Antifolates

Question 1

What are the groups of antifolates?

Answer 1

Sulfonamides
TMP/SMX
Misclellnaeou DNA Abx
Urinary tract antiseptics

Question 2

MOA of sulfonamides

Answer 2

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

Question 3

Bacteria use this to make folic acid

Answer 3

PABA + pteradine with the synthesis dihydropteroate synthase

Question 4

What drugs target dihidropteroate synthase

Answer 4

Sulfonamides

Question 5

What enzyme do bacteria have that humans do not

Answer 5

Hihydropteroate synthetase

Question 6

What enzyme do humans have for folic acid?

Answer 6

Dihydrofolate reductase

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

Question 7

What drug do we use that will target dihydrofolate reductase

Answer 7

This is in both humans and bacteria

-use trimethoprim

Question 8

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

Answer 8

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

Question 9

What is tetrahydrofolate important for

Answer 9

A cofactors essential for DNA synthesis

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

Question 10

Clinical use of sulfonamides

Answer 10

Limited

Topically in the eye for conjunctivitis and infections of the cornea

Question 11

Resistance of sulfonamides

Answer 11

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

Question 12

Pharmacokinetics of sulfonamide

Answer 12

Ointment or drops

Question 13

Adverse effects of sulfonamides

Answer 13

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)

Question 14

MOA of trimethoprim

Answer 14

• competitively inhibits dihydrofolate reductase

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

Question 15

MOA of TMP/SMX (trimethoprim/sulfonamide)

Answer 15

Work synergistically to prevent the formation of tetrahydrofolic acid

Question 16

What are the two examples of ABx that work synergistically

Answer 16

Pens + AGs

TMP/SMX

Question 17

Clinical use of TMP/SMX

Answer 17

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

Question 18

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

Answer 18

TMP/SMX

Question 19

What type of MRSA can be treated with TMP/SMX

Answer 19

Community acquired

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

Question 20

Pneumocystitis jiroveci pneumonia

Answer 20

PCP

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

Question 21

Adverse effects of TMP/SMX

Answer 21

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

Question 22

Miscellaneous DAN Abx

Answer 22

Metronidazole

Fluoroquinolones

Question 23

MOA of metronidazole

Answer 23

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

Question 24

Clinical use of metronidazole

Answer 24

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)

Question 25

How to remember what metronidazole does

Answer 25

GET BaC on the Metro, G GET: giardia, entamoaeba, trichomonas BaC: bacteroides, clostridium Metro: metronidazole G: gardnerella

Question 26

Pharmacokinetics of metronidazole

Answer 26

Metabolized by the liver | -adjust in liver failure (Hepatic failure)

Question 27

What abx do we not need to adjust in renal failure

Answer 27

Ceftriaxone Doxycycline Metronidazole Antistaph but not as imprtoant

Question 28

Adverse effects of metronidazole

Answer 28

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

Question 29

Fluorinated quinolone

Answer 29

Fluoroquinolones

Question 30

What are fluoroquinolones limited to

Answer 30

Gram negative organisms

Question 31

MOA of fluoroquinolones

Answer 31

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

Question 32

Positive supercooling

Answer 32

Tension - inhibited replication - DNA will break

Question 33

Which Abx is great for gram negative

Answer 33

FQs

Question 34

Generations of FQs

Answer 34

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

Question 35

Respiratory FQs

Answer 35

3rd and 4th generation | Levofloxain and gemifloxacin

Question 36

Why is FQs backup drugs

Answer 36

- too many people Rxed cipro for UTIs even though TMP/SMX was DOC - now resistance

Question 37

Spectrum of FQs

Answer 37

- 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

Question 38

Resistance of FQs

Answer 38

Mutation of the bacterial DNA gyrase

Question 39

Adverse effects of FQs

Answer 39

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

Question 40

What two drugs can cause phototoxicity

Answer 40

FQs and tetracycline

Question 41

What are the abx that are ok for pregs and kids

Answer 41

Pens/cephs

Question 42

Drug interactions with FQs

Answer 42

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

Question 43

How is FQ similar to tetracycline (doxy)?

Answer 43

They both have phototoxicity and both chelate metals

Question 44

Urinary tract antiseptic

Answer 44

Nitrofurantoin

Question 45

MOA of nitrofurantoin

Answer 45

We dont really know

Question 46

Uses of nitrofurantoin

Answer 46

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

Question 47

First choice therapy for gonorrhea

Answer 47

Cetriaxone

Question 48

First choice therapy for syphillis (treponema)

Answer 48

Beneath one Pen G

Question 49

First choice drug for chlamydia trachomatis

Answer 49

Azithromycin