Macro, Clinda, Quinu/Dalfo, Linezo Flashcards
what do macrolides include?
erythromycin, azithromyci, clarithromycin
the picture below sums up all of the drugs way of inhibiting protein synthesis
macrolides are characterized as bacteriocidal or bacteriostatic? What is their mechanism? List 2
bacteriostatic;
- bind reversibly to a site on the 50S subunit which causes the dissociation of the peptidyl tRNA from the ribosome.
- macrolides also inhibit the translocation step. Translocation is when there’s movement of the peptidyl tRNA from the acceptor site to the donor site allowing the next amino acid to come in. So macrolides interfere with this process so that you wind up with little sections of amino acids.
bacteria can become deficient to macrolides because of 3 reasons
- methylase enzyme. because of diminished affinity for the binding site on the 50S subunit due to methylation of an adenine nucleotide in the 23S rRNA.
- may also gain resistance to macrolides because there are changes in the ability of the drug to get into the cell. The resistant bacteria may also develop pumps that pump out the macrolide so fast that you can’t achieve adequate concentration of the drug inside the cell for effective antibacterial effects.
- have developed an esterase that can inactivate the macrolide and this can particularly be seen with erythromycin resistance.
what is the disadvantage in having resistance with macrolides?
it confers resistance to other drugs; i.e cross resistivity
what is the characteristic of the methylase enzyme that confers the resistance for the bacteria to the macrolide
it can be inducible or constitutive
the development of the esterase resistance seen in macrolides is present in which macrolide?
erythromycin
what is the preferred treatment of C. Trachomatis
single dose of 1 gram of Azithromycin
less active vs streptococci and staphylococci
azithromycin is less active than erythromycin
similar in its effect to erythromycin but clarithromycin has an additive effect active against
H. Influenzae
if a patient presents with chlamydia and gonorrhea what would you use to treat respectively
azithromycin for chlamydia and cephalosporin for gonorrhea
macrolides are special in that they can act on
intracellular pathogens
you want to treat syphillis but the person is allergic to penicillin
give them erythromycin
what intracellular pathogens can erythromycin be treated against
- Mycoplasma, Legionella, Chlamydia spp., and certain atypical mycobacteria.
what gram + can erythromycin be treated against
is effective against Gram positive organisms like Streptococci, Staphylococci, and Corynebacterium (i.e. diphtheriae).
what is the drug of choice for you to use to treat a chlamydial infection while the person is pregnant
erythromycin
what is the pharmacokinetics for macrolides and what is so special about erthromycin
macrolides are absorbed well orally and is distributed with high intracellular concentration. Erythromycin is given as esters or in enteric coated tablet to protect against stomac acid(unstable in acid). It will then be absorbed in the small intestine
explain the metabolism of the different types of macrolides
erythromycin is metabolized by Ctycrome p450 into an inactive metabolite
clarithromycin unlike erythromycin, clarithromycin does have an active metabolite which does actually play a role in its antibacterial activity
macrolides are excreted as
excreted both in the urine as well as the bile. These are pretty large molecules and so they are more likely to be excreted in the bile rather than in the urine
macrolides have no effect on
pregnant women
patient comes in with epigastric distress from taking an antibiotic…what do you think it is and why
erythromycin becuase of the stimulation of the gastric motilin receptor
clarithromycin and erythromycin exhibit similar effects…what are they
- epigastric distress
- Cholestatic jaundice (estolate)
- Ototoxicity(like vancomycin)
Drug interactions- inhibits the metabolism of many drugs including warfarin, cyclosporine, and theophylline; digoxin
erythromycin causes cholestatic jaundice when it is given as
as a salt estolate
ototoxicity occurs in clarithromycin and erythromycin only at
high doses
which macrolide does not inhibit cp450 metabolism of other drugs
azithromycin
what are the results of the drug interactions of clarithromycin and erythromycine
- Hemorrhaging(warfarin)
- Nephrotoxicity renal damage (Cyclosporine)
- erythromycin inhibits the metabolism of (theophylline), high levels of theophylline can lead to agitation and GI distress
cross resistance of erythromycin is between which two other protein synthesis inhibitors
clindamycin and chloramphenicol
what is the mechanism of clindamycin
also binds to the bacterial 50S ribosomal subunit which interferes with the peptidyl transferase reaction.
Clindamycin is also bacteriostatic just like the macrolides
what are clindamycins four resistance mechanisms
- Decreased penetrability
- Decreased affinity to binding site of 50s subunit
- Enzymatic inactivation by an O-nucleotidyl transferase (staph aureus)
used topically to treat rosacea (i.e. red veins and puffy nose) and acne and dental infections by anaerobic bacteria
clindamycin
effective against streptococci, most anaerobes including Bacteroides, Prevotella, Porphyromonas and other oral anaerobes
clindamycin
clindamycin is used to treat toxoplasmosis with a combination with
pyrimethamine an analog of trimethoprim
what are the pharmacokinetics of clindamycin
it is distributed well into bone and body fluids; it has 90% bioavailability, crosses placenta; does NOT cross the CNS
similar to macrolides clindamycin accumulates where
in the macrophages and leukocytes
how is clindamycin metabolized and excreted
metabolize most of the clindamycin and some of the metabolites are active. The metabolic products of clindamycin are excreted primarily via the bile and only a very small amount is excreted in the urine. The metabolites that are conjugated by liver enzymes are the ones that tend to undergo enterohepatic circulation.
what are some therapeutic uses with clindamycin
used to treat refractory bone infections because it can penetrate bone
treatment of anaerobic pelvic infections and abdominal penetrating wounds
clindamycin can serve as a substitute for what for acute orofacial infections in situations where the organisms are pencillinase producing
amoxicillin or pen V
you can use clindamycin as an alternate to
amoxicilin or pen V for acute orofacial infections
or
as an alternative to penicilin-sensitive pateints requiring prophylaxis to prevent endocarditis
adverse effects of clindamycin are
NVD
hypersensitivity rashes and fever
risk of superinfection(pseudomembranous colitis)
neuromuscular blockad at high IV doses
another name for clindamycin is
lincosamidine
what are the streptogramins and what is their mechanism of action
Group B: Hexadepsipeptides and Quinupristin
Group A: Macrolactones and Dalfopristin
the combination of quinupristin and dalfopristin is called
synercid
30 quinupristin and 70 dalfopristin
WHat is the mechanism of action of Dalfopristin and Quinupristin
Dalfopristin binds to 50s ribosomal subunit inactivates both the donor and acceptor sites of peptidyltransferase, and induces a conformational change to increase the binding of the group B streptogramin
Quinupristin prevents the translocation step
Together, Dalfopristin and Quinupristin are what but individually they are ____
individually they are bacteriostatic, together they are bactericidal
what are the mechanisms of resistance of synercid 3 ways
Methylation of 23 S rna binding site prevents binding of Group B(Quinupristin)
Bacterial enzymatic inactivation; particulary dalfopristin
increased efflux
methylation of 23s RNA binding site prevents binding of
quinupristin
dalfopristin is prevented from working by
enzymatic inactivation
what are the pharmacokinetics of synercid(Quinu and Dalfo)
must be given IV
penetrates macrophages and PMNs
both undergo extensive non-enzymatic conversion to non-active products
what is the excretion and relative half lives of Quinu and Dalfo
excretion 80% bile, 20% urine
they both have short half-lives
Quinuprisitin 0.85 hr
Dalfo 0.7 hr
what are the adverse effects of Dalfo and Quinu
injection related pain, inflammation, edema, injection rreactions
NVD, headache
Myalgia, arthralgia
synercid(quinu and dalfo) is not compatible with
saline
what are the drug interactions in taking synersid and something else
Even though quinupristin and dalfopristin are not substrates for the cytochrome p450 enzymes, they can inhibit CYP3A4. People who are immunocompromised because they are taking an immunosuppressant like cyclosporine are at risk for serious infections and so in these cases you might have to use more serious and potentially dangerous antibiotics like Synercid. Therefore if the patient is on cyclosporine and needs to take Synercid, cyclosporine levels should be monitored.
what do you even use streptogramin(Quinu and Dalfo) for
treatment of vancomycin resistant enterococcus faecium
NOT faecalis
what two drugs do we reserve for really serious infections
Oxazolidinone and Streptogramins
What drugs go under oxazolidinone
Linezolid(synthetic) and thats IT
what is the mechanism of linezolid
binds to 50 s subunit similar to chloramphenicol and prevents the formation of the 70S initiation complex
Linezolid mechanism has some resistant strains with
staph aureus but no cross resistance with other antibiotics
what organisms confers cross resistance
macrolides and clindamycin
what is linezolid treated for
similar to vancomycin and gram positive anaerobes
approved for nosocomial pneumonia, community-acquired pneumonia, skin infections, vancomycin resistant enterococcal infections, MRSA
what is the pharmacokinetics of linezolids
orally active: 100 % bioavailability
Distributed to well perfused tissues
Metabolized to 3 inactive metabolites non-enzymatically
30% renal and 65% biliary
adverse effects for linezolid include
GI disturbances NVD, tongue discoloration
Hematologic: anemia thrombocytopenia, neutropenia requires weekly monitoring
headache
rashes
pseudomembranous colitis
