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.
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.
The presentation gives an in-depth review of the Anti-fungal drugs used to treat various acute and chronic fungal infections along with their uses and MOA.
The all the content in this profile is completed by the teachers, students as well as other health care peoples.
thank you, all the respected peoples, for giving the information to complete this presentation.
this information is free to use by anyone.
Description on types of fungal organisms with differences between bacteria and fungi. A note on useful and harmful fungi. Brief insight on Antifungal classification, mechanism of actions and pharmacological profile with drug of choices for various fungal infections.
The presentation gives an in-depth review of the Anti-fungal drugs used to treat various acute and chronic fungal infections along with their uses and MOA.
The all the content in this profile is completed by the teachers, students as well as other health care peoples.
thank you, all the respected peoples, for giving the information to complete this presentation.
this information is free to use by anyone.
Description on types of fungal organisms with differences between bacteria and fungi. A note on useful and harmful fungi. Brief insight on Antifungal classification, mechanism of actions and pharmacological profile with drug of choices for various fungal infections.
Model Attribute Check Company Auto PropertyCeline George
In Odoo, the multi-company feature allows you to manage multiple companies within a single Odoo database instance. Each company can have its own configurations while still sharing common resources such as products, customers, and suppliers.
The Roman Empire A Historical Colossus.pdfkaushalkr1407
The Roman Empire, a vast and enduring power, stands as one of history's most remarkable civilizations, leaving an indelible imprint on the world. It emerged from the Roman Republic, transitioning into an imperial powerhouse under the leadership of Augustus Caesar in 27 BCE. This transformation marked the beginning of an era defined by unprecedented territorial expansion, architectural marvels, and profound cultural influence.
The empire's roots lie in the city of Rome, founded, according to legend, by Romulus in 753 BCE. Over centuries, Rome evolved from a small settlement to a formidable republic, characterized by a complex political system with elected officials and checks on power. However, internal strife, class conflicts, and military ambitions paved the way for the end of the Republic. Julius Caesar’s dictatorship and subsequent assassination in 44 BCE created a power vacuum, leading to a civil war. Octavian, later Augustus, emerged victorious, heralding the Roman Empire’s birth.
Under Augustus, the empire experienced the Pax Romana, a 200-year period of relative peace and stability. Augustus reformed the military, established efficient administrative systems, and initiated grand construction projects. The empire's borders expanded, encompassing territories from Britain to Egypt and from Spain to the Euphrates. Roman legions, renowned for their discipline and engineering prowess, secured and maintained these vast territories, building roads, fortifications, and cities that facilitated control and integration.
The Roman Empire’s society was hierarchical, with a rigid class system. At the top were the patricians, wealthy elites who held significant political power. Below them were the plebeians, free citizens with limited political influence, and the vast numbers of slaves who formed the backbone of the economy. The family unit was central, governed by the paterfamilias, the male head who held absolute authority.
Culturally, the Romans were eclectic, absorbing and adapting elements from the civilizations they encountered, particularly the Greeks. Roman art, literature, and philosophy reflected this synthesis, creating a rich cultural tapestry. Latin, the Roman language, became the lingua franca of the Western world, influencing numerous modern languages.
Roman architecture and engineering achievements were monumental. They perfected the arch, vault, and dome, constructing enduring structures like the Colosseum, Pantheon, and aqueducts. These engineering marvels not only showcased Roman ingenuity but also served practical purposes, from public entertainment to water supply.
This is a presentation by Dada Robert in a Your Skill Boost masterclass organised by the Excellence Foundation for South Sudan (EFSS) on Saturday, the 25th and Sunday, the 26th of May 2024.
He discussed the concept of quality improvement, emphasizing its applicability to various aspects of life, including personal, project, and program improvements. He defined quality as doing the right thing at the right time in the right way to achieve the best possible results and discussed the concept of the "gap" between what we know and what we do, and how this gap represents the areas we need to improve. He explained the scientific approach to quality improvement, which involves systematic performance analysis, testing and learning, and implementing change ideas. He also highlighted the importance of client focus and a team approach to quality improvement.
How to Create Map Views in the Odoo 17 ERPCeline George
The map views are useful for providing a geographical representation of data. They allow users to visualize and analyze the data in a more intuitive manner.
How to Make a Field invisible in Odoo 17Celine George
It is possible to hide or invisible some fields in odoo. Commonly using “invisible” attribute in the field definition to invisible the fields. This slide will show how to make a field invisible in odoo 17.
2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
2. Introduction to Fungal Diseases
• In 1839, Schonlein and Gruby- identified Trichophyton and C. albicans
• Langenbeck- isolated fungus from potato slices.
• Disease caused by fungi is generally called mycosis. This is of two types:
Superficial Mycosis( Dermatophytoses) and Deep-Seated Systemic
Mycosis.
• The other type of fungal infection which are developed due to overuse of
antibiotics, immunosuppressant, cytotoxins, steroid and due to underlying
medical manipulation or disease- Opportunistic Fungal Infections. Ex:
Candidiasis, Aspergillosis, Mucormycosis, Pneumocystis
• Most common oppurtunist is C.albicans
3. • Superficial Mycoses: Generally these fungi feed on the protein called
Keratin and all are called Dermatophytes.
Tinea manuum- hand Tinea cruris- groin
Tinea sycosis-beard Tinea capitis- hair & scalp
Tinea unguium/Onchomycosis-nail Tinea pedis-foot
• Deep-seated Systemic Mycosis:
Histoplasmosis
Cryptococcosis
Blastomycosis
• This systemic fungal infections occur by inhalation of fungal spores and
shows some cold like symptoms.
• Some infections become severe, deep spreading and often-fatal disease.
9. • Fatty acids: Zinc propionate, sodium and zinc caprylate, undecylenic acid,
triacetin, salicylic acid and benzoic acid with resorcinol
• Phenols and their derivatives: Haloprogin, clioquinol, ciclopirox
• Nucleoside antifungals: Flucytosine
• Anti fungal antibiotics: Amphotericin B, Nystatin, Natamycin, Griseofulvin.
• Allylamine and related compounds: Naftifine, tolnaftate, terbinafine
• Azole antifungals: Imidazole and Triazole anti fungals
• Echinocanadins and Pneumocanadins: Capsofungin, Anidulafungin, Micafungin
• Aureobasidins: Aureobasidin A
Chemical Classification of Antifungal Agents
10.
11. NATURAL ANTI FUNGALS
Polyene Anti fungals:
– Obtained from soil bacteria called Streptomyces.
– The first anti fungals used for deep-seated mycosis.
– They resemble in structure with the macrolide antibiotics, in their macrocyclic
lactone( Cyclic ester) while the difference exists with size of lactone ring and 4-
7 conjugated double bonds.
– Based on size of the ring polyenes are categorised into
• 26-membered lactone: Natamycin
• 38- membered lactone: Nystatin, amphotericin B
– They are highly potent antifungal agents
Acid derived portion
Mycosamine
12. Mechanism of action
Polyenes are selective towards ergosterol-containing membranes
Fungistatic-low concentration(bind to ATPase of cell membrane) fungicidal-
high concentrations.
They resemble structural cell membrane component and they acquire micelle
shape
Insert into the membrane near Ergosterol
Create pore or leaky channels
Loss of K+ ions, other ions and small inorganic molecules
Death of cell
13.
14. The no. of conjugated double bonds in Polyenes α antifungal activity
α 1/toxicity
Uses: mainly to treat deep-seated systemic infections.
• Only Amphotericin B is used systemically (Candida, Cryptococcal, Mucor,
Aspergillus and Blastomyces infections) with a detergent.
• The others were used to treat superficial infections.
• They are also effective on protozoan called Leishmania.
Nystatin: First tetraene anti fungal obtained from Streptomyces noursei.
Used to treat superficial fungal infections (cutaneous and muco cutaneous candidiasis)
and administered through mouth to treat mouth and GIT fungal infections.
Vaginal tablet for vaginal candidiasis, along with tetracycline used to treat monilial
infection.
15. Amphotericin B: obtained as a mixture from Streptomyces nodosus.
Used to treat CNS fungal infection(Administered along with CSF).
Adverse effects : nephrotoxicity, muscle and joint pains, GIT distress, fever, shaking
chills, hypotension, anorexia, malaise, hemolysis
Pain occur at site of IV injection ( a complex of Amphotericin B with deoxycholic
acid, liposomal encapsulation and liposomal complexes) and thrombophlebitis
(blocks of blood in one or more veins generally near skin) occur
Should never be given through IM.
Natamycin: a tetraene obtained from Streptomyces natalensis
used as suspension to treat fungal infections of eye such as fungal conjunctivitis,
blepheritis and keratitis
Active in vitro on Candida, Aspergillus, Cephalosporium, Fusarium, Penicillium
16. Griseofulvin: obtained from Penicillium griseofulvium.
• a rare natural chemical with spiro carbon and is also
called “curling factor”. And also called “mitotic spindle poison”.
• Initially used in plants and animals.
• Later this is used systemically for long time to treat refractory ring worm
infections of fingernail and toenail infections.
Adverse effects: urticaria, GIT distress, headache, dizziness, rash and insomnia.
17. MOA: orally administered Griseofulvin through the systemic
circulation reaches the tissues rich in keratin
Accumulates in the keratin precursor cells of skin, nails, hair follicles
where exfoliation occur
Binds to tubulin dimer for microtubule assembly
inhibits the mitotic spindle apparatus, reversibly dissolves mitotic
spindle apparatus
Arrests the cell division in metaphase
18. AZOLE ANTI FUNGALS
• Largest group of anti fungals present in the market.
• Azole anti fungals are broad spectrum anti fungal agents
• Used to treat topical fungal and yeast infections & are also used to treat systemic
yeast infections.
• All the azoles have five-membered aromatic ring with two or three nitrogen atoms.
• The nitrogen aromatic rings present include imidazole and triazole.
• Early azoles were extensively metabolised by first-pass metabolism.
• Clotrimazole, tioconazole, econazole, sulconazole, terconazole, butoconazole,
oxiconazole, miconazole– for topical use and intravaginal use.
• Ketoconazole, itraconazole, voriconazole, posconazole—used systemically.
• Azole drugs are inhibitors of Cytochrome P450 enzymes and P-glycoprotein.
• Adverse effects: Endocrine effects and hepatotoxicity.
20. Azole binds to the CYP 51 or 14α- demethylase enzyme
Inhibits oxidative removal of methyl group from 14th carbon
The sterols with improper structure is incorporated into the membrane
Repaired by chitin synthesis
Membrane destabilizes
Degradation of cell membrane and leakage of important constituents
Resistance: Mutations in ERG 11 gene
cross resistance is seen among the azole anti fungals.
21. • Basic structural requirement—weakly basic (pKa 6.5-6.8) imidazole or
1,2,4-triazole nitrogen bonded to carbon.
Structure Activity Relationship (SAR)
Z
Y
X
N
R
imidazole X=CH- Y=N Z=CH-
triazole X=N- Y=CH- Z=N-
side chain with two or three Aromatic rings
which resembles the non polar steroidal portion and fits
into the pocket of 14-demethylase
Substitution on one aromatic ring
@ 2 or 2,4 -X atoms- effective anti fungal agents
with -F or -SO3H-- potent anti fungals
@ other positions- inactive compounds
Amidine Nitrogen -C=N- i.e N3 of imidazole
N4 of triazole
binds with heme of 14-demethylase and
inhibits transfer of electrons to oxygen
22. Imidazole anti fungals
• Clotrimazole: topical tinea infection and candidiasis
• Econazole: local tinea infections and candidiasis.
• Butaconazole: Vaginal candidiasis
• Oxiconazole: tinea pedis, corporis, capitis
• Tioconazole: Vulvovaginal candidiasis
• Miconazole: candidiasis, cryptococcosis, coccidiodomycosis and chronic
mucocutaneous candidiasis.
Adverse effects: thrombophlebitis, pruritis, fever, GIT distress
• Ketoconazole : cis-2S, 4R and cis-2R, 4S are more active enantiomers.
systemically- candidiasis, cryptococcosis, coccidiodomycosis, blastomycosis,
histoplasmosis, chromomycosis
orally- refractory cutaneous dermatophytic infections
topically- cutaneous candidiasis and tinea infections.
Antacids, H2-antihistaminics, anti cholinergics- decrease oral absorbtion
Phenytoin, carbamazine, cyclosporine, terfenadine, rifampin- decrease the levels
of ketoconazole.
Hypnotic triazolam, coumarin anticoagulants and sulfonylurea hypoglycemics- response
enhanced
High levels of ketoconazole- lower tetosterone and corticosterone levels.
23. Triazole anti fungals
• Terconaole: to treat vulvovaginal moniliasis or vaginal candidiasis
• Itraconazole: used to treat histoplasmosis, blastomycosis, sporotrichosis.
– Drug interactions: plasma levels of drugs are reduced by co administration of
phenytoin, carbamazine, rifampin.
– Co administration with either lovaststin or simvastatin reduces the adverse
effect called rhabdomyolysis.
– Incrase the levels of terfenadine and astemizole
• Fluconazole: can cross BBB and effective against Cryptococcus.
to treat disseminated or deep organ candidiasis,
esophageal and oropharyngeal candidiasis , treatment
and prophylaxis of cryptococcosis in AIDS patients
Vaginal candidiasis
24. Allylamine antifungals
• Limited efficacy and used to treat fungal infections of skin and nails.
• Fungicidal on dermatophytic fungi and other filamentous fungi while
fungistatic on yeast.
• Both naftifine and terbinafine have allyl amine group
• Naftifine: extensively first pass metabolised.
so used only topically to treat ringworm infections of beard,
scalp and skin
• Trebinafine: potent than naftifine
used to treat tinea pedis, corporis, cruris.
orally active to treat onchomycosis
Extensively metabolised by CYP450 enzymes.
Cimetidine increases the plasma levels of terbinafine
It is strong inhibitor of CYP2D6 enzyme
25. Mechanism of action
Inhibits squalene epoxidase during ergosterol synthesis
Decreased total sterol results in build up of hydrocarbon
content in membrane Squalene
Altered physicochemical abnormal accumulation of squalene
properties of membrane is toxic
Embedded protein malfunction Cell death occur
Alters transports of nutrient
and maintainance of pH
26. MORPHOLINES
• Amorolfine is the only drug under
this class to treat fungal infections but not used today.
• Inhibits the enzyme Δ14 reductase and Δ8,7 isomerase enzymes of ergosterol
synthesis
• These are membrane disruptors.
MISCELLANEOUS DRUGS
Flucytosine
• Powerful anti fungal drug used to treat serious systemic
fungal infections like Cryptococcosis, Candidiasis
• 5-fluorouridine interferes with protein and RNA biosynthesis
• Used in combination
with Amphotericin B
27. Haloprogin
• Iodinated acetylene derivative
• Used to treat dermatophytic infections
MOA: Interferes with DNA replication and cell respiration and also inhibits
non specifically some metabolic process.
Ciclopirox
• Hydroxylated pyridinone specifically used to treat
Onchomycosis
MOA: chelates multivalent metal ions like Fe3+ and inhibits the important
enzymes which are metal dependent.
Undecylenic acid
• Obtained from destructive distillation of castor oil.
• Used to treat Athlete’s foot.
MOA: Fungistatic by interacting nonspecifically with fungal membrane
components.
