Vaginitis Presentation by fjzhangxiaoquan

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									King Saud university
Collage of pharmacy
Pharmacognosy dept.




                        Prepared by:
                        Fatimah BalHarith
                          Nouf Alwadei
                          Alaa Flemban
                         Najla Almuteiri

                       Supervised by:
                       Dr. Qadria AL-Deab
                        Dr. Areej Altaweel
Fungi is:
  Eukaryotic – a true nucleus
  Do not contain chlorophyll
  Have cell walls
  Produce filamentous structures
  Produce spores
  Contain ergosterol
  The Term mycosis (plural: mycoses) refers
to conditions in which fungi pass the
resistance barriers of the human or animal
body and establish infections.
Classification of Mycoses:
Mycoses are classified according to the tissue
 levels initially colonized:
 1. Superficial mycoses - limited to the
 outermost layers of the skin and hair.
 2. Cutaneous mycoses - extend deeper into
 the epidermis, as well as invasive hair and
 nail diseases. These diseases are restricted
 to the keratinized layers of the skin, hair,
 and nails. The organisms that cause these
 diseases are called dermatophytes.
Classification of Mycoses:
 3. Subcutaneous mycoses - involve the
  dermis, subcutaneous tissues, muscle, and
  fascia. These infections are chronic and can
  be initiated by piercing trauma to the skin,
  which allows the fungi to enter.
  4. Systemic mycoses due to primary
  pathogens - originate primarily in the lungs
  and may spread to many organ systems.
Classification of Mycoses:
  5. Systemic mycoses due to opportunistic
pathogens - infections of patients with immune
deficiencies who would otherwise not be
infected. Examples of immunocompromised
conditions include AIDS, alteration of normal
flora by antibiotics, immunosuppressive
therapy, and metastatic cancer. Examples of
opportunistic mycoses include Candidiasis,
Cryptococcosis and Aspergillosis.
  Another example of a fungal infection is
Tinea versicolor: Tinea versicolor is a fungus
infection that commonly affects the skin of
young people
Treatment
  Unlike bacteria, both fungi and humans are
eukaryotes. Thus fungal and human cells are
similar at the molecular level. This means it is
more difficult to find a target for an antifungal
drug to attack that does not also exist in the
infected organism.
 Antifungal drugs are used to treat mycoses.
Depending on the nature of the infection, a
topical or systemic agent may be used.
Photochemotherapy or photopheresis is a
technique used at major medical centers for
the treatment of mycosis
Treatment
Photochemotherapy

Shown is close up of
  surgeons' hands in an
  operating room with a
  "beam of light" traveling
  along fiber optics for
  photodynamic therapy
Treatment
photopheresis is a form of apheresis in which
blood is treated with photoactivable drugs
which are then activated with ultraviolet light.
Apheresis (Greek: "to take away") is a medical
technology in which the blood of a donor or
patient is passed through an apparatus that
separates out one particular constituent and
returns the remainder to the circulation.
Classification of antifungals
Polyene antifungals:-
A polyene is a circular molecule consisting of a
hydrophobic and hydrophilic region.
The polyene antimycotics bind with sterols in the
fungal cell membrane, principally ergosterol. As a
result, the cell's contents leak out (usually the
hydrophilic contents) and the cell dies. Animal cells
contain cholesterol instead of ergosterol and so
they are much less susceptible. (Note: as
polyene's hydrophobic chain is reduced, its sterol
binding activity is increased. Therefore, increased
reduction of the hydrophobic chain may result in it
binding to cholesterol, making it toxic to animals.)
Classification of antifungals
Examples:
* Natamycin -- 33 Carbons, binds well to ergosterol
* Rimocidin
* Nystatin
* Amphotericin B
Classification of antifungals
Non polyenes antifungals
Griseofulvin: The drug binds to tubulin, interfering
with microtubule function, thus inhibiting mitosis.
It binds to keratin in keratin precursor cells and
makes them resistant to fungal infections. It is only
when hair or skin is replaced by the keratin-
griseofulvin complex that the drug reaches its site
of action. Griseofulvin will then enter the
dermatophyte through energy dependent transport
processes and bind to fungal microtubules. This
alters the processing for mitosis and also
underlying information for deposition of fungal cell
walls.
Classification of antifungals
Imidazole and triazole antifungals
The imidazole and triazole antifungal drugs inhibit
 the enzyme cytochrome P450 14α-demethylase.
 This enzyme converts lanosterol to ergosterol, and
 is required in fungal cell membrane synthesis.
 These drugs also block steroid synthesis in
 humans.
    * Miconazole (Miconazole nitrate)
    * Clotrimazole - marketed as Lotrimin
The triazoles are newer, and are less toxic and
 more effective
    * Fluconazole
    * Itraconazole
  Classification of antifungals
Allylamines
Allylamines inhibit the enzyme squalene epoxidase,
  another enzyme required for ergosterol synthesis:
*Terbinafine - marketed as "Lamisil"
*Amorolfine
*Naftifine - marketed as "Naftin
Classification of antifungals:
Echinocandins
Echinocandins inhibit the synthesis of glucan in the
cell wall, probably via the enzyme 1,3-β glucan
synthase:
Anidulafungin
Caspofungin
Micafungin
Polyene antifungal:
Structure activity relationship (SAR):


             hydrophobic




                 hydrophilic
Amphtericin B




Nystatin
Polyene antifungal:
Structure activity relationship (SAR):
  The polyene antibiotic produced by actinomycetes
contain alarge lactone ring with 4 to 7 unsubstituted
conjugated double bond .
  The conjugated system are usually in all-trans
configuration so that the ring contains a planner
lipophilic segment and a less rigid hydrophilic
portion.
  With increase conjugation (double bond) the
activity and toxicity will increase.
  The polyenes have polyhydroxyl groups.
Polyene antifungal:
 Structure activity relationship (SAR):
  Amphotericin B have 7conjugated double bond
while nystatin have 6 conjugated double bond so,
amphotericin B more active and more toxic.
  Most polyene antifungal drugs are macrocyclic
lactones.
  Ring sizes varying from 12 to 37 atoms in size .
Amphtericin B & Nystatin
Mechanism of action:
Amphtericin B & Nystatin
Amphtericin B & Nystatin
Amphtericin B
  polyene antifungal drug.
  Used intravenously for systemic fungal
infections.
  It was originally extracted from
Streptomyces nodosus, a filamentous
bacterium.
  There areTwo amphotericins:
 Amphotericin A and Amphotericin B
  only B is used clinically.
Amphtericin B
Trade names:
 Fungilin®
 Fungizone®
 Abelcet®
 AmBisome®
 Fungisome®
 Amphocil®
 Amphotec®
 Amphtericin B
Uses and spectrum:
  Amphotericin B for injection (IV) administered
primarily to patients with progressive, potentially life-
threatening fungal infections such as:
 Aspergillosis
 cryptococcosis (torulosis)
 North American blastomycosis
 systemic candidiasis
 coccidioido-mycosis
 histoplasmosis
 zygomycosis including mucormycosis
  Its spectrum is the broadest of all antifungals.
 Amphtericin B
Precaution:
  Acute reactions including fever, shaking chills,
hypotension, anorexia, nausea, vomiting, headache,
and tachypnea are common 1 to 3 hours after starting
an intravenous infusion.
  Rapid intravenous infusion.
  Whenever medication is interrupted for a period
longer than 7 days, therapy should be resumed by
starting with the lowest dosage level.
  Pregnancy: Teratogenic Effects, category B.
  Nursing Mothers
  Pediatric Use
Amphtericin B

Contraindication:
This product is contraindicated in those patients
who have shown hypersensitivity to
Amphotericin B or any other component in the
formulation.
Amphtericin B
Pharmacokinetic:
  Poorly absorbed from GIT.
  Start with small initial dose then gradually increase it.
  An elimination half-life approximately 15 days.
  Amphotericin B circulating in plasma is highly bound
(>90%) to plasma proteins.
  Amphotericin B is excreted very slowly (over weeks
to months) by the kidneys.
  After treatment is discontinued, the drug can be
detected in the urine for at least seven weeks.
Amphtericin B
Side effects:
 acute reaction:
 fever
 shaking chills
 hypotension
 anorexia
 nausea
 vomiting
 headache
 dyspnea
 tachypnea
Amphtericin B
Side effects
  Nephrotoxicity (kidney damage).
  Electrolyte imbalances (e.g. hypokalemia and
hypocalcemia).
  Increased liver enzymes and hepatotoxicity up to
acute liver failure.
  several forms of anemia.
  serious cardiac arrhythmias.
  Skin reactions.
 Amphtericin B

Drug interaction:
 Flucytosine
 Diuretics or Cisplatin
 Corticosterioids
 Cytostatic drugs
 Foscarnet, Ganciclovir, Tenofovir, Adefovir
Amphtericin B

Drug interaction:
  Nephrotoxic medications: agents such as
aminoglycosides, cyclosporine, and
pentamidine.
  Imidazoles (e.g., ketoconazole,
miconazole, clotrimazole, fluconazole, etc.)
  Skeletal muscle relaxants.
  Digitalis glycosides.
                   Nystatin
Drug description:
Nystatin is an antimycotic polyene antibiotic
obtained from Streptomyces noursei.

Nystatin is a polyene antifungal drug to which many
molds and yeast infections are sensitive, including
Candida spp.

Nystatin has some toxicity associated with it when
given intravenously, but it is not absorbed across
intact skin or mucous membranes.
It is considered a relatively safe drug for treating oral
or gastrointestinal fungal infections.

It is only insoluble in water and sparingly soluble in
organic solvent. It is unstable to moisture, heat and
light.

Administered orally in the treatment of gastrointestinal
candidiasis and oral thrush, intestinal monilial
infection.
Drug of choice for vaginal & cutaneous candidiasis.

Administered in vaginal tablets or topically, sometimes
combined with iodochlorohydroxyquine.
This product is available in the following
dosage forms:
Suspension
Tablet
Capsule

Spectrum and Uses:
Nystatine has awide spectrum of antifungal activity,

nystatine used for Cutaneous, vaginal, mucosal and
esophageal Candida infections.

Cryptococcus is also sensitive to nystatin.

treating neonatal oral thrush.
Brand names:
Nystan Infestat
Nystalocal
Nystamont
Nystop
PRECAUTION:
General
This medication is not to be used for the treatment of
systemic mycoses. Discontinue treatment if
sensitization or irritation is reported during use.
Carcinogenesis, Mutagenesis, Impairment
of Fertility:
There also have been no studies to determine
mutagenicity or whether this medication affects
fertility in males or females.
Pregnancy:
Teratogenic Effects:
Category C. Animal reproduction studies have not
been conducted with nystatin oral suspension. Nystatin
oral suspension should be given to a pregnant woman
only if clearly needed.

Nursing Mothers:
It is not known whether nystatin is excreted in human
milk. Because many drugs are excreted in human milk,
caution should be exercised when nystatin is
administered to a nursing woman.
SIDE EFFECTS:
Nystatin is well tolerated even with prolonged therapy.
Oral irritation and sensitization have been reported.

Gastrointestinal: Diarrhea ,nausea, vomiting,
gastrointestinal upset/disturbances.

Dermatologic: Rash, including urticaria has been
reported rarely.

Other: Tachycardia, bronchospasm, facial swelling.
Pharmacokinetics:
Gastrointestinal absorption of nystatin is insignificant
(poorly absorbed).
Most orally administered nystatin is passed unchanged
in the stool.
In patients with renal insufficiency significant plasma
concentrations of nystatin may occur.

Microbiology:
Nystatin is both fungistatic and fungicidal gainst a
wide variety of yeasts and yeast-like fungi.
Candida albicans demonstrates no significant
resistance to nystatin on repeated subculture in
increasing levels of nystatin other Candida species
become quite resistant.
OVERDOSE:
Oral doses of nystatin in excess of five million units
daily have caused nausea and gastrointestinal upset.


CONTRAINDICATION:
The preparation is contraindicated in patients with a
history of hypersensitivity to any of its components.
Griseofulvin

Brand Names:
Fulvicin P/G, Fulvicin U/F, Grifulvin V, Gris-PEG,
Grisactin 250, Grisactin 500, Grisactin Ultra
Penicillium niciklium griseofulvum.

Spectrum of activity and Resistance:
1) Effective against various species of Trichophyton,
Microsporum, and Epidermophyton
2) Not effective against candida and bacteria
Structure Activity Relationship:
   Four possible stereoisomers only (+)-enantiomer
is active
   Cl replaced by F → same activity
   Cl replaced by Br or H → ↓ activity
   Placement of the halogen on C5 → ↓ activity
   Replacement of CH3O on ring C with either
propoxy or butoxy functions → ↑ activity
Griseofulvin

Mechanism of action :
  Binds to keratin
  disrupts the cell's mitotic spindle structure
  cause defective DNA synthesis
  interferes with tubulin polymerization
Resistance:
is due to alteration of the drug's target site,
by mutation of ribosome sequences.
Griseofulvin
Uses:
is effective against dermatophytes but yeast-like
fugi are less susceptible.
   Tinea capitis (ringworm of the scalp)
   Tinea cruris (ringworm of the high)
   Tinea corporis (ringworm of the body(
   Tinea unguium (onychomycosis)
   Tinea barbae (barber's itch)
Tinea :
species of fungus that causes ringworm
Griseofulvin
Side effects:
 Skin rashes
 Dizziness
 Fatigue
 Headache
 Vomiting
 Swelling
 Loss of taste sensation
 Tingling in the hands or feet
 Oral thrush (yeast infection of the mouth)
Drug interactions:

      drug                          cause
Antacids and H2
                             stop its absorption.
  antagonists
     alcohol                nausea and vomiting
                    (thinning the blood less than required)
                      because Griseofulvin increase liver
    Warfarin
                    enzyme reducing the concentration of
                                   warfarin

                     (increasing the chance of pregnancy)
                    because Griseofulvin cause increase in
Oral contraceptive
                   liver enzyme reducing the concentration
                             of Oral contraceptive
Griseofulvin
Pharmacokinetic:
Oral
Diatery fat increase absorption
Half life 9-21 hours
Demethylated and conjugated with glucuronide

Precautions:
use machines or do other things that could be
dangerous if you are dizzy. Stay out of direct
sunlight..
Griseofulvin

Contraindicatios:
 Systemic Lupus.
 Erythematosus.
 Porphyrias.
 Hepatic Failure.
 Not be used in pregnant
woman.
Conclusion:
    Nystatin              Amphotericin B               Griseofulvin
                             Nephrotoxicity,        Loss of taste sensation
  SE: Oral irritation
                          hepatotoxicity, cardiac
  and sensitization                                 Tingling ,Oral thrush
                          arrhythmias & anemia
                                                    Binds to keratin>>>
                                                    disrupts mitotic spindle
  MOA: bind to ergosterol in cell memb. >>>         structure>>>defective
      leakage of ions >>> cell death.               DNA synthesis>>>
                                                    interferes with tubulin
                                                    polymerization

ROA: topical,and orally              IV                        oral

     SOU: widely                  widely
There is no single type of structure thus far discovered
possesses Useful broad spectrum activity .


Successful treatment of human fungal disease may well
require appropriate combination of vaccines, transfer
factor, Antifungal drugs, and iron binding agent.

								
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