Pharmacology: Antimicrobials (50S Of Ribosomes)

Front 1

What are the AMA's that work on the 50S subunit of bacterial ribosomes?

Back 1

(1) Chloramphenicol
(2) Macrolides [Ery-, Clari-, & Azi-thromycin]
(3) Clindamycin & Lincomcyin
(4) Streptogramins [Quinupristin & Dalfopristin]
(5) Linezolid

Front 2

Macrolides: Examples?

Back 2

(1) Erythromycin [prototype]
(2) Clarithromycin
(3) Azithromycin

Front 3

Macrolides:
MOA/PD?
Resistance?

Back 3

ERY-, CLARI-, & AZI-thromycin
MOA/PD: Binds to 50S subunit & inhibits translocation step from A to P site

Resistance: X-resistance between the 3 macrolides is COMPLETE
(1) Efflux of drug by active pump
(2) 50s modification --> Inducible or constitutive methylase adds methyl group to binding site
(3) Hydrolysis of macrolides by esterases --> Enterobacteriaceae

Front 4

Macrolides:
DOC In?
Spectrum & Use?
Newer generation spectrum & uses?

Back 4

ERY-, CLARI-, & AZI-thromycin
DOC In:
(1) Atypical pneumonias [mycoplasma pneumonia, chlamydia pneumonia, legionella pneumophilia] along w/ tetracyclines for mycoplasma
(2) Campylobacter jejuni & Bordetella pertussis [also very effective]

Spectrum & Use:
(1) All gram +ve, -ve, rods, & cocci
(2) All: Streptococcal pharyng & mastoid-itis, Pneumococcus
(3) Syphilis, Gonorrhoeae, Diphtheria

Newer generation specific uses:
(1) Clari: H. pylori
(2) Azi: Single dose for PID due to chlamydia in non-compliant pts., Also used for treatment of trachomas [eye]
(3) Extended spectrum of both: Prophylaxis against MAC in AIDS [long half-life], B. burgdoferi, Toxoplasmosis, Crytosporidium, Plasmodium spp., Chl. trhachomatis

Front 5

Macrolides: AE & differences?

Back 5

ERY-, CLARI-, & AZI-thromycin
(1) GIT --> High incidence of effects associated w/ stim of motilin receptors
(2) Allergic rxn --> Fever, eosinophilia and skin eruptions

Differences: AE of clari & azi are much less than w/ erythro
(1) Erythro estolate & sometimes w/ stearate or ethyl succinage --> CHOLESTATIC HEPATITIS [hyper sensitivity rxn]

Front 6

Macrolides: DI & Differences?

Back 6

ERY-, CLARI-, & AZI-thromycin
(1) P-450 Inhibition
(2) Ery- [potent] > Clari [minimal] > Azi [none]

Front 7

Choramphenicol: Initial & Current Use?

Back 7

Initial: Epidemic & scrub typhus [since replaced by newer cephalosporins, quinlones, etc.]

Current: Wide coverage [gram -ve & +ve, Salmonella, Bacteroides, Klebsiella] but used only if all other drugs can't [serious AE]
(1) Anaerobic CNS & PID
(2) Rickettsial [Doxycycline DOC]
(3) Meningitis [H. influenza pneumococcal, meningococcal] [Cell wall synth inhib DOC]
(4) Brucellosis [Doxycycline DOC in combination w/ others]
(5) EYE & OTIC infections as topical agent

Front 8

Chloramphenicol:
Route?
Distribution?
Elimination?

Back 8

Route: Rapid and complete from GI, Parenteral, & Topical

Distribution: [CNS] = [Serum]

Elimination: Conjugation w/ glucuronic acid in liver by glucoronyl transferase

Front 9

Chloramphenicol:
MOA/PD?
Resistance?

Back 9

MOA/PD: Binds to 50S & inhibits peptidyl transferase

Resistance:
(1) Acetyl transferase to attach acetyl to side chain
(2) Reducing nitro group of benene ring
(3) Decrease permeation
(4) 50S mutation

Front 10

Chloramphenicol: AE?

Back 10

Can inhibit human mitochondrial protein synth [particularly erythropoeitic cells]:
(1) Bone marrow disturbance --> Aplastic anemia, Leukemia later
(2) Blockade of ECT in cardiac, liver, & skeletal muscle --> Gray baby syndrome --> Hypothermia, Hypotension, Abdominal distension, Lethargy
(3) Superinfection, Hypersensitivity, G.I. irritation
(4) Rare --> Blurring of vision, Digital paresthesias, optic neuritis
(5) Jarisch-Herxheimer

Front 11

Chloramphenicol: Contra?

Back 11

B/c needs to be glucorinated to excrete chlremphenicol should be avoided in neonates and cirrhosis

Front 12

Chloramphenicol: DI?

Back 12

Potent CYP450 inhibitor & increases the 1/2 life of many drugs

Front 13

Clindamycin & Lincomycin:
Spectrum?
DOC & very useful in?
Combination therapy?
Penicillin alternative in?
Other?

Back 13

Spectrum: Gram +ve cocci [Linco older & inferior to clinda]

DOC & very useful in:
(1) DOC --> Mixed aerobic & anaerobic intra-abdominal, lung abscess, & pelvic infections
(2) Very useful --> Staph aureus & epidermidis, Acne vulgaris, B. Fragilis,

Combination therapy: Broad spectrum penicillins or cephalosporins

Penicillin alternative in: (1) Staphylococcal osteomyelitis (2) Prophylaxis after dental surgery

Other: Certain malaria [50% cure], Toxoplasmosis, PCP

Front 14

Clindamycin & Lincomycin:
MOA/PD?
Resistance?

Back 14

MOA/PD: Similar to macrolide [binds to 50S subunit & inhibits translocation step from A to P site]

Resistance: Plasmid mediated due to methylation

Front 15

Clindamycin & Lincomycin:
Distribution?
Elimination?

Back 15

Distribution: Wide EXCEPT CNS

Elimination: BILIARY

Front 16

Clindamycin & Lincomycin: AE?

Back 16

(1) GI irritation, PSEUDOMEMBRANOUS colitis
(2) Skin rashes
(3) Neutropenia
(4) INHIBIT NMJ TRANSMISSION
(5) Stevens-Johnson Syndrome

Front 17

Streptogramins [Quinupristin + Dalfopristin 30:70]: MOA/PD?

Back 17

Synergistically inhibit protein synthesis by binding to 50S of ribosome

Front 18

Streptogramins [Quinupristin + Dalfopristin 30:70]: DI?

Back 18

Inhibit CYP450

Front 19

Streptogramins [Quinupristin + Dalfopristin 30:70]: AE?

Back 19

(1) Phlebitis
(2) Pain, Arthralgia, Myalgia
(3) HYPERBILLIRUBINEMIA

Front 20

Streptogramins [Quinupristin + Dalfopristin 30:70]: Use?

Back 20

(1) MRSA & VRSA
(2) Eterococcus faecium

Front 21

Linezolid:
MOA/PD?
X-resistance w/ other drugs?

Back 21

MOA/PD: Inhibit protein synthesis by binding to 50S

X-resistance w/ other drugs: None with other protein synth inhibitors

Front 22

Linezolid: Use?

Back 22

Vancomycin resistant E. faecium & other drug resistant G+ve cocci

Front 23

Linezolid:
Route?

Back 23

Route: Oral & parenteral

Front 24

Linezolid: AE?

Back 24

In IMMUNOSUPRESSED PTS:
(1) Thrombocytopenia
(2) Neutropenia