Protein Synthesis Inhibitors

Question 1

What is a ribosome?

Answer 1

the machine of protein synthesis; composed of many subunits

Question 2

What is the difference b/n mammalian and bacterial ribosomes?

Answer 2

mammals: 80S (40S + 60S subunits)
bacteria: 70S (30S + 50S subunits)

Question 3

What happens when drugs bind to 30/50 subunits?

Answer 3

protein synthesis is interrupted in the bacteria

Question 4

How does toxicity occur with protein synthesis inhibitors?

Answer 4

mammalian mitochondrial ribosomes look like bacterial ribosomes (70S)

Question 5

Explain the APE of ribosomes.

Answer 5

two subunits of ribosome clamp down on mRNA; each subunit has 3 areas (APE); A is where charged amino acids bring in next amino acid; P is where growing peptide is still affixed to one tRNA molecule; E is the exit site

Question 6

**How do bacteria show resistance to tetracyclines?

Answer 6

• -**increased efflux pump to decrease intracellular levels
• -expression of proteins that protect ribosomes from drug
• -enzymatic inactivation of drug
• -**widespread resistance has limited clinical use

Question 7

What is the distribution of tetracyclines?

Answer 7

wide; accumulation in liver, spleen, bone marrow, bone, dentine, enamel of unerupted teeth; penetration into CNS; cross the placenta

Question 8

How do tetracyclines compromise efficacy of bactericidal antibiotics?

Answer 8

penicillin works best against dividing cells; if you use a bacteriostatic antibiotic to stop cells from dividing, the penicillin won’t work

Question 9

**How are aminoglycosides used for gram+ pathogens?

Answer 9

combo therapy w/ penicillin or vanc; acts synergistically & extends coverage to gram+; cell wall disrupting agent allow better penetration of aminoglycosides

Question 10

**What causes resistance to aminoglycosides?

Answer 10

enzymatic inactivation of the drug; used in combo w/ vanc or penG

Question 11

Macrolides are competitive inhibitors of what? How?

Answer 11

They competitively inhibit ribosome binding of streptogramins, clindamycin, chloramphenicol b/c of the proximity of their sites of action

Question 12

three mechanisms of induced resistance to macrolides

Answer 12

• -efflux pump
• -**methylase modifies the bacterial ribosome so unable to bind drug (MLS-type B resistance)
• -hydrolysis of macrolides by esterases produced by Enterobacteriaceae

Question 13

What is MLS-type B resistance?

Answer 13

resistance to macrolide, lincosamide, streptogramin

methylases put methyl groups on the amino acids to change the structure; methylation affects macrolide binding, etc.