Therapeutics ID Bergman Flashcard

Penicillins: Mechanisms of Resistance

  • Beta Lactamase Producing
  • Alteration of PBPs (MRSA)
  • Modification of outer cell membrane (Most G-)

Penicillin G Route of Administration
IV
Penicillin VK Route of Administration
PO
Benzathine Penicillin G Route of Administration
Long Acting IM
Procaine Penicillin G Route of Administration
Short Acting IM
Oxacillin Route of Administration
IV
Nafcillin Route of Administration
IV
Dicloxacillin Route of Administration
PO
Ampicillin Route of Administration
IV
Amoxicillin Route of Administration
PO
Ticarcillin Route of Administration
IV
Piperacillin Route of Administration
IV
Why is Ticarcillin not used much in the hospital?
It is formulated with Na+ and is harmful to sick patients — don’t want to overload someone that has CHF with Na+
Amoxicillin/Clavulanic Acid Route of Administration
PO
Ampicillin/Sulbactam Route of Administration
IV
Ticarcillin/Clavulanic Acid Route of Administration
IV
Piperacillin/Tazobactam Route of Administration
IV
Which antibiotics out of the penicillin classes do not need to be renally dosed?

  1. Nafcillin (primarily hepatic)
  2. Oxacillin (renal and hepatic)

Adverse Reactions of Penicillins

  • Allergic Rxns

Anaphylaxis (can’t rechallenge with another beta lactam)

Urticaria (hives)

Drug Fever

  • GI (N/V/D – occurs with PO classes)
  • Hematologic
  • Neurologic (seizures)

Cephalosporins: Mechanism of Resistance

  1. Beta Lactamases
  2. Alteration of PBPs
  3. Outer cell membranes changes

Cefazolin Route of Administration
IV
Cephalexin Route of Administration
PO
Cefuroxime Route of Administration
IV/PO
Cefoxitin Route of Administration
IV
Cefotetan Route of Administration
IV
Ceftriaxone Route of Administration
IV
Cefotaxime Route of Administration
IV
Ceftazidime Route of Administration
IV
Cefepime Route of Administration
IV
Route of Elimination for Cephalosporins

Renal

 

Exception:

Ceftriaxone (biliary)

Cefoperazone

Adverse Reactions of Cephalosporins

  • Allergic Rxns

Anaphylaxis

Urticaria

Drug Fever

  • Hematologic
  • Neurologic
  • Disulfiram-Like Reactions (MTT side chain only)

Cefotetan, cefamandole, cefmetazole, cefoperazone, moxalactam

Flushing, Vomiting – with concomitant alcohol consumption

Increased INR

Carbapenems: Mechanism of Resistance

  • Decreased penetration (G- bacilli)
  • Altered PBPs
  • Production of broad spectrum Beta Lactamases

Carbapenems are excreted by which route?
Renal
Imipenem Route of Administration
IV
Meropenem Route of Administration
IV
Ertapenem Route of Administration
IV
Doripenem Route of Administration
IV
Which Carbapenem is administered with Cilastatin?

Imipenem

  • It is susceptible to dehydropeptidase 1 of the renal brush border
  • Cilastatin is a DHP 1 inhibitor

Adverse Reactions of Carbapenems

  • Diarrhea

high risk of C. difficile

  • Allergic reactions

Anaphylaxis, urticaria, drug fever

Cross reaction with penicillins is higher than cephalosporins

  • Seizures (Imipenem > all other beta lactams, due to accumulation of cilastatin)

Aztreonam Route of Administration
IV
Aztreonam: Mechanism of Resistance
Extended Spectrum Beta Lactamases
Adverse Reactions of Aztreonam

Weakly Immunogenic (due to one ring)

 

People with PCN allergy can use aztreonam

Aminoglycosides: MOA

  • Binds irreversibly to 30S bacterial ribosomal subunit –> interference of genetic code and inhibition of protein synthesis
  • Bactericidal

Aminoglycosides: Mechanism of Resistance

  • Ribosomal mutation –> drug cannot bind to 30S subunit
  • Reduce transport into cell
  • Plasmid-mediated aminoglycoside-modifying enzymes

Aminoglycosides route(s) of elimination

Renal

 

Good for G- UTIs

Advantages of Once Daily Dosing of Aminoglycosides

  • Improves peak to MIC ratio and maximizes concentration dependent bactericidal activity
  • Takes advantage of post-antibiotic effect
  • Gives kidneys time to recover so possibly less nephrotoxicity
  • Less potential for resistance
  • Lower cost of supplies at nursing time

Aminoglycosides can be used in synergy to fight what types of infections?

G+ Infections


MSSA

Enterococci

Which aminoglycoside has the best Pseudomonas aeruginosa activity?
Tobramycin
Adverse Reactions of Aminoglycosides

Aminoglycosides are Mean O’l Guys!

  • Nephrotoxicity
  • Ototoxicity (vestibular and auditory)
  • Neuromuscular Blockade (if infused too quickly)

Sulfamethoxazole: MOA

  • Structural analoge of p-aminobenzoic acid (PABA), the building block used by bacteria to make dihydrofolic acid
  • Dihydrofolic acid is used to make folic acid, which is used for nucleotide synthesis
  • Sulfamethoxazole competitively inhibits bacterial dihydropteroate synthetase, an enzyme critical for folic acid biosynthesis

Trimethoprim: MOA

  • Competitively inhibits dihydrofolate reductase, inhibiting conversion of dihydrofolic acid to tetrahydrofolic acid, the metabolically active cofactor for synthesis of purines, thymies, and DNA

TMP-Sulfamethoxazole is the DOC for what infections?
Enterobacteriaceae
TMP-Sulfamethoxazole is the only PO drug for:
Staphylcoccus aureus (including MRSA) infections
Gentamicin Route of Administration
IV
Tobramycin Route of Administration
IV
Amikacin Route of Administration
IV
Streptomycin Route of Administration
IV
TMP-Sulfamethoxazole are eliminated by what routes?

Renal

;

Good for UTIs

Adverse Reactions of TMP-Sulfamethoxazole

  • Hypersensitivity reactions
  • Crystallization in the Kidneys – counsel patients to take with water
  • Hematologic – bone marrow suppression at high doses

Tetracyclines: MOA

  • Binds reversibly to 30S bacterial ribosomal subunit
  • Blocks attachment of tRNA to an acceptor site on the mRNA ribosomal complex

Doxycycline Route of Administration
PO/IV
Indications of Tetracyclines

  • Respiratory Infections
  • Genital Infections
  • Skin Infections

Adverse Reactions of Tetracyclines

  • Photosensitivity
  • Discoloration of Developing TeethCI ; 8 yo, pregnant, nursing mothers
  • Esophageal Ulceration

Tigecycline: MOA

  • A glycylcycline antibiotic
  • Similar MOA as tetracyclines (inhibits 30S ribosomal subunit)
  • 5X binding affinity — overcomes resistance mechanisms (ribosomal and efflux pumps)

Tigecycline: Spectrum of Activity

  • Staph. aureus (inclusing MRSA)
  • Enterococcus (including VRE, excluding Proteus mirabilis)
  • Strep. pneumoniae (including PRSP)
  • Enterics (including ESBLs)
  • Non-Enterics (excluding P. aeruginosa)
  • Respiratory G-
  • Anaerobes
  • Atypicals

 

Adverse Effects of Tigecycline
Nausea/Vomiting
Tigecycline Route of Administration
IV
When should you decrease maintenance dose of Tigecycline?
Patients with liver failure
Macrolides: MOA
Reversibly inhibits 50S ribosomal subunit
Adverse Effects of Macrolides
Nausea
Erythromycin Drug Interactions
Hepatic Cytochrome P450 – inhibits CYP 3A4
Clarithromycin Drug Interactions
Hepatic Cytochrome P450 – inhibits CYP 3A4
Major Problem with Telithromycin
Hepatic Failure
Quinolones: MOA
Inhibits bacterial Topoisomerase II and IV
Quinolones: Mechanism of Resistance

  • Point mutations
  • Decrease outer membrane permeability

Ciprofloxacin Route of Administration
PO/IV
Levofloxacin Route of Administration
PO/IV
Moxifloxacin Route of Administration
PO/IV

Which of the following are used for systemic AND urinary tract infections?

  1. Moxifloxacin
  2. Levofloxacin
  3. Ciprofloxacin
  4. Gemifloxacin

Ciprofloxacin and Levofloxacin are used for bacteremia and UTIs

 

Moxifloxacin is NOT used for UTIs

Gemifloxacin is used for respiratory tract infections ONLY

Adverse Effects of Quinolones

  • CNS effects (dizziness)
  • Arthropathy
  • Tendonitis/Tendon Rupture (Black Box Warning for kids – inhibits cartilage development)
  • QT Interval Prolongation

What is a critical counseling point for a patient that is on a quinolone and is taking an iron supplement?

  • CI when taking both at same moment in time
  • Separate Quinolone and Iron supplement
  • Iron supplement 1 hr before Quinolone or 2 hours after Quinolone
  • Some say 4 before or 4 after

Clindamycin: MOA

Lincosamide Antibiotic

 

Inhibits bacterial protein synthesis by binding to 50S ribosomal subunit

Route of Elimination for Clindamycin

Hepatically Metabolized

 

No dosage adjustment for renal impairment

T/F: Clindamycin requires dosage adjustment in patients that are renally retarded

False

 

Only patients that are hepatically retarded need dosage adjustments, b/c it is hepatically metabolized

Adverse Effects of Tigecycline

  • Diarrhea
  • GI upset

Metronidazole: MOA

  • Enters cell by passive diffusion and is activated by reductive processes
  • This produces short-lived metabolites that damage bacterial DNA and subsequently causes cell death

Metronidazole Route of Elimination

  • Hepatically metabolized
  • No dosage adjustment unless severe kidney failure

Metronidazole Route of Administration
PO/IV
Adverse Effects of Metronidazole

  • CNS effects
  • GI upset
  • Metallic taste
  • Disulfiram-Like Reaction (possible but not likely – don’t use with alcohol)

Chloramphenicol: MOA

  • Binds reversibly to 50S bacterial ribosomal subunit
  • Inhibits protein synthesis

Chloramphenicol Route of Elimination
Primarily metabolized in liver
Adverse Effects of Chloramphenicol

  • Aplastic anemia (irreversible)
  • Bone marrow suppression (reversible)
  • Gray Baby Syndrome (primarily neonates)

Vancomycin Route of Administration
IV
Vancomycin Route of Elimination
Renal
Adverse Effects of Vancomycin

  • Nephrotoxicity – not as bad as aminoglycosides
  • Drug Fever
  • Infusion-Related Side Effects

“Red Man” Syndrome

Hypotension

 

Quinupristin/Dalfopristin: MOA
Dalfprostin has been shown to inhibit the early phase of protein synthesis while Quinupristin inhibits the late phase of protein synthesis
Quinupristin/Dalfopristin Route of Elimination

  • Metabolized to several active major metabolites
  • Fecal excretion constitutes the main elimination route for both parent drugs and their metabolites

Quinupristin/Dalfopristin Spectrum of Activity

  • Enterococcus faecium (VRE), not E. faecalis
  • Staph. aureus
  • Strep. pyogenes

Adverse Effects of Quinupristin/Dalfopristin

  • Inflammation at infusion site
  • Arthralgia/myalgia

Linezolid: MOA

Oxazolidine Antibiotic

 

Binds to 23S rRNA of the 50S subunit –> prevents formation of a functional 70S initiation complex

 

-static against Staph.

-cidal against Strep.

Linezolid Route of Elimination

  • Renal clearnace is low and suggests net tubular reabsorption
  • Mainly Non-Renal

Linezolid Spectrum of Activity

MRSA

VRE

Strep. pneumoniae

Adverse Effects of Linezolid
Thrombocytopenia
Linezolid Drug Interactions
MAOI – may lead serotonin syndrome
Daptomycin: MOA

Cyclic Lipopeptide Antibiotic

  • Inserts lipophilic tail into cytoplasmic membrane –> forms a channel that causes depolarization
  • Efflux of K+ and perhaps other ions inhibits macromolecular synthesis and leads to cell death
  • Kills bacteria but leaves cell wall intact which may potentially lead to toxins being suddenly released into the system

Daptomycin Spectrum of Activity

Aerobic G+

MRSA

VRE

Adverse Effects of Daptomycin

Myopathy

 

Not a selective agent and can target cell membranes of skeletal muscles

Daptomycin Route of Administration
IV
Telavancin Route of Administration
IV
Telavancin: MOA

Lipoglycopeptide

  • Combines mechanisms of both vancomycin (glycopeptide) and daptomycin (cyclic lipopeptide)
  • Works on cell wall and cell membrane
  • Bactericidal

 

Adverse Effects of Telavancin

Nephrotoxicity

Black Box Warning: Birth Defects

Telavancin Route of Elimination
Renal
Chloramphenicol Route of Administration
IV
Azithromycin Route of Administration
PO/IV
Quinupristin/Dalfopristin Route of Administration
IV
Linezolid Route of Administration
PO/IV

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