Ch 42 - Penicillins Flashcards
To what classification of drug do penicillin belong?
- member of a group of drugs known as β-lactams because of their characteristic four-membered lactam ring.
- They are bactericidal agents
Define β-lactamase:
- is a bacterial enzyme that hydrolyzes the amide bond of the β-lactam ring.
- also known as penicillinase.
What are penicillin-binding proteins (PBPs)?
PBPs are enzymes that are involved in the synthesis of the cell wall and in the maintenance of the morphological structure of the bacteria.
What are transpeptidase?
transpeptidases are bacterial enzymes responsible for the cross-linking peptidoglycan chains, which is the final step in the bacterial cell wall synthesis
What is the major mechanism by which penicillins kill bacteria?
Penicillins bind to PBPs and inhibit the transpeptidase step, which result in bacterial cell lysis
What additional mechanism is involved?
Penicillins also release autolysins, bacterial degradative enzymes involved in the normal remodeling of the bacterial cell wall
Which type of organisms are not susceptible for penicillins?
organisms that are not actively growing or do not have a cel wall
Do penicillins enter the CNS?
- normally these drugs do not distribute well into the CNS.
- however when the meninges are inflamed, as occurs in in meningitis, penicillins easily reach therapeutic concentrations within the CNS
How are penicillins classified?
- natural penicllins
- antistaphylococcal penicillins
- antipseudomonal penicillins
- extended-spectrum penicillins
Gove 4 examples of natural penicillins and their routes of administration?
- Penicillin G, the prototype drug- PO, IV, IM
- Penicllin V - PO only
- Penicillin G procaine (Crysticillin AS) - IM only
- Penicillin G benzathine (Bicillin LA) - IM only
How do the various natural penicillins differ from each other?
these drugs all work the same way; they differ in their route of administration and stability to gastric acid
What can natural penicillin be used for?
- large spectrum
- affects gram+ org. the most
- e.g
- Streptococci
- Meningococci
- Clostridium
- Listeria
- Enterococci
- Diphteria
- Anthrax
- Syphilis
- Spirochetes, such as Treponema pallidum
- Actinomycosis
- Bacteroides species (except Bacteroides fragilis)
- Anaerobic organisms that don´t produce β-lactamase
Describe the absorption of natural penicillins:
absorption depends on their acid stability and protein binding
Is the absorption of penicillin influenced by food
yes, therefore, these drugs (except for amoxicillin) should be administered at least 1 to 2 hr before or after a meal
How are the natural penicillins excreted?
penicillins are mostly unchanged as they are excreted in urine (by glomerular filtration and active tubular secretion), although some penicillins, such as nafcillin and ampicillin, undergo hepatic inactivation and are excreted in the bile
How can the excretion of penicillin be altered?
excretion by renal tubular secretion can be delayed by coadministration of probenecid, which inhibits the organic acid secretion system.
What are the adverse effects seen with patients who are medicated with penicillin?
- hypersensitivity reactions
- seizures
- GI disturbances
- hemolytic anemia
- nephritis
- cation toxicity
Antistaphylococcal penicillins =
penicillinase-resistant penicillin
Give some examples of penicillinase-resistant drugs and indicate their routes of administration:
- methicillin
- nafcillin
- oxacillin
- dicloxacillin
- cloxacillin
When do you use penicillinase-resistant penicillin?
these drugs have a very narrow spectrum; they were developed solely for the purpose of killing staphylococci that produce pencillinase
What should you do if you encounter methicillin-resistant staphylococcus aureus
use vancomycin immediately for serious infections
What is the distinctive toxicity of methicillin?
although all penicillin have the potential to cause interstitial nephritis, it was most likely with methicillin
What other toxicity is associated with these drugs?
methicillin, nafcillin, and some other penicillin occasionally cause granulocytopenia, especially in children
Give two examples of antipseudomonal penicillins?
- piperacillin
- ticarcillin
- mezlocillin
- azlocillin
- carbenicillin
What is the route of administration for piperacillin and ticarcillin?
both of these drugs are extremely unstable in gastric acid and therefore must be given IV or IM
Are antipseudomonal penicillins inactivated by pencillinase?
yes, therefore, they are commonly paired with beta lactamase inhibitors
What is antipseudomonal penicillins antimicrobial spectrum?
gram-negative bacilli Enterobactor, especially Pseudomonas species (hence the name)
What toxicity is likely to be seen with ticarcillin?
platelet dysfunction
Give some examples of extended-spectrum penicillins and indicate their route of administration?
- amoxicillin -> PO
- ampicillin -> PO, IV, and IM
Against what organisms can ampicillin and amoxicillin be used?
in general, all of the organisms affected by the natural penicillins plus some Gram-negative organism such as E. coli, Proteus mirabilis, Salmonella, Shigella, Haemophilus influenzae, and Listeria monocytogens.
Are the extended-spectrum penicillins inactivated by β-lactamase?
yes!
What important toxicities are associated with ampicillin?
- β-lactamase inhibitors, which inhibit the enzyme by binding to it and thus protecting the accompanying antibiotic.
- On their own, β-lactamase inhibitors are not effective in eliminating bacteria
Give three examples of β-lactamase inhibitors:
- Clavulanic acid
- Sulbactam
- Tazobactam
With which drugs are each of these three β-lactamase inhibitors paired
- Clavulanic acid with amoxicillin or with ticarcillin
- Sulbactam with ampicillin
- Tazobactam with piperacillin
Aside from inactivation of the antibiotic by β-lactamase, how else does bacterial resistance develop?
- Alteration in PBPs
- Decreased cell permeability, which prevents the antibiotic from penetrating its target
