Pharm Ii: Protein Synthesis Inhibitors

Front 1

What class of drugs often produces antibiotic associated colitis (pseudomem. colitis by toxins from C. difficile) ?

Back 1

Tetracycline

Front 2

What is the MOA of Tetracyclines?

Back 2

Inhibit bacterial protein synthesis by binding to 30S ribosomal RNA and blocking amino acyl-charged tRNA binding to the acceptor site on the mRNA-ribosome complex.

Front 3

How do organism gain resistance against Tetracycline?

Back 3

Naturally occuring R-factor confers an inability of the organism to accumulate drug. Efflux is mediated by a Mg2+ dependent pump mediated by protein Tet A.

Front 4

What is the function of protein Tet A?

Back 4

Mediates Mg2+ dependent pump that allows efflux of tetracycline from bacterial cell. Confers RESISTANCE.

Front 5

What impairs absorption of Tetracycline in the GI?

Back 5

divelent and trivalent cations, especially Ca2+, Mg2+, and Al3+

Front 6

What tetracycline is useful in eradicating MENINGOCOCCAL CARRIER-STATES due to its ability to enter the meninges in the absence of inflamation and reaches high levels in tears and saliva?

Back 6

Minocycline

Front 7

What tetracycline is the DOC for extra-renal infections in pts with renal insufficiency due to it's unique elimination through NON-RENAL mechanisms?

Back 7

Doxycycline

Front 8

What is the main use of Demeclocycline?

Back 8

Inhibits action of ADH in the renal tubule, and has been used in the inappropriate secretion of ADH in the renal tubule.

Main application is NOT antibiotic use, it's SIADH!

Front 9

What class of drugs binds to Ca2+ deposited in the newly formed teeth and bone of young children?

Back 9

Tetracyclines

Front 10

What drug is effective againts tetracycline resistant organisms, MRSE, MRSA, PRSP (pen. resist. strep. pneum) , and VRE (Vanc. Resistant Enterococic) ?

Back 10

Tigecycline (Tygacil)

Front 11

What is the MOA for Macrolides (Erythro-,Clarithro-,Azithro- mycin) ?

Back 11

Inhibition of protein synthesis via binding reversibly to the 50s ribosomal subunits. Aminoacyl translocation reaction is blocked.

Front 12

Erythromycin has increased activity at what pH and in what type of organisms?

Back 12

Alkaline pH and Gram (+),

Not effective against aerobic enteric gram-negative bacilli

Front 13

What drugs have enhanced activity against Mycobacterium avium intracellulare and some protozoa?

Back 13

Clarithromycin and azithromycin

Front 14

How does G(+) and G(-) resistance against Macrolides differ?

Back 14

G(-) rods produce esterases for hydrolysis

G(+) organisms modify ribosomal binding site of the drug by methylase enzyme that is macrolide inducible or constitutive.

Front 15

What is the MOA for Macrolides (Erythro-,Clarithro-,Azithro- mycin) ?

Back 15

Inhibition of protein synthesis via binding reversibly to the 50s ribosomal subunits. Aminoacyl translocation reaction is blocked.

Front 16

Erythromycin has increased activity at what pH and in what type of organisms?

Back 16

Alkaline pH and Gram (+),

Not effective against aerobic enteric gram-negative bacilli

Front 17

What drugs have enhanced activity against Mycobacterium avium intracellulare and some protozoa?

Back 17

Clarithromycin and azithromycin

Front 18

How does G(+) and G(-) resistance against Macrolides differ?

Back 18

G(-) rods produce esterases for hydrolysis

G(+) organisms modify ribosomal binding site of the drug by methylase enzyme that is macrolide inducible or constitutive.

Front 19

What are the unique pharmacokinetic properties of Azithromycin?

Back 19

Extensive tissue distribution, and high drug concentrations within cells. This results in great tissue and secretion drug concentrations including phagocytes.

Also, Does not cause drug interaction with drugs metabolized by p450 enzyme of liver

Front 20

Clarithromycin and Azithromycin have enhanced activity against what organisms?

Back 20

Mycobacterium avium intracellulare (atypical mycobacteria) and protozoa

Front 21

Erythromycin is metabolized to what compound?

Back 21

Metabolised to 14-hydroxy metabolite by hydroxylation.

Front 22

What is the main mechanism of elimination of Erythromycin?

Back 22

HEPATIC! - in bile

note: Clarithromycin is excreted by renal AND nonrenal mechanisms.

Front 23

What is the elimination half life of Azithromycin?

Back 23

68 hours because of extension tissue sequestration and binding

Front 24

Hepatitis and Cholestatic Jaundice are rare side effects of what class of drugs?

Back 24

Macrolides (-thromycins)

Front 25

What is the use of Telithromycin (Ketolide)

Back 25

Used in upper respiratory tract infections and its spectrum of activity is good against respiratory pathogens including erythromycin and penicillin resistant pneumococci. (acute sinusitis)

Also, useful against intracellular and atypical bacteria

Front 26

What is the advantage of Telithromycin dosing?

Back 26

ONCE daily dose is as effective as clarithromycin, trovafloxacin, and high dose amoxicillin for some infections.

Front 27

Aminoglycosides are primarily used to treat infections caused by what type of organism?

Back 27

Aerobic gram (--) bacterial.

Front 28

Which protein synthesis inhibitor is bacteriCIDAL?

Back 28

Aminoglycosides

Front 29

What is the MOA of Aminoglycosides?

Back 29

Aminoglycosides diffuse through aqueous channels formed by porin proteins of G(-) bact.

Energy-dependent Phase I - transport across cytoplasmic membrane dependent on electron transport

After transport across the membrane, they bind to polysomes and interfere with protein synthesis:
1. Block formation of translation initiation-complex
2. misread the mRNA code
3. disrupt polysomes resulting in nonfunctional monosomes.

Energy-dependent phase II-abarrant proteins made are inserted into the cell membrane and cause increased aminoglycoside transport.

Front 30

What can interfere with phase I of Aminoglycosides MOA?

Back 30

Can be blocked by divalent cations, hyperosmolarity (acidic urine), a reduction in pH, and anaerobic conditions (penetration of the drug is oxygen dependent active transport - i.e - ABCESS)

Front 31

What aminoglycoside has a limited spectrum and should not be used against Serratia and pseusomonas aeruginosa?

Back 31

Kanamycin

Front 32

What organisms are HIGHLY resistant to aminoglycosides?

Back 32

Streptococcus pneum and strep pyogenes.

Front 33

T/F: Aminoglycosides are absorbed well from the GI and thus, can be given orally.

Back 33

FALSE.

NOT absorbed from the GI and less that 1% of the dose is absorbed following oral or rectal administration

note: should be given PARENTERALLY.

Front 34

What are the side effects of aminoglycosides?

Back 34

- Vestibular and auditory damage
- Tubular necrosis
- Neuromuscular blockade

Front 35

What drugs potentiate the adverse effects of aminoglycosides?

Back 35

loop diuretics (ethacynic acids and furosemide)

Front 36

Gentamycin and Tobramycb are active against most strains of what organism?

Back 36

Staph Aureus and Epidermidis

Front 37

What is the use of Spectinomycin?

Back 37

Spectinomycin is used as an alternative tx for gonorrhea in patient allergic to penicillin or when gonococci are resistant to other agents.

Front 38

What is the name of an aminocyclitol antibiotic?

Back 38

Spectinomycin

Front 39

What is the clinical use of Streptomycin?

Back 39

TB, Plague, Brucellosis, TULAREMIA, Infective endocarditis

Front 40

What is the clinical use of Gentamycin, Amikacin, Tobramycin, Netilimicin?

Back 40

Aerobic G(-) infections (E.coli, Enterobacte, Klebsiella, Proteus, Pseudomonas, and Serratia)

Front 41

What 3 drugs are used in Neosporin topical antibiotic and which is for G(+) ?

Back 41

Neomycin - (--)
Bacitracin - (+)
Polymixin B - (--)

Front 42

What is the clinical use of Chloramphenicol?

Back 42

Back up drug for severe salmonella infection (GI) and in pneumococcal and meningococcal meningitis in beta-lactam sensitive persons.

Crosses BBB and is in high concetrations in brain tissue!

Also used in rickettsial diseases

Front 43

What drug causes Gray Baby Syndrome?

Back 43

Chloramphenicol - due to lack of hepatic glucoronosyl transferase enzyme req. for elimination of the drug.

Other toxic effects: bone marrow disturbance (inhibition of RBC maturation), GI disturbance.

Front 44

Chloramphenicol is effective against what type of organism?

Back 44

BROAD SPECTRUM - anaerobic/aerobic - G(+), G(--)

Front 45

Clindamycin is effective against what type of organisms?

Back 45

Anaerobes, and G(+) Aerobes.

NOT G(-) AErobes.

Front 46

What is the main clinical use for Clindamycin?

Back 46

Tx of severe infections due to anaerobes such as Bacteroides.

Also used as alternative to Amoxicillin for prophylaxis of endocarditis before dental surgery in patients with vavlular disease who are penicillin allergic.

Drug also has good activity against P. carinii and T. gondii

Front 47

What are the adverse effects if Clindamycin?

Back 47

Superinfections such as C.difficile pseudomembranous colitis (won't get from dental prophy use cause it's only 1 dose), GI irritation, rash, neutropenia, hepatic dysfunction.