Protein Synthesis Inhibitors Flashcards by Aisha Farah

What do Protein Synthesis inhibitors target?

the ribosome that synthesizes the protein from the mRNA code

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What is the Bacterial ribosome unit?

50S and 30S

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What is the Mammalian ribosome unit?

60S and 40S

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Which are the Amninoglycosides

GANS
Gentamycin
Amikacin
Neomycin: tropical ONLY
Streptomycin

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Spectrum of Aminoglycosides

Bactericidal
Aerobic gram -ive infections: narrow
Some gram _ive infections
Myobacterial Infections
DOC: Pseudomonas Aeruginosa

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Topical admin of Aminoglycosides are for

serious sight-threatening eye infections, Otitis media, infection of nasal vestibuli
*not recommended for skin infections

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How are Aminoglycosides used for Anaerobic gram +ive infections

co-admin with Metronidazole or Clindamycin

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How are Aminoglycosides used synergistically

with Penicillins against serious infections caused by:
Satphylococci
Streptococci
Enterococcci

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How do Aminoglycosides enter the cell?

Penetrate across the outer membrane via the porins via passive diffusion
-> actively transported across bacterial cell membrane into cytoplasm

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MOA of Aminoglycosides

inhibit protein SYnthesis by:
1. prevent the formation of initiation complex
2. Polyribosomes are broken down to non-functional monosomes
3. mRNA is incorrectly read and incorrect AAs are joined to form non-functional or toxic proteins

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MOA of Streptomycin

changes the shape of the 30S r-RNA and causes mRNA to be read incorrectly

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Resistance mechanisms against Aminoglycosides

mutation of 30S ribosomal unit binding site: against Streptomycin ONLY
Inhibition of its transport into cell: change in porins
Inactivation by enzymes (Acetyl transferases, Adenyl transferases and Nucleotidyl transferases)

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Admin of Aminoglycosides

IM admin: once daily dose is preferable for incr. efficacy and decr. toxicity
NO GIVEN ORALLY

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Absorption of Aminoglycosides

rapidly and completely absorbes–> distributed in ECF and tissues
Penetration into CSF is weak

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Excretion of Aminoglycosides

mainly unaltered (70-90%) within 24 hrs in urine

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Bactericidal effect of Aminoglycosides depend on

its concentration
–> greater the conc., the higher the rate of killing

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Effect of Aminoglycosides

exert a prolong post-antibiotic effect

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Toxcity of Aminoglycosides depen on

critical plasma levels and time of exposure

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Exceptions in Aminoglycosides use

when used for synergy againt Endocarditis

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SEs of Aminoglycosides

Narrow TI toxicity
Nephrotoxic and ototoxic: therapy of >5 days, incr. doses, in elderly and renal insufficiency
Neuromuscular blockage
Electrolyte disturbance
Liver damage
Headache
Skin rash
Fever

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Aminoglycosides Narrow TI toxicity depends on

Plasma conc.
Duration of exposure
Dosages are in accordance with age, body weight and renal function

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How do Aminoglycosides cause Nephrotoxicity

they move into the proximal tubule cells vua an uptake system for Oligopeptides
*tubular cells are very sensitive and can be easily damaged

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Is the Nephrotoxicity caused by Aminoglycosides reversible

yep, generally

Which are the most Nephrotoxic Aminoglycosides

Neomycin
Gentamycin
Tobramycin

What is Ototoxicty

damage to the inner ear sensory cells of Vestibular apparatus and Organ of Corti

Is Ototoxicty caused by Aminoglycosides reversible

only partly

Vestibular damage AEs due to Aminoglycosides

vertigo Ataxia loss of balance

Which are the most Vestibulotoxic Aminoglycosides

Gentamycin Streptomycin

Cochlear damage AEs due to Aminoglycosides

deafness

Which are the most Ototoxic Aminoglycosides

Amikacin Neomycin Kanamycin

Effect of Streptomycin taken during Pregnancy

causes deafness in child

How do the Aminoglycosides cause Neuromuscular Blockage

by decr. prejunctional ACh release and decr. post synaptic sensitivity SEs: drooping of eyelid)

DIs with Aminoglycosides

General Anaesthetics: incr. neuromuscular blocking effect--> respiratory distress Neuromuscular blocking agents: Oto/Nephrotoxic agents: vancomycin, Amphotericin B Loop diuretics: incr. nehprotoxicty

Cautions and CIs in Aminoglycosides

Elderly Renal insufficency Neonates Strong Caution-CI: Pregnancy(Streptomycin) CIs: Myasthenia gravis

Effect of Macrolides at different dosages

Low: Bacteriostatic High: Bactericidal

Name a Protoype Macrolide

Erythromycin

Which are the newer Macrolides

Azithromycin Clarithromycin Roxithromycin

PK of Newer Macrolides

longer elimination T1/2=less dosing lower GIT SEs

Spectrum/Uses of Macrolides

Alternative drug for those allergic to Penicillin Respiratory infections Neonatal infections Ocular infections Genital Chlamydial infections Treatment of Community-acquired pneumonia (shows incr. resistance)

Macrolides are 2nd line agents in

Endocarditis

Uses of Newer Macrolides

Eradication of H.Pylori in PUD in penicillin allergy patients: C/A+ metronidazole+ Omeprazole 2nd line agents in Rickettsial infections

Spectrum/Uses of Erythromycin

Corynebacterium Diphtheriae infections 2nd line agent in acne

Which Macrolides are CI in Pregnant women

Erythromycin/Azithromycin *CI in syphilis for pregnant women allergic to Pencillins

MOA of Macrolides

Attach reversibly to bacterial 50S subunit--> bind to it close to the sites for Chloramphenicol and Clindamycin--> competitively inhibit binding when given together --> inhibit translocation

MOA of Erythromycin

binds to 50S and prevents movement along mRNA

Resistance mechanisms against Macrolides

1. Reduced cell membrane permeability or active efflux--> reduced entry+efflux 2. Production of Esterases that hydrlise macrolides 3. Modification of ribosomal binding site

What affects Erythromycin absorption

formulation uses Gastric acidity Food

Admin of Macrolides

Orally as Stearate salt or Esterified form(estolate: shows nest absorption not affected by gastric activity)

Admin of Erythromycin

Base and stearate: food decr. its absorption

T1/2 of Macrolides

E: 1.5-2 hrs C: 3-4 hrs A: 11-14 hrs

Metabolism and Excretion of Macrolides

M: liver, high protein binding E: bile, small unchanged amount in urine

SEs of Macrolides

GIT intolerance: abd pain, cramping, NV, diarrhea Allergic rxns: rare Hepatotoxicty: estolate admin >10 day Inhibit liver enzymes: only 2

Which Macrolides inhibit the CYP450 enzymes

Erythromycin Clarithromycin

How do Macrolides cause Hepatotoxicty

-Estolate taken >10 days cuases IRREVERSIBLE Cholestatic Jandice -Benign serum elevations of Serum Transaminase

DIs with Macrolides

1. Serum conc. of different drugs incr. (theophylline and warfarin 2. Reduced efficacy of COC

Caution/CIs with Macrolides

Liver disease Impaired biliary function CIs: porphyria (erythromycin) Heart disease (clarithromycin & Azithromycin): prolonges QT interval=arrythmias may occur