Inhibitors of protein synthesis Flashcards
List the drug groups part of inhibitors of protein synthesis
Tetracyclines
Aminoglycosides
Macrolides
Lincomycin
Streptogramins
Amphenicols
Which ribosomal unit does Aminoglycosides and tetracyclines bind to?
30S
Describe Aminoglycosides:
- examples
- Mechanism of action
- Pharmacokinetics
- Clinical uses
- Adverse effects
- Resistance
Gentamicin, Neomycin, Streptomycin
- Bactericidal
- Binds to the 30S ribosome
- Interferes with the initiation complex of peptide formation
- Introduces misreading of the code on the mRNA template= abnormal proteins and errors in translation
- Breaks up polysomes into non-functional monosomes
- Water soluble, poorly absorbed from the GIT, IV or IM
- Concentration dependent, single large dose is preferred
- significant post- antibiotic effect
- Unchanged by glomerular filtration-> high conc in urine
- Accumulation in renal cortex (need for monitoring)
- Concentration > 2ml = toxicity
- Combined with penicillins
- Gram -ve and +Ve
- Enteric bacteria
RAPES TPBC - Septicemia, renal, pelvic and abdominal sepsis, endocarditis, TB, plaque, brucellosis
Gentamicin is the drug of choice - Neomycin topically for conjunctivitis and ear infections
Adverse reactions: ONNO
Ototoxicity: hearing loss, vestibular damage, tinnitis–> Rx last more than 5 days
Nephrotoxicity Rx lasting more than 5 days
Neuromuscular blockage- respiratory paralysis
Other: Rash, bleeding, bone marrow suppression
- Production of transferase enzyme: adenylation, acetylation and phosphorylation
- reduced permeability/ transport
- Deletion or alteration of receptor protein on 30 S subunit
- Anaerobic microorganisms
Discuss Tetracylines:
- Examples
- MOA
- Antimicrobial activity
- Clinical uses
- Adverse reactions
- Resistance
- Tetracycline, oxytetracycline, chlorotetracycline
-Bacteriostatic
- Binds to 30 S reversibly
- prevents the elongation of the peptide chain by preventing the binding of a-TRNA to the mRNA ribosomal complex
- Broad spectrum
- Active against nearly all gram - and + bacteria
- Mycoplasma pneumonia
- Chlamidia
- Richetsia
- Spirochets
- Protozoa e.g. amoeba
- docycyline for malaria
- Minor skin infections
-MRSA strains - Helibactor Pylori ulcers
Very DY MG
- Vitamin B complex deficiency ** supplementation needed
- Deposition in bones and teeth- Enamel dysplasia, chelation with calcium–> contraindicated in children and pregnancy
- Yellow or brown teeth syndrome
- Modification of normal GIT flora
- GIT : nausea, heartburn (direct irritation)
- Photosensitization
- Dizziness, headache, visual disturbances
- Hepatic and kidney damage
- Drug interations (reduced absorption from milk and antiacids)
- Enzymatic inactivation
- Ribosome protection
- Imparied influx, increased efflux
Explain Macrolides
- Examples
- MOA
- Antibacterial activity
- Clinical uses
- Adverse effects
- What can lower the adverse effects?
Erythromycin
- Binds to the 50S ribosomal subunit
- Inhibits peptide chain elongation
- peptidyl tRNA dissociates from the ribosome
- Inhibits the formation of the 50 S ribosomal subunit
- Interferes with aminoacyl translocation reaction
- Similar to penicillins, pts allergic to penicillins
- Pneunomocci, streptococci, staphylococci (mostly grm +)
Some gram -:
- Mycoplasma, legonella, chalmidia, gonorhea
- Alternative to patients allergic to penicillin
- Respiratory, skin and genital infections
- Prophylaxis against endocarditis during dental procedures
GIC
Cholestatic jaundice
Inhibits cytochrome P450 (interaction with warfarin and carbamezipene)
GIT: anorexia, vomiting diarrhoea **prokinetic agent
Stearate and succinate salts
Explain the antibacterial activity of azithromycin
Explain the contraindiactions
Similar to clarithromycin
Gondi, Lepare, Pylori
Cardiac issues
Explain the antimicrobial activity of clarithromycin
Identical to erythromycin
Lipare, Gondi, pylori
Less GI intolerance
MAC
Explain the resistance of macrolides
reduced permeability
Efflux pump
Production of esterase which hydrolyse macrolides
Modification of ribosomal binding site
Explain
- the structure of clindamycin
- MOA
- Antibacterial activity
- Clinical uses
- Adverse effects
- Lincomycin
- Similar to macrolides
Interferes with the initiation complex and aminoacyl translocation - Penicillin resistant staph
- Bacteriodes fragialis
BDSM
Bone and joint infections
Dental infections
Skin and soft tissue infection caused by strep or staph, serious abdominal sepsis
MRSA
- Alternative to penicilins and macrolides for orofacial infections
Diahorhea
pseudomembranous collitis
Discuss chloroamphenicol:
- Antimicrobial activity
- MOA
- Adverse effects
Salmaonella- typhoid fever
H influenza
CNS infections -meninococcal and pneumococcal
Eye infections
Binds reversibly to 50S, interferes with incorporation of newly formed peptides, blocks peptidyl transferase, inhibits mitochondiral protein synthesis
Bacteriostatic
Bone marrow depression
Gray baby syndrome
inhibits liver enzymes
Clinical uses of streptogramins
MRSA
Multidrug resistant streptococci
