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Systemic Pharm I > DNA Replication and Folic Acid Synthesis Inhibitors > Flashcards

DNA Replication and Folic Acid Synthesis Inhibitors Flashcards

1
Q

2nd gen fluoroquinolones

A

ciprofloxacin and ofloxacin

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2
Q

3rd gen fluoroquinolones

A

levofloxacin

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3
Q

4th gen fluoroquinolones

A

gemifloxacin and moxifloxacin

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4
Q

Antifolate drugs

A

sulfacetamide, sulfadiazine, sulfamethoxazole, trimethoprim, cotrimoxazole/bactrim= trimethoprim + sulfamethoxazole

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5
Q

What is bactrim?

A

old name cotrimoxazole, combination of trimethoprim and sulfamethoxazole

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6
Q

What drug class inhibits DNA synthesis via DNA gyrase and topoisomerase IV?

A

fluoroquinolones

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7
Q

What drug classes inhibit DNA synthesis via folic acid?

A

trimethoprim and sulfonamides

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8
Q

What is the predecessor to fluoroquinolones?

A

naladixic acid – fluoroquinolones discovered in the 1960s

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9
Q

What is the MOA of fluoroquinolones?

A

inhibit replication of DNA by interfering with DNA gyrase AND topoisomerase IV

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10
Q

How do fluoroquinolones enter bacteria?

A

passive diffusion

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11
Q

What do fluoroquinolones treat?

A

relative broad spectrum, gram - and + coverage with dual mechanism giving added protection against resistance

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12
Q

Are fluoroquinolones bacteriostatic or bactericidal?

A

bactericidal, more pronounced as concentration increases

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13
Q

What gram (-) organisms are treated by fluoroquinolones?

A

pseudomonas, H. influenzae, moraxella, chlamydia

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14
Q

T/F earlier generations of fluoroquinolones have increased gram (+) coverage?

A

false the later generations are more broad spectrum

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15
Q

Which fluoroquinolone is most effective against pseudomonas?

A

ciprofloxacin

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16
Q

Which fluoroquinolone is the drug of choice for anthrax?

A

ciprofloxacin

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17
Q

Which fluoroquinolone does not concentrate in urine and is therefore not indicated for UTIs?

A

moxifloxacin

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18
Q

Which two fluoroquinolones have the longest half-lives?

A

levofloxacin and moxifloxacin, allow for once a day dosing

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19
Q

What interferes with fluoroquinolone absorption?

A

antacids, iron, zinc, calcium

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20
Q

Which fluoroquinolone is excreted by the liver instead of the kidney?

A

moxifloxacin

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21
Q

What are the adverse reactions of fluoroquinolones?

A

GI, CNS toxicity, phototoxicity, connective tissue problems, new FDA warning for hypoglycemia

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22
Q

What are the contraindications for fluoroquinolones?

A

patients with arrhythmia, avoid in pregnancy, nursing mothers and children under 18

23
Q

Why can’t pregnant women and young children be given fluoroquinolones systemically?

A

shown to cause cartilage erosion, topical drugs okay

24
Q

What drug interactions do ciprofloxacin and ofloxacin have?

A

increase theophylline levels

25
Q

What drug interactions do fluoroquinolones have?

A

increase levels of warfarin, caffeine and cyclosporine

26
Q

What factors do DNA and RNA synthesis depend on?

A

folate derived cofactors

27
Q

How do humans get folic acid?

A

diet

28
Q

How do bacteria get folic acid?

A

make their own, many bacteria are impermeable to folic acid

29
Q

T/F sulfa drugs are seldom given alone

A

true

30
Q

What is the MOA of sulfa drugs?

A

sulfonamides are structural analogues of PABA and compete with dihydropteroate synthetase and inhibit folate production

31
Q

What do sulfonamides treat?

A

wide antibacterial spectrum, not active against anaerobes, pseudomonas is resistant

32
Q

How does sulfonamide resistance come about?

A

organisms that can obtain folic acid from the environment are not sensitive and there can be acquired resistance

33
Q

How do sulfonamides acquire resistance?

A

altered enzyme, decreased cellular permeability, enhanced production of PABA

34
Q

What is the absorption of sulfonamides?

A

most absorbed from the small intestine, not usually applied topically because of risk of sensitization

35
Q

What is true of the distribution of sulfonamides?

A

bound to serum albumin, penetrate well into CSF, can pass placenta

36
Q

Where are sulfonamides metabolized?

A

in the liver, metabolites can be toxic

37
Q

How are sulfonamides excreted?

A

eliminated through glomerular filtration and breast milk

38
Q

What are the adverse effects of sulfonamides?

A

crystalluria, hypersensitivity, hemopoietic disturbances, kernicterus, drug potentiation

39
Q

What is crystalluria?

A

precipitate at neutral or acidic pH that can cause nephrotoxicity

40
Q

What is the result of a hemopoietic disturbance?

A

anemia

41
Q

What is kernicterus?

A

increased bilirubin in the CNS, occurs in newborns

42
Q

What do sulfonamides do to warfarin?

A

increases circulating warfarin levels

43
Q

What is the MOA of trimethoprim?

A

inhibits dihydrofolate reductase, preventing conversion of dihydrofolic acid to tetrahydrofolic acid

44
Q

T/F the antibacterial spectrum of trimethoprim is similar to sulfonamides but much more potent

A

true

45
Q

How does resistance to trimethoprim occur?

A

develops in gram (-) bacteria due to presence of altered enzyme

46
Q

What are the pharmacokinetic properties of trimethoprim?

A

drug is a weak base (accumulates in more acidic environments), penetrates CSF, excreted via kidney

47
Q

What is the adverse effect of trimethoprim?

A

folic acid deficiency, especially in pregnant patients or those with poor diets, can co-administer with folinic acid

48
Q

What is cotrimoxazole/bactrim?

A

combination of trimethoprim and sulfamethoxazole, has greater activity and similar half life to each drug alone

49
Q

T/F bactrim (trimethoprim and sulfamethoxazole) have a broader spectrum than sulfa drugs

A

true

50
Q

What does bactrim (trimethoprim and sulfamethoxazole) treat?

A

UTIs, respiratory tract infections, pneumocystis jiroveci, MRSA (especially skin and soft tissue infections)

51
Q

T/F resistance is a problem in trimethoprim + sulfamethoxazole

A

false, less frequent resistance

52
Q

How is bactrim administered and excreted?

A

orally and via kidney

53
Q

What are adverse effects of bactrim?

A

skin rash, nausea and vomiting, anemias or thrombocytopenia, adverse effect in immunocompromised patients

54
Q

What drugs can bactrim react with?

A

warfarin, phenytoin, methotrexate

Systemic Pharm I (13 decks)

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