Flashcards in Sulfonamides & Miscellaneous Antibiotics Deck (29):
pharmacodynamics of sulfonamides
- only antibiotics that target metabolic pathway
- target folic acid pathway
- compete w/ para-aminobenzoic acid (PABA) for incorporation into folic acid
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
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
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)
what does sulfadoxine + pyrimethamine do to help w/ malaria?
- inhibits DHFR (dihydrofolate reductase)
what is sulfadiazine + pyrimethamine for?
what is methotrexate for?
anti-cancer drug, inhibits rapidly growing cells/DHFR
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)
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
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
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
contraindications of SULFAMETHOXAZOLE + TRIMETHOPRIM, CO-TRIMOXAZOLE, TMP-SMX (BACTRIM)
- near term
- nursing premature infants
- jaundiced infants
* never give to infants < 2 months age
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
what class of antibiotics is Daptomycin (cubicin)?
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
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
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
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
characteristics of mupirocin (bactroban)?
- good against G+ and some G-
- BACTERIOSTATIC at low concentrations
- BACTERICIDAL at high concentrations
- admin topically to skin or nares
what is used to treat IMPETIGO?
- impetigo caused by s. aureus and b-hemolytic streptococci incl strep pyogenes
when would an intranasal application of mupirocin (bactroban) be used?
- ppl who carry methicillin resistant strains of s. aureus (MRSA)
why does mupirocin (bactroban) have little resistance with other antibiotics?
b/c of its unique mechanism
name 2 polypeptide antibiotics
- polymyxin B (aerosporin)
- colistin (polymyxin E)
what infections are polypeptide antibiotics used for?
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)
in which bacteria does one find lipid A?
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
toxicity of polypeptide antibiotics
- NEPHROTOXICITY - use topically
- paresthesia, ataxia, dizziness
- visual/speech disturbances, leukopenia, granulocytopenia