Sulfonamides

Question 0

what type of characteristics differentiate the different sulfonamides?

Answer 0

rate of absorption
excretion
solubility in the urine

Question 1

List the four sulfonamides and their modes of administration:

Answer 1

Sulfamethoxazole (PO)
Sulfasalazine (PO)
Silver Sulferdiazine (topical)
TMP-SMX (PO/parenteral)

Question 2

what group is essential for antibacterial activity of sulfonamides?

Answer 2

free para amino group

Question 3

how do sulfonamides function?

Answer 3

sulfonamides are antimetabolites and act as competitive inhibitors of PABA which is needed for folic acid synthesis. they inhibit the synthesis of folic acid. they are bacteriostatic

Question 4

how does TMP-SMX function?

Answer 4

TMP and SMX target two different parts of folic acid synthesis.
SMX competes with PABA (inhibit dihydropteroate synthase)
TMP inhibits dihydrofolate reductase

They act synergistically and result in inhibition of DNA/RNA synthesis

Question 5

how can bacteria develop resistance to TMP-SMX?

Answer 5

1. increase [PABA]
2. active efflux
3. decreased permeability
4. use an alternative folic acid synthesis pathway (plasmids)

Question 6

TMP-SMX: bacteriostatic vs bactericidal and UTIs

Answer 6

typically TMP-SMX is bacteriostatic. It can reach bactericidal concentration in the urine. It is active against G+/G-. Most UTIs are caused by G- bacteria but can be caused by G+

Question 7

DOC for UTI (first attack):

Answer 7

co-trimoxazole (TMP-SMX)

Question 8

what are some of the therapeutic uses of sulfonamides?

Answer 8

UTIs
Pneumocystis jiroveci prophylaxis for children and HIV positive adults
Chlamydia
toxoplasma gondii: sulfadiazine + pyrimethamine
Ulcerative colitis and RA: sulfasalazine

Question 9

TMP-SMX pharmacokinetics:

Answer 9

PO/IV
Liver metabolism
Renal excretion
Urine concentration 10-20x greater than plasma concentration
Crosses BBB, placenta and into breast milk: pregnant woman, premature and jaundiced babies
IV only in extreme circumstances

Question 10

Sulfa drug toxicities:

Answer 10

Allergies
SJS
Kernicterus
*not for infants less than 2 months bc of bilirubin displacement

Question 11

List the lipopeptide antibiotics?

Answer 11

daptomycin

mupirocin

Question 12

what is the general structure of lipopeptide antibiotics?

Answer 12

cyclic lipoprotein that is not able to penetrate the bacterial cytoplasm

Question 13

how does daptomycin work?

Answer 13

it binds to cell membranes and cause rapid depolarization of membrane potential
this leads to inhibition of DNA/RNA/protein synthesis and eventual cell death

Question 14

what type of bacteria are affected by daptomycin?

Answer 14

G+ aerobics and anaerobics

Question 15

Daptomycin pharmacokinetics

Answer 15

IV
Renal excretion
empiric therapy for serious G+ infections; alternate for vancomycin

Question 16

how does mupirocin work?

Answer 16

inhibition of protein and RNA synthesis

reversibly binds to isoleucyl tRNA synthetase

Question 17

Mupirocin spectrum of activity

Answer 17

G+/G-

bacteriostatic or cidal depending on concentration

Question 18

how is mupirocin administered?

Answer 18

topically

Question 19

mupirocin uses:

Answer 19

impetigo (s. aureus)

intranasal application for carriers of MRSA

Question 20

list the polypeptide antibiotics:

Answer 20

polymyxin b

colistin

Question 21

what type of bacteria do polypeptide antibiotics treat?

Answer 21

G-

Question 22

what is the mechanism of action for polypeptide antibiotics:

Answer 22

binds to the cell membrane lipid A (only found in G- bacteria). this increases cell membrane permeability and causes loss of essential metabolites which causes cell death
bactericidal

Question 23

administration of polypeptide antibiotics:

Answer 23

topical. no GI absorption so cannot be taken orally