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39 Cards in this Set
- Front
- Back
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Sulfonamide MOA & resistance
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-block dihydropterate synthetase.
-mimic PABA --| purine & pyrimidine synthesis --| cell division BACTERIOSTATIC (not cidal) Resistance by synthesizing 70x more PABA (precursor to dihydrofolate), to become competitive enough to bind dihydropterate synthetase (1000x affinity for sulfonamide) Resistance 2: change dihydropterate synthetase structure Resistance 3: bypass 1-carbon transfer step by "salvage" pathway |
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List of sulfonamides
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sulfamethoxazole
sulfisoxazole sulfadiazine sulfasalazine sulfacetamide sulfadoxine (Trimethoprim) - works synergistically |
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Trimethoprim MOA
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Inhibits bacterial Dihydrofolate reductase.
Synergism with sulfonamides: cotrimoxazole (1 trimeth:5sulfamethoxazole) cotrimazine (1 trimeth:5sulfadiazine) |
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Sulfonamide bacterial toxicity, absorption & distribution
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Toxicity: selectively toxic to bacteria b/c folate synthesis = obligatory
Absorption: oral or topical (soluble solts given parenterally) Readily absorbed w/ peak [drug]blood in 30 min Plasma protein bound (displaces other drugs & biliruben --> neonatal jaundice when given late term) Distribution: total body water, readily enters CNS, synovial & ocular fluid, fetal circulation, milk |
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Sulfonamide metabolism, elimination, & toxicity
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Metabolism: 1. Acetylation at free-amino group (rendered inactive) 2. Some oxygenation of aeromatic ring or side chain.
Elimination: majority eliminated unchanged. Concentrated in urine (useful for UTI). Older types form crystals in tubules and ureter. Toxicity: low CTI (theraputic index), toxicity in 5% of patients: 1) renal tox (crystalized in urine, 8-10g/day, give water) 2) blood dyscrasias (hemolytic anemia, agranulocytosis, aplastic anemia, thrombocytopenia. immune response to sulfonamide hapten?) 3) Dermal toxicity (rashes, pruritus, erythema, exfoliative dermatitis, stevens-johnson syndrome ~fatal) 4) rare - hepatitis, fever 5) less serious - headache, gi discomfort |
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Trimethoprim/sulfonamide drugs
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cotrimoxazole-aka bactrim/septra (1 trimeth:5sulfamethoxazole)
cotrimazine (1 trimeth:5sulfadiazine) |
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Trimethoprim synergism
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with sulfanomides
--| dihydrofolate reductase --| NT synthesis later in pathway than sulfonamides 100,000x higher affinity for bacterial enzyme decrease risk of resistance when used with sulfonamide |
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Sulfonamide structural site of difference
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substituents on N1 nitrogen.
substitution on N4 nitrogen terminates activity (acetylation) |
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Sulfisoxazole, Sulfamethoxazole, sulfadiazine
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short acting, rapidl abs/exc.
3 most common prescribed last 2 in combo with Trimethoprim |
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Sulfadimethoxine
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long acting sulfonamide, poor exc, useful in protozoal infections (AIDS patients)
toxic |
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Sulfadiazine
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silver salt of drug --> topical use in burns
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Sulfacetamide
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topical use in eye, low irritation
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Poorly absorbed sulfonamides
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(pthalylsulfathiazole)
used to sterilize gut pre-bowel-surgery (but prefered drug is aminoglycosides). Non absorbed Gut flora cleaves N4 group. |
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Dapsone
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Sulfone drug (not sulfonamide)
Antileprosy MOA: similar to sulfonamides |
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Clinical use: sulfonamides
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against most Gram+ and many Gram-
lower UTI (cotrimoxazole) from E. coli & prostatitis combo w/ trimeth --> bacterial dysentery sometimes --> meningococcal infection (other Ab's prefered) Topical --> eyes (conjunctivitis) or prophylactic for burns Protozoal infections (respond poorly to Ab's): Chlamydia, nocardia, toxoplasma Chloroquine resistant plasmodium falciparum Pneumocystis carinii (or trimeth alone) high toxicity in AIDS. |
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Quinolone list
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Nalidixic acid
norfloxacin (fluoroquinolone) ciprofloxacin (fluoroquinolone) |
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Quinolone MOA/selective tox/resistance
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--| DNA gyrase (bacterial topoisomerase)
Sel Tox: much less inhibition to mammalian topoisomerase Resistance: Altered DNA gyrase/drug transport properties. R-plasmids ID'd. not wide spread, not understood. |
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Quinolone Toxicity/clinical uses
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Toxicity: rare. GI distubrances, CNS effects, allergic skin reaction.
Clinical use: UTI (nalidixic acid limited, newer quin's used). Gonorrhea (* beta-lactam resistant strains) Diarrhea (shigella, toxigenic e. coli, salmonella, typhoid) Respiratory Infections: bacterial (hemophilus, streptococcus, pseudomonas) & nonbacterial (chlamydia, mycoplasma, legionella) Osteomyelitis - potential not yet tapped. |
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Drugs for uncomplicated UTI (by enterobacteria)
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cotrimoxazole
newer quinolones (nalidixic acid, limited use) |
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Penicillins
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Penicillin G
Penicillin V nafcillin methicillin oxacillin cloxacillin dicloxacillin flucoxacillin ampicillin amoxacillin carbenicillin ticarcillin azocillin mezlocillin pipericillin |
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Cephalosporins
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cephalothin
cefazolin cefalexin cefurixime cefamandole cefoxitin cefaclor moxalactam cefaperazone ceftazidime ceftriaxone |
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Other beta-lactams
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clavulanic acid
sulbactam imipenem aztreonam |
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Aminoglycosides
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neomycin
gentamycin streptomycin amikacin tobramycin kanamycin |
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Tetracyclines
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tetracycline
doxycycline |
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Misc
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bacitracin
vancomycin polymyxin chloramphenicol erythromycin clindamycin clarithromycin azithromycin |
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Anti-tuberculosis drugs
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isoniazid
pyrazinamide rifampin ethionamide ethambutol aminosalicylic acid (PAS) streptomycin cycloserine |
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Antifungal drugs
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nystatin
amphotericinB itraconazole griseofulvin ketoconazole flucytosin miconazole clotrimazole fluconazole |
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Antiprotozoal drugs
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metronidazole
primaquine mefloquine chloroquine haloxatrine quinine pyrimethamine doxycycline artimisinin proguanil dapsone sulfadoxine |
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Antihelmintics
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niridazole
ivermectin mebendazole metronidazole thiabendazole diloxanide fluorate niclosamide iodoquinol praziquantel pyrantel pamoate albendazole piperazine diethylcarbamazepine |
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Antineoplastic Groups
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alkylating agents
antimetabolites natural products |
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Alkylating agents
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mechlorethamine
cycloposphamide melphalan chlorambucil bis-chlorethyl nitrosourea (BCNU) hydroxyurea |
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Antimetabolites
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methotrexate
fluorouracil cytarabine mercaptopurine |
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Natural products
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vincristine
actinomycin D L-asparaginase daunorubicin doxorubicin bleomycin vinblastine |
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Immunosuppressant groups
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1) corticosteroids
2) cytotoxic agents 3) T-cell suppressants 4) antibodies 1) prednisone, prednisolone 2) cyclophosphamide, azathioprine 3) cyclosporine, tacrolimus 4) antithymocyte globulin, muromonoab - CD3 |
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Antiviral agents
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amantadine
rimantadine acyclovir valcyclovir famciclovir penciclovir ganciclovir foscamet sorivudine idoxuridine vidarabine trifluridine ribavarine & Anti-HIV agents |
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Anti-HIV agents
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lamivudine
abacavar tonofovir emtricitabine nevirapine delaviridine efavirenz saquinavir ritonovir indiavir nelfinavir amprenavir |
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NRTIs
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retrovir
didanosine zalcitabine stavudine inverase lamivudine abacavar tonofovir emtricitabine |
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NNRTIs
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nevirapine
delaviridine efavirenz |
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Protease inhibitors
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invirase
saquinavir ritonovir indiavir nelfinavir amprenavir |
