Antibiotics Part2
Transcript of Antibiotics Part2
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ANTIBIOTICS.
PART 2
L. YurgelL. Yurgel
Basic & Clinical
PharmacologyVitebsk State MedicalUniversity
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Bactericidal Bacteriostatic
MACROLIDES If high bacterialsensitivity orantibiotic
concentration
+ (mainly)
TETRACYCLINES - +
AMINOGLYCOSIDES oncentration-
dependent
LINCOSAMIDES + (primarily)
CHLORAMPHENICOL +
OXAZOLIDINDIONES Against some Str.,Pneum., B. fragilis
+ (primarily)
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First generation Secondgeneration
Third generation
Streptomycin Gentamicin Amikacin
Neomycin Tobramycin
Kanamycin Netilmycin
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oncentration-dependent bactericidalactivity
Mechanism of action Transport through the bacterial cell wall
and cytoplasmic membrane Bind to the 30S ribosome, disrupt the
normal cycle of ribosomal function,thereby inhibiting bacterial proteinsynthesis
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poorly absorbed orally but are wellabsorbed from the peritoneum, pleuralcavity, and joints and from denuded skin
distributed well into organism except forvitreous humor, CSF, respiratorysecretions, and bile
excreted by glomerular filtration and have
a serum half-life of 2 to 3 h; the half-lifeincreases exponentially as the GFR falls(eg., in renal insufficiency, in the elderly)
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I generation preparations(Streptomycin, Neomycin,Kanamycin):
Mycobacterium tuberculosis (S,K)
Yersinia pestis (S)
Francisella tularentis (S)
Brucella
Few strains of V. cholerae
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II and III generation: Gentamicin,Tobramycin, Netilmycin, Amikacin
Gram-negative aerobic and facultative
anaerobic bacillibacilli: Enterobacteriaceae (E.coli, Proteus spp.,
Klebsiella, Enterobacter, Serratia) P. aeruginosa,Acinetobacter
Most staphylococci(except methicillin-resistant, MRSA)
Mycobacterium tuberculosis (S), M.avium(A)
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Parenterally Orally Topically
Streptomycin + (Powder, Sol) - -
Gentamicin + (Sol) - + (Eye drops)
With GCS + (Eye dr. andoint., ear drops)
Tobramycin(+ dexamethasone)
+ (Powder, Sol) - + (Eye drops,eye oint.)
Netilmycin + (Sol) - -
Amikacin + (Powder, Sol) - -
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Antimicrobial activity is reduced inthe anaerobic environment of anabscess, in hyperosmolaric acidicurine, if decrease in pH
The postantibiotic effect ischaracteristic
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Falure of permeable of the antibiotic
Inactivation of the drug by microbial
enzymes (phosphorylation,adenylation, acetilation)
Low affinity of the drugs forbacterial ribosome
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Lincomycin, Clindamycin are primarilybacteriostatic drugs
Mechanism of action
binds to the 50S subunit of the ribosome, thusinhibiting bacterial protein synthesis.
Mechanism of resistance active efflux mechanism or to erythromycin-inducible modification of
the ribosomal target
Use as a reserve antibiotics!
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Main side effects:
Vestibular and cochlear toxicity
Renal toxicity (advanced age, liverdisease, septic shock are riskfactors)
Neuromuscular blockade
Allergy
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are derived from Streptomyces bacteria, andgot their name because they all have amacrocyclic lactone chemical structure.
group of drugs whose activity stems fromthe presence of a large macrocycliclactone ring
are primarily bacteriostatic, but can cause
bactericidal effect (if high bacterialsensitivity or antibiotic concentration)
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by ways of reception and quantity of atoms of carbonin macrocyclic lactone ring
14-membered 15-membered 16-membered
Natural
Erythromycin
Oleandomycin
Spiramycin
Josamycin
Midecamycin
Semi-synthetic
Clarithromycin
Roxithromycin
Azithromycin Midecamycinacetate
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Mechanism of action
inhibit protein synthesis by binding to the50S ribosomal subunit
Cross-resistance occurs among the followingantibiotics because they bind to the sametarget:
Macrolides Clindamycin Chloramphenicol
However, cross-resistance does not occurbetween these antibiotics and linezolid,which bind to different targets on the 50Sribosomal subunit.
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Spectrum of action
Similar range of action and efficacyto penicillin
Effective against gram-positiveorganisms (selectively accumulatedcompared with Gram negatives)
Active against atypical pneumoniaorganisms especially legionella,mycoplasma and chlamydia
H. pylori (gastritis, ulcer)
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Azithromycin is an azalide, a subclass of macrolides is one of the world's best-selling antibiotics,
marketed under the nameZithromax, andunder a variety of brand names and generic
labels (ex. Sumamed, Azithral) Has better tolerability and drug interactionprofiles (unique, because does not inhibitCYP3A4)
Higher concentration in tissues (the highest
among macrolides) Has much longer T1/2 (up to 55 h.), that
enables to use a drug once a day Is more active concerning .influenzae,
N.gonorrhoeae and H.pylori;
http://en.wikipedia.org/wiki/CYP3A4http://en.wikipedia.org/wiki/CYP3A4 -
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Azithromycin
Forms: Tablets and capsules 0.25 and 0.5 g;Regimes:a) 0.5 g 1 t.p.d. 3 days
b) 0.5 g 1 t.p.d 1-t day, from 2-d to 5-th days -0.25 g 1 t.p.d.c) 1 g single dose Powder for oral suspension; Zithromax has also
prolong form 2 g (single dose) Syrup - 0.1g or 0.2g/5 ml 1% ophthalmic solution Powder 0.5 g in bottle for solution for I.V.
injection
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As alternative to penicillin if allergic
P450 inhibitors; can block metabolism
of warfarin and some antihistamines(e.g. Terfenadine)
Clarithromycin causes less GIdisturbance
Azithromycin has less gram-positivecover but very effective againstchlamydia, haemophilus and neisseria
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Adverse effects
Diarrhoea (Motilin receptor agonistactivity), nausea, extreme irritability,abdominal pain
Dry mouth, alteration in senses of smelland taste, including a metallic taste
Cholestatic jaundice and hepatitis(particularly with the estolate ester)
Risk of QT prolongation
Can cause thrombophlebitis on IVadministration Dizziness/motion sickness
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Clindamycin: Similar mechanism of action to
erythromycin
Very effective against bacteroides Absorbed well orally and can be givenparenterally
Good tissue penetration especially bone,phagocytes
Metabolites are excreted in bile and urine Uses for treatment colitis associated with
C. difficile
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Clindamycin: spectrum of action Similar to that of the
macrolide erythromycin but not reliably
active against mycoplasmas,chlamydiae and legionellae
Very effective against bacteroides
Pneumocystis jiroveci Falciparum malaria
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Tetracyclines got their namebecause they share a chemicalstructure that has four rings.
They are derived from a species ofStreptomyces bacteria.
Tetracyclines are broad-spectrum
bacteriostatic agents
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The most commonly prescribed tetracyclineantibiotics are:
Natural - Tetracycline
Semisynthetic - Doxycycline
Mechanism of action inhibit bacterial protein synthesis by
binding to the 30S subunit of theribosome
They are primarily bactriostatic
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Tetracycline
Tablets 0,05 g, 0,1 g and 0,25 g; capsules 0,25 g;ointment 1 % and 3 %.
Doxycycline
Tablets and capsules 0.05 g, 0.1 and 0.2 gRegime: 0.2 g 1-t day, 0.1g next days
More modern way: 0.2 g each 12 hours
Syrup
Powder for preparation of a solution for I.V. inj. 0,1gand 0.2g in bottles
Sol. 0,2% - 5 ml for inj.
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In uptake they are well absorbed, andDoxycycline is better, than Tetracycline.Bioavailability of doxycycline does notchange, and Tetracycline - in 2 timesdecreases under influence of food.
are distributed in the body, D>T possess high ability to pass through a
placenta and to get into chest milk Excretion: T. primarily by kidneys, D. -
by kidneys and GIT (bile)
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Cocci Gram+ (Clostridia, Listeria etc.) and
gram- bacilli (Yersinia, Helicobacter
pylori, V. cholerae etc.) Spirochetes Rickettsiae, Actinomyces Atipical microorganisms: Chlamydia,
Mycoplasma, Legionella Entamoeba and Plasmodia Borelia recurrentis P.falciparum
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Infections of the: respiratory tract sinuses, middle ear
urinary tract skin (specially for moderately severe acne
and rosacea) intestines (including peptic ulcers,
cholera, salmonelliosis)
GonorrhoeaBoreliosisPlague
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GIT: cramps or burning of the stomach,diarrhea, sore mouth or tongue, hepatotoxicity.
Teeth: brown discolouration (T. should not be
used in children under the age of 8, andspecifically during periods of toothdevelopment).
Skin photosensitivity, which increases the risk
of sunburn under exposure to UV light Tetracyclines are classed as pregnancy
category D. Use during pregnancy may causealterations in bone development.
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Nephrotoxicity Antianabolic effect (prevalence
catabolism)
Vestibular toxicity Local reactions: a thrombophlebitis Rarely or very rarely: allergic reactions
severe headache and vision problemsmay be signs of dangerous secondaryintracranial hypertension