Protein Synthesis Inhibitors: Clindamycin, Macrolides, Streptogramins

Question 1

Clindamycin: MOA

Answer 1

–inhibits protein synthesis–

Binds the 50s ribosomal subunit

BacterioSTATIC
(-cidal in very high conc w/susceptible organisms)

Question 2

Clindamycin - what is important at where it to on its target site?

Answer 2

Tends to buy close to the binding sites of macrolides and synercid combo –> can competitively inhibit

Question 3

Clindamycin: Spectrum of Activity

Answer 3

Gram positive aerobes:
MSSA, PSSP

ANAEROBES
some bacteriosides spp, peptostrepto, actinomyces, propionibacterium, prevotella, clostridium NOT cdiff

p. carinni, toxo, malaria

Question 4

Whoazzers so many bacteria Clin targets….its specialty is??

Answer 4

ANAEROBES!!

Question 5

What area can Clin not get to??

Answer 5

NO CSF!! thus doesn’t work against any infection in CNS

Question 6

Clin’s clinical use:

Answer 6

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

Question 7

Clin’s AEs

Answer 7

GI - N/V/D with dyspepsia
*Clostridium Difficle COLITIS! (clin is one of the worst inducers; others: FQ, Pens)

rare- hepatotoxicity, allergy,

Question 8

Clin’s Pharmo:

Answer 8

Good absorption orally/IV, good serum concentration and tissue concentration
NO CSF

Eliminated by the liver, not removed by HD

Question 9

What drugs belong to the Macrolides group??

Answer 9

ACE! the - mycins
Azythromycin,
Clarithromycin
Erythromycin

Question 10

Macrolides MOA

Answer 10

–inhibit protein synthesis–

binds the 50S ribosomal unit reversibly

BacterioSTATIC

Question 11

Macrolides MOR

Answer 11

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

Question 12

Macrolides spectrum of activity

Answer 12

Gram +
clarithro>erythor>azythro
MSSA

Gram -
azithro>clarithro>erythro
NO enterobacteriae activity!

Anaerobes - upper respiratory only

ATYPICAL!!
DOC: Legionella
chamydias, mycoplasma

Question 13

Macrolides clinical use

Answer 13

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

Question 14

Macrolides: AEs

Answer 14

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

Question 15

Macros Pharm:

Answer 15

Absorption - pretty low (clarithro>azythro>erythro)

Widely distributed, good penetration, NO CSF

Elimination:
Erithro: heptatic and biliary
Clarithro: hepatic + renal

Question 16

Macro drug-drug interactions:

Answer 16

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

Question 17

Are Macs time or concentration dependent??

Answer 17

Erythro and Clarithro - TIME dependent

Azithromycine = CONCENTRATION dependent

Question 18

Streptogramins
AKA: quinupristin/daltopristin
AKA: synercid

MOA!

Answer 18

Each agent acts individually on 50s, to inhibit both EARLY and LATE stages of protein synthesis

bacterioSTATIC

TIME-dependent

Question 19

Synercid MOR

Answer 19

Erm gene involved - alt binding site (along with macrolides, clindamycin)

ENZYMATIC inactivation

Question 20

Synercid Spectrum of activity

Answer 20

in response to increasing resistance to VRE

Gram + activity, no gram-, some atypical
Mainly VRE*
MSSA, MRSA, strep pneumo, PRSP, E. faceium

Question 21

Macrolides - clinical uses

Answer 21

VRE bactremia
Complicated SSSI - MSSA, S pyogenes
MRSA?

Question 22

Macrolides - pharmocology

Answer 22

Only use IV

Widely distributed, minimal CSF
Elimination: hepatic/biliary

Question 23

Macrolides AE

Answer 23

GI (N/V/D)
Venous irritation reaction 
hypersensitivity
rase
m

Question 24

Macros on CYP450

Answer 24

drug interactions, increasing concentrations!