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Pharm Block 12 > Antifolates > Flashcards

Antifolates Flashcards

1
Q

What are the groups of antifolates?

A

Sulfonamides
TMP/SMX
Misclellnaeou DNA Abx
Urinary tract antiseptics

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2
Q

MOA of sulfonamides

A
  • All sulfonamides are PABA analogs
  • bacteriostatic
  • compete with PABA for the enzyme dihydropteroate synthase and prevents bacterial folic acid synthesis
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3
Q

Bacteria use this to make folic acid

A

PABA + pteradine with the synthesis dihydropteroate synthase

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4
Q

What drugs target dihidropteroate synthase

A

Sulfonamides

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5
Q

What enzyme do bacteria have that humans do not

A

Hihydropteroate synthetase

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6
Q

What enzyme do humans have for folic acid?

A

Dihydrofolate reductase

-we get folic acid from the diet and use this to turn it into tetrahydrofolate

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7
Q

What drug do we use that will target dihydrofolate reductase

A

This is in both humans and bacteria

-use trimethoprim

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8
Q

Which drug will have more side effects and why; sulfonamides and trimethoprim?

A

Trimethoprim because it targets the second enzyme, which is an enzyme that both the bacteria and humans have

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9
Q

What is tetrahydrofolate important for

A

A cofactors essential for DNA synthesis

-cant make DNA if you dont have this, this is how you kill the bacteria

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10
Q

Clinical use of sulfonamides

A

Limited

Topically in the eye for conjunctivitis and infections of the cornea

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11
Q

Resistance of sulfonamides

A

Bacteria will increase PABA synthesis which will competitively bind and outcompete sulfonamides

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12
Q

Pharmacokinetics of sulfonamide

A

Ointment or drops

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13
Q

Adverse effects of sulfonamides

A

Blurred vision
Hypersensitivity
-rashes, angioedema, and Stevens Johnson syndrome (crusty, red, bleeding lips)
-cross allergenic it’s occurs with CAI (diuretics, they are similar in structure to sulfonamides)

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14
Q

MOA of trimethoprim

A
  • competitively inhibits dihydrofolate reductase

- greater affinity for the bacterial enzyme than for the mammalian enzyme

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15
Q

MOA of TMP/SMX (trimethoprim/sulfonamide)

A

Work synergistically to prevent the formation of tetrahydrofolic acid

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16
Q

What are the two examples of ABx that work synergistically

A

Pens + AGs

TMP/SMX

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17
Q

Clinical use of TMP/SMX

A
  • uncomplicated UTIs (E. Coli)
  • CA-MRSA
  • pneumocystis jiroveci pneumonia
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18
Q

What is the drug of choice of uncomplicated UTIs (E coli)

A

TMP/SMX

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19
Q

What type of MRSA can be treated with TMP/SMX

A

Community acquired

  • hospital acquired treated with vancomycin
  • this is less serious than hospital acquired
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20
Q

Pneumocystitis jiroveci pneumonia

A

PCP

  • seen in immunosuppressed, most common opportunistic infection in HIV/AIDS. Takes advantage of suppressed immune system
  • treated with TMP/SMX
21
Q

Adverse effects of TMP/SMX

A

Bone marrow suppression

  • TMP mostly
  • common to all antifolate drugs
  • not making DNA enough with these drugs so that it why there is bone marrow suppression
22
Q

Miscellaneous DAN Abx

A

Metronidazole

Fluoroquinolones

23
Q

MOA of metronidazole

A

Don’t really know, but think it ends up being a free radical

24
Q

Clinical use of metronidazole

A

Anaerobes and some parasites

  • bacteroides, clostridium (difficile and nondifficile)
  • not active against pseudomonas
  • not active against aerobic bacteria
  • active against trichomonas vaginalis, entamoeba hystolytica, giardia, and bacterial vaginosis (Gardnerella)
25
Q

How to remember what metronidazole does

A

GET BaC on the Metro, G

GET: giardia, entamoaeba, trichomonas

BaC: bacteroides, clostridium

Metro: metronidazole

G: gardnerella

26
Q

Pharmacokinetics of metronidazole

A

Metabolized by the liver

-adjust in liver failure (Hepatic failure)

27
Q

What abx do we not need to adjust in renal failure

A

Ceftriaxone
Doxycycline
Metronidazole
Antistaph but not as imprtoant

28
Q

Adverse effects of metronidazole

A

Metallic taste
Disulfiram-like effect if taken with alcohol
-get really sick like you are hungover
-accumulate acid aldehyde
-blocks alcohol metabolism and get hangovers

29
Q

Fluorinated quinolone

A

Fluoroquinolones

30
Q

What are fluoroquinolones limited to

A

Gram negative organisms

31
Q

MOA of fluoroquinolones

A

Inhibition of bacterial DNA gyrase (topisomerase II)

  • topoisomerases are enzymes that change the configuration or topology of DNA by a nicking, pass-through, and resealing mechanism
  • cut the rubber band to relax it and then seal it back up
  • relaxation of positive supercoils in the DNA
  • bactericidal
32
Q

Positive supercooling

A

Tension

  • inhibited replication
  • DNA will break
33
Q

Which Abx is great for gram negative

A

FQs

34
Q

Generations of FQs

A

1st: meh
2nd: ciprofloxacin
3rd: levofloxacin
4th: gemifloxacin

As you move down generations, you can target more gram negatives. You get gram negatives at the first generation

35
Q

Respiratory FQs

A

3rd and 4th generation

Levofloxain and gemifloxacin

36
Q

Why is FQs backup drugs

A
  • too many people Rxed cipro for UTIs even though TMP/SMX was DOC
  • now resistance
37
Q

Spectrum of FQs

A
  • UTIs (alternative to TMP/SMX)
  • gram negative
  • community acquired pneumonia (alternative to macrolides); 3rd and 4th only due to coverage of strep pneumo and atypical
38
Q

Resistance of FQs

A

Mutation of the bacterial DNA gyrase

39
Q

Adverse effects of FQs

A
  • black box warning: tendinitis and tendon rupture
  • effects on collagen metabolism and cartilage development so dont give to pregs and kids
  • phototoxicity
40
Q

What two drugs can cause phototoxicity

A

FQs and tetracycline

41
Q

What are the abx that are ok for pregs and kids

A

Pens/cephs

42
Q

Drug interactions with FQs

A

Avoid using antacids, chelates Mg, Al, iron, zinc

43
Q

How is FQ similar to tetracycline (doxy)?

A

They both have phototoxicity and both chelate metals

44
Q

Urinary tract antiseptic

A

Nitrofurantoin

45
Q

MOA of nitrofurantoin

A

We dont really know

46
Q

Uses of nitrofurantoin

A

Used for uncomplicated UTIs as alternate to TMP/SMX (E coli)

47
Q

First choice therapy for gonorrhea

A

Cetriaxone

48
Q

First choice therapy for syphillis (treponema)

A

Beneath one Pen G

49
Q

First choice drug for chlamydia trachomatis

A

Azithromycin

Pharm Block 12 (7 decks)

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