Anti-fungal drugs.pdf

At the end of this e-learning session you are able to…
Discuss type of fungal infection and classify Anti-fungal drugs.
Explain pharmacology of anti-fungal drugs.
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1. Prof. Shaikh Abusufiyan
Assistant Professor,
AIKTC-School of Pharmacy,
New Panvel-410206
Antifungal Drugs
Pharma Learning Forever

2. At the end of this e-learning session you are able to…
A.Discuss type of fungal infectionand
classify Anti-fungal drugs.
B.Explain pharmacologyof anti-fungal
drugs.

3. ●Thefungalinfectionaretermedas
mycoses.
2Typesoffungalinfection:
1.Superiorfungalinfection:affectingskin,
nails,scalpormucousmembrane.
2.Systeminfection:affectingdeepertissues
andorgan.

4. ●Thecommonestsystemicfungaldiseaseissystemic
candidiasis-->infectionwithyeastlikemicroorganism.
●Othermoreseriousconditionsare:
●Cryptococcalmeningitis
●Endocarditis
●Pulmonaryaspergillosis

5. ●Colonizationofthelungsofpatientby
aspergillus-->canleadtoallergic
bronchopulmonaryaspergillosis.

6. Prevalence:
Following people are more prone to fungal infections:
●Older people
●Diabetic patients
●Pregnant women
●Burn wound victims

7. ●Thesuperficialfungalinfectioncanbeclassifiedas:
●Dermatomycoses-infectionofskin,nailsandhairs.
●Candidiasis-yeastlikeMOinfectthemucous
membranesofthemouth,vaginaorskin.

8. Anti-fungal drugs
1.Antibiotics:
A.Polyenese.gAmphotericinB,Nystatin,Hamycin,
Natamycin
B.Heterocyclicbenzofurane.g.Griseofulvin.
2.Antimetabolitese.g.Flucytosine(5-FU)

9. 3.Azoles:
Eg.Imidazole's
-Topical-Clotrimazole,Econazole,Miconazole
-Systemic-Fluconazole,itraconazole
4.AllylamineegTerbinafine
5.Othertopicalagents:
●Tolnaflate,benzoicacid,quinido-chlore,sod.
thiosulphate

10. I.Polyeneantibiotics:
A.AmphotericinB:
-Itisamacrolideantibioticsofacomplexstructure-
characterizedbymanymembercarbonring.

11. MOA:
●Fungal cell contain large amt of ergosterolin the
plasma membrane
Facilitate the attachment ofpolyene antibiotics
Act as ionophoresand cause leakage of the cation

12. Pharmacokinetics:
●Amphotericin is poorly absorbed and remains in GIT
It is given for the fungal infection of GIT.

13. ●Itcanalsobegiventopically.
●Forsystemicinfection-itcomplexwithsodium
deoxycholateandgivenasasuspensionbyslowIV
injection.

14. ●OtherpreparationofamphotericinforIVinfusion
includeamphotericincomplexedwith–lipid-beta
cyclodextrin
●Orencapsulatedinliposomeornanospheres.

15. Q&A: Activity I
Q.1 What is happen in case of allergic
bronchopulmonary aspergillosis.
Q.2 Name antifungal drug under
Antimetabolites category?
Q.3 Give MOA of Amphotericin
Q.4 In which form Amphotericin is given
for systemic administration?

16. Activity II: Self learning of e-content

17. Distribution:
●Itishighlyproteinbound
●ItnormallycrossesBBBpoorly-->butpenetrationis
morewhenmeningesareinflamed

18. ●Itisexcretedslowlyviakidney-->tracesarefoundin
theurinefor2monthsormore.

19. Unwanted effects:
●Renal toxicity: Some degree of reduction of renal
functionoccurs in more then 80% of patients.
●Hypokalaemia:occurin25%ofpatients
●Hypomagnesemia

20. ●Impaired hepatic functions
●Thrombocytopenia
●Anaphylactic shock
●Frequent injection result in
●Chills
●fever
●tinnitus
●Headache

21. ●Localthrombophlebitis-duetoirritanteffectof
drugonvein
●Neurotoxicity-withintrathecalinjection
●Skinrashes-withtopicalapplication

22. Nystatin
●Nystatin(Alsocalledasfungicidin)ispolyene
macrolideantibiotic
●Similarinstructurewithamphotericinandwithsame
mechanismofaction.

23. ●Notabsorbfrommucousmembraneofthebody
orfromskin
UsemainlylimitedtotheCandidainfectionsofthe
skin,mucousmembranesandtheGIT.

24. ●Unwanted effects:
●Nausea
●vomiting
●diarrhoea

25. Griseofulvin
●Itisanarrowspectrumantifungalagent-->isolated
fromcultureofpenicilliumgriseofulvum.
MOA:
●Fungistaticaction
●Interreactwithfungalmicrotubuleandinterferewith
mitosis.

26. ●Used to treat dermatophyte infectionof skin or nails
--> when local treatment is ineffective -but treatment
need to be very prolonged.

27. Pharmacokinetics:
●It is given orally.
●It is poorly soluble in water
●Peak plasma concentration is reached in about 5 hrs.
●It is taken up selectively by newly formed skinand
concentrate in the keratin.

28. Unwanted effect: Are frequents and includes:
●Gastrointestinal upsets
●Headache
●Photosensitivity
●Allergic reaction (rashes, fever)
●Drug should not be given to pregnant women.

29. Q&A: Activity III
Q.1 Enlist unwanted effects of
Amphotericin.
Q.2 What is category of Nystatin?
Q.3 Give MOA of Griseofulvin

30. Echinocandins:
●Itconsistofaringofsixaminoacidlinkedtothe
lipophilicsidechain.
MoA:
●Itinhibitthesynthesisof1,3betaglucan(aglucose
polymernecessaryformaintainingthestructureof
fungalcellwalls).
Intheabsenceofthispolymerfungalcellsloss
integrity(andleadtolysisofthecell)

31. Azoles:
●Theazolearegrpofsyntheticfungistaticagentswitha
broadspectrumofactivity.
●Theyareclassifiedas:
A.Imidazole(Topical)eg.Clotrimazole,
econazole,ketoconazole,miconazoleetc
B.Triazolenucleus(Systemic)Eg.
Itraconazole,fluconazoleetc.

32. MoA:
●Itinhibitthefungal
●CytochromeP4503Aenzyme
●Lanosine14alphademethylase
Theseenzymesareresponsibleforconvertingthe
lanosteroltoergosterol(Themainsterolinthefungal
cellmembrane)

33. MoA:........
●The resultant depletion of ergosterol alter the
fluidity of the membrane.
Inhibition of replication

34. MoA:.......
●Italsoinhibitthetransformationofcandidalyeast
cells
intohyphae(Theinvasiveandpathogenicformofthe
parasite).

35. Ketoconazole:
●Ketoconazolewasthefirstazole-->thatcanbe
givenorallytotreatsystemicfungalinfection.
●Itiseffectiveagainst-->severaldifferenttypeof
organism

36. Activity IV: Self learning of e-content

37. Pharmacokinetic:
●ItiswellabsorbedfromGIT
●Itisdistributedwidely-->throughoutthetissueand
tissuefluid
●Butitdoesnotreachthetherapeuticconcentrationin
thecentralnervoussystemunlesshighdoseisgiven.

38. Pharmacokinetic........
●It is inactivatedin the liver
●It is excreted in the bileand urine

39. Unwantedeffect:
●Livertoxicity-itisrarebutsometimefatal
●GITdisturbance,pruritus.
●Inhibitionofadrenocorticoid
●Inhibitionoftestosterone–resultingingynecomastia

40. Adverse interaction with the drugs:
Cyclosporine, terfenadine, and astemizole-interfere
with drug metabolizing enzymes.
Causing increase plasma concentrationof ketoconazole.

41. ●Rifampicin,histamineH2receptorantagonistand
antacidsdecreasestheabsorptionofketoconazole.

42. Q&A: Activity V
Q.1 Explain mechanism of action of
Echinocandins.
Q.2 ------was the first azole that can be
given orally to treat systemic fungal
infection.
Q.3 Enlist few unwanted effect of
ketoconazole

43. Flucytosine:
MoA:
●Converted to antimetabolites --> 5 Fluorouracilin fungal
but not in human cell
●5 fluorouracil --> inhibits thymidylate and DNA
synthesis

44. Terbinafine:
●it is a highly lipophilic fungicidalcompound
●active against a wide range ofskin pathogen.
●it is particularly usefulagainst nail infections.

45. -itactbyselectiveinhibitionof-->enzymesqualene
epoxidase
involveinthesynthesisof-->ergosterolfromsqualene
inthefungalcellwall.
-theaccumulationof-->squalenewithinthecellis
toxictotheorganism.

46. Pharmacokinetics:
●Itisgivenorally.
●Itisrapidlyabsorbedandistakenupbytheskin,
nails,andadiposetissue.

47. ●Giventopically-->itpenetratetheskinandmucous
membranes.
●Metabolisedintheliver-->bycytochromep450
system.
●Metabolites-->excretedintheurine.

48. Unwanted effects:
●GIT disturbance
●Rashes
●Pruritis
●Headache
●Dizziness
●Joint and muscle pains
●And more rarely hepatitis.

49. Q&A: Activity VI
Q.1 Explain mechanism of action of
Flucytosine.
Q.2 Identify the drug which act by selective
inhibition of enzyme squalene epoxidase.
Q.3 Discuss Pharmacokinetic of Terbinafine.

50. Reference:
•H.PRang.MMDale,J.MRitter,R.JFlower,G
Henderson.Pharmacology,SeventhEdition.Elsevier
ChurchillLivengstonPublication.Pageno:649-654