Test 5: Antibiotics Specific Drugs Flashcards
Which antibiotics are the Beta Lactam Compounds?
-Penicillins
-Carbapenems (Imipenem, Meropenem)
-Cephalosporins (1st-4th gen)
All contain Beta Lactam ring. Risk of cross-sensitivity.
What is the MOA of Beta Lactam Compounds?
Inhibit bacterial growth!! (Bactericidal)
-Interfere with the transpeptidation (creation of peptidoglycans) of bacterial cell wall synthesis.
-Peptidoglycans are the cross-linked mesh that provides rigid structure and protection to bacteria.
-B-Lactam antibiotics bind to PBPs (Penicillin Binding Proteins) and inhibit bacterial growth.
What breaks down the Beta Lactam antibiotics?
Beta Lactamase.
-Resides on the cytoplasmic membrane
-Breaks down B-Lactam antibiotics as they attempt to bind to PBPs (penicillin binding proteins)
What are cellular differences between Gram-Negative and Gram-Positive bacteria?
Gram Negative:
-Has an outer membrane that contains Porins (proteins with binding sites that allow hydrophillic access to the inside of the cell)
-Stains red/pink
Gram Positive:
-No outer membrane
-Retains crystal violet dye
-Easier to kill
-Multiple layers of Peptidoglycan
What are the 4 Mechanisms of resistance to Beta-Lactam antibiotics?
1) Inactivation of ABX by β-lactamases
-Most common
2) Modification of target PBP’s
-Ex: MRSA
3) Impaired penetration of ABX to the target PBP
-Particularly in gram-negative. Can have down regulation of Porins. Hydrophillic drugs are less effective.
4) Efflux
-Bacteria pumps antibiotic right back out before it had time to work
What is the drug of choice in individuals with a history of penicillin allergy other than immediate hypersensitivity? (Blue Box!)
Cephalosporin
-Can use it as long as they don’t have true anaphylactic reactions
-Cross sensitivity is 0.2 -10% occurrence.
What are the Cephalosporins?
More stable to many bacterial β-Lactamases:
-Broader spectrum of activity
Classified into 4 major groups (generations) depending on antimicrobial activity
What are the effects of the 1st generation Cephalosporins?
Very effective on gram positive bacteria.
Gram Positive Cocci:
-Pneumonococci
-Steptrococci
-Staphylococci
Ex: Cefazolin (Ancef)
-Only agent still in use
-Drug of choice for surgical prophylaxis
-Does not penetrate CNS
-Not useful in meningitis
What are the effects of the 2nd generation Cephalosporins?
-Ex: Cefuroxime (Zinacef)
-Active against organisms inhibited by 1st Generation ABX.
-Extended gram negative coverage
Improved activity against:
-Haemophilus influenzae
-Pneumococcus
-Oral & IV
-Treatment against commonly acquired pneumonia
-Crosses the Blood Brain Barrier (Not as effective as Ceftriaxone or Cefotaxime)
What is the difference between the 1st and 2nd generation Cephalosporins?
First-generation cephalosporins are active predominantly against Gram-positive bacteria, and successive generations have increased activity against Gram-negative bacteria (albeit often with reduced activity against Gram-positive organisms).
What is Cefuroxime (Zinacef) used for?
1.5 g - used often in urology for cysto cases
What is the only Monobactam used in the US?
Aztreonam (Azactam)
-Same MOA as B-Lactams
-Bactericidal against gram negative
-Renal cleared
-No toxicity
-No cross allogenicity with PCN. Used if hypersensitivity to PCN
What are the kinetics associated with Cefazolin?
-IV
-Renal clearance
-Half-Life 1.5 hours
-Poor penetration into CNS
-Bactericidal to mostly gram positive and a little gram negative
Toxicities:
-Rash
-Drug fever
What is Ceftriaxone (Rocephin)?
-3rd generation cephalosporin.
-Same MOA as B-Lactams
-More coverage in the CNS
What are the uses of Penicillins?
Penicillins treat steptococcal infections, meningococcal infections, & neurosyphilis
What are the S/Sx of Neuromuscular Hypersensitivity?
-Agitation
-Hallucinations
-Asterixis: tremor of the hand when the wrist is extended, sometimes said to resemble a bird flapping its wings.
-Encephalopathy
-Confusion
-Seizures
What is the usual dose of Vancomycin?
30-60mg/kg/day in patients with normal renal function
-2-3 divided doses
What is the MOA of Vancomycin?
Glycopeptide class.
Inhibits cell wall synthesis by binding to the D-Ala-D-Ala terminus of nascent peptidoglycan.
-Bactericidal. Slower killing than B-Lactam group.
-Only kills cells that are actively dividing.
What are the effects of Vancomycin?
Bactericidal activity against susceptible bacteria; slower kill than β-lactam ABX
What are the clinical applications for Vancomycin?
Infections causes by gram (+) bacteria:
-Endocarditis
-Sepsis
-Meningitis
-C. Diff colitis
-MRSA
What are the kinetics of Vancomycin?
-Oral & IV
-Renal clearance
-Directly proportional to creatinine clearance
-Decrease dose in pts with renal insufficiency
-Half-Life 6 hours
What is Red Man’s Syndrome?
Histamine reaction associated with Vancomycin.
-Benadryl
-Administer infusion slowly
What are adverse reactions associated with Vancomycin?
-Red Man syndrome
-Irritating to tissues = phlebitis at site of injection (use central line if you have it or rotate sites of injection)
-Chills & fever
-Ototoxicity & nephrotoxicity
What is Vancomycin + Gentamycin used for?
Treatment for enterococcal endocarditis.
-Treatment for patients with serious penicillin allergy
What is the drug of choice for dental procedures in patients with valvular heart disease (who have PCN allergies)? (Blue Box!)
Clindamycin.
Drug of choice for prophylaxis of endocarditis in patients with valvular heart disease who undergo certain dental procedures and have significant penicillin allergies.
What is the dose of Clindamycin?
600 mg q8 hours
-No change in dose for renal patients!
What is the MOA of Clindamycin?
-Lincosamides Class
-Prevents bacterial protein synthesis by binding to the 50S ribosomal subunit
-Gram (+)
-Does not penetrate the CNS
What are the effects of Clindamycin?
-Bacteriostatic (!) against susceptible bacteria (Gram positive)
What are the clinical applications for Clindamycin?
-Skin & soft tissue infections - MRSA
Anaerobic infections:
-Streptococci
-Staphylococci
-Pneumococci
Lung abscesses
Infections of Female genital tract
Resistant to Clinda:
-Enterococci
-Gram (-)
What are the Kinetics of Clindamycin?
PO & IV:
-Max 30mg/min
-Infuse over 15-60 min
-Hypotension
Hepatic clearance (inactive and active metabolites)
Half Life 2.5 hrs
90% Protein bound
What are the toxicities associated with Clindamycin?
-GI upset
-C. Diff colitis
-Rashes
-Decreased Liver Fxn
-Neutropenia
What is the dose of Gentamicin?
5-6mg/kg/day IV in 3 equal doses
-Smaller dose. More potent drug.
What is the MOA of Gentamicin?
-Aminoglycoside class
-Prevents bacterial protein synthesis by binding to the 30S ribosomal subunit
-Results in a defective bacterial cell membrane
-Gram (+) & (-)
What are the effects of Gentamicin?
-Bactericidal activity against susceptible bacteria
-Synergistic effects when combined with β-lactams or Vanco!!
-Concentration dependent killing with significant post-antibiotic effect (staves off bacterial events event after course of treatment is done)
What are the clinical applications for Gentamicin?
-Sepsis caused by aerobic gram (-) bacteria
-Synergistic activity in endocarditis caused by streptococci, staphylococci, & enterococci
-Can give Intrathecally for meningitis but not as effective as 3rd gen cephalosporins
What are the kinetics of Gentamicin?
-IV
-Active metabolites
-Renal Clearance
-Half-Life 2.5 hrs
What are the toxicities associated with Gentamicin?
-Nephrotoxicity (usually reversible and mild)
-Ototoxicity (Irreversible vestibular dysfunction (vertigo) and potential loss of hearing. Due to neural injury.)
-Neuromuscular blockade
-*Hypersensitivity reactions are uncommon
What is the MOA of Ciprofloxacin?
-Fluoroquinolones class
-Inhibits DNA replication by binding to DNA gyrase and topoisomerase IV (has 2 sites of action)
-Gyrase is required for normal transcription and replication
-Topoisomerase is responsible for the separation of chromosomal DNA into the daughter cells during cell division
-Gram (+) & Gram (-)
What are the effects of Ciprofloxacin?
Bactericidal activity against susceptible bacteria
What are the clinical applications for Ciprofloxacin?
-UTIs
-Gastroenteritis
-Osteomyelitis
-Anthrax
What are the kinetics of Ciprofloxacin?
PO & IV (administer over 60 min)
Mixed clearance (hepatic & renal)
Half-life 4 hrs
What is the toxicity associated with Ciprofloxacin?
-Tendonitis (joint and tendon inflammation, commonly in the ankles)!
-GI upset
-Neurotoxicity
What is the dose of Metronidazole?
500 mg TID
What is the MOA of Metronidazole?
-Nitroimidazoles class
-Disruption of electron transport chain
Selectively absorbed and nonenzymatically reduced
-Toxic byproducts that accumulate in anaerobic cells
-Taken into bacterial DNA forming unstable molecules
-Leads to cell death (little effect on human or aerobic cells. Only selective to anaerobic bacteria)
What are the effects of Metronidazole?
-Bactericidal activity against susceptible anaerobic bacteria and protozoa
-Little effect on human cells or aerobic cells
What are the Clinical Applications for Metronidazole?
Technically an anti-fungal. Given due to planned or unplanned disruption of the bowel.
-Used in GYN procedures to prevent opportunistic infections
-Prevents peritonitis due to fecal matter
-Anaerobic infections
-Vaginitis
-C. Diff Colitis
-Brain abscess
What can occur with prolonged use of Metronidazole?
N/D, stomatitis, & peripheral neuropathy with prolonged use
What are the kinetics of Metronidazole?
-PO & IV
-Hepatic clearance
-Half-life 8 hrs
-Disulfuram like reaction when given with alcohol (N/V, GI upset)
What toxicities are associated with Metronidazole?
-GI upset
-Metallic taste
-Neuropathy
-Seizures
