PROTEIN SYNTHESIS INHIBITORS Flashcards
Inhibitors that selectively inhibit bacterial protein synthesis
Protein Synthesis Inhibitors
Total ribosomes of Bacteria
70S consisting
* 50S Large Subunit
* 30S Small Subunit
Differences found between bacterial and mammalian protein synthesis
- Ribosomal subunits
- Chemical composition
- Functional specificities of component nucleic acids and proteins
Bactericidal protein inhibitors
- Oxazolidinones
- Pleuromutilins
TIP: OP = “Out of Place ang Oxazolidinones and Pleuromutilins”
Broad Spectrum Protein Synthesis Inhibitors
- Chloramphenicol
- Tetracyclines
Moderate Spectrum
- Macrolides
- Ketolides
Narrow Spectrum
- Lincosamides
- Streptogramins
- Linezolid
T/F
Chloramphenicol has equal bioavailability for oral and IV/IM
True
MOA of Chloramphenicol
Binds to the 50S subunit of bacterial ribosome
Chloramphenicol is bactericial for what infections
- H. influenzae
- N. meningitis
- Bacteroides
T/F
Resistance of Chloramphenicol is Plasmid-Mediated
True
Enzyme that inactivates chloramphenicol
Chloramphenicol Acetyltransferases
Clinical Use of Chloramphenicol
- Ricketsial Infections :Typhus
& Rocky Mountain Spotted Fever - Bacterial Meningitis
T/F
Chloramphenicol can be used as an alternative for meningitis for patient who have major hypersensitivity to penicillin
True
T/F
Chloramphenicol can only cross the placenta and not the blood-brain barrier
False
Chloramphenicol readily cross the placental and blood-brain barrier
Chlorampheniucol is inactivated by ____ acid
a. Carbonic Acid
b. Acetic Acid
c. Glucoronic Acid
d. Citric Acid
Glucoronic Acid
Excretion of Chloramphenicol
Eliminated by the Urine and small amount is excreted into bile and feces
Notable toxicities of Chloramphenicol
- Inhibition of Red Cell Matiration
- Aplastic Anemia
- Gray Baby Syndrome
Toxicity of Chloramphenicol due to lack of effective glucoronic acid conjucation for the degradation and detoxification
Gray Baby Syndrome
Chloramphenicol prolongs the effect of these drugs
PHEN TO - CH WARS
- Phenytoin
- Tolbutamide
- Chlorpropamide
- Warfarin
MOA of Tetracyclines
Binds reversibly to the 30S subunit of the bacterial ribosome
Prevents new peptide bonds
a. Tetracycline
b. Chloramphenicol
b. Chloramphenicol
Prevents new amino acids
a. Tetracycline
b. Chloramphenicol
a. Tetracycline
Antimicrobial Activity of Tetracycline
- Rickettsiae
- Chlamydiae
- Mycoplasma
Primary Use of Tetracyclines
- Mycoplasma Pneumoniae
- Chlamydiae
- Rickettsiae
- Borrelia sp.
- Vibrios
- Some Spirochetes
- Anaplasma phagocytophilum
- Ehrlichia
Secondary Use of Tetracyline
- CAP
- Syphilis
- Chronic Bronchitis
- Leptospirosis
- Acne
Clinical Use: GI ulcers caused by H. pylori
a. Doxycycline
b. Tetracycline
c. Minocycline
d. Demeclocycline
b. Tetracycline
Clinical Use: Lyme Disease
a. Doxycycline
b. Tetracycline
c. Minocycline
d. Demeclocycline
a. Doxycycline
Clincal Use: Malaria Prophylaxis
a. Doxycycline
b. Tetracycline
c. Minocycline
d. Demeclocycline
a. Doxycycline
Clincal Use: Amoebiasis
a. Doxycycline
b. Tetracycline
c. Minocycline
d. Demeclocycline
a. Doxycycline
Clinical Use: Meningococcal Carrier State b
a. Doxycycline
b. Tetracycline
c. Minocycline
d. Demeclocycline
c. Minocycline
Clinical Use: ADH-secreting tumors
a. Doxycycline
b. Tetracycline
c. Minocycline
d. Demeclocycline
d. Demeclocycline
Clinical Use: Inhibit renal actions from ADH
a. Doxycycline
b. Tetracycline
c. Minocycline
d. Demeclocycline
d. Demeclocycline
Clincal Use: Coagulase Negative Staphylococus
TIGECYCLINE ERAVACYCLINE OMADACYCLINE
Clinical Use: MRSA & VRE
TIGECYCLINE ERAVACYCLINE OMADACYCLINE
Clinical Use
* Streptococci
* GRAM (+) RODS
* Enterobacteriaceae
* Acinetobacter
* Rickettsiae
* Chlamydiae
* Legionella pneumophila
TIGECYCLINE ERAVACYCLINE OMADACYCLINE
Clinical Use: Rapidly Growing Mycobacteria –> Tuberculosis
TIGECYCLINE ERAVACYCLINE OMADACYCLINE
60 - 70% Bioavailability
a. Tetracycline & Demeclocycline
b. Doxycycline & Minocycline
a. Tetracycline & Demeclocycline
95 - 100% Bioavailability
b. Doxycycline & Minocycline
T/F Absoprtion of Tetracyclines occurs mainly in the Colon
False
Upper Small Intestine
Tetracyclines should not be given to patients who are:
- Drinking multivitamins
- Milk
T/F
Tetracyclines cannot cross the BBB therefore cannot be used for CNS infections
True
Excretion of most Tetracyclines
Bile & Urine
Excretion of Tetracycline
Feces
Tetracycline eliminated by nonrenal mechanisms
Doxycycline & Tigecycline
Short Acting Tetracycline
a. Demecycline
b. Tetracycline
c. Doxycycline & Minocycline
b. Tetracycline
TT mo short eyyyyyy
Tetracyclines with long half-life
- Tigecycline (IV)
- Eravacycline (IV)
- Omadacycline (Oral & IV)
T/F
Broad-spectrum antibiotics can usually cause bacterial infections (e.g., candidiasis and C. difficile infections) by disturbing normal gut flora due to their wide range of effectiveness
True
Toxicity caused by patient taking outdated tetracyclines
Fanconi Syndrome
Tetracyclines causes what toxicity to younger children
- Tooth enamel dysplasia
- Irregularities in bone growyth
- Crown deformation
In tetracyclines, Hepatic toxicity is usually seen in
- High doses
- Pregnant patients
Toxicity caused by combination of Tetracycline + Diuretic
Nephrotoxicity
Photosensitivity is a toxicity of what tetracycline
a. Doxycyline
b. Democlocycline
c. Minocycline
d. Tigecycline
b. Democlocycline
Vestibular toxicity: dizziness & vertigo is caused by what tetracycline
a. Doxycycline
b. Minocycyline
c. Both a & B
d. Neither
c. Both a & B
Contains macrocyclic lactone ring with attached rings
Macrolides
Prototype drug of macrolides
Erythromycine
MOA of Macrolides
Inhibition of protein synthesis occurs via binding to the 50S subunit of bacterial ribosomes.
Well-known adverse effect of macrolides
Torsades de pointes Arrhythmia
Absoprtion of this Macrolide is impeded by food
a. Erythromycin
b. Azithromycin
c. Clarithromycin
b. Azithromycin
Metabolism of Macrolides
Hepatic
half-life: 2 hours
has the Shortest half-life
a. Erythromycin
b. Azithromycin
c. Clarithromycin
a. Erythromycin
half-life: 6 hours
a. Erythromycin
b. Azithromycin
c. Clarithromycin
b. Azithromycin
half-life: 2-4 days
a. Erythromycin
b. Azithromycin
c. Clarithromycin
b. Azithromycin
Erythromycine is resisted by what enzyme
Enterobacteriaceae - Esterases
T/F
Erythromycin is also resisted by modification of ribosomal binding site
True
T/F
Cross-resistance occurs between erythromycin and other macrolides
True
Excretion of Eyrthromycine is mainly in the ____
a. Bile
b. Hepatic
a. Bile
T/F
Erythromycine is taken up by intracellular organism and is effective against polymorphnuclear leukocytes and macrophases
False
Taken up by polymorphonuclear leukocytes and macrophages; o Effective against organisms that are intracellular
Clinical Use
* Corynebacterial & Chalmydial infection
* M. pneumoniae & L. pneumophilia
* Staphylococci & Streptococci
a. Erythromycin
b. Azithromycin
c. Clarithromycin
a. Erythromycin
Drug interaction of Eyrthromycin and Clarithromycin
- Theophylline
- Warfarin
- Cyclosporine
- Methylprednisolone
- Digoxin
Notable adverse reaction of Erythromycin
Acute Cholestatic Hepatitis
Antimicrobial activity: Tuberculosius
a. Erythromycin
b. Azithromycin
c. Clarithromycin
c. Clarithromycin
Antimicrobial activity: Leprosy
a. Erythromycin
b. Azithromycin
c. Clarithromycin
c. Clarithromycin
Antimicrobial activity: T. gondii
a. Erythromycin
b. Azithromycin
c. Clarithromycin
c. Clarithromycin
Antimicrobial activity: H. influenzae
a. Erythromycin
b. Azithromycin
c. Clarithromycin
c. Clarithromycin
Metabolized in the liver and partially eliminated in the urine
a. Erythromycin
b. Azithromycin
c. Clarithromycin
c. Clarithromycin
Antimicrobial activity: M. avium complex
a. Erythromycin
b. Azithromycin
c. Clarithromycin
b. Azithromycin
Penetrates into most tissues and phagocytic cells extremely well and exceeding serum concentrations is by 10 - 100 fold
a. Erythromycin
b. Azithromycin
c. Clarithromycin
b. Azithromycin
Rapidly absorbed and well tolerated orally
a. Erythromycin
b. Azithromycin
c. Clarithromycin
b. Azithromycin
Chlorine-substituted derivative of lincomycin
Clindamycin
Antimicrobial activity of Clindamycin
- Streptococci
- Staphylococci
- Pneumococci
- Bacteroides
Metabolism of clindamycin
Hepatic
Half-life of Clindamycin
6 - 8 hrs
Clinical Use of Clindamycin
- Bacteroides
- Fusobacterium
- Prevotella
- MRSA
Toxic Shock Syndrome is treated with
Clindamycin and Penicillin G
Penetrating wounds of the abdomen and gut is treated with
Clindamycine combined with aminoglycoside & cephalosphorin
Treatment for pneumonia in AIDS patient
Primaquine
Treatment for AIDS-related toxoplasmosis
Pyrimethamine
Toxicities caused by Clindamycin
- Neutropenia
- Pseudomembranous colitis
Steptogramins is a combination of
- 70%: Dalfopristin (Streptogramin A)
- 30%: Quinupristin (Streptogramin B)
Streptogramins are bactericidal except for
E. faecium
Antimicrobial activity of Streptogramins
- Gram (+) cocci
- Multidrug-resistant strains of streptococci
- Penicillin-resistant strains of S. pneumoniae
- Methicillin-susceptible and resistant trains of staphylococci (MRSA)
- o E. faecium
Resistance of Streptogramins
- Modificartion of the Quinupristin binding site
- Enzymatic inactivation of Dalfopristin
Streptogramins is excreated mainly by
FECES
Clinical Use of Streptogramins
- Staphylococci (MRSA)
- Vancomycin-resistant sterains of E. faecium (VRSE)
MOA is by binding to 23S ribosomal rna of the 50S ribosomal subunit
Linezolud
Notable adverse effect of Streptogramins
Arthralgia-Myalgia sYNDROME
Half-life of Linezolid
4 - 6 hrs
T/F
Linezolid has 91% bioavailability
False
100% bioavailability
Clinical Use of Linezolid
- Vancomycine-resistant E. faecium infection
- HCAP
- CAP
- Skin and Soft tissue infections
Off-label use of Linezolid
- MDR-TB: Multi-drug resistant TB
- Nocardia Infections
Adverse Effects of Linezolid
- Thrombocytopenia
- Anemia
- Neutropenia
- Optic and Peripheral neuropathy
- Lactic Acidosis
- Serotonin syndrome
Active moiety of the prodrug tedizolid phosphate
tedizolid
Antimicrobial activity of Tedizolid
- MRSA
- VRE
- Streptococci
- Gram (+) anaerobes
T/F
Bioavailability of Teduzolid is 100%
Fallse
Bioavailability of Teduzolid is 91%
Clinical Use of Tidezolid
Skin and Soft tissue infection
Adverse Effect of Tedizolid
- Bone Marrow suppression
- Serotonergic toxicity
MOA of Lefamulin
Binding the 50S ribosome and inhibits bacterial protein synthesis
Clinical Use of Lefamulin
CAP
Adverse Effects of Lefamulin
● Infusion-site reactions
● GI disturbances
● Congenital malformations