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Anti Fungal & Anthelminthic Drugs
Anti Fungal & Anthelminthic Drugs
&
ANTHELMINTHIC DRUGS
Dr Swathy A R
Dept of Pharmacology
SDMCMSH
• Fungal infection may be classified
Superficial mycosis
Clinically as :
Azoles inhibit
Hydrophilic part
Lactone ring
Lipophilic part
Mechanism of action
Pharmacokinetics
• Poorly absorbed orally
• Insoluble in water so given as iv
suspension prepared with sodium
deoxycholate(1:1 complex)
• 90% bound to plasma proteins
• Metabolized in liver slowly
excreted in urine
• t ½ = 15 days
• No dose adjustments in renal and
hepatic impairment
Uses
Amphotericin B is toxic
SIDE EFFECTS OF AMB
Nephrotoxicity
anemia
Nystatin
Similar to AMB in antifungal properties, high systemic
toxicity so used locally only
Available as ointment ,cream , powder, tablet
Uses: (primarly to treat candidial infection )
vaginitis
Prevention of oral candidiasis
Can be used in oral, cutaneous candiasis
Adverse events:
Bitter taste on oral use`
• Imidazoles:
• Topical: miconazole, clotrimazole
• Systemic : ketoconazole
• Newer : butaconazole, oxiconazole
• Triazoles :
• Systemic : Fluconazole, itraconazole,
voriconazole
• Terconazole: Topical for superficial infections
GIT upset
Headache, alopecia, skin rashes
Teratogenic effect
CYP450 Enzyme inhibiting property less
Effects hepatic drug metabolism to lesser extent than Ketoconazole
H2 blockers & PPI do not effect its absorption
No anti androgenic & other endocrine effects
Uses(superficial &deep)
Candida:
150 mg oral dose can cure vaginal candidiasis with few
relapse
Oral candidiasis- 2 weeks treatment required
Tinea infections & cutaneous candidiasis: 150 mg
weekly for 4 weeks, tinea unguim : 12 months
systemic fungal infections: Disseminated candidiasis,
cryptococcal, coccidiodal meningitis 200-400 mg / day
4- 12 weeks or longer
Meningitis: preferred drug
Eye drops for fungal keratitis
Triazoles
Itraconazole Fluconazole
- Varied absorption. - Completely absorbed and
Metabolized by cyt P450 better tolerated, Renal
excretion
- less endocrine effects but - Less endocrine effects
occur at high doses
- Penetrates well into CSF
- Less penetration in CSF
- Many drug interactions - Drug Interactions less
(due to inhibition of CYT
P450/ 3A4)
Voriconazole
II generation triazole
High oral bioavailability, low protein binding
Good CSF penetration
Doesn’t require gastric acidity for absorption
T1/2= 6 hrs
Uses:
DOC for invasive aspergillosis
Most useful for esophageal candidiasis
Useful in resistant candida infections
Dose and Adverse effects
• Dose : 200 mg BD
• Adverse events:
• Transient visual changes like blurred vision , altered color perception &
photophobia
• Rashes in 5 -6 %
• Elevated hepatic enzymes
• Prolongation of QT
Terbinafine
Orally & topically effective drug against candida &
dermatophytes
Fungicidal : shorter courses of therapy required & low
relapse rates
Pharmacokinetics:
Well absorbed orally 75%, Highly keratophilic & lipophilic
High protein bound , poor BBB permeability
Negligible effect on CYP450
Mechanism of action:
Terbinafine
Squalene
Ѳ
squalene 2,3 epoxide
Lanosterol
Ѳ Azoles
14 α demethylase
Ergosterol
Adverse events and uses
Adverse events:
Taste disturbances
Topical: erythema , itching , dryness , urticaria, rashes
Uses: (superficial &deep fungal infection )
Dermatophytosis: topically/ orally 2- 6 weeks
Onychomycosis: first line drug 3- 12 months
Candidiasis: less effective 2- 4 weeks therapy may be used
as alternative 250 mg OD
Caspofungin
• Benzoic acid:
• Used in combination with salicylic acid
• Whitfields ointment: ( benzoic acid 6% + salicyclic acid 3 %)
• Salicyclic acid due to its keratolytic action helps to remove infected tissue &
promotes penetration of benzoic acid in fungal infected lesion
• Adverse events: irritation & burning sensation
Spectrum of action
AMB 5FC KTZ FLU ITR
Aspergillus -- -- -- Y
Blastomycosis -- Y Y Y
cryptococcus Y -- Y Y
Coccidiodo -- Y Y Y
candida Y Y Y Y
Histoplasma -- Y Y Y
mucor -- -- -- --
Sporotrichosis -- -- Y Y
Anthelminthic Drugs
Albendazole
• Subsequently introduced congener of mebendazole
• broad-spectrum activity
• excellent tolerability
• One dose treatment has produced cure rates in ascariasis, hookworm
(both species) and enterobiasis.
MOA
• The major site of action appears to be the microtubular protein ‘β-
tubulin’ of the parasite.
• Binds to β-tubulin of susceptible worms with high affinity and inhibits
its polymerization.
• Intracellular microtubules in the cells of the worm are gradually lost.
• Blocks glucose uptake in the parasite, inhibits some mitochondrial
enzymes and depletes its glycogen stores.
Adverse effects
• well tolerated;
• GI side effects have been noted.
• dizziness.
• Prolonged use, as in hydatid or in cysticercosis, has caused headache,
fever, alopecia, jaundice and neutropenia.
• Ascaris, hookworm, Enterobius and Trichuris: a single dose of 400 mg
(for adults and children above 2 yrs; 200 mg for 1–2 yr age) is
sufficient.
• Trichinosis: Three day treatment with 400 mg twice daily expels the
adult worm from intestine,
• Neurocysticercosis: Albendazole is the anthelmintic of choice for the
treatment of neurocysticercosis.
• Tropical pulmonary eosinophilia: DEC (2–4 mg/kg TDS) for 2–3 weeks
produces dramatic improvement in the signs and symptoms of
eosinophilic lung or tropical eosinophilia.
Adverse effects
• Nausea, loss of appetite, headache, weakness and dizziness are the
usual complaints.