• UDP-NAG
• UDP-NAM (w/pentapeptide that has D Ala D Ala terminal end)

• inhibits the racemase and synthase responsible for producing the D-Ala D Ala terminal end of the UDP-NAM building block

1. act as an anologue for D Ala-D Ala terminal end
2. bind to and inactivate peptidoglycan tansferase (one of the PBP's that penicillin binds to that is unique to every bacteria)
3. NO MORE CROSS LINKING
4. this creates a defective cell wall that can no longer maintain osmolarity
5. activate murein hydrolase (endogenous autolytic enzymes)
   1. normally, it just allows for new cell wall synthesis by taking out small parts
   2. however, in this case, it will lead to cell lysis and death

It can only affect growing microorganisms

• MAJOR- beta lactamases (hydrolyze the beta lactam bond, making the antibiotic inactive)
• minor
  • decrease peremability to drug
  • reduced affinity of PBP's foor drug

• narrow spectrum
  • gram positive aerobes and anaerobes

• absorption
  • inactivated by gastric acid, so only 25% gets absorbed orally
  • soln: Pen V more acid stable, better absorbed orally
• distribution
  • widely distributed
  • poor penetration of CNS
• excretion- kidney via secretion into PCT
  • probenecid inhibits secretion, leading to increases and prolonging plasma levels
• half life of 30 minutes
• metabolism- hepatic inactivation minor except with renal dysfunction

• thrombophlebitis
• hypersensitivity
• at high doses, CNS effects- tremors, convulsions
• superinfection- bacterial overgrowth
  • good bact. destroyed by antibiotics
  • overgrowth of bad bacteria
  • lead to pseudomembranous colitis

types of hypersensitivity seen to penicillin G and the mechanism

• immediate
• accelerated
• delayed

Formation of specific haptens upon reaction leads to hypersensitivity for those who have taken penicillin G and those who have been unknowingly exposed to it.

• time: 0-30 minutes
• mechanism (most serious form of hypersensitivity, but most rare)
  • anaphylactic rxn
  • IgE mediated and rare
• symptoms/signs
  • urticaria
  • angioedema
  • asthma
  • laryngeal edema
  • hypotension leading to death

• time: 1-72 hrs
• symptoms
  • similar to immediate
  • although severe anaphylaxis, hypotension, death are rare

• time: 3-30 days
• characteristic- usually self limiting
• symptoms/signs
  • most commonly skin rxn
  • less common
    • serum sickness
    • hemolytic anemia
    • thrombocytopenia
    • nephropathies
    • Stevens Johnson syndrome

• h/o allergy- use different drug
• skin testing with benzylpenicilloyl polylysine
  • must be safe (do in setting where reaction can be treated)
  • some predictive value, but not absolute
• desensitization- help reduce risk of anaphylaxis

• improved gastric stability
• improved activity against resistant bacteria
• broadened spectrum of activity
• better oral absorption

They tried to decrease allergenicity, but failed. All penicillins produce cross hypersensitivity with each other.

• drugs resistant to beta lactamases- produce penicillase resistant penicillin
• add on an inhibitor of beta lactamases- add clavulanic acid to dose of amoxicillin

• gram positive cocci that produce penicillases (doesnt work for gram negative bacilli)

Indicative of specificity of penicillin binding proteins.

• Nafcillin
• Oxacillin
• Cloxacillin
• Dicloxacillin

• variable GI absorption
  • must administer IV due to erratic oral absorption
• elimination- biliary excretion mainly

• acid stable
• orally active

• aminopenicillins
  • ampicillin
  • amoxicillin
• antipseudomonal penicillins- piperacillin

• spectrum- gram positive and negative organisms
• pharmacokinetics- acid stable, so well absorbed
• resistance- inactivated via beta lactamase
• adverse effects
  • increase incidence of diarrhea, GI distress (cant give with food cause it will impair absorption)
  • increase incidence of delayed hypersensitivity- skin rashes

• spectrum- gram positive and negative (resemble ampicillin)
• structure- resemble ampicillin
• pharmacokinetics- better GI absorption than ampicillin and it can be given with food
• resistance- inactivated by beta lactamases

• pharmacokinetics
  • only given IM or IV
  • nonlinear pharmacokinetics (plasma conc. not proportional to dose)
• spectrum- gram negative organisms, esp. P. aeruginosa
• resistance/inactivation
  • inactivated by beta lactamases
  • inactivated by gastric acid

• synergistic
• provides inhibitor of beta lactamse, but has no intrnsic antibacterial activity

Remember, inhibitors of beta lactamases only inhibit CERTAIN KINDS of beta lactamases.

• the first generation was mainly for gram positive cocci with limited use among gram negative
• as generations go on, there is increasing activity to gram negative and decreasing to gram positive

• structurally related to penicillin (contains beta lactam ring)
• mechanism of action- IDENTICAL TO PENICILLIN

• distribution- penetrate into most tissue well
  • 1st, 2nd generation do not penetrate well into CNS
  • 3rd generation do get into CNS
• half life: 0.5-2 hrs
• absorbed- well absorbed oral (no effect of food)
• excretion- kidney
  • probenicid delays renal tubular secretion of cephalosporins

• hypersensitivity- cross reactivity with other cephalosporins and penicillins (similarity of side chains, esp. generation 1)
  • CI- h/o penicillin anaphylaxis
• mild nephrotoxicity
• superinfection
• diarrhea
• thrombophlebitis with IV admin.

• Cefazolin
• Cephalexin

• spectrum- gram positive
• great for skin, soft tissue infection

• first generation cephalosporin
• pharmacokinetics
  • parenterally administrated
  • distribution- penetrate most tissue
  • excretion- glomerular filtration
  • longer half life, so less frequent administration
• use- prophyllaxis in surgery

• administer orally
• similar spectrum of activity to cefazoline

• cefuroxime
• cefoxitin
• cefotetan
• cefmandol

• gram positive and some gram negative
  • relatively, more activity against gram negative bacilli than first generation
  • relatively, less activity against gram negative than third

• pharmacokinetics- IV administration
• indications (resistant to beta lactamases)
  • mixed aerobic anaerobic/infections
    • PID
    • lung abscess
  • surgical prophylaxis of infection caused by gram negative organisms

• penetrates CNS
• administrated orally and IV
• less effective than third generations against CNS infections

• ceftriaxone
  • half life- 8 hrs
  • pharmacokinetics- good CNS penetration
  • indications
    • gonorrhea
    • severe Lyme disease
    • meningitis
• ceftazidime
  • half life- 1-2 hrs
  • pharmacokinetics- penetrates CNS
  • indications- P. aeriginosa

• extended spectrum beta lactamases
  • mutated to hydrolyze a broader range of beta lactams, including third generation cephalosporins

• Cefepime
• extended spectrum of activity (compared to third generation)
• resistance- it has increased stability from hydrolysis by beta lactamases
• penetrates CNS, so it can be used in treatment of bacterial meningitis

• absorption- does not absorb orally
• rapidly hydrolyzed by renal enzyme dehydropeptidase I, so we add cilastatin to inhibit that enzyme so impenem will not be broken down
• excretion- renal (modify for renal insufficiency)

• cross allergenicity with other beta lactams (ex: penicillin)
• seizures in high doses and those with CNS lesions
• nausea, vomit

• these drugs are not metabolized by dehydropeptidase, so no need for cilastatin
• broad spectrum (although inactive against MRSA, Vancomycin R enterococi)
  • wide range of gram positive and negative including aerobic and anaerobic gram positive and negative bacilli

• spectrum- limited to gram negative bacteria (enterobacteriaceae and pseudomonas)
• resistance to beta lactamase inactivation
• adverse effets
  • hypersensitivity, but little cross allergenicity with penicillins or cephalosporins
  • thrombophlebits at injection site

• spectrum- gram positive bacteria
• structure- cyclic glycopeptide
• mechanism
  • inhibits peptidoglycan synthase (adds dissacharide subunit to growing cell wall) in the membrane phase of cell wall synthesis

1. pentapetide terminal end converted to D-Ala D lactate
2. mutate strand incorperated into cell wall and will not affect cell wall
3. however, affinity for vancomycin is vastly reduced

• IV administration (poor oral absorption)
• excretion- kidney (90% glomerular filtration)
  • not removed by hemodialysis, so half life in anephric patients is 6-10 days
  • dosage adjustment in renal dysfunction

adverse effects of vancomycin

• thrombophlebitis at injection site
• chills, fever
• in large doses and administration with another ototoxic drug, ototoxicity
• flushing due to rapid infusion, leading to histamine release- RED MAN's SYNDROME