DRUGS - Protein Synth Inhibitors [Wk 4 FOM] Flashcards Preview

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Flashcards in DRUGS - Protein Synth Inhibitors [Wk 4 FOM] Deck (36)
1

Pair each Protein Synthesis Inhibitor with the proper prokaryotic subunit affected

30S inhibitors

  1. Aminoglycosides
  2. Tetracycline

50S inhibitors

  1. Chloramphenicol
  2. Clindamycin
  3. Linezolid
  4. Macrolides
  5. Streptogramins

 

2

Identify the 1) Mechanism of inhibition, 2) Spectrum of activity, 3) Mechanism of resistance, and 4) Adverse effects associated with the following agent(s):

Linezolid

• MECHANISM
Binds to 23s rRNA on 50s unit of ribosome, inhibits initiation of tln

• SPECTRUM
Reserved for Grm+ (MRSA, VRE)

• RESISTANCE
Alters target (23s rRNA)

• SIDE EFFECTS

  1. Bone Marrow Suppression

3

Name two additional qualities that make Linezolid an excellent pharmaceutical

  1. No Cross-Resistance
  2. Excellent Bioavailability (even better than Vanco)

4

Identify the 1) Mechanism of inhibition, 2) Spectrum of activity, 3) Mechanism of resistance, and 4) Adverse effects associated with the following agent(s):

Aminoglycosides Class:

  1. Gentamycin
  2. Neomycin
  3. Tobramycin
  4. Streptomycin
  5. Amikacin

• MECHANISM
Prevents initiation complex formation, misreading of mRNA, early termination; 
*Note: Unique: Can stop initiation, elongation, and termination of tln

• SPECTRUM
Gram – aerobic only (eg Pseudomonas)

• RESISTANCE
1. Intrinsic: drug can’t enter bac
2. Acquired: drug target methylation, enzyme inactivation of drug
*Note: Amikacin – less susceptible to enzyme inactivation

• SIDE EFFECTS
• Tubular Necrosis – nephro/oto toxicity,
• teratogen – hearing loss in fetus
• IV administration

5

Why are the Aminoglycosides coupled with Penicillins?

This coupling increases permeability of Grm + cell wall so aminoglycoside can enter the cell  (Yes, this is the only way you're going to get Aminiglycosides to be active against gm+ agents)

6

Identify the 1) Mechanism of inhibition, 2) Spectrum of activity, 3) Mechanism of resistance, and 4) Adverse effects associated with the following agent(s):

Tetracyclines Class:

  1. Tetracycline
  2. Doxycycline
  3. Demeclocycline
  4. Minocycline

• MECHANISM
Bind to 30s unit – prevents tRNA attachment

• SPECTRUM
• BROAD:  B. burgdorferi (lyme), H. pylori (ulcer),  M. pneumoniae

• RESISTANCE

  1. Intrinsic: dec. drug uptake
  2. Acquired: Efflux!, alter target

• SIDE EFFECTS

  1. Chelates with metal ions (dec. absorption of drug)
  2. GI irritation
  3. photosensitivity
  4. teeth discoloration
  5. Inhibits bone growth – children
  6. DO NOT GIVE TO: Pregnant women, children under 8

7

Identify the 1) Mechanism of inhibition, 2) Spectrum of activity, 3) Mechanism of resistance, and 4) Adverse effects associated with the following agent(s):

Macrolides Class:

  1. Erythromycin
  2. Azithromycin
  3. Clarithromycin

• MECHANISM
Binds to 23s rRNA on 50s unit – inhibits tRNA translocation

• SPECTRUM
BROAD (Respiratory Pathogens, Chlamydia, Mycobacteria)

• RESISTANCE

Efflux!
Drug target methylation
Esterases alter drug

**CROSS-RESISTANCE WITH Clindamycin & Streptogramins

• SIDE EFFECTS

  1. GI irritation
  2. Hepatic Failure
  3. Prolonged QT interval
  4. Inhibit Cyt P450
  5. drug-drug interactions
  6. DO NOT GIVE Clarithromycin TO: Pregnant women

8

Identify the 1) Mechanism of inhibition, 2) Spectrum of activity, 3) Mechanism of resistance, and 4) Adverse effects associated with the following agent(s):

Chloramphenicol

MECHANISM

Binds 50s unit – inhibits peptide bond formation• SPECTRUM

SPECTRUM

Extended
Limit use(due to side effects)

Can cross B-B barrier, treat meningitis

RESISTANCE

 

Acetyltransferase modifies drug

• SIDE EFFECTS

  1. TOXIC side effects!!
    Bone marrow depression and aplastic anemia
  2. DO NOT GIVE TO: Pregnant women, children under 8
  3. Gray Baby

9

What is Gray Baby Syndrome, and what causes it?

Gray Baby Syndrome: infants lack the transferase needed to break down drug, in this case CHLORAMPHENICOL, high levels of drug accumulate, results in cardio and respiratory collapse

10

Identify the 1) Mechanism of inhibition, 2) Spectrum of activity, 3) Mechanism of resistance, and 4) Adverse effects associated with the following agent(s):

Clindamycin

• MECHANISM
Binds to 23s rRNA on 50s unit – inhibits tRNA translocation

• SPECTRUM
BROAD  (Aerobic and anaerobic, acne)

• RESISTANCE
Alter/methylate ribosome target, adenylase modifies drug

**CROSS-RESISTANCE WITH Macrolides & Streptogramins

 

• SIDE EFFECTS

  1. Hypersensitivity – rash, fever
  2. Superinfection – C. diff
  3. Diarrhea, abdominal pain, mucus/blood in stool

11

Identify the 1) Mechanism of inhibition, 2) Spectrum of activity, 3) Mechanism of resistance, and 4) Adverse effects associated with the following agent(s):

Streptogramins:
Quinupristin/
Dalfopristin
(together)

• MECHANISM
Binds to 23s rRNA on 50s unit – inhibits tRNA translocation

• SPECTRUM
Reserved for Grm + MRSA, VRE

• RESISTANCE
Alter/methylate ribosome target, enzymes modify drug,
Efflux!

**CROSS-RESISTANCE WITH Macrolides & Clindamycin

• SIDE EFFECTS

  1. Arthralgias and myalgias
  2. Inhibits Cyt P450, drug – drug interactions

     

12

RESISTANCE MECHANISMS #1: Drugs that don't reach their target due to either a) decreased uptake, or b) efflux

• Primarily decreased uptake (it's a TASC! -or- SuCh a TeAm!)

  1. o Tetracyclines
  2. o Aminoglycosides
  3. o Sulfonamides
  4. o Chloramphenicol

• Increased efflux ("To create Flux: set a Magnetic Strip on the Floor, and then get yourSulf a newspaper; read it A-->Z while Cepping Tetley)

  1. Quinupristin/dalfopristin
  2. Macrolides
  3. Fluoroquinolones
  4. Aztreonam
  5. Cephalosporins
  6. Tetracyclines (most impt), minocycline the exception
  7. Sulfonamides

13

RESISTANCE MECHANISMS #2: Drugs whose targets are altered due to either a) direct alteration, or b) upregulation of target/substrate

• Altered Target

  1. o Beta-lactams – altered penicillin binding proteins (MRSA)
  2. o Vancomycin- altered target
  3. o Rifampin - DNA dependent RNA polymerase
  4. o Fluoroquinolones - DNA topoisomerase II or IV
  5. o Sulfonamides - Dihydropteroate synthetase
  6. o Trimethoprim - Dihydrofolate reductase
  7. o Linezolid – altered ribosome
  8. o Aminoglycosides – altered ribosome (uncommon)
  9. o Erythromycin, clindamycin, quinupristin/dalfopristin – methyltransferase modified ribosome
  10. o Tetracyclines – production of proteins that interfere with ribosomal binding

• Upregulation of target or its substrate

  1. o Sulfonamides- Increased levels of para-amino benzoic acid synthesis

14

RESISTANCE MECHANISMS #3: Drugs that are not active primarily due to enzymatic alteration of the antibiotic, and 

  1. o   Penicillins  beta-lactamases
  2. o   Cephalosporins  beta-lactamases
  3. o   Aminoglycosides  Amikacin most resistant, acetyl group
  4. o   Chloramphenicol  Acetyltransferase action
  5. o   Tetracyclines  minor- acetylation
  6. o   Macrolides  bacterial esterases
  7. o   Clindamycin  adenylation
  8. o   quinupristin/dalfopristin 
  9. o   metronidazole  decreased drug activation

15

Name the drugs where resistance RARELY occurs

  1. Bacitracin
  2. Polymyxins

16

List the drugs that shouldn't be used with:

  1. Newborns
  2. Children

1. Don’t use with Newborns "ChEry Softdrink"

  • Chloramphenicol (can’t glucuronidate)
  • Sulfonamides
  • Erythromycin (pyloric stenosis)

2. Don’t use in Children "FluTe"

  • Tetracyclines
  • Fluoroquinolones

 

17

Which drugs must be adjusted for Renal function in Elderly patients (i.e. half-lives increase)?

"Old people love Beets & FlAmingos"
  • Beta lactams
  • Aminoglycosides
  • Fluoroquinolones

18

Which drugs should not be given to pregnant women?

"conservative Claire knew her FATe: get pregnant and have Children"

  • Tetracycline
  • Aminoglycosides
  • Clarithromycin
  • Fluoroquinolones
  • Chloramphenicol

19

Which two drugs cause complications in patients with Gluc-6-phos DH deficiency?

o Sulfonamides (Trimethoprim/Sulfamethoxazole)
o Nitrofurantoin

20

Which drugs are implicated in hypersensitivity?

"In the Star Trek universe, Cling-ons can Be themSulves at Hyperspeed"
  1. • Sulfonamides  (Patients should not be given other sulfa drugs such as diuretics)
  2. • Beta-lactam (Skin test can be used to confirm and patient can be desensitized)
  3. • Clindamycin

21

Which of the beta-lactams is least likely to cause an allergic reaction?

Aztreonam

22

Provide an example for each of the following "combination drug therapy" effects:

  1. Enhancement of antibacterial activity in the treatment of specific infections (synergism)
  2. Addition of inhibitors to prevent degradation of the enzyme

1. Enhancement of antibacterial activity in the treatment of specific infections (synergism)

  • Trimethoprim – Sulfamethoxazole:  Inhibits multiple steps in folate synthesis
  • Aminoglycoside + Penicillin:  Penicillin increases permeability of cell membranes increasing the ability of aminoglycosides to enter the cell

2. Addition of inhibitors to prevent degradation of the enzyme

  • Ampicillin-sulbactam, Amoxicillin-clavulanate, Piperacillin-tazobactam, Ticarcillin-clavulanate, Imipenem-cilastatin (blocks renal dehydropeptidase)

23

Provide an example for each of the following "combination drug therapy" DRAWBACKS:

  1. Risk of Toxicity from two agents
  2. Antagonism

1.  Risk of toxicity from two agents

  •  Vancomycin or Aminoglycosides each alone have some nephrotoxicity.  If given together you get marked renal impairment.

2.  Antagonism

  • Pneumococcal meningitis
       Penicillin - 21% mortality
       Penicillin + Tetracycline - 79% mortality  (both of these drugs together are not as effective as alone)

24

Which of the following is true regarding aminoglycosides?

  1. Bactericidal for Gram-positive aerobic bacteria
  2. Absorbed from the GI tract
  3. Bind to the 50S ribosomal subunit
  4. Time-dependent inhibitors
  5. Require energy to enter the cell

25

Which of the following antibacterial drugs, that we discussed previously, should not be consumed with milk or antacids due to the formation of an insoluble complex between the drug and cations?

  1. Nitrofurantoin
  2. Ciprofloxacin
  3. Metronidazole
  4. Penicillin G 
  5. Rifampin

Ciprofloxacin

26

A 42 year old male presents with a ruptured appendix and peritonitis resulting in severe infection with both aerobic and anaerobic Gram negative organisms.
 
1)  Why is monotherapy with an aminoglycoside inappropriate?
 
2)  What drugs are effective against anaerobic organisms?


 

1) Aminoglycosides are only effective against gm(-) AEROBES. So the anaerobic organisms wouldn't be treated. 

2) Clindamycin, etc...

27

Which of the following contributes to gray baby syndrome when chloramphenicol is administered to neonates?

  1. Decreased intestinal absorption
  2. Increased glomerular filtration
  3. Lack of CNS penetration
  4. Alteration of gastrointestinal flora by a broad spectrum antibiotic
  5. Low hepatic glucuronyl transferase activity 

Low hepatic glucuronyl transferase activity 

28

Treatment of a bacterial culture with an antibacterial drug results in the cytoplasmic accumulation of monosomes.  The antibacterial drug is most likely:

  1. Amikacin
  2. Azithromycin
  3. Ciprofloxacin
  4. Meropenem
  5. Tetracycline 

Amikacin

*Monosomes accumulate when the INITIATION stage is inhibited.  The only drug listed here that affects initiation is Amikacin (Remember: Aminoglycosides affect all three phases: Initiation, Elongation, and Termination).  Note:  although not an option given here, Linezolid is a drug that specificially inhibits initiation, so would have been a solid choice as well.  

29

Your initial treatment with tetracycline is ineffective so you switch to erythromycin.   Unfortunately, your patient still doesn’t respond to the new therapy.  This is mostly likely because of resistance due to:

  1. Enzymatic degradation of the drugs
  2. Active efflux of the drugs from the bacteria by a transporter
  3. Modification of the 50 S ribosomal subunit by methyltransferase preventing binding of the drugs
  4. Acetylation of the drugs
  5. Overproduction of the ribosomal target

Active efflux of the drugs from the bacteria by a transporter 

30

NB is a 21-year-old college football player (linebacker) who presents to the clinic with a large, red abscess on his right arm, likely due to community-acquired methicillin-resistant Staphylococcus aureus.  It is lanced and drained, and antibiotic therapy is to be prescribed.  Which drug would be the most appropriate choice for NB’s infection?  He is to be treated as an outpatient.

  1. Cephalexin (1st gen)
  2. Ciprofloxacin
  3. Erythromycin
  4. Vancomycin
  5. Linezolid 

Linezolid 

31

Identify the drugs that are reserved for infections due to hard to treat drug resistant bacteria like MRSA and VRE (vancomycin resistant enterococcus).

5th gen cephalosporin- ceftaroline, vancomycin (MRSA only, obviously), daptomycin, Quinupristin-Dalfopristin, Linezolid, Clindamycin (not specifically RESERVED for these, though)

32

Your patient has a severe infection and a suppressed immune system which of the following antibiotics is the best choice for your patient.

  1. Doxycycline
  2. Gentamicin
  3. Erythromycin
  4. Linezolid
  5. Clindamycin

Gentamicin

*The Bacteriocidal Prot Synth Inhibitors:  Aminoglycosides & Streptogramins

33

Name the bactericidal Inhibitors of protein synth

  1. Aminoglycosides (GNATS)
  2. Streptogramins

34

A 30 year old woman who is pregnant has a severe lung infection.  She needs to be treated with an antibiotic.  Assume each of the following is effective against the bacteria in question.  Which would you choose?

  1. Azithromycin
  2. Clarithromycin
  3. Gemifloxacin
  4. Minocycline
  5. Moxifloxacin 

Azithromycin

*while in the same class (Macrolides), Azithromycin can be given to pregnant women, while Clarithromycin CANNOT. 

35

A 23-year old female is being treated for a severe infection in the hospital.  Every time she gets up and attempts to move around her room, she loses her balance.  The antibiotic treatment that is most likely responsible for her symptom is:

  1. Gemifloxacin
  2. Linezolid
  3. Piperacillin
  4. Quinupristin/ dalfopristin
  5. Tobramycin 

Tobramycin

*Aminoglycosides are ototoxic. 

36

What are rifampin's 4 R's?

  1. RNA polymerase inhibition
  2. Revs up microsomal P-450
  3. Red/orange body fluids
  4. Rapid resistance is used alone.