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Zey øving > Inhibitors of bacterial protein synthesis 1 > Flashcards

Inhibitors of bacterial protein synthesis 1 Flashcards

1
Q

Aminoglycosides

A

Amikacin Gentamicin Neomycin Streptomycin Tobramycin

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2
Q

Aminoglycosides administration

A

IV: Amikacin IV or Topical: Gentamicin and Tobramycin IM: Streptomycin Topical or Oral: Neomycin The amino group become protonated and ionized in body fluids, that is why they are poorly absorbed from the gut and must be administered parentally. Occasionally, aminoglycosides are administered orally to treat GI infections such as neonatal necrotizing enterocolitis. They are also administered topically to treat infections of the skin, mucous membranes, and ocular tissues.

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3
Q

Bacterial resistance to aminoglycosides

A

Primarily caused by inactivation of the drugs by bacterial enzymes that combine the drug with acetate, phosphate, or adenylate Also caused by decreased binding of the drugs to the 30S ribosomal subunit or to decreased uptake of the drugs by porins in bacterial membranes

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4
Q

Aminoglycosides - Advers 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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5
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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6
Q

Most nephrotoxic aminoglycosides

A

Neomycin, Tobramycin and Gentamicin

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7
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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8
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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9
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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10
Q

Tobramycin - Clinical use

A

The most active aminoglycoside against many strains of Pseudomonas aeruginosa Enterococcus faecalis

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11
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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12
Q

Neomycin - Clinical use

A

Gram-positive and gram-negative and some mycobacteria Superficial infections Prevents Hepatic encephalopathy and Hypercholesterolemis

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13
Q

Paromomycin - Clincal use

A

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

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14
Q

Drugs that have similar properties as Neomycin

A

Kanamycin and Paromomycin

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15
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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16
Q

Tetracyclines

A

Doxycycline Minocycline Tetracycline Tigecycline

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17
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)

18
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

19
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.

20
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

21
Q

Tigecycline - Special consideration

A

Increased affinity to 30S subunit and decreased susceptibility to resistance Should only be used when other treatments are not suitable because of increased mortality

22
Q

Routes of administration of tetracyclines

A

Oral or IV: Doxycyline and Minocycline Oral: Tetracycline IV: Tigecycline

23
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 Single-dose treatment for uncomplicated chlamydial urethritis (Azithromycin) Mycobacterium laprae (Clarithromycin) Peptic ulcer disease from H. pylori (Clarithomycin)

24
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

25
Q

Macrolides: Adverse effects

A

Stomatitis Heart burn Uncoordinated peristalsis Nausea Anorexia Abdominal discomfort Diarrhea Erythomycin: Tinnitus & impaired hearing Thrombophlebitis Estolate: acute cholestatic hepatitis (fever, jaundice, impaired liver function). Allergic reactions (eosinophilia, rashes)

26
Q

Tetracyclines - Contraindications

A

Contraindicated for pregnant women and children <8 y

27
Q

Bacterial resistance to tetracyclines

A

Caused by transmission of plasmids containing resistance factors by bacterial conjugation. The resistance factors include genes that express modified bacterial porins that do not permit uptake of the tetracyclines. Resistance can also result from increased drug efflux, decreased ribosomal binding, and enzymatic inactivation.

28
Q

Macrolides, Ketolides and Aminosugar - MoA

A

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

29
Q

Macrolides

A

Azitromycin Clarithromycin Erythromycin (Base, stearate, estolate)

30
Q

Macrolides administration

A

Usually administered orally, but azithromycin is available in intravenous formulations for treating serious infections such as Legionnaire disease. Erythromycin can also be administered topically to treat acne.

31
Q

Erythromycin - Clinical use

A

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

32
Q

Bacterial resistance to macrolides

A

Result from decreased binding to the 50S ribosomal subunit, enzymatic inactivation, and increased bacterial efflux

33
Q

Macrolides interactions

A

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.

34
Q

Ketolide

A

Telithromycin

35
Q

Telithromycin - Clinical use

A

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

36
Q

Telithromycin - Contraindications

A

Contraindicated for myasthenia gravis and for driving

37
Q

Telithromycin - Adverse effects

A

Diarrhea Nausea Elevated liver enzymes Severe liver toxicity (very rare) Prolongation of QT Resp failure in myasthenia gravis Visual disturbances Loss of conciousness

38
Q

Aminosugar antibiotic

A

Clindamycin

39
Q

Clindamycin - Clincal use

A

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

40
Q

Clindamycin - Adverse effects

A

Higher incidence of superinfections (clostridium) than other antibiotics Severe diarrhea Psuedomembranous colitis Impaired liver function Neutropenia

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