this class is in brief for under graduate understanding and examination purpose

1. Dr. RAGHU PRASADA M S
MBBS,MD
ASSISTANT PROFESSOR
DEPT. OF PHARMACOLOGY
SSIMS & RC.
1

3.  Inhibition Of Fungal Cell Wall Synthesis-
ECHINOCANDINS- CASPOFUNGIN, MICAFUNGIN,
ANIDULAFUNGIN,
 Binds to fungal cell membrane ergosterol and
increase membrane permeability-polyene group-
AMPHOTERICIN-B, NYSTATIN
 Inhibition of Ergosterol+ Lanosterol Synthesis-
(Allylamine group)-TERBINAFINE
 Inhibition of ergosterol synthesis- (Azole group)
 KETOCONAZOLE, FLUCONAZOLE, ITRACONAZOLE,
VORICONAZOLE, POSACONAZOLE

4. Inhibition of nucleic acid synthesis
5-FLUCYTOSINE
Disruption of mitotic spindle and inhibition of fungal
mitosis-GRISEOFULVIN
OTHER TOPICAL agents- CICLOPIROX, TOLNAFTATE,
CLIOQUINOL, NAFTIFINE, BUTENAFINE,
CLOTRIMAZOLE, ECONAZOLE, SULCONAZOLE,
SERTACONAZOLE

5. SUPERFECIAL
Dermatomycoses affecting skin, hair or nails.
Epidermophyton (skin and nails)
Trichophyton (skin,hair & nail)
Microsporum (skin and hair)
b) Candidiasis (commonly normal flora of mouth, skin,
intestines and vagina) infection caused by genus candida
affecting skin, mucous membrane of mouth or G.I.T or female
genital tract
SYSTEMIC
Candidiasis ,cryptococosis, Aspergillosis,
Blastomycosis, Histoplasmosis,
Coccidioidomycosis, Paracoccidioidomycosis etc

6.  Fungal cell membranes have a unique sterol,
ergosterol, which replaces cholesterol found in
mammalian cell membranes

9. CASPOFUNGIN
It is echinocandin class of antifungal drugs
it interferes with the synthesis of fungal cell wall by
inhibiting synthesis of 1,3-β-glucan.
Mammalian cell wall does not require 1,3-β-glucan
Selective toxicity to host
For aspergillus and candida.
Not active orally
Higly bound to serum proteins
Has half life of 9-11 hours

10.  slowly metabolized by hydrolysis and N-acetylation.
 eliminated equally by urinary and fecal route.
Adverse effects include Headache, rashes, nausea,
vomiting, flushing, abnormal liver function tests
 very expensive
D/I- Enzyme inducers increase metabolism
increase clearance of tacrolimus
Micafungin and anidulafungin – more potent

11.  It is a natural polyene macrolide
 (polyene = many double bonds )
 (macrolide = containing a large lactone ring )
MOA- It is a selective fungicidal drug. Disrupt fungal
cell membrane by binding to ergosterol , so alters the
permeability of the cell membrane forms
poresleading to leakage of intracellular ions &
macromolecules.
Selective toxicity-mammalian cell membrane-
cholesterol

12. Amphotericin B is packaged in a lipid- associated
delivery system to reduce binding to human cell
membrane , so reducing :
A. Nephrotoxicity
B. Infusion toxicity
Also, more effective
More expensive
AMP-B-lipid complex-non liposomal
formulation that complexes the drug
with two phospholipids

13. Ergosterol binding is impaired by
Decreasing the membrane concentration of ergosterol.
Modyfing the sterol target molecule other sterols
fungi that lacks ergosterol are not suseptible

14. Poorly absorbed orally , is effective for fungal infection
of gastrointestinal tract.
For systemic infections given as slow I.V.
Insoluble in water so prepared as colloidal suspension
with sodium desoxycholate
Highly bound to plasma protein .
Poorly crossing BBB.
Metabolized in liver
Excreted slowly in urine over a period of several days.
Half-life 15 days.

15. Slow I.V.infusion for systemic fungal disease.
Intrathecal for fungal C.N.S. infections.
Topical drops & direct subconjunctival injection for
Mycotic corneal ulcers & keratitis.
Local injection into the joint in fungal arthritis.
Bladder irrigation in Candiduria.

16. Has a broad spectrum of activity & fungicidal action.
The drug of choice for life-threatening mycotic
infections in immunocompromised patients
Invasive aspergillosis, mucormycosis, histoplasmosis
Also, for chronic therapy & preventive therapy of
relapse.
In cancer patients with neutropenia who remain febrile
on broad –spectrum antibiotics.
Kala azar- reserve drug

17. 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
corticosteroids.
D. A test dose.

18.  Most serious is renal toxicityrenal tubular
necrosis, hypokalemia, azotemia, Hypomagnesaemia
 Impaired liver functions
 Thrombocytopenia
 Anemia-hypochromic normocytic
 Arachnoiditis, seizures

19.  They are antibacterial, antiprotozoal, anthelminthic
and antifungal
 These are group of synthetic fungistatic agents
 They have broad spectrum of activity
 Inhibit the fungal cytochrome P450 3A enzyme ,
lanosine 14-demethylase which is responsible for
converting lanosterol to ergosterol the main sterol
in the fungal cell membrane this alters fluidity of
the membrane, thus inhibiting the growth of fungi.
 Inhibits respiration under aerobic conditions

20. Ketoconazole, miconazole, clotrimazole,
isoconazole , Tioconazole
Triazoles-Fluconazole, itraconazole, voriconazole
They are selective Penetrate to CNS
Resistant to degradation
Cause less endocrine disturbance

21. First azole that could be given orally to treat systemic
fungal infections.
Well absorbed orally as acidic environment favors its
dissolution.
Bioavailability is decreased with H-2 blocking drugs,
proton pump inhibitors and antacids and is impaired with
food.
After oral administration of 200,400 and 800 mg,
Half life increases with dose and it is 7-8 hrs with 800 mg

22. Metabolized extensively in liver and inactive products
appear in the feces.
84 % is bound to plasma proteins.
It does not enter CSF.
Moderate hepatic dysfunction has no effect on drug
concentration.
Induction of microsomal enzymes
by other drugs reduces
the concentration.
Warfarin ,Rifampin increase
its metabolism
H2 blockers ,antacids decrease
its absorption.

23. Dose dependent nausea, anorexia ,vomiting
Liver toxicity is rare but may prove fatal.
Hair loss
As it inhibits steroid biosynthesis, several
endocrinological abnormalities may be evident as
menstrual abnormalities, gynecomastia, decreased
libido and impotency.
Fluid retention and hypertension.

24. It is a synthetic triazole
It lacks endocrine side effects of ketoconazole.
It has broad spectrum activity
Food increases its absorption
Metabolized in liver extensively by cytochrome CYP3A4
It is highly lipid soluble, it is well distributed to bone,
sputum and adipose tissue.
Highly bound to plasma protein
Do not penetrate CSF adequately, therefore its
concentration is less to treat meningeal fungal infection

25. Half life is 30-40 hours
Steady state reaches in 4 days, so loading doses are
recommended in deep mycosis.
Dose 100 mg twice daily with food, initially 300 mg
thrice daily as a loading dose.
Intravenously reserved only in serious infections.
Adverse effects: Nausea, vomiting,
hypertriglyceridemia, Hypokalemia, increased
aminotransferase, hepatotoxicity

26. It is fluorinated bistriazole.
Completely absorbed from GIT
Excellent bioavailability by oral route.
Concentration in plasma is same by oral or I/v route.
Bioavailability not altered by food or gastric acidity
It has least effect on hepatic microsomal enzymes.
It easily penetrate CSF and is a drug of choice in
cryptococcal meningitis and coccido mycosis.
It can safely be administered prophylactically in
patients receiving bone marrow transplants.

27. Resistance not a problem except in patients with HIV
100mg repetitive dose.
Renal excretion 90%
t1/2 -25-30 hours.
Diffuse in all body fluids including CSF concentration
50-90 %.
Candidiasis: 200 mg on 1st day then 100 mg daily for 2
weeks.
Cryptococcosis: 400 mg daily for 8 weeks in meningitis.
In AIDS 200 mg for life.
Coccidial meningitis it is drug of choice

28. It has also activity against histoplasmosis,
blastomycosis, spirotrichosis ,and ring worm
Not effective in aspergillosis.
Adverse effects
Nausea, vomiting, headache, skin rash, abdominal
pain, diarrhea, reversible alopecia
No endocrine adverse effects.
Hepatic failure may lead to death
It is highly teratogenic

29. Second generation triazole
High oral bioavailability-96%
Low plasma protein binding -55%
Good CSF penetration
T1/2- 6hrs
Therapeutic uses- invasive aspergillosis
Useful I esophagial candidiasis
Candida resistant to fluconazole are sensitive to
voriconazole
Dose- 200mg 12th hourly

30. Blurred vision, photophobia-30%
Rashes, nausea, raised hepatic enzyme levels
Drug interactions
Inhibitors or inducers of CYP may increase or decrease
voriconazole plasma concentrations
Rifampicin, Rifabutin, Phenytoin and Ritonavir
accelerate metabolismand reduce efficacy
voriconazole retards metabolism of sirolimus,
tacrolimus, cyclosporine and Warfarin

31. It is a fluorinated analogue of cytosine
Structurally related to antineoplastic agent 5-
Flurouracil
Taken up into the fungal cell by means of permease
converted to 5-fluorouracil (5-FU) by cytosine
deaminase
5-FU eventually inhibits thymidylate synthetase
blocks formation of thymidylate mono phosphate
fungal DNA formation is inhibited

32. Mechanism
of action

33.  Has useful activity against Candida and
Cryptococcus.
 It is synthetic pyrimidine antimetabolite that is often
used in combination with amphotericin B
 It is fungistatic, effective in combination with
itraconazole for treating chromoblastomycosis and
with Amphotericin for treating cryptococosis
 Given orally, penetrates into CNS
 Excreted in urine-80% unchanged
 t 1/2 3-6 hours, but in renal failures it may be 200
hours

34. Systemic fungi, mainly candida, and cryptococcus.
Effective in combination with itraconazole for
treating chromoblastomycosis and with
Amphotericin-B for treating cryptococosis
(cryptococcal meningitis)
Adverse effects-
Nausea, vomiting, colitis, Bone marrow suppression
Thrombocytopenia, alopecia, decreased liver function

35.  In superficial fungal infections those drugs are
preferred which get confined to stratum corneum,
squamous mucosa or corneadermatophytosis
(ring worm), candidiasis tinea and fungal keratitis.
 Topical administration of antifungal agents is usually
not successful in mycoses of the nails and hair and
has no place in the treatment of subcutaneous
mycoses.

36. The efficacy of topical agents in the superficial mycosis
depends on
1. Type of lesion
2. Mechanism of the drug action
3. Viscosity,
4. Hydrophobicity and acidity of the formulation.
The preferred formulation for cutaneous application
usually is a cream or solution.

37. Topical anti fungal
preparations
Topical azole derivatives
Ciclopirox olamine
Naftifine
Terbinafine
Butenafine
tolnaftate
Nystatin and
Amphotericin
Oral anti fungal agents
used for topical
infections
Griseofulvin
oral azoles
Terbinafine

38. These are synthetic and used both topically and
systemically
Vaginal creams, suppositories and tablets for vaginal
candidiasis used once a day preferably at bed time
Erythema, edema, vesication, pruritus, urticaria mild
vaginal burning sensation may occur.
Clotrimazole is effective in 60-100%.
Cutaneous candidiasis is 80-100%
Vulvovaginal candidiasis is 80%.

39. Isolated from Pencillium griseofulvum
It has largely been replaced by terbinafine for
treatment of dermatophytic infections of the nails.
Much insoluble in water
It is useful for dermatophytes (fungistatic)
It has narrow spectrum.
It interacts with microtubules and interferes with
mitosis.

40. Absorption increases with fatty meal
It is ineffective topically.
Extensively metabolized in liver.
Induce CYP450. t 1/2 -1day
Drug is deposited in keratin, nail and hair
5-15 mg /kg for children and
0.5 -1 gram for adults.
Uses-
Treatment required is
1 month for scalp and hair (T. capitis)
6-9 months for finger nails, and at least
1 year for toe nails
It is also highly effective in athlete's foot

41. Adverse effects
 Headache
 Peripheral neuritis , lethargy , mental confusion,
impairment in performance of routine task, fatigue,
vertigo ,syncope, blurred vision.
D/I-Barbiturates decreases the absorption from GIT.

42. It is synthetic allylamine
It is a drug of choice for treating dermatophytes
It is better tolerated , requires shorter duration of
therapy
MOA-It inhibits fungal sequalene epoxidase, decreases
synthesis of ergosterol affects cell membrane
integrity and function
Also accumulation of toxic amounts of squalene
causes cell death.
It is fungicidal but activity is limited to C. albicans and
dermatophytes.

43. Oral bioavailability is 50-70%
Highly lipophilic and keratophilic – resulting in high
concentrations in corneum, hair and nails
Effective for the treatment of onychomycosis 250 mg
daily for 6 weeks for finger nail infection and for 12
weeks in toe nail infection
Protein binding more than 99% in plasma.
Drug accumulates in skin, nails and fat.
Rarely hepatotoxic , liver failure even death.
Rifampicin decreases its serum concentration and
cimetidine increases

44.  It is polyene macrolide,similar in structure to
amphotericin and with same mechanism of action
 Too toxic for systemic use
 Not absorbed from GIT, skin or vagina, therefore
administered orally for candidial infection of the
mucosatablets 500,000 U are used to decrease
GIT colonization with Candida
 Prevent or treat superficial candidiasis of mouth,
esophagus or intestinal tract, oral suspension of
100,000 U/ml 4 times a day

45.  For vaginal candidiasis in form of pessaries used for
2 weeks
 In Cutaneous infection available in cream, ointment
or powder form and applied 2-3 times a day
 Can be used in combination with antibacterial
agents and corticosteroids

46. Synthetic antifungal drug
Distorts hyphae and mycelial growth of yeast-like fungi
and moulds
Effective in most cutaneous mycosis.
It is ineffective against Candida.
In tinea pedis cure rate is around 80%.
Available in 1% con.as cream, powder and topical
solution.
Applied locally twice a day.

47. It is broad spectrum, fungicidal.
Available as 1% cream or gel
Effective for tropical treatment of tinea cruris.

48. THANKYOU
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