Pharmacology Exam I: Sulfonamides
What are the three major groups of sulfonamides?
1: oral, absorbable 2: oral, nonabsorbable 3: topical
What are some examples of gram negative cocci?
Neisseria, Pasteurella, Acinetobacter
Do sulfonamides work against anaerobes?
No, not really.
Are sulfonamides bactericidal or bacteriostatic?
bacteriostatic
Is trimethoprim/sulfamethoxazole bactericidal or bacteriostatic?
bacteriostatic
Which sulfa drug is poorly absorbed and good for bowel treatment?
sulfasalazine
What are quinolones?
DNA gyrase inhibitors
What is the mechanism of action of pyrimethamine?
a potent inhibitor of dihydrofolate reductase
What is the major biotransformation of sulfonamides?
acetylation but it also undergoes gluconidation
When are sulfonamides more soluble?
at an alkaline pH than an acidic pH
What is sulfonamide active against?
streptococcus, haemophilus, haemophilus, actinomyces, chlamydia, escherichia
What is sulfasalazine used for?
ulcerative colitis, enteritis, and other inflammatory bowel disease
What is the dosing for trimethoprim/sulfamethoxazole?
160mg trimethoprim + 800mg sulfamethoxazole one tablet per day up to twice per day
What are the adverse effects of trimethoprim/sulfamethoxazole?
1: allergic reactions from mild rash to stevens-johnson syndrome 2: hemolytic anemia in patients with G6PD deficiency 3: crystalluria but is less common than other sulfa drugs
What are the toxic reactions of sulfa drugs?
1: crystal formation in urinary tract 2: hemolytic anemia found in G6PD deficiency 3: agranulocystosis following sulfadiazine 4: aplastic anemia (supression of bone marrow) 5: hypersensitivity dermatitis, fever, pruritus 6: Stevens-Johnson syndrome
What are the mechanisms of resistance to sulfa drugs through random mutations?
1: lower the binding affinity of the dihydropteroate synthase for sulfa drug 2: develop an active transport in the cell wall to remove sulfa drug 3: develop an alternate pathway for synhthesis of folic acid 4: increase the synthesis of PABA to overcome block by sulfa
Mutations that cause sulfonamide resistance cause what?
1: overproduction of PABA 2: production of a folic acid-synthesizing enzyme that has low affinity for sulfonamides 3: impair permeability to the sulfonamide
What are the 7 key points to know about antibiotics?
1: structure/source 2: mechanisms of action 3: pharmacokinetics 4: antimicrobial activity 5: clinical uses 6: ADR's 7: mechanisms of resistance
Which sulfonamides are oral absorbable agents?
1: sulfisoxazole 2: sulfamethoxazole 3: sulfadiazine in combination with pyrimethamine 4: sulfadoxine
Why is an MIC useful?
1: test for resistance 2: adjust dose up or down 3: find less toxic/costly antibiotic, use drug with lowest MIC and largest ring
When can you see peak plasma concentration levels of sulfonamides?
2-6 hours post po dose
What are the therapeutic concentrations of sulfonamides?
40-100 mcg/mL
How many different sulfonamides are there?
5 different ones with 4/5 having "sulf" in their name
What is the drug of choice for nocardiosis pneumonia (Norcardia, soil bacterium)?
6 months po sulfasoxazole
How many differentquinolones are there?
7 different kinds and all end in "oxacin"
What is the bioavailability of sulfonamides following a po dose?
70-100%
What limits the use of mafenide acetate?
It can be absorbed from burn sites and its primary metabolite inhibits carbonic anhydrase which can cause metabolic acidosis
What are some examples of gram negative bacilli?
Pseudomonas, Bacteroides, Escherichia, Salmonella, Shigella, Proteus
What is the drug of choice for UTI's?
Sulfisoxazole
Are sulfonamides analogs of PABA?
Yes
What does extended spectrum mean?
a narrow spectrum drug changed to increase it's range
What is sodium sulfacetamide ophthalmic solution used for?
bacterial conjucntivitis and as adjunctive therapy for trachoma
What does antibiotic mean?
chemical produced by one organism to kill or inhibit another organism
What are some examples of gram positive rods?
clostridium, actinomyces, bacillus
What is trimethoprim-sulfamethoxazole used for?
combination-two enzymes
What is pyrimethamine-sulfadoxine used for?
combination-two enzymes-malaria
What is another name for trimethoprim/sulfamethoxazole?
cotrimoxazole
What chemical can't be made when using sulfonamides?
dihydrofolic acid
What does bacteriostatic mean?
does not kill, requires host defense to kill the bacteria
What bacteria can absorb folic acid from patient tissue fluids?
enterococci
What are examples of gram positive cocci pairs/chains?
enterococcus and streptococcus
What is sulfadiazine in combination with pyrimethamine used for?
first-line therapy for treatment of acute toxoplasmosis
What must be taken with sulfadiazine in combination with pyrimethamine and why?
folinic acid 10mg po daily to minimize bone marrow suppression
What organisms do sulfonamides inhibit?
gram positive and gram negative bacteria, Nocardia sp, Chlamydia trachomatis, some protozoa, some enteric bacteria such as E. coli, klebsiella pneumoniae, salmonella, shigella, and enterobacter
What does the loss of folic acid result in?
impaired DNA synthesis which doesn't kill the bacteria but makes it so it can't grow.
Where is prontosil biotransformed?
in the liver and it is turned into sulfonamide
When is sulfonamide active?
in vitro and in vivo
When is prontosil active?
in vivo and not in vitro
Are most sulfonamide metabolites active or inactive?
inactive
What does nosocomial mean?
infection aquired in the hospital
What is the mechanism of action of sulfonamides?
inhibit dihydropteroate synthase and folate production
Where do sulfonamides distribute?
into most tissues including brain and CSF
What does bactericidal mean?
kills bacteria in absence of host defense mechanisms
What is the minimum inhibitory concentration?
measurement of the concentration of antibiotic necessary to inhibit growth of a standardized inoculum.
What is trimethoprim/sulfamethoxazole used for?
mostly used for UTI's but high distribution into tissues after po dosing makes it useful for lower extremity infections
What does nosokomos mean?
one who tends to the sick
The synthesis of folic acid starts with what?
p-amino benzoic acid (PABA)
What is silver sulfadiazine used for?
prevention of infection of burn wounds
What is given in combination with sulfadoxine?
pyrimethamine
What is the drug of choice for toxoplasmosis?
pyrimethamine and sulfadiazine combination
What does spectrum mean?
range of bacteria that a drug is effective against. narrow, broad, extended
What are sulfisoxazole and sulfamethoxazole used for?
short to medium acting agents used almost exclusively to treat urinary tract infections
What sulfonamides are topical agents?
sodium sulfacetamide ophthalmic solution, mafenide acetate, and silver sulfadiazine
What is the mechanism of action of trimethoprim?
specific inhibitor of bacterial dihydrofolate reductase
What bacteria is trimethoprim/sulfamethoxazole used for?
staph, MRSA, and pneumocystis pneumonia in AIDS patients
What is an example of a gram positive cocci cluster?
staphylococcus
What is the mechanism of action of sulfonamides?
sulfa substitutes for PABA and blocks folic acid synthesis
Which sulfa drugs are for topical use?
sulfacetamide and sulfadiazine
Which sulfa drug is long acting, absorbed rapidly, and excreted slowly?
sulfadoxine
Which sulfonamide is the only long-lasting sulfonamide drug in the USA?
sulfadoxine
Which sulfonamide is an oral nonabsorbable agent?
sulfasalazine
Which sulfa drugs have rapid absorption and excretion?
sulfisoxazole and sulfadiazine
What are the different types of antifolate drugs?
sulfonamides, trimethoprim/sulfamethoxazole combination, pyrimethamine
What can't be made when dihydrofolate reductase is inhibited?
tetrahydrofolic acid
What part of the sulfonamide drug is essential for antibiotic activity?
the para-NH2
Why is trimethoprim combined with sulfamethoxazole?
they both have the same halflife
Which drug is more active against most bacteria, trimethoprim or sulfamethoxazole?
trimethoprim is 20x more active
What is the sulfa drug of choice for a UTI?
trimethoprim-sulfamethoxazole po for 3 or more days at least this was for the case study
Is prontosil a prodrug?
yes
