Ribosomal and DNA Abx

Question 1

Tetracyclines

Answer 1

• Tetracycline
• Minocycline
• Doxycycline***

Question 2

Tetracycline MOA/MOR

Answer 2

MOA: 30S bacterial ribosome inhibition

MOR: Ribosomal binding site alterations, efflux pumps

Question 3

Tetracycline pharm/interactions

Answer 3

• May increase INR
• Can’t combine isotretinoin –> Causes pseudotumor cerebri
• Multivalent cations may decrease absorption

-Split excretion (60% hepatic/40% renal)

Question 4

Tetracycline Pearls

Answer 4

• Doxy can come in many different “salts” that drastically vary in price
• Use generic doxycycline hyclate
• These drugs seem protective against C diff

Question 5

Tetracycline ADRs

Answer 5

• Nausea
• Photosensitivity
• Contraindicated pregnant women
• Hyperpigmentation (minocycline)
• Black hairy tongue

Question 6

Doxycycline microbial coverage

Answer 6

• CAP typicals
• CAP atypicals
• Rickettsia, Ehrlichia/Anaplasma, B burger
• Pasteurella
• Staph aureus
• Chlamydia trachomatis

Question 7

Common indications for Doxycycline

Answer 7

• URTI*
• CAP
• NGU
• Tick-borne disease (cutaneous manifestations)

Question 8

Extended-spectrum Tetracyclines

Answer 8

• Tigecycline
• Omadacycline
• Eravacycline

MOA: 30S ribosome inhibition

Question 9

Extended-spectrum Tetracyclines pharmacology

Answer 9

• Drug interactions
• Split excretion
• Bacteriostatic
• Higher mortality, don’t use unless we have to!

Question 10

Extended-spectrum tetracyclines

Answer 10

• Broad-spectrum of activity that includes G=, G-, atypical, & anaerobic pathogens
• Does NOT get pseudomonas
• Used mostly for nosocomial infections

Question 11

Macrolides

Answer 11

• Erythromycin
• Azithromycin***
• Clarithromycin

MOA: 50S ribosome
MOR: Binding site alterations, efflux pumps

Question 12

Macrolide interactions/pharm

Answer 12

• All agents known to increase INR
• Clarith/erythromycin: potent inhibitor of CYP3A4
• All agents should not be used with other QT prolongers

-Hepatic excretion, bacteriostatic

Question 13

Macrolide class ADRs

Answer 13

-All associated with prolonged QTc

Question 14

Erythromycin ADRs

Answer 14

• Activate motilin receptors causing uncoordinated peristalsis and N/V/D
• Used off-label as an agent in gastroparesis

Question 15

Clarithromycin ADRs

Answer 15

-Metallic taste

Question 16

Azithromycin ADRs

Answer 16

• Generally well tolerated

- high dose can cause N/V

Question 17

Macrolide coverage

Answer 17

Azithromycin: S pyogenes, S pneumo, Hib, M catarrhalis, chlamydial, legionella, mycoplasma, Bordetella pertussis (resistance to S pneumo + Hib limits use)

Clarithromycin: mostly used for H. pylori

Question 18

Macrolide indications

Answer 18

• URTIs ID hates em tho
• CAP*
• NGU*
• Enteritis
• H pylori (Clarithromycin)

Question 19

Fidaxomicin pearls

Answer 19

MOA: Macrolide inhibits RNA polymerase

-BACTERICIDAL against C diff

Little to no activity against anything else other than clostridia

Question 20

Lincosamides

Answer 20

-Clindamycin

MOA: 50S ribosomal inhibition

MOR: Efflux pump, ribosomal target modification

Question 21

Lincosamides coverage

Answer 21

• Covers most anaerobes
• best above the diaphragm with oropharyngeal microbes
• Often used to cover SA, S pyogenes, viridans strep in those with serious PCN allergies

Question 22

Lincosamide indications

Answer 22

• Substitute for B lactam allergy in SSTI, strep pharyngitis
• Anaerobic infections/abscesses

Question 23

Oxazolidinones, drug and MOA and MOR

Answer 23

• Linezolid
• Tedizolid
• MOA: binds ribosomal 50s subunit
• MOR: multiple mutations, slow to develop

Question 24

Drug interactions with oxazolidinones

Answer 24

• MAOI -> levodopa

- Concomitant serotonergic drugs -> serotonin syndrome

Question 25

Oxazolidinones ADRs

Answer 25

- Reversible thrombocytopenia (monitor platelets x2 weeks) - Watch dietary tyramine due to MAOI - Peripheral neuropathy - Serotonin syndrome

Question 26

Oxazolidinones uses

Answer 26

-MRSA and VRE infections (has broad gram + activity)

Question 27

Aminoglycosides, main drugs and MOA and MOR

Answer 27

- Gentamicin - Tobramicin - Amikacin - MOA: inhibits 30s ribosome - MOR: ribosomal binding site alterations, efflux pumps, AGases

Question 28

Aminoglycoside pharmacology

Answer 28

- Additive nephrotoxicity - Renal excretion - Bactericidal - Measure trough conc 30 min before next dose - Narrow spectrum abx, only covers aerobic gram negative****

Question 29

Aminoglycosides ADRs

Answer 29

- Nephrotoxicity | - Ototoxicity (genta>tobra)

Question 30

Aminoglycosides clinical indications

Answer 30

- Genta: aerobic GNBs (severe infections), endocarditis | - Tobra: most GNBs including pseudomonas

Question 31

Aminoglycosides claim to fame on the small drugs including: amikacin, streptomycin, neomycin, kanamycin, paromomycin, and spectinomycin

Answer 31

- Amikacin: MDR GNBs - Streptomycin: TB - Neomycin: bowel cleansing - Kanamycin: surgical irrigation - Paromomycin: parasite and tapeworm infections - Spectinomycin: gonorrhea tx for allergic pts

Question 32

Pleuromutilins drug and MOA

Answer 32

- Lefamulin | - MOA: binds peptidyl transferase center of 50s subunit of bacterial ribosome, inhibits bacterial protein synthesis

Question 33

Pleuromutilins pharmacology and ADRs

Answer 33

- Pharm: hepatic excretion and bacteriostatic | - ADRs: N/D, QT prolongation

Question 34

Pleuromutilins microbial coverage:

Answer 34

- Respiratory microbes - STI microbes - Tx indications: CAP

Question 35

FQs, drug MOA and MOR

Answer 35

- Non respiratory: cipro - Respiratory: levo, moxi - Anti-MRSA: delafloxacin - MOA: inhibits DNA topoisomerases (unwinds), prevents replication - MOR: alterations in DNA topo, efflux pumps

Question 36

FQ interactions

Answer 36

- Multivalent cations decrease absorption - Not with QT-prolonging agents - Clinically may raise INR

Question 37

FQ split excretion for levo, moxi, and cipro

Answer 37

- Levo: 100% renal - Moxi: 90% hepatic - Cipro: 50/50

Question 38

FQ ADRs

Answer 38

- Tendinopathy - Arthropathy (CI in kids <18, okay in CF kids) - Anaphylaxis and AIN - CNS toxicities (HA, anxiety; peripheral neuropathies)

Question 39

FQ Robert's Nail in the Coffin ADRs

Answer 39

- Photosensitivity (exaggerated sunburn) - QT prolongation - Dysglycemia* - HTX/liver failure

Question 40

You should not use FQ in these 3 diagnoses

Answer 40

- Sinusitis - Bronchitis - Uncomplicated UTIs (cystitis) - HTN - Connective tissue disorders - Do not use under 18 yo

Question 41

Non-respiratory FQ coverage and tx indications

Answer 41

- Coverage: aerobic GNBs | - Indications: diaphragm to pelvis (upper and lower UTI, tx of enteric infections/travelers diarrhea)

Question 42

Respiratory FQ coverage and tx indications

Answer 42

- Coverage: increase activity for Strep pneumo and atypical respiratory/genital pathogens - Indications: upper and lower UTI (not moxi), enteric infections, URI/LRTIs

Question 43

Anti-MRSA FQ coverage and tx indications

Answer 43

- Coverage: Kills MRSA, drug-resistant gono | - Indications: SSTIs and CAP (last resort)

Question 44

When should you use FQs?

Answer 44

When you are desperate

Question 45

Nitroimidazoles

Answer 45

-Metronidazole

Question 46

Nitroimidazole drug interactions (CYP)

Answer 46

-3A4 and 2C9 inhibitor (massive issues with Warfarin)

Question 47

Nitroimidazole ADRs

Answer 47

- Metallic taste - Disulfuram-like rxn (avoid ETOH) - Fetotoxic in first trimester - Neurotox with several 2 week pulses

Question 48

Nitroimidazole coverage and tx indications

Answer 48

- Coverage: most anaerobes (best below diaphragm), + C. diff, various protozoa (trich, giardia, entamoeba) - Indications: bacterial vaginosis, CDI, giardiasis and trichomoniasis, intrabd abscess