Chapter 7 anti infective agent - inhibitors of protein synthesis Flashcards
gentamicin
tobramycin
kanamycin
streptomycin
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amikacin
aminoglycosides (bacetericidal)
- binds 30s/50s subunit interfae l/t abnormal reading of mRNA and defective bacterial proteins
resistance:
top —
* mutation of binding sites
* inhibit drug transport and permeability
* enzymatic inactivation of aminoglycosides
bottom —
* different enzyme resistance
* bacterial impermeability
spectrum
* aerobic and faculative ( capability to switch between an aerobic or anaerobic respiratory mode for the generation of energy ) gram negative bacilli
* anaerobic bacteria are RESISTANT b/c transport of drug into bacteria is o2 dependent
Drug of choice
* enterobacter, e coli (gram negative), K. pneumoniae, proteus, serratia, pseudomonas (TOP)
* often reserved for gram neg infections resistant to other aminoglycosides (BOTTOM)
effects
* nephrotoxicity
* ototoxicity
slow IM or IM; not distributed to eyes or CNS
chloramphenicol (chloromycetin)
bacteristatic; agent binds to 50s ribosomal subunit
- reversibly binds 50s subunit
- prevent peptide chain elongation
- stop tRNA from associating with peptidyl transferase ( peptide bond formation and peptide release.)
resistance:
* r-tactors code for acetyl transferases which inactivate the drug
spectrum
* cover most gram positives and gram negatives, including anaerobes
drug of choice
* salmonella tyhposa (typhoid fever [enteric fever, is caused by salmonella bacteria. Typhoid fever is rare in places where few people carry the bacteria. It also is rare where water is treated to kill germs and where human waste disposal is managed.])
* haemophilius influenzae meningitis or epiglottis
* hesitation to use this drug b/c aplastic anemia (bone marrow doesn’t make enough new blood cells)
effects:
* reversible bone marrow suppression (binds mitochondrial ribosomes 50s subunit in bone marrow)
* or irreversible aplastic anemia
* gray syndrome – adverse reaction to chloramphenicol that is characterized by abdominal distention, hemodynamic collapse, and ashen-gray skin discoloration, hypothermia, or collapse in neonates (unable to conjugate drug)
PO/IV – crosses BBB, inhibits aminoglycoside transport into bacteria
linezolid (zyvox)
tedizolid (sivextro)
bacteristatic; agent binds to 50s ribosomal subunit
- binds to 50s subunit
- prevents peptide chain elongation
- stop tRNA from associating with peptidyl transferase ( peptide bond formation and peptide release.)
spectrum
* gram positive organisms
Drug of choice:
* vancomycin resistant gram positve organisms
Linezolid IV / PO
Erythromycin (E.E.S)
macrolides
- binds to ribosomal 50s subunit
- prevents translocation (piece of one chromosome breaks off and attaches to another chromosome.) of polypeptide chan
resistance:
mutation of binding site via methylation
spectrum:
bacteria lacking cell wall (mycoplasma, legionella, chlamydia)
* most gram positive aerobes
* gram negative aerobes except campylobacter, pasteurella, some H. influenza
* poor anaerobic agent
drug of choice
* mycoplasma penumonia
* neonate with chlamydia pneumonia
* pertussis
dithromycin — for upper resp infection m. catarrhalis, s. pneumoniae
* it is a prodrug converted to erythromy-cylamine
effects:
* Ilsone prep (erthromycin) may cause cholestatic hepatitis (virulent form of chronic viral hepatitis B or hepatitis C )
* injections painful —- vendodestruction
* increase plasma level of many drugs
* toxicity — w/ theophylline, anticoaugulants, carbamazepine
notes
* caution with liver disesae
* if taking terfenidine (antihistamine) – prolonged QT and other arrhythmias possible
clarithromycin (Biaxin)
macrolides
- binds to ribosomal 50s subunit
- prevents translocation (piece of one chromosome breaks off and attaches to another chromosome.) of polypeptide chan
resistance:
mutation of binding site via methylation
spectrum:
bacteria lacking cell wall (mycoplasma, legionella, chlamydia)
* most gram positive aerobes
* gram negative aerobes except campylobacter, pasteurella, some H. influenza
* poor anaerobic agent
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* mycobacterium avium intracecllulare
* H flu and some anaerobes
Drug of choice
* mycoplasma
* strep throat
* upper respiratory infections
effects
* similar to erythromycin (GI upset, cholestatic hepatitis, venodestruction, increase other drug serums)
* headache
azithromycin (zithromax)
macrolides
- binds to ribosomal 50s subunit
- prevents translocation (piece of one chromosome breaks off and attaches to another chromosome.) of polypeptide chan
resistance:
mutation of binding site via methylation
spectrum:
bacteria lacking cell wall (mycoplasma, legionella, chlamydia)
* most gram positive aerobes
* gram negative aerobes except campylobacter, pasteurella, some H. influenza
* poor anaerobic agent
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* mycobacterium avium intracecllulare
* H flu and some anaerobes
Drug of choice
* mycoplasma
* strep throat
* upper respiratory infections
effects
* GI upset (less than erythromycin)
* abdominal pain
take on empty stomach; long half - daily dosing
telithromycin (ketek)
ketolides
- binds to 50s subunit
spectrum
* s pneumoniae
* h influenza
* m catarrhalis (otitis media)
drug of choice
* bacterial exacerbation of bronchitis
* mild-moderate pneumonia
* sinusitis (Sinuses are structures inside your face that are normally filled with air. Bacterial infections, viral infections and allergies can irritate them, causing them to get blocked and filled with fluid)
effects
* exacerbation of myasthenia gravias (antibodies destroy the communication between nerves and muscle, resulting in weakness of the skeletal muscles. Myasthenia gravis affects the voluntary muscles of the body, especially those that control the eyes, mouth, throat and limbs.)
* hepatotoxicity
once daily
clindamycin (cleocin)
lincomycin (lincolin)
lincosamides
- binds to 50s
- blocks transpeptidation (preventing chain elongation)
resistance:
* inactivation of durg (enzymatic)
* alteration of ribosome binding site
spectrum
* covers gram pos
* most anaerobes
drug of choice
* for clindamycin — severe anerobic GI infections, also for b. gragilis and staph infections
effects
* reversible elevation of liver enzymes
* GI upset, diarrhea
* pseudomembranous colitis ( inflammation of the colon associated with an overgrowth of the bacterium Clostridioides difficile (formerly Clostridium difficile) — often classically seen with clindamycin
actively transported into abcesses
* reduce dose with impaired liver fx
normal gut bacteria killed by these drugs
tetracyclin
doxycycline
minocycline
demeclocycline
agents that bind to the 30s (bacteristatic)
- inhibits protein synthesis
- binds 30s subunit blocking amino acid linked tRNA from binding to A site of ribosome
resistance
* R factor codes for proteins which transport drug out of cell
spectrum
* most staphylococcus and streptococcus strains
* enterics, mycoplasma, spirochetes
* rickettsiae (febrile diseases or like typhus - an infectious disease caused by rickettsiae, characterized by a purple rash, headaches, fever, and usually delirium, and historically a cause of high mortality during wars and famines. There are several forms, transmitted by vectors such as lice, ticks, mites, and rat fleas.)
* neisseria gonorrhea
* **doxycycline — malaria prophylaxis **
indication
* acne
* chlamydial infections
* for borrelia burgdorferi (lyme disease) - transmitted to humans through the bite of infected blacklegged ticks. Typical symptoms include fever, headache, fatigue, and a characteristic skin rash called erythema migrans.
effects
* GI distress
* reversible nephrotoxicity
* hepatotoxicity
* dental staining
* increased intracranial pressure (rare)
pharmacokinetics
* strong chelator — don’t vie with ilk, antacid, Ca++ or Fe++
note
* not effective with nystatin
* doxycycline (less nephrotoxic) better alternative for pts w/ renal disorders
tigecycline (tygacil)
agents that bind to 30s r subunit (bacteristatic)
- inhibits protein synthesis
- binds 30s subunit blocking amino acid linked tRNA from binding to A site of ribosome
resistance
* R factor codes for proteins which transport drug out of cell
spectrum
* broad gram-negative + positive acitivty
indication
* bacteria resistant to tetracyclines
* methicilin resistant staph
* vancomycin resistant enterococci
effects
* nausea
IV only
