Protein synthesis inhibitors

Question 1

What are the four main steps of bacterial protein synthesis (translation)?

Answer 1

tRNA binding to the ribosome (acceptor site)

Peptide bond formation (by peptidyl transferase)

tRNA release from the donor site

Translocation of the ribosome to the next codon

Question 2

What step of translation do tetracyclines inhibit?

Answer 2

Step 1 – They bind the 30S subunit and block binding of incoming charged tRNA.

Question 3

What step do chloramphenicol and macrolides inhibit?

Answer 3

Step 2 – They bind the 50S subunit and block peptide bond formation.

Question 4

T or F: tetracycline, doxycycline, minocycline all have the same mechanism of action

Answer 4

True

Question 5

What metal-binding property do tetracyclines have?

Answer 5

They are potent chelators and bind to divalent and trivalent metals like Mg²⁺, Ca²⁺, Al³⁺, and Fe²⁺.

Question 6

Are tetracyclines bacteriostatic or bactericidal?

Answer 6

Bacteriostatic — they inhibit growth, and bacteria can resume growth if the drug is removed before immune clearance.

Question 7

What affects tetracycline absorption from the GI tract?

Answer 7

Absorption is rapid but inhibited by calcium and metal ions—avoid dairy, iron supplements, antacids, and certain vitamins.

Question 8

What are key pharmacokinetic properties of tetracyclines?

Answer 8

Minimal metabolism (except minocycline)

Minocycline has a significantly longer half-life than others

Question 9

What is a major mechanism of resistance to tetracyclines?

Answer 9

The TetA gene (on R-factor plasmid) encodes a membrane protein that pumps tetracycline out of the cell, reducing intracellular drug concentration.

Question 10

What is the clinical spectrum of tetracyclines?

Answer 10

Very broad — effective against both gram-positive and gram-negative bacteria.

Question 11

What are specific clinical uses of tetracyclines?

Answer 11

Rickettsia infections (e.g., Rocky Mountain spotted fever, typhus)

Lyme disease (Borrelia)

Helicobacter pylori (ulcers)

Adult periodontitis (e.g., Periostat® — doxycycline at sub-antibiotic levels inhibits metalloproteinases)

Question 12

What are major toxicities of tetracyclines?

Answer 12

Moderate renal and hepatic toxicity (especially in pregnancy or liver impairment)

Contraindicated in pregnancy and children under 9

Question 13

Why do tetracyclines cause permanent tooth staining in children?

Answer 13

They chelate calcium, accumulate in developing teeth and bones, and discolor with age and light exposure.

Question 14

What is a common gastrointestinal side effect of tetracyclines?

Answer 14

Superinfection due to disruption of normal gut flora, allowing overgrowth of resistant organisms.

Question 15

What does streptomycin block in protein synthesis?

Answer 15

Ribosome initiation complex and translocation along mRNA.

Question 16

What error does streptomycin cause during translation?

Answer 16

Misreading of mRNA, leading to miscoded proteins.

Question 17

Are aminoglycosides bacteriostatic or bactericidal?

Answer 17

Bactericidal and only aminoglycosides

Question 18

What are some other aminoglycosides besides streptomycin that share the same mechanism?

Answer 18

Gentamicin, kanamycin, neomycin, tobramycin, amikacin.

Question 19

Why are aminoglycosides not given orally?

Answer 19

They are very poorly absorbed from the gastrointestinal tract so they are given IV or IM.

Question 20

What is the typical half-life of aminoglycosides?

Answer 20

About 1 to 3 hours.

Question 21

How are aminoglycosides metabolized?

Answer 21

They undergo little metabolism.

Question 22

Aminoglycosides are generally effective against which type of bacteria?

Answer 22

A wide range of gram-negative bacteria.

Question 23

What was streptomycin the first effective drug against?

Answer 23

Tuberculosis but is rarely used now due to naturally occurring strains are now resistant.

Question 24

What serious infection is streptomycin still used to treat?

Answer 24

Plague (Yersinia pestis).

Question 25

What is gentamicin, kanamycin, and neomycin commonly used for?

Answer 25

Gentamycin - used for undefined sepsis Kanamycin - bowel sterilization for surgery Neomycin – topical antibiotic (e.g. used in Neosporin)

Question 26

How can bacteria resist aminoglycosides by altering ribosomes?

Answer 26

Mutations in 30S rRNA or proteins prevent drug binding.

Question 27

What’s the main clinical mechanism of aminoglycoside resistance?

Answer 27

Enzymes that modify the drug (phosphorylation, adenylation, acetylation).

Question 28

What serious side effect of aminoglycosides can be permanent?

Answer 28

Ototoxicity.

Question 29

What organ can aminoglycosides damage, usually reversibly?

Answer 29

Kidneys.

Question 30

What should be avoided when using aminoglycosides?

Answer 30

Other ototoxic or nephrotoxic drugs like vancomycin.

Question 31

Is chloramphenicol bacteriostatic or bactericidal?

Answer 31

Bacteriostatic.

Question 32

What serious side effect limits chloramphenicol use and what is it caused by?

Answer 32

Aplastic anemia due to Effects on mitochondrial 55S ribosomes.

Question 33

What is gray baby syndrome?

Answer 33

A severe reaction in infants lacking the enzyme to metabolize chloramphenicol.

Question 34

What type of bacteria is chloramphenicol effective against?

Answer 34

Both Gram-positive and Gram-negative (broad spectrum).

Question 35

When is chloramphenicol typically used?

Answer 35

For multiple drug-resistant infections, typhoid fever, and Haemophilus influenzae meningitis.

Question 36

What enzyme causes resistance to chloramphenicol?

Answer 36

Chloramphenicol transferase (CAT).

Question 37

What does chloramphenicol transferase do?

Answer 37

Acetylates hydroxyl groups, inactivating the drug.

Question 38

What encodes chloramphenicol transferase?

Answer 38

R-factor plasmid.

Question 39

What class of antibiotic is erythromycin?

Answer 39

Macrolide.

Question 40

Is erythromycin bacteriostatic or bactericidal?

Answer 40

Bacteriostatic.

Question 41

How does erythromycin inhibit protein synthesis?

Answer 41

It blocks the exit channel for the growing peptide chain.

Question 42

What happens to peptidyl-tRNA as a result?

Answer 42

It dissociates after only a few amino acids.

Question 43

What problem occurs with oral erythromycin?

Answer 43

It is degraded by stomach acid.

Question 44

How is erythromycin protected from stomach acid?

Answer 44

Given as a coated capsule or estolate conjugate.

Question 44

How is erythromycin excreted?

Answer 44

In bile, with little metabolism.

Question 45

What is the half-life of erythromycin?

Answer 45

About 2 hours.

Question 46

What type of bacteria is erythromycin mainly effective against?

Answer 46

Gram-positive (like Streptococcus and Enterococcus).

Question 47

Who commonly receives erythromycin instead of penicillin?

Answer 47

Patients with a penicillin allergy.

Question 48

Is erythromycin generally considered toxic?

Answer 48

No, it is relatively nontoxic.

Question 49

Name some infections treated with erythromycin.

Answer 49

Diphtheria, pertussis, syphilis, gonorrhea, Legionnaires disease, tetanus, staph, strep.

Question 50

What are common gastrointestinal side effects of erythromycin?

Answer 50

Cramps, nausea, vomiting, diarrhea.

Question 51

What rare liver issue is associated with erythromycin estolate?

Answer 51

Temporary hepatitis (possibly a hypersensitivity reaction).

Question 52

Why should erythromycin be used cautiously in patients with arrhythmias?

Answer 52

It can be lethal in some cardiac arrhythmia cases.

Question 53

How does erythromycin affect drug metabolism?

Answer 53

It is metabolized by and inhibits CYP3A4, reducing metabolism of other drugs.

Question 54

What enzyme causes resistance to erythromycin?

Answer 54

rRNA methyltransferase.

Question 55

How does rRNA methyltransferase cause resistance of erythromycin?

Answer 55

It methylates 23S rRNA, preventing erythromycin from binding.

Question 56

What class do azithromycin and clarithromycin belong to?

Answer 56

Macrolides.

Question 57

How are azithromycin and clarithromycin related to erythromycin?

Answer 57

They are newer analogues with similar structure and mechanism causing cardiac arrhythmia.

Question 58

Which one inhibits CYP3A4 Clarithromycin or azithromycin?

Answer 58

Clarithromycin and erythromycin

Question 59

What is the mechanism of action of clindamycin?

Answer 59

Clindamycin binds to the 50S ribosomal subunit, inhibiting peptidyl transferase, blocking the peptide exit channel, and promoting peptidyl-tRNA dissociation.

Question 60

How do erythromycin and clindamycin inhibit protein synthesis?

Answer 60

block access to the peptidyl exit channel. Clindamycin also binds closer to the peptidyl transferase site and directly inhibits its function.

Question 61

What is the half-life of clindamycin?

Answer 61

2.5 hours.

Question 62

How is clindamycin secreted from the body?

Answer 62

secreted in bile.

Question 63

What is the spectrum of activity of clindamycin?

Answer 63

relatively narrow spectrum of activity, chiefly against anaerobes, especially in patients with penicillin allergies.

Question 64

What type of bacteria does clindamycin primarily target?

Answer 64

Clindamycin primarily targets gram-positive bacteria by binding to their ribosomes.

Question 65

In what clinical situation is clindamycin used as prophylaxis?

Answer 65

prophylaxis of infective endocarditis

Question 66

What is a major limitation of clindamycin use?

Answer 66

severely limited by its toxicity, particularly causing colitis.

Question 67

What is a major toxicity associated with clindamycin?

Answer 67

A major toxicity is superinfection with Clostridium difficile, which can lead to pseudomembranous colitis.

Question 68

What fungal superinfection can occur with clindamycin use?

Answer 68

Superinfection with Candida albicans (fungus) can occur, though less frequently.

Question 69

What are some less common toxic effects of clindamycin?

Answer 69

Less common toxic effects include allergic reactions, renal, hepatic, and hematopoietic issues.

Question 70

What are the mechanisms of resistance to clindamycin?

Answer 70

Resistance to clindamycin can occur through altered rRNA or rRNA-modifying enzymes (methyltransferases), which block clindamycin binding to the 50S ribosomal subunit.

Question 71

What is the relationship between clindamycin resistance and erythromycin?

Answer 71

Resistance to clindamycin often involves cross-resistance to erythromycin due to similar mechanisms of action.