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Inhibitors of Bacterial Protein Synthesis Flashcards

1
Q

Aminoglycosides

A 
Amikacin
Gentamicin
Neomycin
Streptomycin
Tobramycin
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2
Q

Aminoglycosides - Adverse effects

A

Most serious: Nephrotoxicity and Ototoxicity (vestibular and cochlear)

Vestibular toxicity manifestations: Dizziness, impaired vision, nystagmus, vertigo, nausea, vomiting, and problems with postural balance and walking

Cochlear toxicity manifestations: Tinnitus and hearing impairment and can lead to irreversible deafness

Drug-induced renal failure (acute tubular necrosis, when they accumulate in proximal tubule cells)

Glomerular toxicity

High dose: respiratory paralysis (cuarare-like effect with neuromuscular blockade). Reversible by calcium gluconate or neostigmine.

Hypersensitivity (infrequently)

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3
Q

Aminoglycosides tendency to cause cochlear or vestibular toxicity

A

Amikacin produces more cochlear toxicity (deafness),

Gentamicin and streptomycin cause more vestibular toxicity.

Tobramycin appears to cause similar degrees of cochlear and vestibular toxicity.

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4
Q

Most nephrotoxic aminoglycosides

A

Neomycin, Tobramycin and Gentamicin

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5
Q

Aminoglycosides - MoA

A

Bind 30S ribosomal subunit, interfering with initiation of protein synthesis and cause misreading of the genetic code

Breakup of polysomes into nonfunctional monosomes

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6
Q

Amikacin - Clinical use

A

Strains of Proteus, Pseudomonas, Enterobacter, and Serratia

Joint infections 
Intra-abdominal infections 
Meningitis
Pneumonia
Sepsis
Urinary tract infections

Strains of multidrug-resistant Mycobacterium tuberculosis, including streptomycin-resistant strains

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7
Q

Gentamicin - Clinical use

A

Mainly in severe infections (eg, sepsis and pneumonia) caused by gram-negative bacteria that are likely to be resistant to other drugs

E. coli, Klebsiella, Enterobacteriae
P. aeruginosa
Serratia marcescens
Proteus
Acinetobacter

In combination with a penicillin to treat serious enterococcal, staphylococcal, or viridans group streptococcal infections such as endocarditis

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8
Q

Tobramycin - Clinical use

A

The most active aminoglycoside against many strains of Pseudomonas aeruginosa

Enterococcus faecalis

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9
Q

Streptomycin - Clinical use

A

Tuberculosis and infections caused by Yersinia pestis (plague) and Francisella tularensis (tularemia)

Sometimes brucellosis

Penicillin plus streptomycin is effective for enterococcal endocarditis and 2-week therapy of viridans streptococcal endocarditis.

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10
Q

Neomycin - Clinical use

A

Gram-positive and gram-negative and some mycobacteria

Superficial infections

Prevents Hepatic encephalopathy and Hypercholesterolemia

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11
Q

Paromomycin - Clincal use

A

has recently been shown to be effective against visceral leishmaniasis when given parenterally

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12
Q

Drugs that have similar properties as Neomycin

A

Kanamycin and Paromomycin

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13
Q

Tetracylines - MoA

A

Binds to 30 S ribosomal subunit, prevents addition of new amino acid to the nascent polypeptide chain. Bacteriostatic

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14
Q

Tetracyclines

A

Doxycycline
Minocycline
Tetracycline
Tigecycline

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15
Q

Tetracylines - Clinical use

A 
Lyme disease
Rocky Mountain spotted fever
Relapsing fever
Ehrlichiosis
Granuloma inguinale
Brucellosis
Cholera
Peptic ulcer disease
Gonorrhea (doxycycline in combination with ceftriaxone)
Community acquired pneumonia
Leptospirosis (leptospira)
Nontuberculous mycobacterial infections (Mycobacterium marinum)

Prophylaxis of protozoal infections (plasmodium falciparum)

H. pylori
Chlamydia trachomatis
Rickettsiae
Acne vulgaris
MRSA
Spirochetes
Mycoplasmas
Protozoa
Borrelia burgdorferi
Borrelia recurrentis
Klebsiella granulomatis
Vibrio cholerae

Good penetration of skin –> Acne treatment (Minocycline)

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16
Q

Tetracyclines - Adverse effect

A

Discoloration of teeth and hypoplasia of the enamel in pregnant women and children under 8 years

Nephrotoxicity and Hepatotoxicity (increased risk in pregnant women) (Fatty degeneration)

Photosensitivity (Increased incidence in Doxycycline)
Erythema, sunburn

Dose-related nausea and vomiting (Tigecycline)

Nausea, vomiting, anorexia

Intestinal functional disturbances, anal pruritus, vaginal/oral candidiasis, Clostridium difficile associated colitis.

Renal tubular acidosis and other renal injury leads to nitrogen retention (outdated prepatarions)

IV: venous thrombosis
IM: local pain

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17
Q

Tetracyclines - Interactions

A

Binds divalent and trivalent cations, including calcium, aluminium, and iron. For this reason, their oral bioavailability is reduced if they are taken with foods containing these ions.

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18
Q

Tigecycline - Clinical use

A

Skin and soft tissue infections caused by MSSA and MRSA, E. coli,

Community-aquired pneumonia and complicated intraabdominal infections caused by various gram-positive and gram-negative organisms

Enterococcus fecalis, various streptococci, and Bacteroides fragilis

Multidrug-resistant strains of Acinetobacter,
Rickettsiae, Chlamydia sp., Legionella pneumophila, rapidly growing mycobacteria

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19
Q

Azithromycin, Clarithromycin - Clinical use

A

Respiratory infections by erythromycin sensitive bacteria, H. influenzae, M. catarrhalis,

Mycobacterium avium-intracellulare in patients with AIDS

Gonorrhea in combination with ceftriaxone

Toxoplasma gondii
Chlamydia
Sinusitis
Otitis media
Bronchitis

Azithromycin: campylobacter jejuni

Single-dose treatment for uncomplicated chlamydial urethritis (Clarithromycin)

Mycobacterium laprae (Clarithromycin)
Peptic ulcer disease from H. pylori (Clarithomycin)
20
Q

Azithromycin - Special considerations

A

Administered 1 h before or 2 h after meals

Aluminium and magnesium antacids delay absorption and reduce peak serum concentration

21
Q

Macrolides: Adverse effects

A 
Stomatitis
Heart burn
Uncoordinated peristalsis
Nausea
Anorexia
Abdominal discomfort
Diarrhea

Erythomycin:
Tinnitus & impaired hearing
Thrombophlebitis
QT prolongation

Estolate: acute cholestatic hepatitis (fever, jaundice, impaired liver function). Allergic reactions (eosinophilia, rashes)

22
Q

Tetracyclines - Contraindications

A

Contraindicated for pregnant women and children <8 y

23
Q

Macrolides, Ketolides and Aminosugar - MoA

A

Binds to 50S ribosomal subunit and prevents peptide elongation and translocation from acceptor site to peptidyl site

24
Q

Macrolides

A

Azitromycin
Clarithromycin
Erythromycin (Base, stearate, estolate)

25
Erythromycin - Clinical use
Gram-positive: Corynebacterial infections (diphteria, erythrasma) Sepsis Resp., Neonatal, ocular, genital chlamydial infections and Community acquired pneumonia by pneumococcus L. pneumophila, M. pneumoniae, Chlamydia pneumoniae Mycobacteria (ex. Mycobacterium kansasii) Gram-negative: Neiserria sp, Rickettsia sp, Treponema pallidum, Campylobacter Penicillin allergic patients (staph, strep. Pneumo) Prophylaxis against endocarditis during dental procedures in patients with valvular heart disease campylobacter jejuni
26
Macrolides interactions
Erythromycin and clarithromycin inhibit cytochrome P450 3A4 and can elevate the plasma concentration of a large number of drugs metabolized by this isozyme. For example, concurrent administration of erythromycin or clarithromycin with carbamazepine can lead to life-threatening carbamazepine toxicity, and this combination should be avoided. Erythomycin and clarithromycin also inhibit metabolism of lovastatin and simvastatin, and concurrent use of these statin drugs can lead to elevated statin levels and rhabdomyolysis.
27
Ketolide
Telithromycin
28
Telithromycin - Clinical use
``` Active in vitro against: Streptococcus pyogenes S pneumoniae S aureus H influenzae Moraxella catarrhalis Mycoplasma sp L pneumophila Chlamydia sp H pylori Neisseria gonorrhoeae Bacteroides fragilis Toxoplasma gondii certain nontuberculosis mycobacteria ```
29
Telithromycin - Contraindications
Contraindicated for myasthenia gravis and for driving
30
Telithromycin - Adverse effects
``` Diarrhea Nausea Elevated liver enzymes Severe liver toxicity (very rare) Prolongation of QT Resp failure in myasthenia gravis Visual disturbances Loss of conciousness ```
31
Aminosugar antibiotic
Clindamycin
32
Clindamycin - Clincal use
``` Bacteroides fragilis Clostridium perfringes (the cause of gas gangrene). ``` MRSA and penicillin-resistant streptococci, including necrotizing fascittis Skin and soft-tissue infections Prophylaxis of endocarditis in patients with valvular heart disease Pneumocystis jiroveci pneumonia in AIDS patients with primaquine AIDS-related toxoplasmosis with pyrimethamine Acne vulgaris
33
Clindamycin - Adverse effects
Higher incidence of superinfections (clostridium) than other antibiotics Severe diarrhea Psuedomembranous colitis Impaired liver function Neutropenia
34
Nitrobenzene antibiotic
Chloramphenicol
35
Chloramphenicol - MoA
It binds reversibly to the 50S subunit of the bacterial ribosome and inhibits peptide bond formation
36
Chloramphenicol - Clinical use
Broad-spectrum antibiotic that is active against pathogens causing meningitis, including pneumococci, meningococci, and H. influenzae Salmonella Bacteroides Brain abcess Rickettsiae (typhus, rocky mountain spotted fever) Neiserria meningitidis
37
Chloramphenicol - Special considerations
High concentrations in CNS Lipophilic, well absorbed from gut Partly metabolized by glucoronate conjugation (neonates obs)
38
Chloramphenicol - Adverse effects
Gray baby syndrome characterized by cyanosis, weakness, respiratory depression, and shock Reversible, dose-dependent anemia caused by blockade of iron incorporation into heme Aplastic anemia (rare) Nausea, vomiting, diarrhea, Oral/vaginal candidiasis
39
Streptogramin antibiotic
Quinupristin-Dalfopristin
40
Quinupristin-Dalfopristin - MoA
Binds to 50S ribosomal subunit. Inhibits tRNA synthesis + inhibits peptidyl transferase Inhibits protein synthesis when administered in 30:70.
41
Quinupristin-Dalfopristin - Clinical use
Bactericidal against susceptible strains of staphylococci and streptococci but bacteriostatic against Enterococcus faecium Active against many gram-postitive bacteria, including multidrug-resistant straphylococci, penicillin-resistant pneumococci, and vancomycin-resistant E. faecium, but not E. fecalis ``` Bacteremia Pneumonia Skin and soft tissue infections Peritonitis Endocarditis Aortic graft infections ```
42
Quinupristin-Dalfopristin - Adverse effects
``` Infusion site reactions Arthralgia Myalgia Diarrhea Nausea ```
43
Linezolid - MoA
Binds to 23S ribosomal RNA of the 50S subunit, preventing formation of 70S initiation complex
44
Linezolid - Clinical use
Active against aerobic gram-positive bacteria Bactericidal against most strains of streptococci Bacteriostatic against enterococci and staphylococci Vancomycin-resistant E. faecium; pneumonia caused by methicillin-sensitive S. aureus and MRSA; and skin and soft tissue infections caused by methicillin-sensitive or methicillin-resistant staphylococci and Streptococcus pyogenes, or Steptococcus agalactiae Given IV for serious infections such as necrotizing fasciits and pneumonia Orally for mild to moderate skin and soft tissue infections
45
Linezolid - Adverse effects
serotonin toxicity with fluoxetine Thrombocytopenia Anemia Neutropenia in patients with renal insufficiency or during prolonged therapy
46
Mupirocin - MoA
Competetive inhibition of isoleucine, preventing addition of isoleucine to protein
47
Mupirocin - Clinical use
Active against gram-positive cocci, including most strains of methicillin-resistant staphylococci Impetigo by streptococci and staphylococci Nasal colonization of methicillin-resistant staphylococci

Pharmacology (55 decks)

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