Br Pharmacology: Chloramphenicol, Tetracyclines, Macrolides, Clindamycin

Front 1

what is the MOA of chloramphenicol? Is it cidal or static?

Back 1

1) inhibits transpeptidation by blocking the binding of the rRNA to the mRNA... inhibits 50S peptidyltransferase activity
2) static

Front 2

What is the MOA of macrolides, telithromycin and clindamycin?

Back 2

bind to 50S ribosome and block transpeptidation

Front 3

What is the MOA of tetracyclines?

Back 3

bind 30S ribosome and prevent tRNA binding to mRNA

Front 4

What is the MOA of streptogramins?

Back 4

bind 50S subunit and constrict exit channel for polypeptide and also inhibit tRNA synthase acitvity

Front 5

Are streptogramins bactericidal or static?

Back 5

cidal

Front 6

Is linezolid cidal or static?

Back 6

static

Front 7

What is the MOA of linezolid?

Back 7

binds 23S portion of 50S subunit and blocks initiation by preventing formation of tRNA-ribosome-mRNA complex

Front 8

Can chloramphenicol inhibit mammalian ribosomes?

Back 8

yes mitochondrial ones

Front 9

Why do tetracyclines not effect mammalian protein synthesis?

Back 9

cells have efflux pumps

Front 10

Is chloramphenicol static or cidal?

Back 10

usually static

Front 11

Is chloramphenicol active against chlamydia? what is it used for?

Back 11

1) no
2) meningitis from:
a. S pneumoniae
b. N meningitidis
c. H influenzae

Front 12

How does resistance to chloramphenicol occur?

Back 12

plasmid gene that codes ofr acetyltransferases

Front 13

Clinically what is chloramphenicol a back up drug for?

Back 13

backup drug for: salmonella, pneumococcal and meningococcal meningitis in beta-lactam sensitive persons

Front 14

What is chloramphenicol occasionally used for?

Back 14

rickettsial infections, bacteroides fragilis

Front 15

What is chloramphenicol commonly used for?

Back 15

1) topical antimicrobial
2) Meningitis with:
a. S pneumoniae
b. N meningitidis
c. Hib

Front 16

What are the toxicities of chloramphenicol? In neonates?

Back 16

Bone marrow: decreased RBC maturation, aplastic anemia (may be fatal because it is irreversible)
Gray baby syndrome: low RBCs, cyanosis, cardiovascular collapse (note neonates do not have glucuronyltransferase and are most sensitive)

Front 17

What drugs does chloramphenicol increase the half lives of?

Back 17

phenytoin, tolbutamide and warfarin

Front 18

Are tetracyclines bacteriostatic or cidal? broad or narrow spectrum?

Back 18

static and broad spectrum

Front 19

What is the mechanism of resistance to tetracyclines? Which drug is not effected by these modes of resistance?

Back 19

efflux pumps and ribosomal changes

tigecycline

Front 20

What two species have multidrug efflux pumps that can resist tigecycline?

Back 20

proteus and pseudomonas

Front 21

Clinically what are tetracyclines the primary treatment of treat?

Back 21

mycoplasma pneumonaie in adults, chlamydia, rickettsia and vibrio, acne, Tularemia

Front 22

What are secondary uses of tetracyclines?

Back 22

syphillis, leptospirosis and in treatment of acne

Front 23

What are selective uses of tetracyclines? Name the specific drug with the specific organism!

Back 23

H pylori (tetracycline), lyme disease (doxycycline), meningococcal carrier state (minocycline)

Front 24

What is demeclocycline used for?

Back 24

inhibits renal actions to ADH used in in SIADH

Front 25

What is tigecycline used for?

Back 25

MRSA, VRE, beta-lactamase gram -, anaerobes, chlamydiae, and mycobacteria

Front 26

What are the side effects of tetracyclines?

Back 26

GI: life threatening colitis

Bone: fetal exposure causes tooth enamel dysplasia and irregular bone growth

Liver: hepatic necrosis

Renal: tubular acidosis, Faconis syndrome

UV sensitivity (tetracyclines, esp demeclocycline) and reversible dizziness and vertigo (doxycycline and minocycline)

Front 27

What is unique about how azithromycin accumulates?

Back 27

has higher levels in the tissues and phagocytes than others

Front 28

What is the means of resistance to macrolides in gram + organisms?

Back 28

efflux pump and a methlyase which alters ribosomal binding site of macrolides

Front 29

How are enterobacteriaceae resistant to macrolides?

Back 29

metabolizing esterases

Front 30

What is erythromycin used for clinically?

Back 30

URIs, STDS

Gram+ cocci, M pneumoniae, Cornybacterium, Campylobacter jejuni, C trachomatis, C pneumoniae, L pneumophila, B pertussis and Ureaplasma urealyticum

Front 31

Is erythromycin active against beta-lactamase gram + cocci?

Back 31

yes except PRSP and MRSA

Front 32

Azithromycin has activity similar to erythromycin except that is also active against?

Back 32

H influenzae, M catarrhalis, and Neisseria, and C trachomatis because of its long half life

Front 33

Clarithromycin has similar spectrum as erythromycin but is used in what two infections?

Back 33

M avium and H pylori

Front 34

What are the adverse effects of macrolides in general?

Back 34

GI irritation via stimulation of motlin receptors, skin rashes and eosinophilia, prolonged QT, cholestatic hepatitis, eosinophilia, increases concentration of coagulant drugs

Front 35

Which drug causes a hypersensitivity of acute cholestatic hepatitis?

Back 35

erythromycin estolate

Front 36

Clarithromycin and erythromycin can increase the half-lives of what drugs?

Back 36

anticoagulants, carbamazepine, cisapride, digoxin, theophylline

Front 37

What is an example of a ketolide? What is its MOA and spectrum of action?

Back 37

1) telithromycin
2) similar to erythromycin
3) similar to erythromycin

Front 38

What are the toxicities of telithromycin?

Back 38

severe hepatotoxicity, visual disturbances and fainting episodes

Front 39

How does resistance to clindamycin occur?

Back 39

methylation of 50S ribosome and enzymatic inactivation

Front 40

What organsims are intrinsically resistant to clindamycin?

Back 40

gram - bacteria because they don't allow penetration through outer membrane

Front 41

What is the main use of clindamycin?

Back 41

severe infections with bacteriodes

Front 42

When is clindamycin used as a backup drug?

Back 42

gram + cocci and p jeroveci with pyrimethamine

Front 43

Clindamycin is used for prophylaxis in what condition?

Back 43

valvular endocarditis when people are allergic to penicillins

Front 44

What are the toxicities of clindamycin?

Back 44

rashes, neutropenia, hepatic dysfunction

Front 45

What are the streptogramins?

Back 45

quinupristin-dalfopristin

Front 46

what can streptogramins be used to treat?

Back 46

MRSA, PRSP, VRSA and resistant E faecium, E faecalis

Front 47

What are the side effects of streptogramins?

Back 47

arthralgia-myalgia syndrome

can also potentiate cyclosporine, diazepam, NNRTIs and warfarin

Front 48

What is linezolid used for?

Back 48

MRSA, PRSP, VRE, L monocytogenes and corynebacterium

Front 49

Is there cross resistance of linezolid with other 50S inhibitors?

Back 49

no because it binds the 23S rRNA of the 50S which is unique to it

Front 50

What are the side effects of linezolid?

Back 50

thrombocytopenia and neutropenia