tetracycline sand chlo ramp he nicol

8/11/2019 Tetracycline Sand Chlo Ramp He Nicol

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Tetracyclinesand

Chloramphenicol

linrong


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Tetracyclines Origin

Absorption, Distribution, Excretion Mechanisms of action Mechanisms of resistance Spectrum of activity Therapeutic Uses Adverse Effects

Contraindications

Chloramphenicol

Mechanisms o f act ion Pharmacologic effects

Mechanisms o f res is tance Clinical uses Adverse effects


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Tetracyclines

Origin Tetracyclin, oxytetracyclin isolated from

Streptomyces

Minocycline, doxycyclin are synthetic

At present, for many reasons such as toxicity,drug resistance, the development of more

effective, the uses of tetracyclines have been

largely declined.

Tetracycline is limited for a few infections andis being gradually substituted by somesemisynthetic tetracyclines such as

minocycline and doxycycline.


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What are spectrum of activi ty of

Tetracyclines?

Tetracyclines are effective against G+ and G-.

They are weaker thanpenicilins and

cephalosporins against G+ organisms.

! They are weakerthan aminoglycosides

and chloramphenicol against G-

organisms.

broad-spectrum


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Spectrum of activi ty

" They have the favourable effects on

! Rickettsiae,

! Mycoplasma,

! Chlamydiae

! Spirochete.

# They are effective against some

protozoa.


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What s the mechanisms of action?

Quickly bacteriostatic drugs, but at high

dosage they are also bactericidal.

They reversibly bind to the 30S ribosomal

subunit of bacteria, blocking the binding ofaminoacyl-tRNA to the site A on the mRNA

ribosome complex. This prevents addition

of amino acids to the growing peptide,

resulting in inhibition of protein synthesis.


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Bacterial resistance to tetracyclines is mainly

due to the follow three mechanisms:

Decreased intracellular accumulation

owning to either impaired influx or increasedeffluxby an active transport protein pump;

! Ribosome protection owning to production of

proteins that interfere with tetracycline

binding to the target site.

" Enzymatic inactivation of tetracyclines.

How many mechanisms of resistance

are there about Tetracyclines?


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Pharmacokinetics-Absorption

All tetracylines are administered orally.

Tetracycline, in particular, is chelated andinactivated by calcium (milk), magnesium,

aluminum (antacids) and iron, and should

be taken when the stomach is empty.Doxycycline is less avidly chelated and can

be taken with a meal.


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Pharmacokinetics-Distribution

Widely distributed in body

Bind in tissues undergoing calcification(teeth, bones) or tumors with high calciumcontent (gastric carcinoma)

All cross placenta and concentrate in fetalbones and teeth

Minocycline best CSF penetration Concentrated in saliva and gingival fluid


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Pharmacokinetics-Excretion

Concentrate in liver and partiallymetabolized

Secreted into bile and excreted in urine

Doxycycline and minocycline largelyexcreted in feces

Use in renal insufficiency


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Clinical Uses

First choice for rickettsial infections

(typhus), chlamydial infections, and

Mycoplasma pneumonia.

!They are effective for many spirochetalinfections, including relapsing fever (first

choice), leptospirosis, Lyme diseases, and

syphilis.


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Clinical Uses

" They are also effective for treatment of

various G+ and G- bacterial infections.

Brucellosis, cholera, and tularemia can be

treated with tetracyclines as the firstchoice.

# Other uses: intestinal amebiasis, acne and

actinomycosis


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Tetracyclines:Adverse Effects

A. Gastrointestinal discomfort

Anorexia, epigastric pain, abdominal

distention, nausea, vomiting, diarrhea,

sore mouth, perianal irritation

B. Hepatic injury (Liver toxicity)

Increased during pregnancy

C. kidney toxicity

Nephrotoxicity


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D. Teeth and depression of bone growth

Discoloration enamel and hypoplasia of teeth

Deposition in fetal and growing bones,

stunted growthE. Photosensitization

Severe sunburn in sun; doxy/demeclocycline

Tetracyclines:Adverse Effects


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Contraindications

Pregnancy

Children

Renal insufficiency

Can use doxycycline


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Tetracyclines Origin

Absorption, Distribution, Excretion Mechanisms of action Mechanisms of resistance Spectrum of activity Therapeutic Uses Adverse Effects

Contraindications

Chloramphenicol




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Although an effective broad-spectrumantibiotics, its uses are limitid by its

serious toxicity. Now is rarely usedexcept

for severe infective diseases.

It is well absorbed and widely distributed,including to theCNS.

It is metabolized by glucuronidatation inthe liver.

Chloramphenicol(CAP)


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inhibits bacterial protein synthesis.

CAP binds 50S subunit and block elongation by

inhibiting the formation of initiation complexes

andpeptidyltransferase; binding site of CAPoverlaps with that of macrolides and clindamycin

CAP is primarily bacteriostatic, but it may be

bactericidal to some strains of microorganisms

even at lower concentration: H.influenzae,N.meningitidis and N.gonorrhoeae

Mechanisms of action


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Pharmacologic effects

Chloramphenical is active against a broad

range of organisms, including G+ and G-

bacteria (including anaerobes) .

But, its effects on G- bacteria is better than

on G+ bacteria, especially Salmonella typhi.


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Mechanisms of resistance

v Selection of permeability mutants thatresults in impaired penetration of the drug

to target site;

v Production of chloramphenicol

acetyltransferase, a plasmid-encodedenzyme that inactivates the drug.


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Clinical uses

1. First choice for the treatment :

typhoid and paratyphoid

2. Used only in serious infections with

the sensitive bacteria.

Chloramphenicol


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Adverse effects

1. Bonemarrow Disturbance-reversible

bone marrow depression

Chloramphenicol inhibits protein

synthesis in the mitochondria of human cells.This inhibition may be the cause of the dose-

dependent toxicity of drug to bone marrow.

Chloramphenicol


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2. Toxicity for Newborn Infants(Gray-baby syndrome)

Be seen in neonates, especially premature infants,

who have been given relatively large doses of

CAP. Cyanosis, respiratory irregularities,

abdominal distention, loose green stool, and anashen-gray color characterize this often-fatal

syndrome.! mainly due to the immature hepatic conjugating mechanism

for the degradation and detoxification of CAP in neonates.

The inadequate renal elimination mechanism of neonate

and the inactive metabolites also contributes to the

occurrence of the syndrome.

Adverse effects Chloramphenicol


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Adverse effects

3. Gastro intest inal react ion .

nausea, vom it ing, diarrhea

4. Superinfect ions

such as Oropharyngeal candidiasis andacute Staphylococcal enterocolitis.

5. Hypersensitivity reactions

6.A rare anemia, probably immunological in

origin but often fatal

Chloramphenicol


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Tetracyclines Origin Absorption, Distribution, Excretion Mechanisms of action Mechanisms of resistance Spectrum of activity Therapeutic Uses Adverse Effects

Contraindications

Chloramphenicol




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tetracycline sand chlo ramp he nicol

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