Protein Synthesis Inhibitors

Question 1

Clindamycin is:

Answer 1

1. Lincosamide
2. Protein 50S Synthesis inhibitor
   3.have bacteriostatic and bacteriocidal effect
3. A. well absorped orally
4. D.distributed well to most tissue
   Poor penetration to CNS and brain
   Protein binding 85 to 94%
5. Metabolised in liver
6. Excreted in renal and bile
7. T1/2 2.5hr
8. Time dependent killing with persistent effect AUC:MIC
9. Clinical indication: SSTI, prophylaxis treatment to prevent IE for patient going for dental teeatment, treat pneumocystic jarovaci infection in pt with HIV
10. Side effect: hypersensitivity, GI (N, v, CD, pseudomonas colitis , hepatotoxicity

Question 2

Linezolid,

Answer 2

1. Linezolid is an 50S protein synthesis inhibitor, by inhibiting the 50S Protein subunit near to the protein 30S
2. Bacteriostatic effect
3. A. 100% absorption after oral
   D: readily distribute to tissues, 30% CNS penetration
   M. By liver (NON CYP450)
   E: Renal and non renal
4. T1/2: 4 to 5hr
5. Time depending killing with persistent effect AUC:MIC
6. Used to treat gram +ve infection that resistant to other antibiotics ( MRSA, VRE)
7. Equivalent to vancomycin and can be take orally

Question 3

What r the side effects of linezolid?

Answer 3

1. GI (NVD)
2. Myelosuppression ( thrombocytopenia anaemia) (after treatment >2/52, or with other myelosuppressuon drugs,) (it is reversible after discontinuation treatment)
3. MAO inhibitor (decrease Serotonim breakdown)
4. Peripheral and optic pneuropathy
5. Lactic acidosis

Question 4

Linezolid + rifamcin ==>

Answer 4

Decrease linezolid AUC 32%

Question 5

What to monitor when pt is on Linezolid?

Answer 5

1. FBC weekly for anaemia , and thrombocytopenia
   2 . BP
2. vision changes

Question 6

E.g. of macrolides:

Answer 6

1. Azithromycin
2. Erythromycin
3. Clarithromycin

Question 7

Drugs that are prtotein 50S Synthesis inhibitor:

Answer 7

1. Macrolides ( azi-, ery- clari-thromycin)
2. Linosamide ( clindamycin)
3. Oxazolidinone (linezolid)
4. Chloramphenicol

Question 8

Macrolides, potency sequency in against Streptococcus and staphylococcus

Answer 8

Clarithromycin > erythromycin >azithromycin

Question 9

Protein synthesis inhibitor + beta lactam or vancomycin

Answer 9

Have synergistic effect
against streptococcus, staphylococcus and enterococcus

Question 10

Aminoglycosides e.g.

Answer 10

1. Gentamicin (IV IM)
2. Tobramycin (IV IM)
3. Neomycin (PO OR topical)
4. Amikacin (IV)
5. Streptomycin (IM)

Question 11

Gentamicin

Answer 11

1. Is an amynoglycoside
2. 30S ribosomal inhibitor
3. Bacteriocidal effect
4. A: not absorped orally. To be givem via IM OR IV
   D: well to body fluid.
   Poorly distributed to CSF, brain, Ocular fluid, prostate, phagocytic cells, lungs and adipose tissues
   Protein binding 10%
   M: NOT metabolised
   E: unchanged in the urine via glumerular filtration
   T1/2 1.5 - 3.5hr
5. Concentration dependent, Cmax/MIC, OR AUC/MIC
   Need to do TDM

6 used for severe sepsis and pneumonia, 1st drug of choice for MRSA , VRE

Question 12

S.e. of aminoglycosides on ear

Answer 12

1. Ototoxicity
   - a.w. excessively high peak concentration in conventional dosing
   - auditory and vestibular damage (haircell damage)
   - auditory: high frequency hearing loss first
   - vestibular: affect balance, n/v, vertigo
   - maybe irriversible

Question 13

S.e of aminoglycosides on kidney:

Answer 13

1. Nephrotoxicity
   - reported upto 20%
   - due to uptake into proximal renal tubular epithelial cells
   - a saturable process
   - reversible

Risk factors for nephrotoxicity
1>. Trough conc > 2 -3 mg/L For gentamicin, tobramycin, betilmicin,
2) trough conc > 10mg/L for amikacin
3. Prolong duratiom of therapy 10 to 14days
4. Advance age
5. Used with other neprotoxicity agents (e.g. vancomycin)
6. Sepsis
7. Gentamicim or amikacim > tobramycin

Question 14

Can tetricycline treat pseudomonas infec?

Answer 14

No.

Question 15

Optitic neuropathy may cause by:

Answer 15

1. Linezolid
2. Ethambutal
3. Vericonazole