POLYENE AND POLYPEPTIDEANTIBIOTICS

G Vijay Narasimha KumarAsst. Professor,

Dept. of. PharmacologySri Padmavathi School of

Pharmacy

CLASSIFICATION OF POLYENES: AMPHOTERICIN –B NYSTATIN HAMYCINCLASSIFICATION OF POLYPEPTIDES: BACITRACIN POLYMYXIN-B COLISTIN/POLYMIXIN-E DACTINOMYCIN/ACTINOMYCIN--D

CLASSIFICATION OF POLYENES AND POLYPEPTIDES

It is obtained from streptomyces Nodosus.

It is amphoteric in nature.

It is a polyene group of anti fungal antibiotic.

It is composed of large lactone ring with several conjugated double bonds

AMPHOTERICIN-B

AMPHOTERICIN –B binds to ergosterol which is a fungal cell membrane

sterol

It alters the permeability of fungal cell membrane by forming pores. CELL DEATH

MECHANISM OF ACTION

leads to

The sterol of mammalian cell membrane is cholesterol for which amphotericin –b has less affinity.

Therefore, drug shows selective toxicity to fungal cell.

If it is binds to human membrane sterol then it may cause drug toxicity.

RESISTANCE to AMPHOTERICINE –B is associated with a replacement of ergosterol by other sterols in fungal plasma membrane

ABSORPTION:-

It is poorly absorbed from GIT. Oral administration is effective only against fungal

infections of intestine, and not for the treatment of SYSTEMIC FUNGAL INFECTIONS .

It is therefore,administered by SLOW IV INFUSION.

PHARMACOKINETICS

DISTRIBUTION:-

It is widely distributed throughout the body.

It does not penetrate into CSF.

It binds to sterols in tissue and lipoproteins in plasma.

Plasma t1/2 --15 days.

METOBOLISM:- Metabolised by LIVER.

EXCRETION:- slowly excreted by both urine and bile.

ADVERSE EFFECTS:- Nephro toxicity ( Renal tubular necrosis, Hypokalaemia,

hypomagnesaemia, Azotemia)

And even irreversible damage if, dose exceeds 5gms.

Hypochromic normocytic anaemia - is common.

Thrombocytopenia & Leukopenia – less common

Intrathecal administration may cause arachnoiditis, seizures, headache, nerve palsies.

Hepatic impairment with jaundice rarely.

Infusion related toxicity like chills, fever, vomiting, hypotension.

AMPHOTERICINE –B + FLUCYTOSINE =synergistic action

AMPHOTEICIN-B + AMINOGLYCOSIDES VANCOMYCIN, CYCLOSPORINE, & other NEPHROTOXIC DRUGS

DRUG INTERACTIONS

=Enhance renal toxicity

Used in the treatment of invasive aspergillosis in immuno compromised & non immuno compromised.

Used in the treatment of mucormycosis(an opportunistic fungal infection in lungs)

Used in the treatment of Disseminated rapidly progressing Histo plasmosis,

Coccidioidomycosis, Meningeal coccidioidomycosis, Blasto mycosis.

THERAPEUTIC USES

It is also used TOPICALLY to treat oropharyngeal candidiasis and cutaneous candidiasis.

It is most effective dug for resistant cases of KALA AZAR & MUCO CUTANEOS LEISHMANIASIS.

DOSE: 1-2gms

o It is obtained from s.nouresi.

o It is similar to amphotericin –B in antifungal action and other properties.

o Due to its higher systemic toxicity ,it is used only locally in

superficial candidiasis.

o It is not absorbed orally ,can be used for monilial diarrhoea.

NYSTATIN

THERAPEUTIC USES It is used in the treatment of monilial vaginitis. It is used in the treatment of oral candidiasis. It is used in the treatment of corneal conjunctival and

cutaneous candidiasis in the form of ointment.

SIDE EFFECTS Nausea Bad taste in the mouth.

DOSE: 1 lacu b.d

It was isolated from S.pimprina .

It is similar to nystatin but more water soluble .

Use is restricted to topical application for oral thrush ,cutaneous candidiasis, monilial & trichomonas vaginitis & otomicosis by aspergillus.

DOSE: 5 lac u/g oint , 2 lac u/ml susp for topical use.

HAMYCIN

CLASSIFICATION OF POLYPEPTIDES:

BACITRACIN POLYMYXIN-B COLISTIN/POLYMIXIN-E DACTINOMYCIN/ACTINOMYCIN-D

POLYPEPTIDES

It is obtained from bacillus subtilis.

It is active mainly against GRAM POSITIVE ORGANISM

(Both cocci &Bacilli),NEISSERIA,H.INFUENZA & few other

bacteria also affected.

BACITRACIN

BACITRACIN not absorbed orally.

It is not given parenterally because of HIGH TOXICITY especially to the kidneys.

It is used topically –skin and eye infections.

Generally in combination with polymixin , neomycin etc…

DOSE: NEBACULF-BACITRECIN 250U+NEOMYCIN5mg +SULFACETAMIDE 60mg/g powder. SKIN &EYE OINTMENT ;IN NEOSPORIN 400u/g powder.

The polymyxins are cation polypeptides that bind to phospholipids on the bacterial cell membrane of gram-negative bacteria. They have a detergent-like effect that disrupts cell membrane integrity, leading to leakage of cellular components and ultimately cell death.

Polymyxins

Polymyxins are concentration-dependent bactericidal agents with activity against most clinically important gram-negative bacteria, including P. aeruginosa, E. coli, K. pneumoniae, Acinetobacter speciesEnterobacter species.

Only two forms of polymyxin are in clinical use today, Polymyxin B Colistin (polymyxin E)Polymyxin B is available in parenteral, ophthalmic, otic, and topical preparations.Colistin is only available as a prodrug, colistimethate sodium, which is administered IV or inhaled via a nebulizer.

The use of these drugs has been limited for a long time, due to the increased risk of nephrotoxicity and neurotoxicity (for example, slurred speech, muscle weakness) when used systemically. However, with the increase in gram-negative resistance, they have seen a resurgence in use and are now commonly used as salvage therapy for patients with multidrug-resistant infections.

POLYMIXIN -B SULFATE is used topically in combination with other drugs in the treatment of skin ear &eye infections. It can be given orally for oropharyngeal decontamination or the suppression of intestinal flora in patient with high risk of endogenous infections. Colistin sulfate can be given orally for treating GIT infection.

THERAPEUTIC USES

Actinomycin D is a well-known antibiotic of the actinomycin group that exhibits high ANTIBACTERIAL and ANTITUMOR activity.

Actinomycin are extracted from streptomyces.

DACTINOMYCIN/ACTINOMYCIN-D

Dactinomycin binds to double stranded DNA through intercalation between adjacent guanine-cytosine base pairs.

Inhibits the all forms of DNA dependent RNA synthesis.

MECHANISM OF ACTION

Actinomycin is a clear, yellow liquid administered intravenously and most commonly used in treatment of a variety of cancers, including

Gestational trophoblastic neoplasia Wilms' tumor Rhabdomyosarcoma Ewing's sarcoma

CLINICAL USES

Sometimes it will be combined with other drugs in Chemotherapy regimens, like the VAC regimen (with Vincristine and Cyclophosphamide) for treating Rhabdomyosarcoma and Ewing's Sarcoma.

ADVERSE EFFECTS : Bone marrow suppression, Fatigue, Hair loss, Mouth ulcer, Loss of appetite, Diarrhea.

DOSE: 15ug/kg i.v daily for 5days