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88 Cards in this Set
- Front
- Back
- 3rd side (hint)
IPS = ?
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Inhibitors of Protein Synthesis
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What do the IPS's target?
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70S Ribosome (vs. 80S for humans)
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Mnemonic for IPS's
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buy AT 30, CELL at 50
30S inhibitors - A = Aminoglycosides - T = Tetracyclines 50S inhibitors - C = Chloramphenicol - E = Erythromycin - L = Lincomycin - L = cLindamycin |
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What is the only IPS that is BACTERICIDAL? Why?
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Aminoglycoside b/c it binds irreversibly
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Why are IPS's substantially less Selectively Toxic than ICWS?
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b/c IPS's take advantage of structural differences in the pathogen to get selective effects while ICWS's take advantage of a unique target
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Tetracycline mechanism of action
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- REVERSIBLE binding to 30S subunit = Bacteriostatic
- block the attachment of aminoacyl tRNA to the acceptor site |
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How is Tetracycline usually administered?
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Orally, but absorption is variable basd on what else is in the GI tract
*rarely given IV |
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What is the caveat when giving Tetracycline orally? Why?
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Do not give with Milk, food, antacids b/c they chelate with metal ions
- not absorbed - lose antibiotic ability |
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Describe the distribution of Tetracycline
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1. well distributed, except CNS and synovial fluid
2. concentrates in TEETH and BONE, liver, and kidney |
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What 2 groups of people should you never give Tetracycline to and why?
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Children and Pregnant/breast-feeding mothers
b/c tetracycline crosses the placenta and is excreted in milk - teeth discoloration - inhibits bone growth |
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How are most Tetracyclines excreted? What is the exception?
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1. in Urine
2. Doxycline is more lipid-soluble = fecal |
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What type of patients can Doxycline be given to and why?
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Those with Renal Failure b/c it is excreted fecally
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What is the mnemonic for the clinical uses of Tetracycline?
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VACUUM THe BedRoom = Gram +/-
V = vibrio cholera A = Acne C = Chlamydia U = Ureaplasma U = Urealyticum M = Mycoplasma pneumoniae T = Tularemia H = H. pylori B = Borrerlia burgdorferi (Lyme Disease) R = Rickettsia |
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List the 5 adverse effects of Tetracycline and why
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1. GI = direct irritation b/c given orally
2. Superinfections b/c of broad spectrum 3. Impaired liver fxn due to high doses, during pregnancy, or pre-existing liver disease 4. Photosensitivity 5. Calcium chelation -teeth discoloration -inhibits bone growth |
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List 2 ways that resistance to Tetracycline occurs
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1. Efflux pumps (plasma-mediated)
2. altered ribosomal proteins |
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Which microbes commonly have altered ribosomeal proteins that allows resistance to Tetracycline?
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Pseudomonas
Proteus *don't use Tetracycline for these |
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What has fostered the emergence of resistance to Tetracycline
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Overuse clinically and AGRICULTURALLY
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Name for the new generation of Tetracyclines
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GlycylCYCLINES
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What is better about the Glycylcyclines?
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retain antibacterial spectrum of tetracyclines but overcome the resistance
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What tetracycline is not affected by efflux pump except in Proteus and Pseudomonas?
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Tigecycline
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Tetracycline that has a particular usefulness in Prostatitis because it reaches high levels in prostatic fluid
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Doxycycline
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Tetracycline that appears at high levels in Saliva and is used in the Meningococcal carrier state
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Minocycline
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Used in the Syndrome of Inappropriate secretion of ADH b/c it blocks the ADH receptor fxn in the collecting ducts and acts as a diuretic
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Demeclocycline
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What is Chloramphenicol's mechanism of action?
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REVERSIBLE inhibitor of 50S
- inhibits the formation of the Peptide Bond = inhibits Peptidyltransferase -BACTERIOSTATIC |
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Protein systhesis inhibitor that is well absorbed from ALL routes -> CNS levels = Serum levels
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Chloramphenicol
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IPS that has these excretion pharmacokinetics:
100% excreted in urine - 10% filtration of parent -90% tubular secretion of glucuronide |
Chloramphenicol
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What is the rate-limiting step in Chloramphenicol clearance?
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Glucuronidation in the liver
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Describe the resistance to Chloramphenicol
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- Plasmid-mediated
- Chloramphenicol Acyl Transferase -Slow development and only slight resistance so increasing the dose 2-4X works |
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List the 5 Adverse effects of Chloramphenicol
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1. GI disturbances followed by Fungal Superinfections
2. Anemia due to bone marrow depression 3. Aplastic anemia 4. Gray Baby Syndrome 5. Drug-drug interactions = inhibits microsomal enzymes ChlorineAM pool has a Gray baby in it who has GI fungal infection, 2 types of anemia, and inhibits CYP |
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Describe Anemia due to bone marrow depression due to Chloramphenicol
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-Arrested Red cell maturation
-Dose and time related -usually reversible |
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Describe Aplastic Anemia due to Chloramphenicol
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- idiosyncratic rxn (1 in 35,000)
- Dose-INDEPENDENT - IRREVERSIBLE and often FATAL |
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Why does Gray Baby Syndrome occur in neonates taking Chloramphenicol?
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they have immature livers = poor Glucuronidation = low clearance = high toxicity
*lack liver UDP-glucuronyl transferase |
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What drugs does Chloramphenicol inhibit the metabolism of? (3)
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1. Phenytoin
2. Sulfonylureas 3. Warfarin **Chloram pool has SulferPee in it to make it look like a FUNNY-WARF |
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What is the clinical use of Chloramphenicol?
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limited use due to toxicity but used in children for:
- Typhoid Fever - RMSF *b/c you don't want to give Tetracycline |
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Mnemonic for Macrolide antibiotics
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mACE (all end in -thromycin
A = Azithromycin C = Clarithromycin E = Erythromycin |
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Macrolide mechanism of action
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Bind to 23S rRNA of 50S subunit
- inhibit translocation of peptidyl-tRNA from acceptor site to donor site |
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Macrolide: static or cidal?
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Either, depends on dose
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Describe the absorption of Macrolides
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Absorbed fro GI tract but ACID-labile
-use enteric coating capsule - Erythromycin esters = acid-stabile |
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IPS that has excellent distribution except to the CNS but CROSSES the Placenta
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Macrolides = mACE
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Describe the excretion of Macrolides
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excreted in Bile = levels are 50X higher than in plasma
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What is the half-life of Macrolides? Exception?
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2-5 hrs
Azithromycin = 2-4 days |
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List the 3 Adverse Effects of Macrolides
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1. GI distress (stimulates motilin receptors) = nausea
2. Hepatoxicity -Erythromycin estolate -> Cholestatic jaundice 3. Microsomal enzyme inhibition -Warfarin, coumadin -Digoxin -non-sedating anti-histamines |
MacroLiar (think Liar Liar) has 1) upset stomach 2) cholestatic jaundice (yellow) 3) Inhibits metabolism of: WAR DIGs at HISTAMINa
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Clinical uses for Macrolides
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Gram +, some Gram -, some Mycobacteria
*backup for Penicillins in Pen-sensitive patients *also for Mycoplasma pneumonia, Legionnaire's disease, Chlamydia **Macrolides = MCL |
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Which Macrolides are Broader Spectrum? What are they used to treat?
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Azithromycin = sinusitis or otitis media (H. influenza, M. catarrhalis), Chlamydia, MAI
**mACe Clarithromycin = increased activity against MAC and H. pylori |
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What microbes may be Macrolide-resistant?
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1. Staph
2. some Strepto 3. Pneumococci (Strep pneumo) |
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What are the 2 ways microbes attain resistance to Macrolides?
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Both plasmid-mediated
1. Methylated rRNA 2. Esterase which hydrolyzes Erythromycins |
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What is the advantage of Clarithromycin?
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Has less GI effects
**Clair Green has less GI effects |
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2 advantages of this IPS are:
1. minimal P450-based interactions 2. tissue level 10-100X plasma levels = longer half-life = 2-4 days vs. 2-5 hrs. |
Azithromycin
*longer half-life than other Macrolides |
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What is Azithromycin particularly active against?
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Mycobacterium avium-intracellulare (MAI) in AIDS patients
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What category of drug does Clindamycin fall in?
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Lincosamide
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Clindamycin: static or cidal?
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Static
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Describe the distribution of Clindamycin
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well absorbed and distributed except for CNS
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Clinical uses of this drug are:
1. Anaerobes = Bacteroides fragilis, C. perfringens 2. Endocarditis prophylaxis 3. Orthopedic surgical cases |
Clindamycin
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What are 3 Adverse Effects of Clindamycin?
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1. GI upset
2. C. difficile superinfection = Pseudomembranous colitis 3. Hepatotoxic |
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List the two Sterptogramins and their trademark name
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Quinupristin and Dalfopristin
Synercid |
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How are the Streptogramins administered and why?
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IV b/c they're too big to be absorbed orally = peptide macrolactones
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How are the Streptogramins (Quinpristin & Dalfopristin) excreted?
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80% bile
20% urine |
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What is the drawback to Streptogramins
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potent inhibitor of CYP 3A4 = major metabolizer of prescription drugs
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IPS that is CIDAL to all organisms except E. faecium (bacteriostatic)
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Streptogramins = Quinupristin & Dalfopristin
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What are the Streptogramins (-pristins) clnically used for?
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Vanco and multi-drug resistant E. faecium
MRSA |
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What is the only relevant drug in the Oxazolidinones group?
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Linezolid
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Linezolid mechanism of action
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prevents formation of 70S ribosome = unique mechanism
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Why does Linezolid have no cross-resistance with other IPS's
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b/c it inhibits a unique mechanism
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What is Linezolid CIDAL against?
What is it STATIC against? |
Streptococci
Staphylococci and Enterococci |
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How is Linezolid administered?
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IV or Oral
*oral AUC = IV AUC |
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What is the primary clinical use for Linezolid?
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VRE (Vancomycin resistant Entercocci)
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What are the 2 adverse effects of Linezolid?
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1. Bone Marrow suppression
2. Thrombocytopenia |
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Aminoglycosides: Cidal or Static?
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CIDAL = irreversible inactivation of 30S
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IPS that has these actions:
1. interfere with formation of initiation complex 2. misreading of mRNA 3. break up polysomes |
Aminoglycosides
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What is the mnemonic for the drugs in the Aminoglycoside class?
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"mean" GNATS canNOT kill anaerobes
G = Gentamicin N = Neomycin A = Amikacin T = Tobramycin S = Streptomycin N = Nephrotoxicity O = Ototoxicity T = Teratogen |
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How are Aminoglycosides administered and why?
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Usually IV, sometimes IM
- poor oral absorption b/c they are polar amino sugars |
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Describe the distribution of AmINoglyCoSides
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Good except for eye and CNS
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How are Aminoglycosides excreted
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UNCHANGED by glomerular filtration
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Where can Aminoglycosides collect in very high concentrations?
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Proximal tubule cells
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What are the clinical uses for Aminoglycosides
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non-resistant Gram - infections
-E. coli -Proteus -Pseudomonas |
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What is the order of drug use for Pseudomonas?
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Carbenicillin > gentamicin > tobramycin > amikacin
**just like DNA bases: CG-TA |
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What is the general rule when prescribing Aminoglycosides?
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Use OLDER ones first and save newer one for when they are needed
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What are the 2 older Aminoglycosides?
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Streptomycin and Gentamicin
- use first **Senile Gent** |
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Why are Aminoglycosides ineffective against Anaerobes?
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b/c they require O2 for microbe uptake (uptake mechanism is dependent on oxygen)
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Group of drugs related to Aminoglycosides that are used against Penicillin-resistant Gonococci (N. gonorrhoeae)
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Spectinomycin
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What is the toxicity of Aminoglycosides dependent on?
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Both time and blood level
*most drugs are just based on blood level |
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IPS that is used by "once daily" dosing
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Aminoglycosides
= give a very high dose of drug which causes a high spike, high killing, but minimizes toxicity due to decreased time in blood |
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What are the 3 adverse effects of Aminoglycosides?
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1. Nephrotoxicity
2. Ototoxicity 3. Neuromuscular blockade |
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Where does Aminoglycoside concentrate in the Kidney?
After how many days do 5-25% of people taking AG show progressive renal impairment? |
Renal Cortex
3 days |
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By what 4 drugs is the Nephrotoxicity of Aminoglycosides exacerbated?
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1. Vancomycin
2. Cyclosporin 3. Amphotericin B 4. Cisplatin VAC-C |
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When is the adverse effect of Neuromuscular Blockade most common with Aminoglycosides?
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-during surgery with the presence of other neuromuscular blockers
-Myasthenia gravis patients *high dose phenomenon |
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What happens if Aminoglycosides are administered alone?
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microbes RAPIDLY develop resistance
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List 3 ways in which microbes may become resistant to Aminoglycosides
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1. Increased BACTERIAL metabolism = adenylation, acetylation, phosphorylation
2. Alteration in bacterial uptake -altered transport system 3. Altered ribosomal protein |
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