Antibiotics Part2

8/4/2019 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

Antibiotics Part2

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