Protein Synthesis Inhibitors

Question 1

What is the classification of Gentamicin and Amikacin?

Answer 1

Aminoglycosides

Question 2

What is the mechanism of action of Aminoglycosides?

Answer 2

Inhibits bacterial protein synthesis by binding strongly

to 30S-subunit, concentration-dependent killing

Question 3

What are the therapeutic indications of Aminoglycosides? (3)

Answer 3

• Life-threatening aerobic Gram negative infections
• Limited Gram positive action
• Pseudomonas aeruginosa

Question 4

What are aminoglycosides used in conjunction with and why?

Answer 4

• used in combinations for severe infections
• Penicillin: staphylococci, streptococci,
  enterococci
• metronidazole / clindamycin: anaerobic infections

Question 5

What is the recommended dosage of Aminoglycosides and why?

Answer 5

Single daily doses, due to prolonged post-antibiotic effect

Question 6

When are aminoglycosides not given in a single daily dose?

Answer 6

In children, critically ill patients and when used with penicillin

Question 7

What is considered to be the standard aminoglycoside in many centres?

Answer 7

Gentamicin

Question 8

How is gentamicin administered?

Answer 8

IM

Question 9

Describe the distribution of gentamicin

Answer 9

rapidly distributed in the extracellular fluid and tissue

Question 10

What is the half-life of gentamicin and what increases this?

Answer 10

2-3 hours, but increases during renal insufficiency or in neonates

Question 11

What is the effect of gentamicin on the CNS?

Answer 11

Minimal effect, crossing into BBB is poor

Question 12

How is gentamicin excreted?

Answer 12

eliminated unchanged by glomerular filtration within 24 hours

Question 13

What are the adverse effects of gentamicin? (9)

Answer 13

• Nephrotoxicity
• Ototoxicity
• Neuromuscular blockade, headache, tremor, electrolyte disturbances, hepatic damage, rashes and fever

Question 14

What is the classification of Doxycycline?

Answer 14

Tetracyclines

Question 15

What is the mechanism of action of Tetracyclines?

Answer 15

Binds reversibly to the 30S subunit of the bacterial ribosome, blocking the binding of amino-acyl-tRNA to the acceptor site on the mRNA-ribosome complex. This prevents addition of amino acids to the growing peptide chain.

Question 16

What is the spectrum of activity of Tetracyclines?

Answer 16

broad

Question 17

What are the therapeutic indications of Tetracyclines? (6)

Answer 17

• G+, G-, anaerobes
• Rickettsia, Chlamydia, Vibrio cholerae, Mycoplasmas and some protozoa
• Leptospirosis, gas-gangrene, tetanus (Oxytetracycline)
• Acne (Doxycycline and minocycline)
• Malaria
• Prophylaxis

Question 18

How do Tetracyclines mainly differ?

Answer 18

Their GIT absorption

Question 19

Describe the absorption of newer generation Tetracyclines?

Answer 19

lipid soluble and are completely absorbed even in the presence of food

Question 20

What inactivates Tetracyclines?

Answer 20

milk and antacids

Question 21

What are the adverse effects of Tetracyclines? (6)

Answer 21

• GIT upsets, nausea, vomiting
• Damage to gut flora causes superinfection with
  pathogens (Candida)
• Pseudomembranous colitis (life-threatening)\
• Bone growth retardation
• Teeth discolouration and enamel hypoplasia
• Hepato- and nephrotoxic.

Question 22

What are the contraindications of Tetracyclines?

Answer 22

children under 8

Question 23

What is the classification of Erythromycin and Azithromycin?

Answer 23

Macrolides

Question 24

What is the mechanism of action of Macrolides?

Answer 24

Bind to the 50S bacterial ribosomal subunit and inhibit protein synthesis by having an effect on translocation

Question 25

What is the spectrum of activity of Macrolides?

Answer 25

Similar to Penicillin G

Question 26

What are the therapeutic indications of Macrolides? (5)

Answer 26

- Legionnaire’s disease - whooping cough - Mycoplasma pneumoniae - Chlamydia - Alternative in penicillin-allergic patients

Question 27

How is Erythromycin administered? (and why)

Answer 27

Orally, it is acid-labile and must be administered with enteric coating to protect the antibiotic until it reaches the absorption site in the duodenum.

Question 28

What are the 2 oral forms of Erythromycin and which one has better absorption?

Answer 28

- stearate salt or the ester (estolate) forms | - estolate has the best absorption

Question 29

Describe the distribution of Ethyromycin

Answer 29

Extensively distributed into most tissues, including prostate fluid, crosses placenta but not BBB

Question 30

What is the half-life of Ethyromycin?

Answer 30

1.5-2 hours

Question 31

Describe the protein binding of Ethyromycin?

Answer 31

protein-binding is high

Question 32

How is Ethyromycin metabolised and excreted?

Answer 32

Partially metabolized in the liver and excreted in bile, 2-5% is excreted unchanged in the urine.

Question 33

What are the adverse effects of Ethyromycin? (3)

Answer 33

- Well tolerated, one of safest antibiotics - Prolologed use of estolate: hepatotoxicity - Erythromycin metabolites: increase serum concentrations of drugs to toxic levels and increases bioavailability of digoxin.

Question 34

What is the classification of Clindamycin?

Answer 34

Lincosamide

Question 35

What is the mechanism of action of Clindamycin?

Answer 35

Inhibits protein synthesis by binding to 50S ribosomal | subunits interfering with the formation of initiation complexes and with the aminoacyl translocation reaction

Question 36

What are the therapeutic indications of Clindamycin? (2)

Answer 36

- gram-positive infections in patients allergic to penicillins - sensitive staphylococcal and anaerobe infections such as Bacteroides species

Question 37

Describe the distribution of Clindamycin

Answer 37

widely distributed in most body tissues and fluids except the cerebrospinal fluid

Question 38

Describe the absorption of Clindamycin

Answer 38

well absorbed from the GIT

Question 39

What is the half-life of Clindamycin?

Answer 39

2-3 hours

Question 40

What % of Clindamycin binds to plasma proteins?

Answer 40

>90%

Question 41

How is Clindamycin metabolised and excreted?

Answer 41

hepatic metabolism and excretion in the bile

Question 42

What are the adverse effects of Clindamycin? (2)

Answer 42

- GIT problems: diarrhoea, nausea and vomiting | - Skin rashes

Question 43

What is the classification of Chloramphenicol?

Answer 43

Amphenicol

Question 44

What is the mechanism of action of Chloramphenicol?

Answer 44

Binds reversibly to the 50S subunit of the bacterial ribosome and inhibits the peptidyl transferase-enzyme during protein synthesis

Question 45

What is the spectrum of activity of Chloramphenicol?

Answer 45

broad

Question 46

What are the therapeutic indications of Chloramphenicol?(5)

Answer 46

- Serious infections such as meningitis - Life- threatening epiglottitis caused by the organism H. influenzae - Typhoid fever - Bacterial eye infections - Not for prolonged infections and for prophylaxis

Question 47

How is Chloramphenicol succinate administered?

Answer 47

parenterally

Question 48

How does Chloramphenicol succinate yield free chloramphenicol?

Answer 48

Hydrolysis (water-soluble)

Question 49

How is Chloramphenicol succinate administered?

Answer 49

orally

Question 50

Describe the absorption of Chloramphenicol

Answer 50

rapidly absorbed and is about 80% bioavailable

Question 51

Describe the distribution of Chloramphenicol

Answer 51

widely distributed to virtually all tissues and body fluids, including the central nervous system and cerebrospinal fluid

Question 52

What % of Chloramphenicol is bound to protein?

Answer 52

30-50%

Question 53

What is the half-life of Chloramphenicol?

Answer 53

1.5-4 hours

Question 54

How is Chloramphenicol metabolised and excreted?

Answer 54

metabolized by the liver and conjugated with glucuronic acid and eliminated in the urine

Question 55

What are the adverse effects of Chloramphenicol? (6)

Answer 55

- severe, idiosyncratic depression of bone marrow - fatal aplastic anaemia - “grey baby syndrome” - GIT effects - Optic or peripheral neuritis - Jarisch-Herxheimer-like reactions