, Used once daily for 1–7 days, preferably at bedtime to facilitate retention. • Three vaginal formulations— – clotrimazole tablets, – miconazole suppositories, – Terconazole cream • Come in both low- and high-dose preparations. • Shorter duration of therapy is recommended for the higher doses. • The action is local and only little is absorbed • Most common side effect is vaginal burning or itching. • A male sexual partner may experience mild penile irritation.62Dr Mrs Borkar ANTIFUNGAL AGENTS Topical Antifungal Agents – Vaginal Applications