Test-2-Protein Synthesis Inhibitors Flashcards
ERYTHROMYCIN
A Macrolide (aka a macro_SLIDES -> block translocation_)
Others:
CLARITHROMYCIN (1992)
AZITHROMYCIN (1992)
Mech of Action:
- Binds to 50 S subunit and doesn’t allow for translocation of the Peptide chain. (MAIN Functino)
- INHIBITS FORMATION OF INITIATION COMPLEXES
Uses: If penicillin is the queen of antibiotics, Erythromycin is the “mistress of antibiotics”
Considered a gram positive antibiotic. (because it is difficult to get into the gram negative cell - consider synergistic function)
Drug of Choice:
*MYCOPLAMSA PNEUMONIAE
*DIPHTHERIA (CARRIER STATE)
Alternative uses:
*STREP INFECTIONS (ALLERGIC TO PENICILLIN)
*STAPH INFECTIONS (ALLERGIC TO PENICILLIN, RESISTANCE PROBLEM)
Site of Excretion:
_***EXCRETED IN BILE (ACTIVE FORM)- No issues with dosing with Kidney or Liver damage (unless VERY damaged)._
Resistance:
All the normal players, main one is induced resistance by patient not taking their full meds!
Different forms:
ESTOLATE FORM (ILOSONE®): The more advanced form - CHOLESTATIC HEPATITIS (10 - 12%)
FREE / STEARATE FORM:
- **EPIGASTRIC DISTRESS: (FREQUENT) – biggest side effect with all of the erythromycin.
Drug interactions:
- Decrease ACTIVITY OF CYTOCHROME P450
- Increase ACTIVITY OF MANY OTHER DRUGS
CLARITHROMYCIN
Another macrolide
Use: *H. PYLORI (PEPTIC ULCERS)
CLINDAMYCIN
A Lincosamide, very similar to a macrolide in mech of action.
Competitive with Macrolides!
BIND PROKARYOTIC 70S RIBOSOME
DO NOT BIND EUKARYOTIC 80S RIBOSOME
VERY USEFUL FOR **ANAEROBIC INFECTIONS
GRAM - NEGATIVE BACTERIA:
** BACTEROIDES (RESPIRATORY STRAINS)
** BACTEROIDES (GASTROINTESTINAL STRAINS)
Toxicities:
Can cause *PSEUDOMEMBRANEOUS ENTEROCOLITIS (C. Difficule)
TETRACYCLINES
Also include: DOXYCYCLINE, MINOCYCLINE
*SPECTRUM: GRAM (+) / GRAM (-) - But almost never drug of choice
Mech of action: binds to the 30 S subunit, inhibit attachment to the A site.
- *BACTERIA – ACCUMULATE the drug, while *MAMMALIAN CELLs – DO NOT ACCUMULATE
Resistance: Usual suspects, also can be transported out.
- ***ENERGY – DEPENDENT EFFLUX
- **RIBOSOME PROTECTION PROTEINS
Absorption is incomplete which can lead to:
*Superinfection
Also can chelate with Milk products, Antacids, iron and not be absorbed (recall story of patient drinking milk shakes)
Toxicity:
*EFFECTS ON TEETH
*EFFECTS ON BONE (CHILDREN):
* SUPERINFECTION
*RENAL TOXICITY: Accumulate in Kidney with reduced function. (**EXCEPTIONS ARE MINOCYCLINE / DOXYCYCLINE)
- **FANCONI SYNDROME (IF ITS AN OUTDATED DRUG) - PROXIMAL RENAL TUBULES
Drug Interactions:
- *PHENOBARBITAL and *PHENYTOIN will reduce Tetracycline half-life.
_- Tetracyclines decrease effect of oral contraception. _
Drug of Choice for:
**DISEASES CAUSED BY RICKETTSIA (RMSF) AND COXIELLA (Q FEVER)
**LYME DISEASE (BORRELIA)
TIGECYCLINE
A Tetracycline.
TOXICITIES:
**NAUSEA
**CONTRAINDICATED IN YOUNG CHILDREN
Use:
**OTHER ANTIBIOTICS NOT USEFUL BECAUSE OF RESISTANT BACTERIA
CHLORAMPHENICOL
Mech of Action: Binds to the 50 S subunit, INHIBITS PEPTIDYL TRANSFERASE.
Prefers Bacterial Ribosomes, BUT:
**MITOCHONDRIAL P.S. IN EUKARYOTIC CELLS (80S) – It is not known if this causes an impact or not.
Use:
Very broad spectrum, but bad press. Really just *SALMONELLA (TYPHOID FEVER)
Resistance:
****INACTIVATION – ACETYLATION due to plasmid encoded gene.
**CAN NOT STOP – No one knows how to stop this R-Factor from spreading (for acetylation)
Pharmakodynamics:
- METABOLIZED BY LIVER INACTIVE: DECREASE DOSE IF LIVER DISEASE
- KIDNEY EXCRETES CHLORAMPHENICOL METABOLITE (NOT TOXIC) SAME DOSE IF KIDNEY DISEASE
Toxicities:
***GRAY BABY SYNDROME: FAILURE TO FORM GLUCURONIC ACID, INADEQUATE RENAL EXCRETION, HYPOTHERMIA / ACUTE VASCULAR COLLAPSE (40 % FATAL)
***HEMATOLOGICAL: TRANSIENT BONE MARROW DEPRESSION (**DOSE RELATED, **REVERSIBLE), APLASTIC ANEMIA (**UNRELATED TO DOSE, ***IRREVERSIBLE) worse if it takes longer to develop after use of drug.
Drug interactions:
PHYSICAL INCOMPATIBILITIES WITH OTHER DRUGS on the Ribosomes.
*CHLORAMPHENICOL decreases HEPATIC MICROSOMAL CYTOCHROME P450. Increases half-life of other drugs.
AMINOGLYCOSIDES
Others end in Micin or Mycin.
Mech of Action: Unclear where they bind but they inhibit the initiation complex. (A “initiates” the alphabet), also incorrect amino acid, and blocks further translation.
- Oxygen dependent transport or diffusion with dependent movement to Ribosomes. Therefore, doesn’t work on Anaerobes.
Uses:
Sterilize bowel, not absorbed orally, but can disinfect bowel - > could lead to superinfection though.
Resistance:
- ***R - FACTOR (PLASMID), ***ACETYLATION
Poor oral absorption, *EXCRETED BY KIDNEY ~ 100 %
Toxicities:
**8TH CRANIAL NERVE
**RENAL DAMAGE: Potential synergism with other renal toxic drugs. - Need to initially monitor Kidney function of patients.
_Therapeutic index is very low, can’t just increase dose really. _
Time is more critical as a toxicity. So, we increase dose and for less time. Time in the toxic range AND concentration in the toxic range determines toxicity. Time is more important. AG have a post-antibiotic effect, means there is not measurable drug, but still kills bacteria. So, we use them like on the right now.
NEOMYCIN
Aminoglycoside
*TOPICAL: COMBINED WITH BACITRACIN, POLYMYXIN B
Produces contact DERMATITIS though
GENTAMICIN
Aminoglycoside with 3 sugars
Gram negative antibiotic
Drug of Choice for:
*KLEBSIELLA PNEUMONIAE (HOSPITAL-ACQUIRED)
*PROTEUS MIRABILIS
**PSEUDOMONAS AERUGINOSA
Combination therapy:
COMBINATION WITH β – LACTAM to EXTEND COVERAGE TO GRAM (+)
USUALLY COMBINED WITH PENICILLIN OR CEPHALOSPORIN FOR SERIOUS GRAM (–) INFECTIONS. HOWEVER, NOT DEMONSTRATED TO BE BETTER THAN SINGLE AGENT - EXCEPTIONS
SPECTINOMYCIN
Aminoglycoside
Uses: Used for Gonorrhea.
CERVICITIS
**ALTERNATIVE: IF PENICILLIN ALLERGY / RESISTANCE
STREPTOGRAMINS
Mech of Action: Binds to 50S subunit, decreases **PEPTIDYL TRANSFERASE
Uses:
**VANCOMYCIN-RESISTANT ENTEROCOCCUS FAECIUM
Reserved for SERIOUS GRAM (+) INFECTIONS
Toxicity:
** Decrease CYTOCHROME P450 (3A4)
** So, it increases OTHER DRUGS - RESULT IS POTENTIAL TOXICITY
OXAZOLADINONES: LINEZOLID
**MECHANISM OF ACTION: decrease PROTEIN SYNTHESIS (50S)
Uses: MULTIPLE – DRUG RESISTANT ORGANISMS
