This document provides information on anti-fungal drugs, including their classification, mechanisms of action, and therapeutic uses. It discusses several major classes of antifungal medications: azoles like fluconazole and itraconazole which inhibit ergosterol synthesis; amphotericin B which binds to ergosterol in fungal cell membranes; flucytosine an antimetabolite; and griseofulvin which disrupts fungal microtubules. These drugs are used to treat superficial fungal infections caused by dermatophytes and yeasts, as well as more serious systemic mycoses depending on their spectrum of antifungal activity and ability to achieve therapeutic drug concentrations
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.
Antiviral Agents,Medicinal Chemistry
•Introduction to Viruses
•Structure of Virus
•Types of Viruses.
•The viral Life cycle.
•Classification of Antiviral Agents
This PPT covers Drug therapy for Viral Infection or disease. It includes Viral replication cycle, classification of antiviral drugs, Anti-Herpes drug, Anti Influenza drugs, Anti hepatitis drugs and anti retroviral drugs
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.
Antiviral Agents,Medicinal Chemistry
•Introduction to Viruses
•Structure of Virus
•Types of Viruses.
•The viral Life cycle.
•Classification of Antiviral Agents
This PPT covers Drug therapy for Viral Infection or disease. It includes Viral replication cycle, classification of antiviral drugs, Anti-Herpes drug, Anti Influenza drugs, Anti hepatitis drugs and anti retroviral drugs
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At the end of this e-learning session you are able to…
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2. Explain pharmacology of Anthelminthic Drugs.
For 30+ video lecture series on Pharmacology Experiment as per PCI B Pharm Syllabus refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1Ba6WSJjeBaK0HMF79hdad3g
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Medicinal Chemistry and Pharmacology of Antifungal Agents and how to take care from fungal infections. Useful Course study material for the undergraduate , postgraduate and aspirants of Pharmacy , Pharmacology and Medicinal Chemistry.
Anti-fungal medication is used to treat to fungal infections. They most commonly affect our skin, hair and nails .Nowadays skin problems are found very often.
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3. Introduction
Pathogenic fungi of animals and humans are generally
filamentous molds or intracellular yeasts.
The fungal cell wall contains chitin and polysaccharides
making it rigid, and acts as a barrier to drug penetration.
The cell membrane contains ergosterol, which influences the
efficacy and the risk of drug resistance.
Most antifungal agents are fungistatic with infection-
clearance largely dependent on host response.
5
4.
5. FUNGI
5
Fungi may be classified as
Y
easts: Blastomyces, candida, histoplasma,
coccidioides,cryptococcus.
Moulds: Aspergillus spp. , Dermatophytes
Clinically classified as:
Superficial mycosis
Deep (systemic) mycosis
7. Fungal Infection in Humans = Mycosis
7
Major Types of Mycoses
superficial
cutaneous
subcutaneous
systemic
opportunistic
Symptoms vary from cosmetic to life threatening
8. Types of fungal infections
10
I. Mucocutaneous (superficial)
infections:
a. Dermatophytes:
cause infection of skin, hair, and
nails
e.g. tinea capitis (scalp), tinea
cruris (groin), tinea pedis (foot),
onychomycosis (nails).
9. Types of fungal infections
b. Yeasts:
cause infections of moist skin and
mucous membranes
e.g. Candida albicans causing oral,
pharyngeal, vaginal, & bladder
infections
9
10. Types of fungal infections
II. Systemic mycoses:
are fungal infections affecting
internal organs.
It occurs in immunocompromized
patients e.g. cryptococcosis, and
aspergillosis (lung).
10
12. Classification of antifungal drugs
Based on chemical structures:
The classes include Polyene macrolides,
Fluorinated pyrimidines, Benzo-furans and Iodides
Imidazoles,
Based on their sites of action:
Either systemic or topical antifungal drugs.
14
13. Classification of antifungal drugs
I. Drugs for mucocutaneous infections:
i. Systemic drugs
Azoles: Fluconazole, Itraconazole, Voriconazole.
Griseofulvin
Terbinafine
13
14. Classification of antifungal drugs
ii. Topical drugs
Azoles: Ketoconazole, Miconazole, Clotrimazole,
Tioconazole, etc.
Nystatin
Terbinafine.
Other drugs: Tolnaftate, Ciclopirox, Naftifine, Whitfield
ointment, Gentian violet, Castellani paint, Tincture
iodine.
14
15. Classification of antifungal drugs
II. Drugs for Systemic infections: :
Azoles: Fluconazole, Itraconazole, Voriconazole.
Amphotericin-B
Flucytosine
Caspofungin
15
16. Classification based on mechanism of
action
16
1. Fungal cell wall synthesis inhibition: Caspofungin.
2. Bind to fungal cell membrane ergosterol: Amphotercin–B, Nystatin.
3. Inhibition of ergosterol + lanosterol synthesis: Terbinafine, Naftifine,
Butenafine.
4. Inhibition of ergosterol synthesis: Azoles
5. Inhibition of nucleic acid synthesis: 5–Flucytosine.
6. Disruption of mitotic spindle and inhibition of fungal mitosis:
Griseofulvin.
7. Miscellaneous: Ciclopirox, Tolnaftate, Haloprogin, Undecylenic acid,
Topical azoles
21. I- Azoles
21
Synthetic antifungals
Broad spectrum
Fungistatic or fungicidal depending on conc of drug
Most commonly used
Classified as imidazoles & triazoles
22. I- Azoles
22
I. Imidazoles: Two nitrogen in structure
o Topical: econazole, miconazole, clotrimazole
o Systemic : ketoconazole
o Newer : butaconazole, oxiconazole, sulconazole
II. Triazoles : Three nitrogen in structure
o Fluconazole, itraconazole, voriconazole
o Terconazole: Topical for sup
23. Azoles
23
Pharmacokinetics
Absorption of azoles from stomach is affected by food
and gastric HCl.
Fluconazole can reach the CSF with good concentrations.
The other drugs cannot.
Fluconazole is excreted in the urine mostly unchanged
24. Azoles
Mechanism of action
Azoles inhibit fungal cytochrome P450
(14 α demthylase )necessary for ergosterol
synthesis, a major component of fungal cell
membrane. This will alter membrane
permeability and disrupt its function.
are broad spectrum fungistatic against
many dermatophytes and candida.
24
26. Azoles
26
Therapeutic uses
I. Superficial fungal infections: [ketoconazole – itraconazole –
miconazole]
1. Dermatophytes infection of the skin (tinea), hair, and nails
(onychomycosis):
For skin infection: treatment continued for 2-4 weeks.
For hair infection: treatment continued for 6-8 weeks.
For nail infection: treatment continued for 3-6 months.
2. Mucocautaneous candidiasis: oropharyngeal, vulvovaginal, etc.
27. Azoles
27
II. Systemic fungal infections: [itraconazole – fluconazole –
voriconazole]
Itraconazole (orally or IV) is the drug of choice for systemic
blastomycosis.
Fluconazole (orally or IV) is the drug of choice for systemic
candidiasis, and cryptococcal meningitis (because it the only azole
that can cross to CSF with good concentration).
Voriconazole is the drug of choice for inVasive aspergillosis of the
lung.
28. Azoles
30
Adverse effects
1. Hepatotoxicity and ↑ of serum transaminases.
2. Azoles inhibit hepatic CYP450 enzymes
(fluconazole is the least among them).
3. Ketoconazole causes antianderogenic
effects: gynecomastia and impotence due to
↓ gonadal steroid synthesis.
4. Voriconazole causes transient Visual
disturbances.
30. Amphotericin-B
Pharmacokinetics
is polar compound that cannot be absorbed from the
GIT or cross the CSF.
Insoluble in water so colloidal suspension prepared
with sodium deoxycholate(1:1 complex)
90% bound to plasma proteins
It should be administered IV or intrathecal.
Half-life is 15 days.
Dialysis is ineffective in case of toxicity.
30
31. Amphotericin-B
31
Pharmacokinetics(cont.)
Because of significant toxicity, amphotericin B is
available in liposomal form in which the drug is enclosed
in lipid microspheres “liposomes”.
These lipid microspheres bind preferentially to ergosterol
in the fungal cell membrane with lower affinity to
mammalian cell membranes.
32. Amphotericin-B
32
Mechanism of action
Amphotericin B is polyene macrolide that binds to
ergosterol of fungal cell membranes and forms “pores”
that alter membrane stability and allow leakage of
cellular contents.
33.
34. Amphotericin-B
34
Therapeutic uses
Amphotericin B has the broadest spectrum of activity.
o Treat severe Systemic fungal infections, including
those caused by Candida albicans, Histoplasma
capsulatum, Cryptococcus neoformans, Coccidioides
immitis, Blastomyces dermatitidis and Aspergillus spp.
35. Adverse effects
I. Acute reaction:
Chills, fever, headache, pain all over, nausea, vomiting,
dyspnoea lasting 2-5 hrs
II. Long term toxicity:
Nephrotoxicity:Azotemia,
Hypokalemia, acidosis, ↓ GFR
anemia
III.CNS toxicity : intrathecal administration, headache,
vomiting, nerve palsies
IV.Hepatotoxicity rarely
35
36. III- OTHER ANTIFUNGAL DRUGS
36
Flucytosine
Prodrug, pyrimidine analog, antimetabolite
Converted to 5-fluorouracil (5-FU)
Human cells cant convert it to 5FU
37. Flucytosine
Mechanism of action
Flucytosine is actively transported into
fungal cells and is converted to the uracil
form 5-fluorouracil (5-FU) which inhibits
nucleic acid synthesis. Human cells lack the
ability to convert large amounts of
flucytosine into 5-FU.
37
38.
39. Flucytosine
39
Uses
Used in combination with other antifungal agents (because
of rapid development of resistance) to treat Severe systemic
fungal infections.
Adverse effects
Flucytosine is relatively nontoxic
1. Depression of bone marrow at high doses
2. Hair loss.
40. Griseofulvin
Pharmacokinetics:
Oral administration, irregular absorption, increased
by fatty food and microfine particles
Gets conc in keratinized tissue
Metabolized in liver, excreted in urine
t1/2=24 hrs
40
41. Griseofulvin
Mechanism of action
Griseofulvin binds to microtubules and
prevents spindle formation and mitosis
in fungi.
It is fungistatic and requires long
duration of therapy.
The drug binds to keratin structures and
accumulates in skin, hair, and nails.
41
42.
43. Griseofulvin
43
Therapeutic uses
used orally for long-term therapy of dermatophyte infections
of the hair and nail.
Adverse effects
1. Hepatotoxicity (liver functions should be checked during
therapy)
2. Hypersensitivity reactions (skin rash)
3. CNS effects: confusion, fatigue, vertigo.
44. Nystain
44
Nystatin is polyene macrolide very similar in kinetics and
mechanism to amphotericin B.
It is too toxic for parenteral administration and is used only
topically.
It is active mainly against Candida, and is used topically for
oralpharyngeal and vaginal candidiasis.
45. Caspofungin
45
It is large cyclic peptide that disrupts the fungal cell wall
resulting in cell death.
Used by i.v. route for therapy in
i. Severe invasive aspergillosis
ii. Esophageal candidiasis who failed to respond to
amphotericin B (second line drug).
48. Terbinafine
50
Act by inhibiting squalene epoxidase, thereby
blocking the biosynthesis of ergosterol, an essential
component of the fungal cell membrane.
Accumulation of toxic amounts of squalene results in
increased membrane permeability and death of the
fungal cell.
The drug of choice for treating dermatophyte
onychomycoses
better tolerated, requires a shorter duration of therapy,
and is more effective than either itraconazole or
griseofulvin