Sulfonamides & Miscellaneous Antibiotics Flashcards Preview

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Flashcards in Sulfonamides & Miscellaneous Antibiotics Deck (29):
1

pharmacodynamics of sulfonamides

- only antibiotics that target metabolic pathway
- target folic acid pathway
- compete w/ para-aminobenzoic acid (PABA) for incorporation into folic acid

2

characteristics of sulfonamides

- all sulfa drugs derivatives of benzene sulfanilamide (sulfonamide) having similar antibacterial action
- produced by substitution at amino group
- differences based on rate of absorption, excretion, solubility in urine, etc...
- for antibacterial action, free para amino group essential
- bacteriostatic

3

list of sulfonamides

- SULFAMETHOXAZOLE + TRIMETHOPRIM, CO-TRIMOXAZOLE, TMP-SMX (BACTRIM) - oral/parenteral --> all same thing but different names
- sulfamethoxazole (gantanol) -- slow excretion, high urine concentration -- ORAL
- sulfasalazine (azulfidine) -- GI action, ulcerative colitis -- ORAL
- silver sulfadiazine (silvadene) -- burns -- topical

4

mechanisms of SULFAMETHOXAZOLE + TRIMETHOPRIM, CO-TRIMOXAZOLE, TMP-SMX (BACTRIM)?

- sulfamethoxazole competes w/ PABA in synthesis of bacterial FOLIC ACID
- trimethoprim prevents reduction of dihydrofolate to tetrahydrofolate (which is essential for one carbon transfer)

5

what does sulfadoxine + pyrimethamine do to help w/ malaria?

- inhibits DHFR (dihydrofolate reductase)

6

what is sulfadiazine + pyrimethamine for?

toxoplasmosis

7

what is methotrexate for?

anti-cancer drug, inhibits rapidly growing cells/DHFR

8

resistance of SULFAMETHOXAZOLE + TRIMETHOPRIM, CO-TRIMOXAZOLE, TMP-SMX (BACTRIM)

- increased production of essential metabolite or drug antagonist (PABA)
- active efflux or decreased permeability
- alternative metabolic pathway for synthesis of essential metabolite (plasmid)

9

characteristics of SULFAMETHOXAZOLE + TRIMETHOPRIM, CO-TRIMOXAZOLE, TMP-SMX (BACTRIM)

- generally bacteriostatic
- in urinary tract bactericidal concentration may be attained
- sulfa drugs inhibit both G- and G+ organisms

10

therapeutic uses of sulfonamides?

- UTIs (FIRST ATTACK), Co-trimoxazole = DOC
- pneumocystitis jiroveci (carinii) infections in children & AIDS patients (prophylaxis)
- chlamydia trachomitis - trachoma (azythro or tetracyclines are DOC)
- toxoplasma gondii - sulfadiazine + pyrimethamine
- sulfasalazine is a prodrug used in treatment of ulcerative colitis, active in arthritis

11

metabolism/absorption of SULFAMETHOXAZOLE + TRIMETHOPRIM, CO-TRIMOXAZOLE, TMP-SMX (BACTRIM)

- oral admin, absorption adequately rapid
- freely cross placenta & blood brain barrier, excreted in breast milk
- urine concentration 10-20x plasma
- sulfa drugs metabolized in liver as acetylated products and excreted through kidneys
- CO-TRIMOXAZOLE available for IV use - only for extreme circumstances

12

contraindications of SULFAMETHOXAZOLE + TRIMETHOPRIM, CO-TRIMOXAZOLE, TMP-SMX (BACTRIM)

- near term
- nursing premature infants
- jaundiced infants
* never give to infants < 2 months age

13

toxicities of sulfa drugs

- DRUG SENSITIVITY - allergy 6% (cross rxns w/ diuretics/celecoxib/some oral anti diabetic agents)
- blood dyscrasia - aplastic anemia (G6PD)
- kidney/liver damage, microscopic hematuria
- peripheral nerve damage
- Stevens-Johnson syndrome
- photosensitivity
- kernicterus

14

what class of antibiotics is Daptomycin (cubicin)?

lipopeptide antibiotics

15

mechanism of Daptomycin (cubicin)?

- cyclic lipoprotein
- don't penetrate bacterial cytoplasm
- binds to bacterial membranes and cause rapid depolarization of membrane potential
- loss of membrane potential leads to inhibition of protein, DNA, RNA synthesis, and bacterial cell death
- forms transmembrane cell channels - leakage of intracellular ions and depolarization

16

characteristics of daptomycin

- lipopeptides appear to be bactericidal against G+ bacteria (MRSA, MSSA) - concentration dependent
- aerobic, anaerobic
- resistance rare
- IV admin
- half life 8-9 hrs - once daily dosing
- 78% excreted by kidneys

17

adverse rxns to daptomycin?

- most rxns mild or moderate
- candidiasis, general discomfort, fatigue, fever, flushing, hypersensitivity rxns, injection site rxns, rigors, weakness
- suitable for empiric therapy in pts w/ serious G+ infections - alternate to vancomycin

18

mechanism of MUPIROCIN (bactroban)

- produced from pseudomonas fluorescens
- structurally unrelated to other antibiotics
- bacterial PROTEIN and RNA SYNTHESIS ARE INHIBITED when mupirocin reversibly binds to bacteria isoleucyl-tRNA synthetase

19

characteristics of mupirocin (bactroban)?

- good against G+ and some G-
- BACTERIOSTATIC at low concentrations
- BACTERICIDAL at high concentrations
- admin topically to skin or nares

20

what is used to treat IMPETIGO?

mupirocin (bactroban)
- impetigo caused by s. aureus and b-hemolytic streptococci incl strep pyogenes

21

when would an intranasal application of mupirocin (bactroban) be used?

- ppl who carry methicillin resistant strains of s. aureus (MRSA)

22

why does mupirocin (bactroban) have little resistance with other antibiotics?

b/c of its unique mechanism

23

name 2 polypeptide antibiotics

- polymyxin B (aerosporin)
- colistin (polymyxin E)

24

what infections are polypeptide antibiotics used for?

G- infections

25

mechanism of action polypeptide antibiotics

- polymyxin B binds to G- bacterial cell membrane phospholipids (lipid A of endotoxin)
- binding increases permeability of cell membrane which results in loss of metabolites needed for bacterial existence
- polymyxin B is bactericidal against most G- bacilli w/ exception of proteus and neisseria species (no effect in G+, lack endotoxin)

26

in which bacteria does one find lipid A?

G-

27

characteristics polypeptide antibiotics

- no GI absoprtion (no oral use)
- distribution after parenteral use poor
- bound very well to plasma proteins
- excretion through kidney is slow

28

toxicity of polypeptide antibiotics

- NEPHROTOXICITY - use topically
- paresthesia, ataxia, dizziness
- visual/speech disturbances, leukopenia, granulocytopenia

29

use of polypeptide antibiotics

- topical in combo w/ neomycin (aminoglycoside) and bacitracin (G+)
- topical application to wounds, burns, etc (pseudomonas infections) and the eye