DRUGS - Nucleic Acid Synth Inhibitors [Wk 4 FOM] Flashcards Preview

Med Year 1 - Foundation > DRUGS - Nucleic Acid Synth Inhibitors [Wk 4 FOM] > Flashcards

Flashcards in DRUGS - Nucleic Acid Synth Inhibitors [Wk 4 FOM] Deck (29):
1

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

Rifamycin 

MECHANISM

Binds bacterial RNA polymerase at the active center (Beta-subunit) blocking the elongation of mRNA

SPECTRUM

Gram +/-  (e.g. Mycobacteria tuberculosis)

RESISTANCE

Intrinsic: the drug is unable to bind to the beta-subunit of polymerase

Acquired: the strain acquires mutations in rpoB gene, which prevents drug binding

• SIDE EFFECTS

  1. GI side effects
  2. Hypersensitivity – Fever
  3. Hepatotoxic (caution in pt w/ chronic liver disease)
  4. Turns body fluids orange/red
     

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):

Fidaxomicin

• MECHANISM

Inhibits RNA polymerase by binding to the sigma subunit;  (better at preventing recurrent infections of C. diff) 

• SPECTRUM

Narrow: Gram + anaerobes (e.g. C. diff)

*note: Spares many of the gut flora

• RESISTANCE

Point mutation in RNA polymerase has been observed in vitro

• SIDE EFFECTS

Low absorption

Nausea, vomiting

 

3

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

Fluoroquinolones Class

  1. Ciprofloxacin
  2. Levofloxacin
  3. Moxifloxacin

• MECHANISM

Inhibit DNA replication by binding bacterial DNA topoisomerase:

  1. Gram neg. = topoisomerase II, prevents relaxation of supercoiled DNA
  2. Gram pos. = topoisomerase IV, interferes with sepearation of replicated chrom DNA

• SPECTRUM

Broad: Gram +/- and atypical organisms like Mycoplasma

• RESISTANCE

Active efflux of the drug
Mutations in topoisomerases

• SIDE EFFECTS

  1. GI side effects
  2. confusion
  3. photosensitivity
  4. Tendon rupture
  5. Contraindicated in pregnant women
  6. Prolongation of QT interval

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):

Sulfonamides Class

  1. -Sulfamethoxazole
  2. -Sulfisoxazole
  3. -Sulfadiozine

• MECHANISM

Para-aminobenzoic acid (PABA) analog and acts as a competitive inhibitor of dhidyropteroate synthetase

• SPECTRUM

Folate Antagonist:  Bacteria & Fungi that synthesize their own dihydrofolic acid

• RESISTANCE

  1. Change in dihydropteroate synthetase
  2. Increased efflux
  3. Increased production of PABA

• SIDE EFFECTS

  1. Hypersensitivity (Rash, ^ T cells)
  2. Stevens-Johnson Syndrome
  3. Cross reaction to other drugs containing sulfonamide moieties
  4. Crystalluria -> acute renal failure

5

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

Trimethoprim

• MECHANISM

Inhibits bacterial dihydrofolate reductase

• SPECTRUM

Folate Antagonist: Bacteria and fungi that synthesize their own dihydrofolic acid 

• RESISTANCE

  1. Altered dihydrofolate reductase
  2. Increased amounts of dihydrofolate reductase
  3. Alternative metabolic pathways

• SIDE EFFECTS

  1. Bone marrow suppression
  2. Hyperkalemia

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):

Trimethoprim/ Sulfamethoxazole [TMP-SMX]

• MECHANISM

Sequential blockage of the folate synthesis pathway

• SPECTRUM

  1. Broad treatment of UTIs
  2. Shigella
  3. Salmonella
  4. Pneumocystis

• RESISTANCE
• SIDE EFFECTS

 

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):

Metronidazole

• MECHANISM

Activated form generates free radicals leading to DNA strand breaks and cell death;  *Also blocks aldehyde dehydrogenase, inhibiting oxidation of acetaldehyde

• SPECTRUM

  1. Protozoa
  2. Anaerobic bacteria including C. diff
  3. NOT AEROBES (only metabolized to the active form in anaerobes)

 

• RESISTANCE

RARELY

• SIDE EFFECTS

  1. Nausea
  2. diarrhea
  3. headache
  4. metallic taste
  5. Avoid during pregnancy
  6. Disulfiram-like reaction w/ alcohol (hang over feeling)

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):

Nitrofurantoin

• MECHANISM

Reduced by bacterial flavoproteins to reactive intermediates, which inactivated or alter bacterial ribosomal proteins and other macromolecules. This leads to an inhibition of the synthesis of DNA, RNA, cell wall, and protein

• SPECTRUM

Broad spectrum;  Rapidly excreted in the urine in an active form

*note:  Only reach high conc. in the urine

 

• RESISTANCE

Lack of bacterial resistance since the drug interferes with a variety of processes

• SIDE EFFECTS

  1. Vomiting
  2. Pulmonary toxicity

9

Which NA Inhibitors are used for UTI infections?

  1. Fluoroquinolones
  2. TMP-SMX
  3. Nitrofurantoin (PREFERRED TREATMENT; ineffective for infections outside the lower urinary tract)

10

Name three special precautions regarding treatment with Fluoroquinolones

  1. Chelate cations (don’t take w/ Ca, Fe, Al, and Zn)
  2. Avoid dairy products or calcium-fortified juice
  3. Adjust for renal dysfunction for all agents except moxifloxacin (not secreted into the urin)

11

What is Kernicterus, and with which NA Inhibitor class is it associated?

Kerniticus = accumulation of bilirubin in the brain, leading to encephalopathy.

Sulfonamides

Sulfonamides can compete for binding to albumin leading to kernicterus in infants and complications with drugs like warfarin

12

What happens when G6PDH deficient patients are (X-linked recessive) treated with Sulfonamides?

Hemolysis

13

Name the two bacteriostatic Nucleic Acid Inhibitors

  1. Sulfonamides class
  2. Trimethoprim

14

If mismanaged, which Nucleic Acid Inhibitor can lead to organ rejection/loss of seizure control, and how does this happen?

Rifamycin

Induction of cytochrome p450 enzymes can induce metabolism of other medicines leading to organ rejection/loss of seizure control

15

What is unique about the treatment protocol for Mycobacteria tuberculosis

Mycobacteria tuberculosis must be treated with 4 different antibiotics due to the high rate of resistance

16

Deacetylation of Rifampin leads to...

Increased excretion of the drug in the feces

17

Would you expect rifampin and fidaxomicin to exhibit cross resistance?

18

If a strain of Pseudomonas aeruginosa has become resistant to levofloxacin which additional drug(s) do you expect the bacteria to be resistant to?

  1. Nafcillin
  2. Ciprofloxacin
  3. Aztreonam
  4. All of the above
  5. Can’t determine

 

19

Which drug is often used in the event of biological warfare, and why?

In the event of biological warfare, ciprofloxacin may be used to treat and prevent dangerous illnesses that are deliberately spread such as plague, tularemia, and anthrax of the skin or mouth. Talk to your doctor about the risks of using this medication for your condition.

20

Of the Fluoruquinones, which has the greatest bioavailability?

Levofloxacin

21

Use the table to identify which organism TMP-SMX is least effective against 

  1. Staphylococcus aureus
  2. Streptococcus pneumoniae
  3. Haemophilus influenzae
  4. Shigella Sonnei
  5. Proteus vulgaris

22

What other antibiotic class did we discuss that can cause disulfiram reaction and should not be consumed with alcohol?

A.  Penicillin
B.  Carbapenems
C.  Daptomycin
D.  2nd Generation Cephalosporins
E.  Polymyxin B

23

A 21 year old woman presents with a 3-day duration of discomfort with urination and increased urinary frequency.  Microscopic examination of the sediment of a centrifuged urine sample reveals 10-15 white blood cells per high power field and numerous Gram negative bacteria. 

Which of the following organisms is most likely?

  1. Escherichia coli
  2. Pseudomonas aeruginosa
  3. Enterococcus
  4. Group B streptococci
  5. Mycoplasma

24

Upregulation of para-aminobenzoic acid synthesis is associated with the development of drug resistance toward which antibiotic

  1. Sulfamethoxazole
  2. Rifamycin
  3. Ciprofloxacin
  4. Metronidazole
  5. Trimethoprim

25

Which of the following drugs is most likely to cause anemia in individuals with glucose-6 phosphate dehydrogenase deficiency?

  1. Aztreonam
  2. Nitrofurantoin
  3. Sulfisoxazole
  4. Metronidazole
  5. Vancomycin 

26

Alex’s tears have turned a reddish color.  What is the mechanism of action of the antibiotic she is currently taking?

  1. Inhibits DNA polymerase
  2. Inhibits G-6-P dehydrogenase
  3. Inhibits RNA polymerase
  4. Inhibits dihydrofolate reductase
  5. Inhibits DNA topoisomerase 

27

Resistance to which drug occurs following the acquisition of mutations in DNA topoisomerase

A.  Rifampin
B.  Ciprofloxacin
C.  Trimethoprim
D.  Nitrofurantoin
E.  Metronidazole 

Ciprofloxacin

28

Which of the following antibiotics would you use for empiric therapy in a patient with signs and symptoms of a urinary tract infection with a positive urinalysis?

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

29

Which drug is able to under go a Disulfiram-like reaction with alcohol?

Metronidazole