09 Antibacterial- protein synthesis inhibitors Flashcards
Protein Synthesis 30s subunit Inhibitors
Protein Synthesis 30s subunit Inhibitors
- *A**minoglycosides (given IM or IV)
- *T**etracyclines
remember AT
Protein Synthesis 50s subunit Inhibitors
Protein Synthesis 50s subunit Inhibitors
- *C**hloramphenicol
- *E**rythromycin (Macrolides)
- *L**inezolid
- *L**incosamides (Clindamycin)
- *S**treptogramin
(CELLS)
what are Aminoglycosides? examples of drugs.
Aminoglycosides (bactericidal)
-Aminoglycosides are bactericidal antibiotics that bind to the 30S subunit of ribosome and inhibit bacterial protein synthesis.
Gentamicin***
Neomycin***
Amikacin***
Tobramycin
Streptomycin***
Kanamycin
Netilmicin
“GNATS KaNot kill anaerobes”
Aminoglycosides mode of action
MOA:
- The aminoglycosides are bactericidal antibiotics that bind to the 30S subunit of ribosome and inhibit bacterial protein synthesis.
- **Inhibit initiation complex* **of peptide formation and also
-
Induce misreading of mRNA*
- **They cause a breakup of polysomes into nonfunctional monosomes. **
- Require oxygen for uptake → inactive against anaerobes
**NOTE: remember to add an aminoglycoside to a b-lactam antibiotic when treating serious P. aeruginosa infection. **
Aminoglycosides mode of administration
Aminoglycosides mode of administration:
They are poorly absorbed orally and must be used parenterally** (IM or IV) for systemic infection.
Mechanism of Resistance to Aminoglycosides
(not really stressed)
Mechanism of Resistance to Aminoglycosides
- Bacterial transferase enzymes inactivate the drug by:
- Phosporylation
- Adenylation
- Acetylation
- Impaired entry of aminoglycoside into the cell.
- The microorganism produces a transferase enzyme or enzymes that inactivate the aminoglycoside
- The receptor protein on the 30S ribosomal subunit may be deleted or altered as a result of a mutation.
- Streptococci and enterococci develop resistanance to aminoglycosides by decreasing penetration)
- Netilmycin and amikacin are resistant to inactivation by bacterial enzymes
Spectrum of aminoglycosides
Spectrum of aminoglycosides
All aminoglycosides have
- good activity against gram-negative aerobic bacilli*****
- Used for severe gram negative infections
- Synergistic action with beta lactam antibiotics
- Lack activity against anaerobes.
Neomycin:
- For bowel surgery**
Streptomycin:
- has a more limited* antibiotic spectrum.
- Used for tuberculosis, plague, brucellosis
Aminoglycosides side effects
Aminoglycosides side effects
Aminoglycosides are toxic to kidneys (nephrotoxic)
- Must measure drug level , blood urea nitrogen and creatinine to avoid toxicity
Toxic to auditory and vestibular
- portions of the 8th cranial nerve (Ototoxicity)
NOTE:
Cochlear damage: Results in hearing loss. High frequency sound is affected first then low frequency.
Vestibular damage: Headache appears first followed by nausea, vomiting, dizziness, nystagmus (fast, uncontrollable movements of the eyes), vertigo and ataxia.
what is Streptomycin used for? What group of drugs does it belong to? side effects?
Streptomycin
Steptomycin is a Aminoglycosides
Uses: Tuberculosis, plague, brucellosis
Side effects: Ototoxic (CN8 damage) and nephrotoxic
Gentamicin and tobramycin
Gentamicin and tobramycin
They are Aminoglycosides
Gentamicin and tobramycin are effective against many gram negative infections including pseudomonas
They are the Most widely used aminoglycoside****
Side effect: Nephrotoxic
Amikacin
Amikacin
Amikacin is a aminoglycoside
Amikacin is the** Broadest spectrum ***** of aminoglycoside.
Uses of Amikacin:
Amikacins are effective against Many gram negative infection including pseudomonas
Effective against some of the bacteria that are resistant to gentamicin
Side effect: Cochlear toxic agents
Neomycin. what kind of drug is that, what is it used for. How is it administered?
Neomycin
Neomycin is a aminoglycoside
Neomycin is used for Preoperative bowel preparation and Hepatic coma
Used orally since it’s not absorbed
Note: After oral administration, the intestinal flora is suppressed or modified and the drug is excreted in the feces.
what are tetracyclines? list the drugs.
Tetracyclines
Group of antibiotics with bacteriostatic activity.
They work by Inhibiting protein synthesis by binding to the 30S subunit- Blocking the aminoacyl transfer RNA (tRNA) from entering*** the acceptor site on the mRNA-ribosome complex. This prevents addition of amino acids to the growing peptide .
Classification
- Tetracycline
-
Doxycycline****
- is eliminated in stool
- Can be used for patients with renal impairment
- Minocycline
-
Demeclocycline*** (effective against siADH)
- Makes renal tubules refractory to the action of ADH
- Used in the management of ADH secreting tumors
- Small cell carcinoma of lung***
Tetracyclines
Spectrum of Action
Tetracyclines (acts on 30s subunits)
Spectrum of Action
Broad spectrum antibiotics
Active against
- Gram positive and Gram negative bacteria including anaerobes.
Active against
- atypical bacteria such as rickettsiae, chlamydiae, mycoplasma.
Also active against some
- protozoa.
Tetracycline is drug of choice (DOC) in infections with
- Mycoplasma pneumoniae, chlamydia, rickettsia, and some spirochetes.
Primary uses of tetracyclines
Primary uses of tetracyclines (acts on 30s subunits)
Primary use: Rx of infections caused by:
- Mycoplasma pneumoniae* (pneumonia),
- Chlamydia*
- Rickettsia *** (Rocky moountain spotted fever)
- Vibrio** (cholera)
- Borrellia burgorferi (Lyme disease. a spirochete infection)***
Secondary use of tetracyclines
Secondary use of tetracyclines (acts on 30s subunits)
Secondary use: alternative drug to penicillin in syphilis***
What is Demeclocycline? *** what is it used for?
Demeclocycline is a tetracyclin drug (that act on 30s subunit) that makes renal tubules refractory to the action of ADH
Demeclocycline is used in the management of ADH secreting tumors
- Small cell carcinoma of lung**
Tetracyclines
Side effects
-Photosensitivity**
- Enhanced sensitivity to UV rays (skin)
-Brown discoloration of teeth**
- In fetuses and young children
- readily bind to calcium deposited in the newly formed bone or teeth.
-Skeletal deformity and growth retardation:**
- Due to its deposition in the bone.
-Contraindicated (cannot be used anymore)** in pregnant women and children below 14 yrs of age
-GI distress
Mechanism of resistance against tetracyclin
Mechanism of resistance against tetracyclin
Development of efflux pump** (encoded by plasmids)
- –Bacteria pump out the drug
Chloramphenicol
Chloramphenicol (acts on 50s subunit)
- *-Broad spectrum*** antibiotic (bacteriostatic)
- Inhibits protein synthesis by binding to 50S ribosomal subunit and
-
Blocking the action of peptidyl transferase**
- This prevents synthesis of new peptide bonds
-Side effects:
- Dose dependent bone marrow suppression**
- Aplastic anemia** (not dose dependent)
- If used in pregnancy → Causes Grey baby syndrome**.
- Infants lack glucuronic acid conjugation mechanism for the degradation of chloramphenicol
- vomiting, gray color(cyanosis), shock.
Chloramphenicol uses and side effects
Chloramphenicol uses and side effects
Clinically useful activity
- Meningitis: H. Influenza, S.pneumoniae, N.meningitidis
- Rocky Mountain Spotted fever (Rickttsia rickettsii)
side effect
- Bone marrow toxicity limits use to only severe infections
what are the Macrolides drug? what are their mechanism of action.
Macrolides (act on 50s subunit)
- *-Erythromycin***
- New ones include:
- Azithromycin*
- Clarithromycin*
-Bind to the 50S subunit
- Protein synthesis is inhibited because
- translocation is blocked (“macroslides”)
Erythromycin uses and side effect
Erythromycin (act on 50s subunit)
Erythromycin is a macrolide that acts on the 50s (subunit)
Uses:
- Pneumonia caused by Mycoplasma and Leoginella.
- Infections by gram positive cocci (Streptococci) in penicillin allergic patients
side effects:
- Generally well tolerated but some diarrhea
what is Azithromycin? what are it’s uses
what is Azithromycin? what are it’s uses
- Same as erythromycin
- Pneumonia caused by Mycoplasma and Leoginella.
- Infections by gram positive cocci (Streptococci) in penicillin allergic patients
- …..plus more activity against Chlamydia, Mycobacterium avium complex (MAC) and Toxoplasma
- longer half life
what are Clarithromycin? what are its uses?
What are Clarithromycin (macrolides that act on 50s subunits)?
Clarithromycin is used clinically against
- URT (upper respiratory tract) and lower respiratory tract infections. Atypical pneumonia
- H.Pylori treatment in recurrent peptic ulcer.
- prophylaxis (action taken to prevent disease) of Mycobacterium avium complex (MAC)
- longer half-life
what is Clindamycin? what is its uses, mode of action and mechanism of resistance?
Clindamycin (a lincoamides)
- Clindamycin mode of action is
- Blocks peptide transfer (translocation) at 50s ribosomal unit**.
- Uses:
- Infections caused by anaerobic bacteria*****
- Gram positive anaerobe: Clostridium perfringens
- Gram negative anaerobe: Bacteroides fragilis
- For prophylaxis (treament to prevent disease) of infective endocarditis in patients with valve diseases
- Active against Pneumocystis carinii and Toxoplasma gondii
- Infections caused by anaerobic bacteria*****
- Mechanism of resistance:
- methylation of binding site** on the 50S ribosomal subunit
NOTE: DO NOT CONFUSE WITH CLARITHROMYCIN
Clindamycin’s side effect
Clindamycin ( is a Lincosamide) side effect
- Most important side effect:
- Suppression of normal GI flora
- Overgrowth of C. difficle
- Superinfection results in development of Pseudomembranous colitis (because of C.difficile)****
- Watery diarrhea, abdominal pain etc.
- Rx: Vancomycin / Metronidazole
- Suppression of normal GI flora
**Note: **symptoms includes:
- GI irritation
- Skin rashes
- Neutropenia
- Superinfection (pseudomembranous colitis due to C. difficile)
What is Linezolid? What is the Mode of action, uses and side effects?
Linezolid ( part of the Oxazolidinone group of drugs)
- MOA:
- Binds to the 23S ribosomal RNA in the 50S subunit**
- Inhibits protein synthesis
- Useful for the treatment of:
- Vancomycin resistant enterococci (VRE)
- Methicillin resistant S.aureus (MRSA) and S.epidermidis (MRSE)
- Penicillin resistant pneumococci
- Side effects:
- thrombocytopenia and neutropenia
- especially in immunocompromised patients
- thrombocytopenia and neutropenia
Streptogramins include what drug? what it is use and side effect?
Streptogramins (ex. Quinipristin-dalfopristin combination)
Streptogramins are effective in the treatment of vancomycin-resistant Staphylococcus aureus (VRSA) and vancomycin-resistant Enterococcus (VRE)
Quinipristin-dalfopristin combination
- Acts by inhibiting the tRNA synthetase*
- Clinical uses:
- MRSA (Methicillin resistant Staph.aureus)
- VRSA & VRE
- Side effects:
- Arthralgia, myalgias
