antifungal agents ,mpharm

1. ANTIFUNGAL AGENTS
SUBMITTED TO :-
ASSOC PROF: DR SANJIV KARALE
DEPARTMENT OF PHARMACOLOGY AND TOXICOLOGY
SUBMITTED BY:- THEERTHA T
M PHARM (IST YEAR)
SREE DEVI COLLEGE OF PHARMACY

2. INTRODUCTION
• Fungi are eukaryotic cells. They possess
mithochondria, nuclei and cell membrane.
• They have a rigid cell walls containing chitin
as well as polysaccharides, and a cell
membrane composed of ergosterol.
• Thus , antifungal drugs are in general more
toxic than antibacterial agents

3. Fungi can be divided into four classes
1) yeasts
2)yeast like fungi
3)dimorphic fungi
4) moulds

4. Systemic fungal infections
• Systemic candidiasis
• Cryptococcal meningitis, endocarditis
• Rhinocerebral neucormycosis
• Pulmonary aspergillosis
• Blastomycosis
• Histoplasmosis
• Coccidiodomycosis
• Phemocystis carinii pneumonia

5. OVERVIEW OF FUNGAL INFECTION
• Fungal infection are termed as mycoses
• In uk, the commonest fungal disesse is systemic candidiasis
CLINICAL CLASSIFICATION OF MYCOSES:
• Cutaneous mycoses:resticted to the keratinized layers of the
skin , hair and nails
• Subcutaneous mycoses: involve the dermis, subcutaneous
tissues, muscles.
• Systemic mycoses due to opportunistic pathogens:
infection to patients with immune deficiencies
• Systemic mycoses due to primary pathogens: originate
primarly in the lungs and spread to may organ systems

8. ECHINOCANDINS
• These are a new class of potent semisynthetic antifungal
antibiotics with a complex cyclic lipopeptide structure
• Three echinocandins are in current use :
Caspofungin, micafungin, and anidulafungin
M/A
Lysis of fungal cell wall by inhibiting the synthesis of 1,3 b
glucan
THERAPEUTIC USE
• Aspergillus infection
• Active mainly against candida and aspergillus

9. PHARMACOKINETICS
-not absorbed orally
-distributed into tissues,but not enter CSF
-metabolites excreted in urine
USES
deep and invasive candidiasis
esophageal candidiasis
ADR
-abnormal liver function
-flushing
-headache
-rashes

10. • DOSE AND BRAND
-70 mg loading dose infused iv over 1 hr
folllowed by 50 mg i.v daily
-CANCIDAS 70 mg in 10 ml and 50 mg in
10 ml inj

11. ANTIBIOTICS
A) Amphotericin-b(polyene group):

13. PHARMACOKINETICS
a)poorly absorbed from GIT
b)not for treatment of systemic fungal
infection of intestine
c)insoluble in water, therefore prepared as a
colloidal suspension with sodium
desoxycholate for iv infusion
ADR
a)Acute reaction:chills, fever,
aches,nausea,vomiting
b)long term toxicity:nephrotoxicity,CNS
toxicity

14. USES
-applied topically for oral, vaginal candidasis
-systemic mycoses
-otomycosis
INTERACTIONS
aminoglycosides, vancomycin,cyclosporine and
other nephrotoxic drugs enhace the renal
impairment caused by AMB
ADMINISTRATION AND DOSE
orally(50-100 mg QID)
FUNGIZONE OTIC 3% ear drop

15. HETEROCYCLIC BENZOFURAN
Griseofulvin: extracted from penicillinum griseofulvum
M/A
Disruption of mitotic spindle
arrest fungal mitosis at metaphase
and inhibit fungal cell division so fungistatic action

16. Pharmacokinetics
-ineffective topically
-administred orally, but it is variably absorbed from git
-micronisation of the drug particles and ingestion with a
fatty meal improves its bioavailability
THERAPEUTIC USE
systemic treatment of dermatophytosis
-terbinafine and azoles are more eficacious
ADR
-headache
-nausea
-vomiting
-peripheral neuritis

17. INTERACTIONS
-efficacy of oral contraceptives may be lost
-cause intolerence to alcohol
DOSE
125 to 250 mg QID with meals
GRISOVIN-FP
WALAVIN

18. ANTIMETABOLITE
FLUCYTOSINE
M/A:
transported to fungal cells by the help of enzyme
cytosine permease enzyme
cytosine deaminase enzyme
5-fluorouracil
fluorodeoxyuridine monophospate (competitive
inhibitor of thymidylate synthetase)
inhibit fungal DNA synthesis

20. USES
used in combination with amphotericin b for
cryptococcal meningitis
ADR
nausea, vomiting, loss of appetite, diarrhea;
headache
numbness, tingling, or burning pain in your hands or
feet, dry mouth

21. AZOLES
 Azole antifungals are broadly divided into imidazoles and
triazoles .both of them are structurally related and have
similar mechanism of action and anti fungal spectum
M/A
azole impair ergosterol synthesis by inhibiting 14alpha
demethylase enzyme
MICONAZOLE AND CLOTRIMAZOLE
USES :
Dermatophytic infection
Candida infections
ADR:
Local irritation, itching or burning

22. KETOCONAZOLE(KTZ)
First orally effective broad spectrum antifungal drug
PHARMACOKINETICS
Oral absorption facilitated by gastric acidity because more
soluble at lower ph
Penetration in CSF poor
USES
Dermatophytosis
Deep mycosis
Effective in seborrhoea of scalp and dandruff

23. ADR
nausea and vomiting
loss of appetite
headache
rashes
hairloss
INTERACTIONS
PPI and antacids decrese oral absorption of KTZ by
reducing gastric acidity
rifampicin ,phenobarbitone induce KTZ metabolism
and reduce efficacy
DOSE
200mg OD OR BD

24. ALLYLAMINE
TERBINAFINE(FUNGICIDAL)
M/A:
terbinafine inhibits fungal enzyme squalene epoxidase
(convert squalene to lanosterol)
Reduction in lanosterol production that decreases ergosterol
production effect fungal cell membrane integrety and function
USES:
Systemically as well as topically
Orally used to treat onychomycosis
ADR:
Headache , git upset, liver enzyme elevation

25. Pharamacokinetics:
Absorption >70%
Bioavailability: 40% (Adults); 36-64% (children)
Peak plasma time: 1-2 hr
Excretion: Urine
DOSE
tablet: 250mg
LAMISIL
SEBIFIN

26. TOLNAFTATE
-Effective in most cutaneous mycosis
-ineffective agaist candida
- it is believed to inhibit squalene epoxidase, an important enzyme
in the biosynthetic pathway of ergosterol
ADR
Sensitization
Mild irritation
Other Indications & Uses
Indicated for Tinea pedis, cruris, corporis, and versicolor

27. REFERENCE
THE PHARMACOLOGICAL BASIS OF
THERAPEUTICS , GOODMAN &
GILMAN
ESSENTIALS OF MEDICAL
PHARMACOLOGY BY K.D TRIPATHI