Protein Synthesis Inhibitors Flashcards
What is the classification of Gentamicin and Amikacin?
Aminoglycosides
What is the mechanism of action of Aminoglycosides?
Inhibits bacterial protein synthesis by binding strongly
to 30S-subunit, concentration-dependent killing
What are the therapeutic indications of Aminoglycosides? (3)
- Life-threatening aerobic Gram negative infections
- Limited Gram positive action
- Pseudomonas aeruginosa
What are aminoglycosides used in conjunction with and why?
- used in combinations for severe infections
- Penicillin: staphylococci, streptococci,
enterococci - metronidazole / clindamycin: anaerobic infections
What is the recommended dosage of Aminoglycosides and why?
Single daily doses, due to prolonged post-antibiotic effect
When are aminoglycosides not given in a single daily dose?
In children, critically ill patients and when used with penicillin
What is considered to be the standard aminoglycoside in many centres?
Gentamicin
How is gentamicin administered?
IM
Describe the distribution of gentamicin
rapidly distributed in the extracellular fluid and tissue
What is the half-life of gentamicin and what increases this?
2-3 hours, but increases during renal insufficiency or in neonates
What is the effect of gentamicin on the CNS?
Minimal effect, crossing into BBB is poor
How is gentamicin excreted?
eliminated unchanged by glomerular filtration within 24 hours
What are the adverse effects of gentamicin? (9)
- Nephrotoxicity
- Ototoxicity
- Neuromuscular blockade, headache, tremor, electrolyte disturbances, hepatic damage, rashes and fever
What is the classification of Doxycycline?
Tetracyclines
What is the mechanism of action of Tetracyclines?
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.
What is the spectrum of activity of Tetracyclines?
broad
What are the therapeutic indications of Tetracyclines? (6)
- G+, G-, anaerobes
- Rickettsia, Chlamydia, Vibrio cholerae, Mycoplasmas and some protozoa
- Leptospirosis, gas-gangrene, tetanus (Oxytetracycline)
- Acne (Doxycycline and minocycline)
- Malaria
- Prophylaxis
How do Tetracyclines mainly differ?
Their GIT absorption
Describe the absorption of newer generation Tetracyclines?
lipid soluble and are completely absorbed even in the presence of food
What inactivates Tetracyclines?
milk and antacids
What are the adverse effects of Tetracyclines? (6)
- 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.
What are the contraindications of Tetracyclines?
children under 8
What is the classification of Erythromycin and Azithromycin?
Macrolides
What is the mechanism of action of Macrolides?
Bind to the 50S bacterial ribosomal subunit and inhibit protein synthesis by having an effect on translocation
What is the spectrum of activity of Macrolides?
Similar to Penicillin G
What are the therapeutic indications of Macrolides? (5)
- Legionnaire’s disease
- whooping cough
- Mycoplasma pneumoniae
- Chlamydia
- Alternative in penicillin-allergic patients
How is Erythromycin administered? (and why)
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.
What are the 2 oral forms of Erythromycin and which one has better absorption?
- stearate salt or the ester (estolate) forms
- estolate has the best absorption
Describe the distribution of Ethyromycin
Extensively distributed into most tissues, including prostate fluid, crosses placenta but not BBB
What is the half-life of Ethyromycin?
1.5-2 hours
Describe the protein binding of Ethyromycin?
protein-binding is high
How is Ethyromycin metabolised and excreted?
Partially metabolized in the liver and excreted in bile, 2-5% is excreted unchanged in the urine.
What are the adverse effects of Ethyromycin? (3)
- 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.
What is the classification of Clindamycin?
Lincosamide
What is the mechanism of action of Clindamycin?
Inhibits protein synthesis by binding to 50S ribosomal
subunits interfering with the formation of initiation complexes and with the aminoacyl translocation reaction
What are the therapeutic indications of Clindamycin? (2)
- gram-positive infections in patients allergic to penicillins
- sensitive staphylococcal and anaerobe infections such as Bacteroides species
Describe the distribution of Clindamycin
widely distributed in most body tissues and fluids except the cerebrospinal fluid
Describe the absorption of Clindamycin
well absorbed from the GIT
What is the half-life of Clindamycin?
2-3 hours
What % of Clindamycin binds to plasma proteins?
> 90%
How is Clindamycin metabolised and excreted?
hepatic metabolism and excretion in the bile
What are the adverse effects of Clindamycin? (2)
- GIT problems: diarrhoea, nausea and vomiting
- Skin rashes
What is the classification of Chloramphenicol?
Amphenicol
What is the mechanism of action of Chloramphenicol?
Binds reversibly to the 50S subunit of the bacterial ribosome and inhibits the peptidyl transferase-enzyme during protein synthesis
What is the spectrum of activity of Chloramphenicol?
broad
What are the therapeutic indications of Chloramphenicol?(5)
- 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
How is Chloramphenicol succinate administered?
parenterally
How does Chloramphenicol succinate yield free chloramphenicol?
Hydrolysis (water-soluble)
How is Chloramphenicol succinate administered?
orally
Describe the absorption of Chloramphenicol
rapidly absorbed and is about 80% bioavailable
Describe the distribution of Chloramphenicol
widely distributed to virtually all tissues and body fluids, including the central nervous system and cerebrospinal fluid
What % of Chloramphenicol is bound to protein?
30-50%
What is the half-life of Chloramphenicol?
1.5-4 hours
How is Chloramphenicol metabolised and excreted?
metabolized by the liver and conjugated with glucuronic acid and eliminated in the urine
What are the adverse effects of Chloramphenicol? (6)
- severe, idiosyncratic depression of bone marrow
- fatal aplastic anaemia
- “grey baby syndrome”
- GIT effects
- Optic or peripheral neuritis
- Jarisch-Herxheimer-like reactions
