Protein Synthesis Inhibitors

Question 1

Tetracylines

Answer 1

tetracycline, doxycycline, minocycline, demeclocycline

Question 2

Aminoglycosides

Answer 2

amikacin, gentamicin, neomycin, streptomycin, tobramycin

Question 3

Macrolides

Answer 3

azithromycin, clarithromycin, erythromycin, fidaxomicin

Question 4

Other synthesis inhibitors

Answer 4

clindamycin and linezolid

Question 5

What subunits does a bacterial ribosome have?

Answer 5

50s and 30s

Question 6

What subunits does a human ribosome have?

Answer 6

60s and 40s

Question 7

What is different about mitochondrial ribosomes?

Answer 7

mammalian mitochondrial ribosomes are closer to bacteria, so drugs targeting it may cause toxic effects

Question 8

Which drugs inhibit protein synthesis at the 30s ribosome?

Answer 8

tetracyclines and aminoglycosides

Question 9

Which drugs inhibit protein synthesis at the 50s ribosome?

Answer 9

macrolides and “others” + chloramphenicol

Question 10

Which group of drugs have adverse effects on the teeth?

Answer 10

tetracyclines

Question 11

What is the tetracycline MOA?

Answer 11

reversibly bind the 30s subunit to prevent binding of tRNA which prevents the addition of new amino acids to the growing peptide chain

Question 12

Are tetracyclines bacteriostatic or bactericidal?

Answer 12

bacteriostatic

Question 13

Which two tetracyclines are longer lasting?

Answer 13

doxycycline and minocycline

Question 14

What do tetracyclines treat?

Answer 14

broad spectrum, gram - and , chlamydia!

Question 15

How does resistance to tetracyclines come about?

Answer 15

mutation preventing organism from taking in the drug, plasma encoded efflux of drug, enzymatic inactivation, or producing proteins that prevent binding to ribosome

Question 16

What does tetracycline bind to?

Answer 16

calcium, aluminum, iron, magnesium

Question 17

What reduces the bioavailability of tetracycline?

Answer 17

dairy products– avoid antacids and iron supplements as well

Question 18

What tissues does tetracycline bind to?

Answer 18

tissues undergoing calcification

Question 19

Which tetracycline can penetrate CSF but is not effective for CNS infections?

Answer 19

minocycline

Question 20

T/F tetracyclines cross the placenta and bind fetal bones and teeth

Answer 20

true– contraindication!

Question 21

Who should you not prescribe tetracycline to?

Answer 21

pregnant/breastfeeding women

Question 22

Describe the elimination of tetracycline

Answer 22

gets concentrated in the liver, secreted into bile, reabsorbed into the intestine and excreted in urine

Question 23

T/F doxycycline is excreted by the kidney

Answer 23

false, good for patients with renal disease

Question 24

What are the adverse effects of tetracycline?

Answer 24

gastric discomfort, effects on calcified tissues, photo-toxicity, vestibular issues, and pseudotumor cerebri

Question 25

What are tetracyclines effects on calcified tissue?

Answer 25

discoloration and hypoplasia of teeth in children, can stunt growth, avoided in children under 12

Question 26

What are tetracyclines effects on the vestibular system?

Answer 26

it concentrates in endolymph in the ear and can cause vertigo

Question 27

What is pseudotumor cerebri?

Answer 27

effect of tetracycline, idiopathic intracranial hypertension, pt symptoms are headache and blurred vision with a swollen appearance to the optic nerve (bilaterally)

Question 28

What are three superinfections that can result from tetracyclines?

Answer 28

candida (yeast), resistant staph, colitis

Question 29

Summarize the four main contraindications of tetracyclines

Answer 29

only doxycycline for those with kidney problems, NO pregnant women, no children under 12, inhibits warfarin (blood thinner) clearance

Question 30

What is a 50 mg or less dose of doxycycline for?

Answer 30

anti-inflammatory effects that work on soft tissue inflammation and do not encourage bacterial resistance to larger dose

Question 31

What is the MOA of aminoglycosides?

Answer 31

bind 30s ribosome proteins and interfere with initiation complex by causing misreading of mRNA

Question 32

Are aminoglycosides bacteriostatic or bactericidal?

Answer 32

bactericidal

Question 33

Which two aminoglycosides often cause allergies?

Answer 33

gentamicin and neomycin

Question 34

What is true of the absorption of aminoglycosides?

Answer 34

oral absorption is inadequate because of highly polar structure

Question 35

How are aminoglycosides administered?

Answer 35

IV, IM, topically

Question 36

What are aminoglycosides used against?

Answer 36

gram - including pseudomonas, with some gram +

Question 37

What can an aminoglycoside be combined with to improve the spectrum?

Answer 37

b-lactam or vancomycin

Question 38

What are two causes of aminoglycoside resistance?

Answer 38

decreased uptake of drug, plasmid associated synthesis of enzyme

Question 39

Describe the aminoglycoside distribution?

Answer 39

inadequate CSF penetration, low tissue penetration, high concentration in renal cortex and inner ear, all cross the placenta

Question 40

What is the elimination of aminoglycosides?

Answer 40

no host metabolism, rapidly excreted into urine

Question 41

What are four main adverse effects of aminoglycosides?

Answer 41

ototoxicity, nephrotoxicity, neuromuscular paralysis, allergic reactions

Question 42

What is ototoxicity?

Answer 42

an adverse effect of aminoglycosides with deafness that may be irreversible, orally will affect the fetus

Question 43

How does aminoglycoside neuromuscular paralysis occur?

Answer 43

after very large doses it causes decrease in acetylcholine release and in post-synaptic sensitivity to acetylcholine

Question 44

Are topical aminoglycosides likely to become resistant?

Answer 44

no

Question 45

What is the MOA of macrolides?

Answer 45

bind to the 50s ribosomal subunit to block peptidyltransferase center and prevent amino acid chain elongation... can also inhibit formation of 50s

Question 46

What is a good macrolide alternative to PCN?

Answer 46

erythromycin

Question 47

Which macrolide is effective against H. influenzae

Answer 47

clarithromycin

Question 48

Which macrolide is best for respiratory infections and chlamydia?

Answer 48

azithromycin (1000 mg once)

Question 49

What are three mechanisms of macrolide resistance?

Answer 49

inability to take up antibiotic/efflux pump, decreased affinity of 50s subunit, and presence of plasmid associated enzyme

Question 50

T/F macrolides are well absorbed orally

Answer 50

true

Question 51

Which macrolide should not be given via IV for thrombophlebitis risk?

Answer 51

erythromycin

Question 52

T/F macrolides only diffuse into one tissue type

Answer 52

false, distributes well into fluids and tissues

Question 53

Which macrolide has a long half life and high V?

Answer 53

azithromycin

Question 54

What is true of erythromycin and telithromycin metabolism?

Answer 54

extensively metabolized and inhibit oxidation of many drugs, interact with P450

Question 55

Which organ excretes macrolides?

Answer 55

kidney

Question 56

What are three macrolide adverse effects?

Answer 56

GI problems, acute hepatitis with jaundice, ototoxicity

Question 57

Which macrolide primarily produces ototoxicity in high doses?

Answer 57

erythromycin

Question 58

What are two contraindications of macrolides?

Answer 58

hepatic dysfunction, arrhythmia

Question 59

T/F macrolides inhibit hepatic metabolism of many drugs

Answer 59

true via P450

Question 60

What is the MOA of clindamycin?

Answer 60

same as erythromycin, bind 50s

Question 61

What is clindamycin used to treat?

Answer 61

MRSA, abdominal anaerobic infections

Question 62

T/F clindamycin has poor absorption to CSF

Answer 62

true

Question 63

What is linezolid used to treat?

Answer 63

resistant gram + organisms like MRSA

Question 64

What is the MOA of linezolid?

Answer 64

inhibits formation of ribosomal complex by binding 50s subunit near the interface with 30s

Question 65

T/F linezolid has no cross-resistance with other drug classes

Answer 65

true

Question 66

Linezolid vs vancomycin for MRSA

Answer 66

linezolid is noninferior to vancomycin for MRSA pneumonia but is not used for MRSA bacteremia

Question 67

What are important pharmacokinetic principles of linezolid?

Answer 67

completely absorbed orally, high V, no interaction with P450, renal and nonrenal excretion

Question 68

What are three adverse effects of linezolid?

Answer 68

thrombocytopenia, anemia, optic and peripheral neuropathy

Question 69

What are contraindications for linezolid?

Answer 69

caution with MAOIs and SSRIs due to case reports of serotonin syndrome