Pharmacology Atb Protein Synthesis Inhibitors Spring 2011

Front 1

ATBs that inhibit prootein synthesis (9)

Back 1

- Aminoglycodsides
- Tetracyclines
- Glycylcyclins
- Macrolides
- Lincosamides
- Chloramphenicol
- Streptogramins
- Oxazolidinones
- Mupirocin

Front 2

Aminoglycosides genera MOA

Back 2

- Prevent initiation meth-t-RNA from binding
- Binds to interface btwn 30 and 50s subunits
- Enhances early breakdown of unit

Front 3

Tetracyclines general MOA

Back 3

- Binds 30s subunit to prevent t-RNA from binding to A site
- Prevents elongation
**When drug is gone, synthesis will resume

Front 4

Macrolides general MOA

Back 4

- Bind 50s subunit
- Interferes with initiation comples and transfer of peptide t-RNA complex from A to P site
- Prevents elongation

Front 5

Ketolides general MOA

Back 5

- Bind 50s subunit
- Interferes with initiation comples and transfer of peptide t-RNA complex from A to P site
- Prevents elongation

Front 6

Lincosamides general MOA

Back 6

- Binds 50s subunit
- Interferes with initation complex
- Binding site is close to thta for Macrolides and Chloramphenicol (so don't combine)
- Prevents elongation

Front 7

Chloramphenicol general MOA

Back 7

- Binds 50s subunit
- Inhibits bond formation between peptide and new amino acid
- Reversible binding (when drug is gone, synthesis resumes)

Front 8

Streptogramins general MOA

Back 8

- Binds 50s subunit
- Dalfopristin prevents peptide bond formation (inhibits peptidyltransferase)
- Quinupristin inhibits t-RNA synthesis (inhibits elongation)

Front 9

Linezolid general MOA

Back 9

- Binds specific 23s ribosomal DNA on 50s subunit preventing formation of functional unit

Front 10

Mupirocin general MOA

Back 10

- Inhibits isoleucyl-t-RNA synthetase to prevent incorportation of isoleucine into proteins
**No cross tolerance

Front 11

Which two groups ONLY bind 30s subunit?

Back 11

Tetracyclines and Spectomycin only bind 30s

Front 12

Which 4 only bind 50s subunit?

Back 12

Macrolides, Chloramphenicol, streptogramins and Lincosamides

Front 13

Which two are bactericidal?

Back 13

Aminoglycosides and Mupirocin

Front 14

Ketolides have same general MOA as?

Back 14

Macrolides

Front 15

Name the AGs. what type of killing?

Back 15

- Amikacin (nocosomial infections)
- Gentamicin
- Kanamycin
- Neomycin
- Netilmicin
-Tobramycin
- Streptomycin (plague)

Concentration dependent killing

Front 16

AG Kinetics

Back 16

Ionized in body, not readily absorbed
Elim by glomerular filtration - must adj dose for kidney insuff
Used in combo for serious infections, spesis, pneumonia, endocarditis
*May be combines with Beta-lac

Front 17

AG Toxicity

Back 17

**Nephrotoxicity - 8-25% get renal impairment; accumulates in proximal tubule to damage brush border cells; incidence related to age, total dose, if female, duration of tx; **Additive with Cisplatin, Cyclosporins!

**Ototoxicity - may be permament; can cause auditory and vestibular problems (balance); increased risk with prolonged administration, repeated doses, high doses; Enhanced by ethacrynic acid, furosemide, cisplatin

**Neuromuscular blockade - blocks presynaptic relsease of Ca so is CI in myasthenia gravis and can interfere with anesthesia in surgery

Front 18

AG toxicities MOA of otot and nephrotox?

Back 18

1. Calcium hypothesis: AG interferes with the calcium channels in hair cells
2. Free Radical hypothesis: AG interacts with Iron to form free superoxide
3. NMDA hypothesis: AG interacts with NMDA receptors and glutamate to cause exicotoxicity

Front 19

AG Resistance

Back 19

Plasmid aquired, can cause altered transport and altered ribosomes

Front 20

AG effective against?

Back 20

Gram NEG bacilli, aerobic bacteria

Front 21

Tetracyclines effective against?Bacteriostatic or cidal?

Back 21

Gram POS and gram NEG anaerobes, aerobes

Rikettsia, Chlamydia, Lyme's disease

Bacteriostatic

Front 22

Tetracycline agents:

Back 22

Demectocycline
Oxytetracycline
Doxycycline
Tetracycline
Minocycline

Front 23

Tetracycline Kinetics

Back 23

Absorption impaired by milk and antacids, will chelate divalent cations

enters CNS, crosses placenta

Glomerular filtration, some in biliary

**Doxycycline is mainly excreted in feces - so could use in renal problems

Front 24

Tetracycline Toxicity:

Back 24

GI disturbances
Photosenstivity
Super-infections (C.Diff = colitis)
Bone and teeth effects
Renal and Hepatic tox
Hypersensitivity

Front 25

Tetracyclines Resistance

Back 25

1. Plasmid mediated to add efflux transports
2. Ribosomal protection protein can displace tetracyclines
3. Increased enzyme inactivation

*there can be cross resistance between tetras - but it depends on the MOResistance

Front 26

Glycylcyclines
only agent?
similar to?

Back 26

Only agent is Tigecycline
IV infusion, excreted unchange in bile and urine

Used in complicated skin and intra-ab infectionws, effective in tetra resistant organisms

Toxicities similar to tetras

Front 27

Macrolides (3) are effective against?

Back 27

Erthryomycin, Azithromycin, Clarithromycin
effective against gram POS, cocci and bacilli, chlamydia and legionella

Front 28

Macrolides kinetics and toxicity

Back 28

- Inactivated by acid so must be enteric coated
- billiary excretion
- will cross placenta (NOT cross BBB)

Toxicities:
Cholestatic hepatitis, sensitivity, GI, Tinnitus (particularly with Clarith), hearing loss
Eryth - QT prolongation with antihistamines and ketoconazole
Eryth and Clarith have 3A4 rxns

Front 29

Specific uses of Macrolides

Back 29

Clarith - H. Pylori
Azith - H. Influenzae
A+C - mycobacterium avium-intracellulare

Front 30

Macrolide Resistance because of

Back 30

Active transport out of bacteria, decreased binding to receptor, increased metabolism, ribosomal mutations

Front 31

Ketolides (1) used for? general notes

Back 31

Telithromycin

Recommended approval by FDA for CAP, bronchitis, sinusitis

Similar ATB activity to macrolides, less metabolic and efflux resistance

Front 32

Ketolides toxicity

Back 32

Hepatotoxicity
Visual disturbances due to slowed accommodation
Colitis
QT prolongation, arrhythmias
3A4 rxns

Front 33

Lincosamides (1) covers? DOC for?

Back 33

Clindamycin
covers gram POS, anaerobic, penicillin resistant staph and strep, cocvers strep pyogenes

DOC for lung abscess and anaerobic lung and pleural space infections

Front 34

Lincosamide toxicity and resistance

Back 34

Tox: 20% experience diarrhea, can lead to pseudomembraneous colitis b.c of C. DIff, 10% get rash

Resistance because of altered metabolism

Front 35

Chloramphenicol notes
Bactericidal against?
resistance?

Back 35

Bacteriostatic for most, cidal against H. influ, Strep pneumo, Neisseria mening

Resistance is plasma encoded actyltransferase prevents binding

Front 36

Chloramphenicol toxici

Back 36

Glucuronidated in liver - babies can't so they will turn gray

will enter CNS,placenta, breast milk

Bone marrow suppression, RBC alterations, peripheral neuropathy, inhibits microsomal enzymes, sensitivity, CYP interactions

Front 37

Streptogramins is?

Back 37

Combination of Dalfopristin and Quinupristin (30 to 70 mix)

IV use

Front 38

Explain Streptogramins resistance?

Back 38

Resistance to Quinu is altered ribosomal binding

Resistance to Dalfo is increased metabolism

Front 39

Streptogramins is used for?

Back 39

Vanco resistant E. Faecium! (NOT faecalis)
MRSA, S. Pyogenes

Front 40

Streptogramins tox

Back 40

Tox
inflammation of veins, N/D, muscle aches, 3A4 rxns, elevates serum transaminaseq

Front 41

Oxazolidinones (1) against? used in?

Back 41

Linezolid against Vanco resistance E. Faecium

Used for Nocosomial pneumonia, MRSA skin infections

Reserved for multiple drug resistant strains

IV and Oral

Front 42

Oxazolidinones tox

Back 42

tox: Nausea, thrombocytopenia, itching, MAOI, peripheral neuropathy

Front 43

Mupirocin notes

Back 43

Used as topical cream for skin lesions or for nasal colonization with MRSA

Bacteriostatic at low conc, cidal at high