Transcript 03. Antibiotics

Inhibitors of protein synthesis
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Macrolides
Tertracyclines
Aminoglycosides
Chloramphenicol
MACROLIDES
Mechanism of action :
Inhibits protein synthesis by binding to
50S ribosomal subunits
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Bactericidal at high concentration &
bacteriostatic at low concentration.
Erythromycin
 Is effective against :
Legionella, cornybacteria, grampositive cocci, chlamydia, helicobacter
 Less effective on : gram-negative
organisms.
Pharmacokinetics
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Destroyed by gastric acidity and must
be administered with enteric coating .
Food interferes with absorption
Half-life 1.5h
Excreted mainly through bile,5%only in
urine.
Cross placenta not B.B.B.
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Distribute well to all body fluids except
CSF.
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It is one of the few antibiotics that diffuses
into prostatic fluids
Clinical uses
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Drug of choice of corynebacterial
infections
Chlamydial infections
Community acquired pneumonia
Mycoplasma
Legionella
Penicillin allergic patients.
Adverse effects
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GIT .upset
Liver toxicity especially with the estolate
coat produce acute cholestatic hepatitis
Drug interactions as it is cytochrome p450 inhibitor.
Hypersensitivity reactions .
Clarithromycin
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Acid stable
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Spectrum as erythromycin but more
active against Mycobacterium avium
complex. & leprae.Toxoplasma gondii.
Half –life 6h.
Metabolized in liver (active metabolites ).
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Enzyme inhibitor for P450
Has a lower frequency of gastric
intolerance
less frequent dosing
More tolerable
More expensive
Azithromycin
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Similar spectrum as clarithromycin. More
active on H-influenza &chlamydia.
Half-life 3 days .
Rapidly absorbed and well tolerated .
Should be given one hour before or 2 hours
after meals
Does not affect P450 enzymes
Excreted in bile and urine
Clinical uses
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Upper and lower respiratory tract
infections
Skin infections
Alternative to penicillin in allergic patients
Urethritis or cervicitis mainly by chlamydial
infections .
Adverse effects
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Gstric upset (less than erythromycin )
Allergic
Superinfections
Tetracyclines
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Broad -spectrum antibiotics
Bacteriostatic
Inhibits protein synthesis by binding to
30 S ribosomal subunit
Pharmacokinetics
Absorption:
 Poorly absorbed( 30%)
chlortetracycline
 Medialy absorbed (60-70%)
demeclocycline
 Highly absorbed (95-100% )
doxycycline and minocycline.
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Absorption is impaired by1- food
except with doxycycline & minocycline.
2- by divalent cations, milk and its
products ,antacids and alkaline pH
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Minocycline reaches very high conc. In
tears and saliva.
Tetracycline group cross placental
barrier & concentrate in fetal bone
& teeth.
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Excreted through bile and urine
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Doxycycline is eliminated via bile .
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Doxycycline can be used for treating
infections in renally compromised patients
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Tetracyclines are also excreted in breast
milk
Half-life :
 Long acting: doxycycline &minocycline
(16-18h once daily ).
 Intermediate:(12h) demeclocycline
 Short acting : ( 6-8 h ) tetracycline
Clinical uses
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Drug of choice in :
Mycoplasma pneumonia
Chlamydial infections
Rickettsial infections
Spirochetal infections
Brucellosis
Effective in :
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Cholera
Traveller,s diarrhea
Helicobacter pylori
Acne
Bronchitis
Protozoal infections
Minocycline to eradicate meningococcal carrier
Not used in:
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Streptococcal & staphylococcal infections .
Gonococcal infections
Meningococcal infections
Typhoid fever
Adverse effects
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I.M. (pain & inflammation)
I.V. (thrombophilbitis)
Gastric upset
Super infections
Damage growing bone
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Yellowish brown discoloration & dental
caries
Hypoplasia in primary teeth
Hepatotoxicity
Phototoxicity
Vestibular problems :
Doxycycline &minocycline.
Contraindications
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With : milk or its products, or antacids.
Pregnancy may cause fatal hepatotoxicity
Children under 8 years.
Chloramphenicol
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Broad spectrum antibiotics
Bactericidal or bacteriostatic
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Inhibits protein synthesis by binding to 50S
ribosomal subunits.
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Cross placental barrier &B.B.B.
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Enzyme inhibitor (p450)
Clinical uses
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Serious rickettsial infections
In children whom tetracyclines are
contraindicated
Meningococcal meningitis
Topically in bacterial eye infections except
in chlamydial infections.
Adverse effects
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Gastric upset
Super infections
Bone marrow depression
Gray baby syndrome
Hypersensitivity reactions
Drug interactions
Aminoglycosides
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Bactericidal antibiotics
Inhibits protein synthesis by binding to
30S ribosomal subunits.
Active against gram negative aerobic
organisms.
Poorly absorbed orally
Given I.M,I.V., intrathecal
Not freely cross BBB, cross placenta
Aminoglycosides
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Excreted unchanged in urine
More active in alkaline medium
Adverse effects :
Ototoxicity
Nephrotoxicity
Neuromuscular blocking effect
Contact dermatitis
Streptomycin
Clinical uses
 T.B. in combination with other drugs.
 Enterococcal endocarditis with penicillin.
 Severe brucellosis with tetracycline
Gentamicin
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Severe infections caused by gram
negative organisms as sepsis ,urinary
tract infections & pneumonia caused by
pseudomonas or enterobacter.
Topically for the treatment of infected
burns, wounds, skin , ocular & ear
infections.
Tobramycin
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More active against pseudomonas than
gentamicin.
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Less nephrotoxic and ototoxic than
gentamicin.
Used in treatment of bacteremia,
osteomyelitis and pneumonia.
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Amikacin
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Has the broadest spectrum
Used for serious nosocomial infections by
gram negative organisms.
In T.B. as alternative to streptomycin
Atypical mycobacterial infections
Neomycin
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Highly nephrotoxic ,used only orally for gut
sterilization before surgery or topically in
skin ,burn or eye infections.
Neomycin
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Highly nephrotoxic ,used only orally for gut
sterilization before surgery or topically in
skin ,burn or eye infections.
Contraindications
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Renal dysfunction
Pregnancy
Diminished hearing
Myasthenia gravis
Respiratory problems
Inhibitors of DNA Gyrase
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FLUOROQUINOLONES
Ciprofloxacin
Mechanism of action:
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Block bacterial DNA synthesis by inhibiting
bacterial topoisomerase11(DNA gyrase ) and
topoisomerase 1V.
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All are bactericidal
Antibacterial activity
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Gram-negative aerobic bacteria.
Gram-positive bacteria.
Mycoplasma, chlamydial, legionella infections
Some mycobacteria.
Anaerobic bacteria ( moxifloxacin)
Pharmacokinetics
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Well absorbed orally or intravenously
Widely distributed in body fluids & tissues.
Half-life(3-10h).
Absorption is impaired by antacids.
Concentrated mainly in prostate, kidney,
bone ,lung.
Pharmacokinetics
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Excreted by the renal route , except
moxifloxacin.
Clinical uses
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U.T.I.caused by multidrug resistance organisms
as pseudomonas.
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Bacterial diarrhea.
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Soft tissues, bones,joints,intra-abdominal,
respiratory infections caused by multidrug
resistance organisms
Clinical uses
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Gonococcal infections
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Legionellosis
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Chlamydial urethritis or cervicitis
T.B & atypical T.B.
Meningococcal carriers
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Adverse effects
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Gastric upset
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Headache ,dizziness, insomnia
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Phototoxicity
Damage growing cartilage causing
arthropathy.
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Drug interactions &
contraindications
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With antacid or divalent cations
Ciprofloxacin increase serum levels of
theophylline , warfarin or cyclosporine.
Contraindicated : children ,adolescents
,epileptic patients or in patients taking
antiarrhythmic drugs .