Protein synthesis inhibitors Flashcards
Macrolides
- have macrocyclic lactone rings
- Erythromycin, Clarithromycin, Azithromycin
Macrolide spectrum
G(+) including MRDA (not first choice), S. pneumoniae (PEN susceptible), strep
G(-): H. influenzae, shigella, Neisseria
Atypical: Legionella, chlamydia
H. pylori (clarithromycin)
clinical uses of macrolides
penicillin substitute for strep or pneumnococcal infections in pts with hypersensitivity. Respiratory, skin and STIs
MoA of macrolides
Mainly bacteriostatic.
high affinity pocket of the peptidlytransferase site on 50s ribosomal subunit. blocks protein progression by stopping elongation.
Absorption/elimination of erythromycin
excellent tissue penetration -> cross placental barrier
half life 1-3hr.
hepatic metabolism
greater activity at high pH
Absorption/elimination of clarithromycin
T1/2=3-5h improved bioavailability than erythromycin. high concentration in phagocytes hepatic and renal metabolism kidney and biliary excretion
Absorption/elimination of azithromycin
VERY LONG half life 48-96h
high concentration in phagocytes and fibroblast
biliary clearance so no hepatic adjustment
AE erythromycin, clarithromycin and azithromycin
RARE: CV effects (palpitations, arrhythmias)
Ototoxicity (renal insufficient, AIDS)
Serious: cholestatic hepatits
Special considerations: erythromycin
- metabolized by CYP450 in liver
- acts reversible inhibitor of CYP3A4, 1A2, 2C9
- highly concentrated in bile
- no adjustment or renal impairment
Special considerations: clairthromycin
- metabolized to nitrosalkane metabolite
- inactive complex with CYP3A
- 14 OH metabolite = abx activity
Special considerations: Azithromycin
- lots of tissue distribution
- lots of drug within cells
- lots of protein binding at low plasma concentration
Chloramphenicol spectrum
- bacteriostatic against H. influenzae, S. pneumoniae, N. meningitis
- anaerobic bacteria & aerobic +/-
Clinical uses of chloramphenicol
Treat CNS infections (bacterial meningitis, brain abscess) in pts with allergies to B-lactams.
when other medications don’t work for anaerobic.
Rickettsial disease (tetracycline is 1st) for rocky mountain fever or typus.
Also for typhoid.
MoA for chloramphenicol
Binds to hydrophobic acyl site on 50s ribosomal subunit. prevents tRNA from binding to P-site. stops the transition state during peptide bond formation.
absorption/ elimination of chloramphenicol
absorbed in GI. widely distributed in body fluids -> goes to CSF and crosses placenta.
long half life 4h.
50% bound to plasma proteins
eliminated through hepatic metabolism
AE of chloramphenicol
Serious: Hematological effects - blood (anemia..ect) & bone marrow. Gray baby syndrome. decreased visual acuity. increased chance of childhood leukemia.
special considerations: chloramphenicol
inhibits CYP3A4 and CYP2C19
involved in: tylenol, cyclosporine (inc. levels), phenobarb. (dec chloramphenicol), phenytoin toxicity, warfarin (enhanced anticoagulation).
Clindamycin MoA
Bacteriostatic:
Prevents bacterial protein synthesis by binding to 50s
Clinical application of clindamycin
skin and soft tissue infection. anaerobic infections and some G(+) like strep, S. pneumoniae, MSSA/MRSA. NO GRAM (-) action. Gangrene, Toxic shock syndrome, prophylactic for neuro surgery.
PK for clindamycin
Hepatic clearance and metabolism CYP3A4. widely spread through body fluids and tissues but not CSF.
AE of clindamycin
Serious: C. difficile colitis
Rare: Neuromuscular block (combo with relaxants)
Streptogramins
Quinupristin, dalfoprostin
: against G(+) aerobic and various anaerobic
Streptogramins MoA
prevents bacterial protein synthesis by binding to 50s subunit. Alone the 2 drugs are bacteriostatic but in combination they are bactericidal. Dalfoprostin directly interferes with polypeptide chain formation
Clinical applications of Streptogramins
serious infections that are vancomycin resistant (E. faccium). complicated skin infections by staph. (aureus and pyrogenes). don’t use with other CYP3A4 (they inhibit it).
PK of Streptogramins
IV. CYP450 inhibitor (not metabolized by this). hepatic clearance. short half life.
AE of Streptogramins
severe infusion related myalgia and arthaglias. abnormal liver enzymes and billirubin.
Linezolid spectrum
G(+)
Linezolid clinical use
infections from MRSA, vancomycin resistant enterococci, nosocomial & community pneumonia
Linezolid MoA
Bacteriostatic: prevents protein synthesis by binding to peptide site on 50s (prevents complex formation)
PK Linezolid
Hepatic clearance, long half life (6h).
AE Linezolid
Bone marrow suppression, neuropathy, optic neuritis. potentiate effects of SSRI -> serotonin syndrome
