Antibiotics Flashcards
Beta Lactam Antibiotics
Cell Wall Synthesis Inhibitors
Beta Lactam Antibiotics:
-Contain a Beta-Lactam Ring, which is essential for their Activity.
1) Pencillins
2) Cephalosporins
3) Monobactams
4) Carbapenems
- Bactericidal
- Absolutely Selectively Toxic
- Beta Lactams:
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Cell Wall Synthesis Inhibitors
Mechanism of Action:
=> Inhibit Transpeptidation Step:
Final Step of Cell Wall Synthesis.
=> Thus, Inhibit Cross-Linking
More Potent in *LOG Phase:
=> b/c Only growing/dividing Bacteria Synthesize Cell Walls.
=> Less Potent in Lag Phase.
Mammalian cells do not have cell walls; thus, are absolutely selectively toxic.
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Resistance:
1) Beta-Lactamases:
(i) Released Free into Medium by Gram Positives,
(ii) Within the Periplasmic Space of Gram Negatives
2) Structural Differences in Penicillin Binding Proteins (PBPs)
3) Decreased Access to Site of Action
4) Decreased Accumulation @ Site of Action: Gram Negatives
Note: it’s harder to penetrate Gram Negatives
Penicillins
Absorption:
- Marked Differences in p.o. absorption
- Not all Penicillins can be given Orally.
1) *Only Amoxicillin Given w/ Food
2) Other Oral Penicillins Give 1-2 Hours Before or 2 Hours After Food
3) *Parenterally for Serious Systemic Infections
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Distribution:
1) Well Distributed to Most of Body
_Low Distribution to Eye, CNS, Prostate
_More Readily Penetrates CSF when Meninges Inflamed (Meningitis)
2) *High Urine Concentration
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Excretion:
=> *Unchanged Via Kidney:
1) *Reduce Dose if Renal Function Impaired
2) *Active Transport Mechanism
3) Probenecid Decreases Tubular Secretion (Increases Concentration in Body)
=> Due to Competition
@ same renal Transporter
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Adverse Effects:
1) Allergy:
=> Cross-Sensitizing w/ Cephalosporins
2) GI Tract (Oral)
=> Diarrhea
=> Oral Contraceptives may be inhibited
3) Candidiasis
=> Oral or Vaginal
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Beta-Lactamase Inhibitors:
1) Clavulanic Acid:
w/ Amoxicillin = Augmentin
=> Oral
w/ Ticarcillin = Timentin
=> IV
2) Sulbactam:
w/ Ampicillin = Unasyn
=> Parenteral
Penicillin G
Penicillin V
Penicillin G:
Administration: => IV => Poor Oral Absorption => Not Acid Stable => Repository Forms (IM) -Local Anesthetic Added: 1) Procaine Penicillin G 2) Benzathine Penicillin G -Repository is more slowly absorbed from the injection site, allowing Drug to last longer.
Penicillin V: => Oral (p.o.) => Acid Stable => Frequent Dosing Required (Poor Bioavailability)
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Susceptible to
Beta-Lactamase
=> Ineffective Against Most Strains of Staph aureus.
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Narrow Spectrum:
-Minimal Gram Negatives
1) Sensitive Strains of
Gram Positive Cocci
2) Bacillus Anthracis (Anthrax)
3) Clostridium Tetanus
4) Listeria Monocytogenes
5) Corynebacterium Diphtheria
6) Actinomyces israelii
7) Treponema Pallidum
(Syphilis) (Spirochete)
8) Neisseria Meningitidis
Dicloxacillin
Oxacillin
Methicillin
Penicillinase Resistant
1) *Dicloxacillin: *Oral
2) *Oxacillin: *Oral and *IV
3) Methicillin:
=> Not used anymore:
Due to MRSA.
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Narrow Spectrum:
-Minimal Gram Negatives
1) Non-Methicillin Resistant
Penicillinase-producing Staphs
2) Plus same spectrum as PenG
Ampicillin
Amoxicillin
Broad Spectrum Penicillins
1) Gram Positives
2) Some Gram Negatives
Amoxicillin:
=> May Be Given with Food!
=> Better Oral Absorption than Ampicillin
=> Causes Less Diarrhea
Ampicillin:
=> Good Oral Absorption
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Not Penicillinase Resistant
=> May be given in Combo wit Beta-Lactamase Inhibitor:
1) Ampicillin + Sulbactam:
=> *IV (Parenteral) Only
2) Amoxicillin + Clavulanic Acid = *Augmentin:
=> *Excellent Oral Absorption
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Rx:
1) UTIs
2) Sinusitis
3) Otitis
4) Respiratory Tract Infections
Ticarcillin
Piperacillin
Extended Spectrum Penicillins:
Anti-Pseudomonals
(Pseudomonas aeruginosa)
Administration: *IV
Not Resistant to Penicillinase
Ticarcillin + Clavulanic Acid:
= Timentin
=> Resistant to Penicillinase
Ticarcillin:
1) Pseudomonas
Piperacillin:
1) Pseudomonas
2) Klebsiella
3) Listeria
Cephalosporins
1st Generation:
1) Good for Gram Positive
2) Modest for Gram Negative
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2nd Generation:
=> Increased Activity
Against Gram Negative
=> Less Active than 3rd Gen
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3rd Generation:
1) More Active Against Enterobacteriaceae
2) Less Active than 1st Generation Against Gram Positive
=> Cefotaxime and Ceftriaxone:
(1) Meningitis
(2) Community Acquired Pneumonia
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4th Generation:
=> Comparable to 3rd Generation
=> More Resistant to Some
Beta-Lactamases
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Adverse Effects
1) Hypersensitivity
2) Cross-Sensitivity w/ Penicillins
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Rx:
1) Surgical Prophylaxis: Cefazolin
- Cefazolin, Cephalexin
2) 2nd Generation: e.g. Cefoxitin
=> Mixed Anaerobic Infections
-Cefaclor, Cefoxitin, Cefuroxime
3) 3rd Generation:
=> Wide Variety of Serious Infections:
e.g. Meningitis due to Gram Negative Enteric,
and Empirical Rx of Sepsis
-Cefotaxime, Ceftriaxone, Ceftazidime
4) 4th Generation:
=> Empirical Rx of Nosocomial Infections when Beta-Lactamase Resistance Anticipated
Cefepime
(1) Penetrates CSF
(2) Excreted by Kidneys
Rx:
=> Nosocomial Infections Empirical Treatment
Active Against
1) Haemophilus
2) Neisseria
3) Pseudomonas aeroginosa
4) Staph
Cefazolin
Cephalexin
1st Generation Cephalosporin
1) Good for Gram Positive
2) Modest for Gram Negative
Rx:
Surgical Prophylaxis: Cefazolin
Cefaclor
Cefoxitin
Cefuroxime
2nd Generation Cephalosporin
Increased Activity Against
Gram Negatives
Less Active than 3rd Generation
Rx:
2nd Generation: e.g. Cefoxitin
=> Mixed Anaerobic Infections
Ceftriaxone
Ceftazidime
Cefotaxime
3rd Generation Cephalosporin
Penetrate CSF
- Expanded Gram Negative
- Less Gram Positive than 1st Generation
- More Active Against Enterobacteriaceae
Ceftazidime: Pseudomonas
Cefotaxime and Ceftriaxone:
=> Meningitis
=> Empirical Rx of Sepsis
Rx:
=> Wide Variety of Serious Infections:
e.g.
(1) Meningitis due to Gram Negative Enteric,
(2) Empirical Rx of Sepsis
Cefepime
4th Generation Cephalosporin
1) Penetrates CSF
2) Excreted by Kidneys
3) More Resistant than 3rd Generation to
Beta-Lactamases
Rx:
=> Nosocomial Infections Empirical Treatment
Active Against
1) Haemophilus
2) Neisseria
3) Pseudomonas aeroginosa
4) Staph
Monobactam: Aztreonam
Admin: IV, IM
Penetrates CSF
-Interacts with PBPs
-Relatively Resistant to
Beta-Lactamases
-Little allergic cross-reactivity with Beta-Lactams
Spectrum:
1) Active Against Gram Negative
2) No Activity Against Gram Positive Anaerobes
Carbapenems: Imipenem
Broadest Spectrum of Beta Lactams
Admin: Parenterally
Enters CNS
Renal Excretion
=> Reduce Dose if Renal Impaired
Binds PBPs
Resistant to most Beta Lactamases
Rx:
1) Infections Resistant to other agents
2) Mixed Aerobic, Anaerobic Infections
Imipenem:
=> Degraded by Dehydropeptidases in Renal Tubules
=> ALWAYS Given in Combo with Cilastin to Prevent the Inactivation by Dehydropeptidases
Tetracyclines:
Doxycycline
Minocycline
Tetracycline
Mechanism: Bacteriostatic
-Inhibit Protein Synthesis
@ 30S Ribosomal Subunit
=> Prevent Adherence to Acceptor Site
-Relatively Selectively Toxic
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Absorption: Oral 1) Affect Enteric Flora => Diarrhea, GI Burning => Body Flora: Candida 2) Bind Divalent, Trivalent Cations: => Don't take w/ Milk, Calcium, Antacids, Iron 3) Doxycycline and Minocycline are More Lipid Soluble => Better Absorbed => Less GI Adverse Effects
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Distribution: 1) Penetrate Most Tissues Well 2) Bind To Calcium => Affect Growing Bones and Teeth => Cause Enamel Hypoplasia and Increased Risk of Dental Caries
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Excretion:
1) Kidney: main route
2) Bile: also
3) Doxycycline: 40% Kidney
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Rx:
1) Mycoplasma pneumoniae
2) Chlamydia
3) Rickettsia
(Rocky Mountain Spotted Fever)
4) Anthrax (in Combo)
5) H. pylori
(Gastric, Duodenal Ulcers)
6) Brucella (+ Aminoglycoside)
7) Borrelia burg (Lyme Ds)
8) Cholera (increased resistance)
9) Tularemia (+Aminoglycoside)
10) Acne
11) Periodontitis
_Low Dose Oral Doxycycline
_Low Dose Minocycline Microspheres
Broad Spectrum
-Effective Against
1) Gram Positive
2) Gram Negative
3) Rickettsia
4) Mycoplasma
5) Chlamydia
6) Legionella
7) Some Protozoa, eg. Amebae
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Adverse Effects:
1) Hypersensitivity (Allergy)
_Uncommon
2) GI:
=> Distress
=> Superinfection (C. Difficile)
3) Candida
4) Photosensitivity
5) Hepatotoxicity
_Large Doses
_Pregnancy
6) Renal Toxicity
_If Drugs Outdated
7) Deposition in Growing Bones and Teeth in Kids up to Age 8: => Brown Discoloration of Teeth => Enamel Hypoplasia: Increases Risk Dental Caries => Depression of Bone Growth (Reversible)
Contraindicated:
1) Liver Disease
2) Pregnancy
3) Kids up to Age 8
Tigecycline
Is a Glycycline
-Similar to Tetracyclines
Broad Spectrum:
=> Active Against MRSA
=> Against many Strains Resistant to Tetracyclines
Admin: IV
Excretion: Biliary mainly
_No Dose adjustment necessary in Renal Ds.
