Hello friends. In this PPT I am talking about anti-fungal drugs. If you like it, please do let me know in the comments section. A single word of appreciation from you will encourage me to make more of such videos. Thanks. Enjoy and welcome to the beautiful world of pharmacology where pharmacology comes to life. This video is intended for MBBS, BDS, paramedical and any person who wishes to have a basic understanding of the subject in the simplest way.
2. Anti-fungal drugs
• Drugs used for superficial and deep (systemic) fungal
infections
• Fungal infections are mostly associated with the use
of broad-spectrum antibiotics, corticosteroids,
anticancer/immunosuppressant drugs, dentures,
indwelling catheters and implants, and emergence of
AIDS
3. • As a result of breakdown of host defence
mechanisms by the above agents, saprophytic fungi
easily invade living tissue
• C. albicans is normally resident in the oral cavity
• It invades to cause inf. when host defence is impaired
or the oral flora is disturbed
6. Polyene antibiotics
• The name polyene is derived from their highly
double-bonded structure
• Amphotericin B (AMB) Not abs. orally
• Cholesterol, present in host cell membranes, closely
resembles ergosterol; the polyenes bind to it as well,
though with lesser affinity
• Selectivity of action of polyenes is low, and AMB is
one of the most toxic systemically used antibiotics
7. • Bacteria do not have sterols and are unaffected by
polyenes
• Active against a wide range of yeasts and fungi—
Candida albicans, Histoplasma capsulatum,
Cryptococcus neoformans, Blastomyces dermatitidis,
Coccidioides immitis, Torulopsis, Rhodotorula,
Aspergillus, Sporothrix, etc.
8. • Dermatophytes are inhibited in vitro, but
concentrations of AMB attained in infected skin are
low and ineffective
• It is fungicidal at high and static at low
concentrations
• Also active on various species of Leishmania, a
protozoa
9. Uses
1. Topically Oral, vaginal and cutaneous candidiasis;
otomycosis
• Most effective drug for various types of systemic
mycoses and is the gold standard of antifungal
therapy
• However, because of higher toxicity of AMB, the
azole antifungals are now preferred
2. Leishmaniasis
10. Adverse effects
1. Acute reaction Occurs with each infusion and
consists of chills, fever, aches and pain all over,
nausea, vomiting and dyspnoea lasting for 2–5 hour,
probably due to release of cytokines (IL, TNFα).
Thrombophlebitis of the injected vein can occur
2. Long-term toxicity Nephrotoxicity is the most
important. Most patients develop slowly
progressing anemia (bone marrow depression)
11. Nystatin
• It is similar to AMB in antifungal action and other
properties
• However, because of higher systemic toxicity, it is
used only locally in superficial candidiasis
• In dentistry, topically applied Nystatin is 2nd choice
drug to Clotrimazole for oral thrush, denture
stomatitis, a.b. assoc. stomatitis, c.s. assoc. oral
candid., mucocut. candid. of lips
12. • 1 lac U (1 mg = 2000 U) tab is placed in mouth to
dissolve slowly 4 times a day or it can be crushed and
suspended in glycerine for application on the lesions
in mouth.
• S/E Bitter foul taste and nausea
• Corticosteroid aerosols (e.g. Beclomethasone) can
cause oral candidiasis: nystatin is effective in
preventing as well as treating it
13. • Nystatin is effective (but less than azoles) in monilial
vaginitis—1 lac U tab inserted twice daily
• Similarly, it is used for corneal, conjunctival and
cutaneous candidiasis in the form of an ointment
• Ineffective in dermatophytosis
• Given orally, not abs. (used in monilial diarrhoea)
14. Imidazoles and Triazoles
• Most extensively used antifungal drugs
• Fluconazole and Itraconazole have replaced
Ketoconazole for systemic mycosis because of
greater efficacy, longer t½, fewer side effects and
drug interactions
• Posaconazole is a new triazole to be used as a
reserve drug for non- responsive cases
15. • The Imidazoles and triazoles have broad spectrum
antifungal activity covering dermatophytes, Candida,
other fungi involved in deep mycosis, Nocardia and
Leishmania
• MOA Inhibit the fungal cytochrome P450 enzyme
‘lanosterol 14-demethylase’ and impair ergosterol
synthesis leading to a cascade of membrane
abnormalities in the fungus
16. • The lower host toxicity of triazoles compared to
imidazoles has correlated with their lower affinity for
mammalian CYP450 enzymes and lesser propensity
to inhibit mammalian sterol synthesis
• Development of fungal resistance to azoles has not
so far posed any significant clinical problem
17. Clotrimazole
• Effective in the topical t/t of tinea infections like
ringworm, Athletes’ foot and otomycosis
• Oral/cutaneous/vaginal candidiasis have responded
in >80% cases.
• M/c used drug for oropharyngeal candidiasis 10 mg
troche of clotrimazole is allowed to dissolve in the
mouth 3–4 times a day, or the lotion/gel is
applied/swirled in the mouth for as long as possible.
18. • For denture stomatitis, pts. are advised to apply
Clotrimazole lotion/gel to the fitting surface of the
denture before wearing it
• Also, the denture should be kept overnight in sod.
hypochlorite/Benzalkonium/Cetrimide soln. and it
should be worn only when needed.
19. • Topical Clotrimazole can be used to treat angular
cheilitis that often is a mixed candidal, streptococcal,
staph. inf.
• Clotrimazole is well tolerated by most patients
• Local irritation with stinging and burning sensation
occurs in some
• No systemic toxicity is seen after topical use
22. Econazole
• It is similar to Clotrimazole; penetrates superficial
layers of the skin and is highly effective in
dermatophytosis, otomycosis, oral thrush, but is
somewhat inferior to Clotrimazole in vaginitis
• No adverse effects, except local irritation in few is
reported
23. Miconazole
• It is a highly efficacious (>90% cure rate) drug for
tinea, pityriasis versicolor, otomycosis, cutaneous
and vulvovaginal candidiasis
• Single application on skin acts for a few days
• Irritation after cutaneous application is infrequent
• No systemic adverse effects are seen
24.
25. Oxiconazole
• A newer topical imidazole antifungal effective in
tinea and other dermatophytic infection, as well as
vaginal candidiasis
• Local irritation can occur in some patients
26. Ketoconazole
• Orally effective broad-spectrum antifungal drug
• Useful in dermatophytosis, superficial candidiasis
and deep mycosis
• Oral absorption facilitated by gastric acidity
• Dose 200 mg OD or BD
• A/E less than with AMB, but more side effects occur
than with Itraconazole or Fluconazole, that have
largely replaced it for systemic use
27. • M/c S/E Nausea and vomiting (can be reduced by
giving the drug with meals) foll. by loss of appetite,
headache, paresthesia, rashes and hair loss
• Interactions H2 blockers, PPIs & antacids ↓ oral
abs. of KTZ by reducing gastric acidity. Rifampin,
phenobarbitone, carbamazepine and phenytoin
induce KTZ metabolism and reduce its efficacy
• Use Rarely used in dental practice
28. Fluconazole
• Wider range of activity than KTZ; indications include
cryptococcal meningitis, systemic and mucosal
candidiasis in both normal and immunocompromised
patients, coccidioidal meningitis and some tinea
infections
• Fungicidal conc. are achieved in nails, vagina and
saliva; penetration into brain and CSF is good
29. • A/E Fluconazole produces fewer side effects:
mostly nausea, vomiting, abdominal pain, rash and
headache. Not recommended in pregnant and
lactating mothers
• Interactions Same as KTZ
30. • Use Fluconazole can be administered orally as
well as i.v. (in severe infections)
• In dentistry
1. Oral fluconazole (100 mg/day for 2 weeks) is highly
effective in oropharyngeal candidiasis, but is
reserved for cases not responding to topical
antifungals
2. Fluconazole (100 mg/day) for 2–3 weeks is the first
line treatment for Candida esophagitis
31. Itraconazole
• Broader spectrum of activity than KTZ or
Fluconazole; includes some moulds like Aspergillus
and some fluconazole resistant Candida
• Fungistatic, but effective in immunocompromised
patients
• Oral abs. enh. by food and gastric acid
• Well tolerated in doses below 200 mg/day.
32. • Gastric intolerance is significant at > 400 mg/day.
Dizziness, pruritus, headache and hypokalaemia are
the other common S/E
• Drug interactions Oral abs. ↓ by antacids, H2
blockers and PPIs
• Use Preferred for most systemic mycosis not
associated with meningitis
• Seldom used in dentistry for oral candidiasis
33. Voriconazole
• 2nd gen. broad spectrum for difficult to treat fungal
infections like invasive aspergillosis, disseminated
infections caused by Fluconazole resistant Candida,
Fusarium infections and febrile neutropenia not
responding to antibacterial therapy
• Serious cases are first treated i.v.
• A/E Rashes, visual disturbances, QTc prolongation
and an acute reaction on i.v. injection
34. Terbinafine (Allylamine)
• Fungicidal
• Noncompetitive inhibitor of ‘squalene epoxidase’,
• Accumulation of squalene within fungal cells
fungicidal action
• High affinity for keratin (conc. in stratum corneum of
skin & nail plates Effective in tinea inf. Of skin and
nails)
• S/E Gastric upset, rashes, taste disturbance
• Topical terbinafine can cause erythema, itching,
dryness, irritation, urticaria and rashes
35. • Use Terbinafine applied topically as 1% cream
twice daily is indicated in localized tinea pedis/
cruris/corporis and pityriasis versicolor
• 2–4 weeks treatment is required
• Oral treatment with 250 mg OD is reserved for
onychomycosis, tinea capitis and wide spread lesions
• Duration of treatment varies from 3–6 months or
more
• Less effective against cutaneous and mucosal
candidiasis: 2–4 weeks oral therapy may be used as
an alternative to fluconazole
obtaining food by absorbing dissolved organic material especially : obtaining nourishment osmotically from the products of organic breakdown and decay
Ergosterol is a sterol that resides on the cell membranes of fungi and acts to maintain cell membrane integrity, similar to mammalian cholesterol.
Dermatophyte a pathogenic fungus that grows on skin, mucous membranes, hair, nails, feathers, and other body surfaces, causing ringworm and related diseases.
Intrathecal administration is a route of administration for drugs via an injection into the spinal canal, or into the subarachnoid space so that it reaches the cerebrospinal fluid (CSF) and is useful in spinal anesthesia, chemotherapy, or pain management applications.
Thrush (oropharyngeal candidiasis) is a medical condition in which a yeast-like fungus called Candida albicans overgrows in the mouth and throat. Thrush may be triggered to occur by a variety of factors, including illness, pregnancy, medications, smoking, or dentures. Stomatitis is inflammation of the mouth and lips. It refers to any inflammatory process affecting the mucous membranes of the mouth and lips, with or without oral ulceration. In its widest meaning, stomatitis can have a multitude of different causes and appearances.
Dermatophytes are aerobic fungi that can invade and infect the keratinized layers of skin, hair, and nails. Three genera of fungi, Trichophyton, Microsporum, and Epidermophyton, account for most dermatophytic infections.
monilial. (məˈnɪlɪəl) adj. (Pathology) pathol denoting a thrush infection, caused by the fungus Candida (formerly Monilia) albicans
Thrush (oropharyngeal candidiasis) is a medical condition in which a yeast-like fungus called Candida albicans overgrows in the mouth and throat. Thrush may be triggered to occur by a variety of factors, including illness, pregnancy, medications, smoking, or dentures.; colon
Thrush (oropharyngeal candidiasis) is a medical condition in which a yeast-like fungus called Candida albicans overgrows in the mouth and throat. Thrush may be triggered to occur by a variety of factors, including illness, pregnancy, medications, smoking, or dentures.
Thrush (oropharyngeal candidiasis) is a medical condition in which a yeast-like fungus called Candida albicans overgrows in the mouth and throat. Thrush may be triggered to occur by a variety of factors, including illness, pregnancy, medications, smoking, or dentures. Ringworm red, itchy, circular rash with clearer skin in the middle; tinea means fungal infection, whereas dermatophyte refers to the fungal organisms that cause tinea.
Troche: A small medicated lozenge designed to dissolve. For example, to soothe the throat as a cough drop. Strictly speaking, a troche should be circular since the word derives from the Greek "trokhiskos" meaning "a little wheel.“Angular cheilitis is a condition that causes red, swollen patches in the corners of your mouth where your lips meet and make an angle
Pityriasis versicolor is a fungal skin infection caused by a type of yeast. It's a common cause of skin rash in teens and young adults. It causes lots of round and oval-shaped patches on the skin, especially on the chest, back, and upper arms. It's also called tinea versicolor.
Tingling or prickling, “pins-and-needles” sensation; usually temporary, often occurs in the arms, hands, legs or feet.
Onychomycosis, also known as tinea unguium, is a fungal infection of the nail.
Athlete's foot (tinea pedis) is a fungal infection that usually begins between the toes; Jock itch (tinea cruris) is a fungal infection that causes a red and itchy rash in warm and moist areas of the body. The rash often affects the groin and inner thighs and may be shaped like a ring. Jock itch gets its name because it's common in athletes.; Tinea corporis is a superficial dermatophyte infection characterized by either inflammatory or noninflammatory lesions on the glabrous skin (ie, skin regions other than the scalp, groin, palms, and soles) ; hairless; Tinea capitis is a disease caused by superficial fungal infection of the skin of the scalp, eyebrows, and eyelashes, with a propensity for attacking hair shafts and follicles.