Protein Synthesis Inhibitors Flashcards
What are the protein synthesis inhibitors
Acts on 30s ribosomal subunit = Aminoglycosides, Tetracycline
Acts on 50s ribosomal subunit = Chloramphenicol , Macrolides, Clindamycin , Linezolide
What are the macrolides?
Azithromycin
Erythromycin
Clarithromycin
Roxithromycin
Tetracycline
Tetracycline
Doxycycline
Minocycline
Aminogylocsides
Acc to route of administration
A)Oral = Neomycin , Kanamycin
B)Parenteral = Gentamicin Amikacin , Streptomycin
Why are they called macrolides? Give criteria of macrolides
They are called macrolides because they contain macrocyclic large lactone ring
Criteria = they contain macrocyclic large lactone ring
They are broad spectrum antibiotic
They are bacteriostatic
They act by protein synthesis inhibition
M/A of macrolides
Azithromycin ==> binds with 50s subunit of ribosome ==> (-) translocation ==>(-) protein synthesis ==> inhibition of bacterial growth
Clinical use of Azithromycin
Acute bacterial exacerbations of chronic obstructive pulmonary disorder
Acute bacterial sinusitis
Community acquired pneumonia
Pharyngitis
Tonsillitis
Sinusitis
Uncomplicated skin and skin structure infection
Toxoplasmosis
Granuloma inguinale
Diarrhoea
Pertussis
Urthetitis cervicitis
Typhoid
Gonorrhoea
Acne vulgaris
A/E of Azithromycin
Nausea
Abdominal pain
Diarrhoea , constipation
Rash , photosensitivity
Fever
Headache
Dizziness
Compare Azithromycin and erythromycin
Azithromycin. Erythromycin
Macrolides. Macrolides
Protein synthesis inhibitor. Psi
Bacteriostatic. Bacteriostatic
Rapid absorption. Slow absorption
Long duration of action. Short
Once daily dose. 4 times daily
Large volume of distribution. Low volume of distribution
Mostly effective in enteric fever , toxoplasmosis. Mostly effective in whooping cough , diphtheria
Indication of clindamycin
Infection of skin and soft tissue
Intra-abdominal sepsis
Infection of the respiratory tract
Dental infection
Infection of genital tract
Infection of bones and joints
Cardiovascular infection (endocarditis )
Anaerobic septicaemia
Osteomyelitis and septic arthritis
Acne vulgaris
A/E of clindamycin
Nausea
Vomitting
Abdominal pain Diarrhoea
Diarrhoea
Pseudomembranous colitis
Rash
Hepatotoxicity
Urticaria
Why called aminoglycosides
They are called aminoglycosides because they contain hexose ring with amino sugar side chain by glycosidic linkages
Common properties of aminoglycosides
Irreversible inhibitors of protein synthesis
Chemically composed of a hexose ring to which various amino sugars are attached by glycosidic linkage
They are water soluble , highly polar and stable in solution
More active in alkaline pH
Must be given parenterally to achieve adequate serum concentration
They can cross placental barrier but cannot pass the blood brain barrier
They are excreted unchanged in urine
Narrow therapeutic index
They accumulate in the renal cortex and endolymph and perilymph of the inner ear and causing nephrotoxicity and ototoxicity
Don’t reach to pharmacological sanctuary = CNS , prostrate , testes , joint cavity and ovary
M/ A of aminoglycosides
Gentamicin / Amikacin ==> Enter into bacteria ( through outer membrane by passive diffusion and across cell membrane into cytoplasm by active transport )===> binds with 30s subunit of microsomal ribosome ==> inhibition of bacterial protein synthesis ===> bacteriocidal action
M/ A of aminoglycosides
Gentamicin / Amikacin ==> Enter into bacteria ( through outer membrane by passive diffusion and across cell membrane into cytoplasm by active transport )===> binds with 30s subunit of microsomal ribosome ==> inhibition of bacterial protein synthesis ===> bacteriocidal action
Clinical uses of gentamycin
Pneumonia
Lung abscess
Abdominal and pelvic abscess
Bacterial endocarditis
Septiciemia
Plague / brucellosis
Conjunctival and ear infection ( tropical use )
Preoperative bowl preparation ( orally )
Tropical uses : ear eye skin burn and wound infection
Clinical uses of streptomycin
Pneumonia
Lung abscess
Abdominal and pelvic abscess
Bacterial endocarditis
Septicemia
TB/ plaque / brucellosis
A/E of streptomycin
Nephrotoxicity
Ototoxicity ( tinnitus , vertigo , dizziness )
Hypersensitivity
Chance of drug interactions
Contraindications of aminoglycosides
Nephropathy
Neuropathy
Pregnancy
Respiratory failure
Tetracycline is
Protein synthesis inhibitor (30s)
Broad spectrum
Bacteriostatic
Classification of tetracycline
ACC TO SOURCE
NATURAL ==>chlortetracycline , oxytetracycline , tetracycline , demeclocyline
SEMISYNTHETIC ==> Doxycycline , Minocycline
ACC TO DURATION OF ACTION
SHORT ACTING ==> chlortetracycline , oxytetracycline , tetracycline
Intermediate acting => demecloclyine
Long acting ==> Doxycycline , Minocycline
Clinical indications of tetracycline
1) Rickettsial infection => Rocky Mountain spotted fever , Q fever
2) Mycoplasma pneumonia
3)Cholera
4) Chlamydial infection ( lymphogranuloma venerum , PID, Trachoma)
5)Brucellosis
6) acne
7) Malaria
8) UTI
9) CAP
A/E of tetracycline
Discolouration of skin
Growth deformity
Hepatotoxicity
Nephrotoxicity
Photosensitivity
Dizziness
Vertigo
Headache
Vaginal candiasis
Contraindications of tetracycline
Pregnancy and lactation
Children less than 8 years
Renal failure
SLE
Any hypersensitivity reaction
M/A of tetracycline
Tetracycline ===> enter into bacteria ( through outer membrane by passive diffusion and across cell membrane into cytoplasm by active transport ) ==> binds with 30s subunit of microsomal ribosome ==> inhibition of bacterial protein synthesis ===> bacteriocidal action
Advantage of long acting tetracycline
More bioavailability
Chronic use of
Less dose frequency
More patients compliance
Compare tetracycline and doxycycline
TETRACYCLINE DOZYCYCLINE
Natural. Semisynthetic
Low potent. High potent
T1/2 = 6=10 hrs. 18-24 hrs
Dosage schedule = 4 times daily. 2 times daily
Renal excretion. Faecal excretion
Can’t use in renal failure. Can
Low plasma binding drug High
Low photosensitivity. High photosensitivity
Chloramphenicol
PSI 50S
Broad spectrum
Bacteriostatic
Bacteriocidal for Hinfluenxa , N meningitis
Clinical uses of chloramphenicol
Bacterial conjunctivitis ( mostly use as an eye drop / ointment
A/E of chloramphenicol
Superinfection
Bone marrow depression
Gray baby syndrome in neonates
Hypersensitivity reaction
Contraindications of chloramphenicol
Neonates
Pregnancy
Lactating mother
Liver disease
Bleeding disorder
Why chloramphenicol is not used first choice in enteric fever
Resistant to Salmonella Typhi
Bacteriostatic in nature
Relapse occur (10%)
Doesn’t cure carrier state
Short plasma half life so more dose needed
More toxic ( due to large dose/ so chance of bone marrow depression , aplastic anemia , typhoid shock syndrome )
Regular blood ( reticulocyte ) count needed for detecting BMD
