Protein Synthesis Inhibitors: Clindamycin, Macrolides, Streptogramins Flashcards
Clindamycin: MOA
–inhibits protein synthesis–
Binds the 50s ribosomal subunit
BacterioSTATIC
(-cidal in very high conc w/susceptible organisms)
Clindamycin - what is important at where it to on its target site?
Tends to buy close to the binding sites of macrolides and synercid combo –> can competitively inhibit
Clindamycin: Spectrum of Activity
Gram positive aerobes:
MSSA, PSSP
ANAEROBES
some bacteriosides spp, peptostrepto, actinomyces, propionibacterium, prevotella, clostridium NOT cdiff
p. carinni, toxo, malaria
Whoazzers so many bacteria Clin targets….its specialty is??
ANAEROBES!!
What area can Clin not get to??
NO CSF!! thus doesn’t work against any infection in CNS
Clin’s clinical use:
Anaerobic infections outside of CNS (pulmonary, abdominal, pelvic, diabetic foot, ulcers)
SSTI -pen-allergic patients! CA-MRSA
Alternative therapy -C. perfinges, toxo, malaria, P. carnii
Clin’s AEs
GI - N/V/D with dyspepsia
*Clostridium Difficle COLITIS! (clin is one of the worst inducers; others: FQ, Pens)
rare- hepatotoxicity, allergy,
Clin’s Pharmo:
Good absorption orally/IV, good serum concentration and tissue concentration
NO CSF
Eliminated by the liver, not removed by HD
What drugs belong to the Macrolides group??
ACE! the - mycins
Azythromycin,
Clarithromycin
Erythromycin
Macrolides MOA
–inhibit protein synthesis–
binds the 50S ribosomal unit reversibly
BacterioSTATIC
Macrolides MOR
ERM gene - alters target binding site (high resistance)
MEF gene - codes for efflux pumps that pump macrolides out of the cell (low resistance)
cross-resistance between all macrolides
Macrolides spectrum of activity
Gram +
clarithro>erythor>azythro
MSSA
Gram -
azithro>clarithro>erythro
NO enterobacteriae activity!
Anaerobes - upper respiratory only
ATYPICAL!!
DOC: Legionella
chamydias, mycoplasma
Macrolides clinical use
Respiratory infections
- OM
- CA pneumo
Uncomplicated Skin Infections
STDs (1 dose of azithro)
MAC* azithro prophylaxis
**ALTERNATIVE FOR PCN-ALLERIGIC PTS*
group A strep, endocarditis prophylaxis, syphilis/gonorrhea, RF
Macrolides: AEs
GI!! (up to 33%)
N/V/D dyspepsia (more common w/erythro)
Cholestatic hepatitis (rare)
Allergic Rxns
Prolong QT! (exaggerated by anti-arrythmics)
Transient, reversible tinnitus or deafness
*drug-drug with COLCHICINE
(treats gout), could potentially cause FATAL arrythmia
Macros Pharm:
Absorption - pretty low (clarithro>azythro>erythro)
Widely distributed, good penetration, NO CSF
Elimination:
Erithro: heptatic and biliary
Clarithro: hepatic + renal
Macro drug-drug interactions:
w/ colchicine - potentially fatal arrythmias
CYP450 INHIBITOR! (erythro and clarithro ONLY)
thus potentially a problem:
INC conc of -
Theophylline, Carbamazepine, Cyclosporine, Phenytoin,
Warfarin, Digoxin, Valproic Acid, Cisapride, Ergot Alkaloids
Are Macs time or concentration dependent??
Erythro and Clarithro - TIME dependent
Azithromycine = CONCENTRATION dependent
Streptogramins
AKA: quinupristin/daltopristin
AKA: synercid
MOA!
Each agent acts individually on 50s, to inhibit both EARLY and LATE stages of protein synthesis
bacterioSTATIC
TIME-dependent
Synercid MOR
Erm gene involved - alt binding site (along with macrolides, clindamycin)
ENZYMATIC inactivation
Synercid Spectrum of activity
in response to increasing resistance to VRE
Gram + activity, no gram-, some atypical
Mainly VRE*
MSSA, MRSA, strep pneumo, PRSP, E. faceium
Macrolides - clinical uses
VRE bactremia
Complicated SSSI - MSSA, S pyogenes
MRSA?
Macrolides - pharmocology
Only use IV
Widely distributed, minimal CSF
Elimination: hepatic/biliary
Macrolides AE
GI (N/V/D) Venous irritation reaction hypersensitivity rase m
Macros on CYP450
drug interactions, increasing concentrations!
