Penicillins and Carbapenems Flashcards
Penicillins Mechanism of Action
Bind to Penicillin binding proteins (Transpeptidase), Defects in cell wall synthesis, Inhibit cross linking
Induce holing-like proteins in bacterial membrane - Cause lesions and collapse of membrane potential
Bacteriocidal
Chemistry of Penicillin
5 member ring attached to 4 member ring
Thiazolidine ring
Beta-Lactam ring
Penicillin G
Benzylpenicillin
Acid Labile - Destroyed in stomach acid - Administered IM or IV
Penicillin V
Phenoxymethylpenicillin
Better oral absorption (Less sensitive to food) - Gram positive organisms - Oral anaerobes or Spirochetes; q6h
Ampicillin
Amino group added on, Gram negative antibacterial spectrum, Reduce efficacy on Gram positive, Oral admin
Amoxicillin
Better oral absorption - More used in dentistry - Gram negative; q8h; No adjustment in compensated cirrhosis but avoid in decompensated; Used in patients with liver/kidney disease but adjust;
Natural Penicillins
Pen G
Pen VK
Procaine
Benzathine penicillin
Penicillin Spectrum
Narrow Spectrum
Gram+ve cocci and bacilli (Bacillus anthraces); Spirochetes - ANUG (Anaerobes and Spirochetes cause) - Treponema pallidum (syphilis); Oral anaerobes - Actinomyces (Actinomycosis - Lumpy tumors of jaw and tongue, Loss of wt. strength); Costridial infection - Gas gangrene (C. perfringens), Tetanus (C. tetani - eradicate vegetative forms of bacteria that persist, Use tetanus immune globulin); Anthrax - Pen G (Ciprofloxacin - Drug of choice); Streptococcal infections - Pen V or G - S. Pyogenes (Pharyngitis, otitis media, pneumonia, bacteremia, scarlet fever - chills, scarlet rash, sore throat, nephritis), Endocarditis (Enterococcal endocarditis - Pen G + Aminoglycoside); Penicillin G and Penicillin V (Natural) - Rat bite fever (Spirilum minor, Streptobacillus monliformis) - Pen G choice, Diptheria (Pen G for carrier state - antitoxin), Neisseria Meningitides (Meningitis - Pen G);
Aminopenicillins Spectrum
Amoxicillin or Ampicillin
Not penicillinase resistant;
Extended Spectrum (More Gram -);
Gram positive cocci and some Gram negative - ex. P.mirabilis, Salmonella, Shigella, E.Coli; Not active against Pseudomonas, Sensitive to Beta-lactamase, Combine with Beta-lactamase inhibitor clavulanic acid, sulbactam or tazobactam; Amoxicillin + Clavulanic Acid = Augmentin; Prevotella intermedia/nigrescens, F. nucleatum, other Prevotella species. P. gingival is found in periodontal pockets and all produce beta lactamase, treat with Amoxicillin + Clavulanic acid or Amoxicillin + Metronidazole; Prophylaxis prior to dental treatment; Spectrum includes more Gram neg organism, Efficacy got Gram pos degraded
Penicillinase-Resistant Penicillins
Methicillin (Injection), Nafcillin (Injection), Cloxacillin (Oral), Dicloxacillin (Best oral absorption), Oxacillin (Parenteral)
Flucloxacillin (Not in US)
Penicillinase-Resistant Penicillins Spectrum
Only used to treat infections caused by Beta-lactamase producing Staph Aureus (Bacteremia, Endocarditis, Pneumonia, Osteomyelitis)
MRSA Treatment
Vancomycin, Linezolid, Quinupristin-Dalfopristin
Anti-Pseudomonal Penicillin
Carboxypenicillins: Ticarcillin (and Carbenicillin) active against P. aeruginosa and Proteus
Ureidopenicillins: Piperacillin(-Tazobactam w/broadest spectrum of penicillins) (and Mezlocillin) extends spectrum of Ampicillin to include Pseudomonas, Enterobacteriaceae, Bacteroides
Sensitive to Beta-lactamase so use inhibitor
Mainly used for serious infections caused by Gram neg organisms [bacteremias, pneumonias, infections following burns, UTI resistant to Pen G, ampicillin - (P. aeruginosa, indole + proteus, enterobacter)]
Mezlocillin, Piperacillin, Ticarcillin - Inactivated by acid, Give IM or IV
Procaine and Benzathine Admin
IM Slow Release forms
Penicillin Distribution
Most 20-50% Plasma bound, Some beta lactamase resistant genes 90-95% bound; Cross placenta are distributed into breast milk as weak acids; Well distributed, Do not enter CSF unless inflamed meninges
Penicillin Metabolism and Excretion
Primarily eliminated by renal route, Rapidly excreted by kidney through filtration and tubular secretion, Pen V 50% metabolized by liver
Biliary excretion - Particularly nafcillin, oxacillin - Piperacillin partly biliary
Renal compromised - Total daily dose reduction or interval reduction or use Clindamycin or Azithromycin (Min urinary excretion)
Take Penicillin 1hr before/2hr after meal
Antibiotics - Prolong Warfarin (EXCEPT Dicloxacillin)
Probenacid
Inhibits tubular secretion, Used to elevate penicillin blood levels
Penicillin Adverse Effects
Allergic Rxns - Hypersensitivity; Skin rashes of various types (High with Ampicillin), Public health problem
Acute Anaphylactic rxns - Rare, But fatal; Treat w/Epi, Skin test with Penicilloyl Polylysine helpful but not always conclusive (May need diphenhydramine &/ glucocorticoid anti-inflammatories)
Superinfection by Resistant organisms - ex. Pseudomembranous colitis (C. difficile), More likely with extended spectrum agents
Electrolyte disorder - Rapid IV infusion of Potassium Salt of Penicillin G produces hyperkalemia leading to arrhythmias and cardiac arrest
Very high doses lower seizure threshold
Metabolite of Penicillin
D-Benzylpenicillenic acid
Mechanism of Resistance to Penicillin
Change in Penicillin Binding Protein - Important in gram-positive cocci ex. S. aureus resistance to methicillin and pneumococcus
Increased production of Beta-Lactamase enzymes - Main mechanism of resistance
Development of tolerance by loss of autolysis mechanism (Agents become bacteriostatic)
Penicillin Uses in Dentistry
Treat post extraction infections, post surgical infections, pericoronitis, dentoalveolar abscesses, osteomyelitis, cellulites, ulcerative gingivitis, periodontitis, prophylaxis
Amoxicillin + Metronidazole
Treat Aggregatibacter (Actinobacillus) Actinomycetemcomitans associated periodontitis and aggressive/and or advanced forms of chronic periodontitis
Oral Regimens for Dental Procedure
Amoxicillin
Adult: 2g
Children: 5mg/kg
Unable to Take Oral Meds Regimens for Dental Procedure
Ampicillin Adults: 2g IM or IV Children: 50mg/kg IM or IV Cefazolin or Ceftriaxone Adults: 1g IM or IV Children: 50mg/kg IM or IV
Allergic to Penicillin/Ampicillin Oral Regimens for Dental Procedure
Cephalexin Adults: 2g Children: 50mg/kg Clindamycin Adults: 600mg Children: 20mg/kg Azithromycin or Clarithromycin Adults: 500mg Children: 15mg/kg
Allergic to Penicillins/Ampicillins and Unable to Take Oral Regimens for Dental Procedure
Cefazolin or Ceftriaxone Adults: 1g IM or IV Children: 50mg/kg IM or IV Clindamycin Adults: 500mg IM or IV Children: 20mg/kg IM or IV
Carbapenems Chemistry
Imipenem/Cilastatin
Meropenem
Contains C instead of S in 5member ring
Carbapenems Spectrum of Action
Broad Spectrum
Active VS Gram - and Gram + organisms
NOT Active VS MRSA (Altered PBP), VRE, Choice for Enterobacter infections, Useful for treatment of pulmonary, intra-abdominal and soft tissue infections caused by mix of bacteria
Carbapenems Mechanism of Action
Bind to PBPs 1 and 2 rather than PBP 3 to which Aminopenicillins bind, Small size allows easy penetration of Gram - envelope through Porins
Carbapenems Pharmacokinetics
Not absorbed from GI tract so IV or IM, Hydrolyzed rapidly by dehydropeptidase 1 present in brush border of proximal renal tubule; Must be administered with Cilastatin - a competitive inhibitor of dehydropeptidase 1 - Cilastatin prevents destruction of Imipenem ring; Meropenem is resistant to degradation by dehydropeptidase 1
Carbapenems Adverse Effects
Imipenem at high doses causes seizures, less with Meropenem; GI complaints of N, V, D, skin rash and rare neutropenia
Carbapenems Resistance
Alteration of porins so drug can’t access periplasmic space
