Polyene and polypeptide antibiotics

1. G Vijay Narasimha Kumar
Asst. Professor,
Dept. of. Pharmacology
Sri Padmavathi School of Pharmacy

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

3.  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

4. 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
leads to

5.  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

6. 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.

7. 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.

8. METOBOLISM:-
Metabolised by LIVER.

9. EXCRETION:-
slowly excreted by both urine and bile.

10. 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

11.  Intrathecal administration may cause arachnoiditis,
seizures, headache, nerve palsies.
 Hepatic impairment with jaundice rarely.
 Infusion related toxicity like chills,
fever,
vomiting,
hypotension.

12.  AMPHOTERICINE –B + FLUCYTOSINE =synergistic action
 AMPHOTEICIN-B
+
AMINOGLYCOSIDES
VANCOMYCIN,
CYCLOSPORINE,
&
other NEPHROTOXIC
DRUGS

13.  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.

14.  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

15. 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.

16. 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

17.  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.

18. CLASSIFICATION OF POLYPEPTIDES:
 BACITRACIN
 POLYMYXIN-B
 COLISTIN/POLYMIXIN-E
 DACTINOMYCIN/ACTINOMYCIN-D

19.  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.

21.  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…

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

23.  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.

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

25. 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.

26. 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.

27.  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.

29.  Actinomycin D is a well-known antibiotic of the
actinomycin group that exhibits high ANTIBACTERIAL
and ANTITUMOR activity.
 Actinomycin are extracted from streptomyces.

30.  Dactinomycin binds to double stranded DNA through
intercalation between adjacent guanine-cytosine
base pairs.
 Inhibits the all forms of DNA dependent RNA synthesis.

31.  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

32.  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.

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