Antifungal drugs Lec 18 - PowerPoint Presentation

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Antifungal drugs

Lec

18

30 -1-2017

Dr.

Naza

M. Ali

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Antifungal Drugs

Unlike bacteria, fungi are eukaryotic.

Fungal infections are generally resistant to

antibiotics used in the treatment of bacterial

infections, and conversely, bacteria are resistant to

antifungal agents.

Infectious diseases caused by fungi are called mycoses, they are often chronic in nature.

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Mycoses divided into:

Cutaneous

mycoses

:

Infection are superficial and only involve the

(skin, hair, nails).

Subcutaneous mycoses

:

Fungi that grow in soil and on vegetation and

are introduced into subcutaneous tissue

through trauma.

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Systemic mycoses

:

I

nfections result from inhalation of the spores

of dimorphic fungi that have their saprophytic

mold forms in the soil.

are most

difficult to treat which are often life

threatening.

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Mechanism of drug acting on fungi

Alter cell membrane permeability

2. Block nucleic acid synthesis

3. Disrupt microtubule functions

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Drugs for subcutaneous

and systemic fungal infections

1.

Amphoteracin

B

2.

Flucytosine

5-FC

3.

Azole

antifungal agents:

-

Ketoconazole

-

Fluconazole

-

Itraconazole

-

Voriconazole

-

Posaconazole

(new)

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4.

Echinocandins

-

Caspofungin

-

Micafungin

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Amphoteracin

B

Is a naturally occurring

polyene

macrolide

antibiotic produced by

Streptomyces

nodosus

.

Is the drug of choice for the treatment of life-threatening systemic mycoses.

Conventional

amphotericin

(

amphotericin

B

deoxycholate

, the

nonlipid

formulation)

has undergone several formulation improvements to reduce the incidence of side effects

(

nephrotoxicity).

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The drug is used in combination with

flucytosine

to achieve more rapid sterilization of the CSF.

Amphotericin

B is either fungicidal or

fungistatic

,

depending on organism and concentration of the drug.

It is often used for initial induction regiments before follow up treatment with an

azole

.

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It has

widest antifungal agents spectrum

than any

agents and the drug of choice for systemic most

infections caused by

Aspergillus

,

Blastomyces

, Candida

albicans

,

Cryptococcus,

Histoplasma

and

Mucor

.

it is usually given by slow IV infusion.

In case of fungal meningitis( by

intrathecal

route).

Local administration in treatment of

mycotic

corneal ulcer

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Mechansim

of action of

Amphoteracin

B

I

s a

polyene

macrolide related to

nystatin

polyenes

are molecules with both hydrophilic &

lipophilic characteristics.

Several amphotericin B molecules bind to

ergosterol

in the plasma membranes of fungal cells, and cause

the formation of artificial pores (channels).

The pores disrupt membrane function, allowing

electrolytes and small molecules to leak from the cell,

resulting in cell death.

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Resistance:

Fungal resistance, is associated with decreased

ergosterol

content of the fungal membrane.

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Pharmacokinetics:

Amphotericin B

is used by slow, (IV) infusion

Is insoluble in water, and injectable preparations require the addition of sodium

deoxycholate

, which produces a soluble colloidal dispersion.

The more dangerous

intrathecal

route is chosen for the treatment of meningitis.

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Amphotericin B has also been formulated with a

variety of artificial lipids that form liposomes

.

Amphotericin B is extensively bound to plasma protein.

Inflammation favors penetration into various body fluids.

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Adverse

effects

Amphotericin B has a low therapeutic index

A total adult daily dose should not exceed

1.5 mg/kg

Small test doses are usually administered to avoid

anaphylaxis or convulsions

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Fever & chills

:

These occur most commonly 1-3 hours after

starting IV, but they usually subside with repeated

administration of the drug.

Premedication with an antipyretic or a corticosteroid

helps to prevent problem.

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2. R

enal impairment

:

Azotemia (elevated blood urea)

adequate hydration can decrease its severity.

3. Hypotension:

A shock-like fall in blood pressure

4. Anemia

5. Neurologic effects

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