Sulfonamides, Trimethoprim, Quinolones Flashcards
As structural analogs of PABA, sulfonamides
inhibit ______ and folate production.
dihydropteroate synthase
Microorganisms stimulated by sulfonamides in their growth.
Rickettsiae
Activity of sulfonamides is poor against?
Anaerobes
intrinsically resistant to
sulfonamide antibiotics
Pseudomonas aeruginosa
Relationship between sulfonamides and trimethoprim or pyrimethamine
synergism
Forms of sulfonamide resistance
Mutations that
(1) cause overproduction of PABA
(2) cause production of a folic
acid-synthesizing enzyme that has low affinity for sulfonamides
(3) impair permeability to the sulfonamide
Sulfonamides are absorbed in the CSF and CNS. True or false?
True
Therapeutic concentrations of sulfonamides are
in the range of ?
40–100 mcg/mL of blood
Long acting sulfonamide
Sulfadoxine (7 - 9 days)
Intermediate acting sulfonamides
Sulfadiazine
Sulfamethoxazole
Sulfapyridine
Trimethoprim half-Life
Intermediate (11 hours)
Pyrimethamine half-Life
Long (4–6 days)
drug of choice for infections such as Pneumocystis
jiroveci (formerly P carinii ) pneumonia, toxoplasmosis, nocardiosis,
and occasionally other bacterial infections
trimethoprim-sulfamethoxazole (bactrim)
sulfonamides used almost exclusively to treat urinary tract infections
Sulfisoxazole and sulfamethoxazole
first-line
therapy for treatment of acute toxoplasmosis
Sulfadiazine-pyrimethamine
should also be administered
to minimize bone marrow suppression when taking Sulfadiazine-pyrimethamine
Folinic acid, 10 mg orally each day
a second-line agent in the treatment of
malaria
pyrimethamine with sulfadoxine (Fansidar)
widely used in ulcerative
colitis, enteritis, and other inflammatory bowel disease
Sulfasalazine (salicylazosulfapyridine)
effective
in the treatment of bacterial conjunctivitis and as adjunctive
therapy for trachoma
Sodium sulfacetamide ophthalmic solution or ointment
used topically but can be absorbed from burn sites
mafenide acetate
AE of mafenide acetate
The drug and
its primary metabolite inhibit carbonic anhydrase and can cause
metabolic acidosis
much less toxic topical sulfonamide and is preferred
to mafenide for prevention of infection of burn wounds
Silver
sulfadiazine
particularly serious and
potentially fatal AE when taking sulfonamides
SJS
The 7 most common adverse effects when taking sulfonamides
fever, skin
rashes, exfoliative dermatitis, photosensitivity, urticaria, nausea,
vomiting, diarrhea
Other unwanted effects when taking sulfonamides include?
stomatitis, conjunctivitis, arthritis, hematopoietic disturbances, hepatitis, and, rarely, polyarteritis nodosa and psych
when given in large doses, particularly
if fluid intake is poor, can cause crystalluria
Sulfadiazine
Crystalluria is treated
by administration?
sodium bicarbonate to alkalinize the urine
and fluids to increase urine flow
Other renal AE of sulfonamides
nephrosis
allergic nephritis
Sulfonamides can cause hemolytic or aplastic anemia, granulocytopenia,
thrombocytopenia, or leukemoid reactions. Sulfonamides
may provoke hemolytic reactions in patients with?
glucose-6-
phosphate dehydrogenase deficiency
Trimethoprim, a trimethoxybenzylpyrimidine, selectively inhibits
bacterial _______ which converts dihydrofolic
acid to tetrahydrofolic acid
dihydrofolic acid reductase
Pyrimethamine, another benzylpyrimidine,
selectively inhibits dihydrofolic acid reductase of _____
compared with that of mammalian cells.
protozoa
Sulfonamides are bacteriostatic or bacteriocidal?
Bacteriostatic when used solely
Resistance to trimethoprim can result from?
reduced cell permeability
overproduction of dihydrofolate reductase
production of
an altered reductase with reduced drug binding
Resistant enzymes against trimethoprim may be coded within _____ that exhibit a broad host range, accounting
for rapid and widespread dissemination of trimethoprim resistance?
transposons on
conjugative plasmids
Trimethoprimsulfamethoxazole
can also be given intravenously. True or False?
True
trimethoprim is more lipid-soluble than sulfamethoxazole,
it has a larger volume of distribution than the latter drug. True or false?
True
Ratio of trimethoprim-sulfamethoxazole in formulation
1T:5S
Ratio of trimethoprim-sulfamethoxazole in peak plasma concentrations
1T:20S
The
dose of trimethoprim-sulfamethoxazole should be reduced by half for patients with creatinine clearances
of?
15–30 mL/min
concentrates in prostatic fluid and
in vaginal fluid, therefore, it
has more antibacterial activity in prostatic and vaginal fluids than
many other antimicrobial drugs.
Trimethoprim (a weak base)
Trimethoprim can be given alone in what dosage in acute
urinary tract infections?
100 mg twice daily
A combination of trimethoprim-sulfamethoxazole is effective
treatment for a wide variety of infections including?
P. jiroveci pneumonia shigellosis systemic salmonella infections urinary tract infections prostatitis some nontuberculous mycobacterial infections most Staphylococcus aureus strains, both methicillin-susceptible and methicillin-resistant, respiratory tract pathogens such as pneumococcus, Haemophilus sp, Moraxella catarrhalis, and K pneumoniae ( Mycoplasma pneumoniae ).
Respiratory tract pathogen that is resistant to trimethoprim-sulfamethoxazole
Mycoplasma pneumoniae
One double strength tablet of trimethoprim-sulfamethoxazole contains?
each tablet contains trimethoprim
160 mg plus sulfamethoxazole 800 mg
DS tablet of trimethoprim-sulfamethoxazole given every 12 hours is effective for?
treatment for urinary tract infections and prostatitis
treatment for infections caused by susceptible
strains of shigella and salmonella
It is the agent of choice for moderately severe
to severe pneumocystis pneumonia
80 mg trimethoprim plus
400 mg sulfamethoxazole per 5 mL diluted in 125 mL of 5%
dextrose in water IV for 60 - 90 minutes
used for treatment of
leishmaniasis and toxoplasmosis
oral Pyrimethamine and sulfadiazine
Patients highly at risk for AE of trimethoprim-sulfamethoxazole
Patients
with AIDS and pneumocystis pneumonia
The important quinolones are?
synthetic fluorinated analogs of
nalidixic acid
Quinolones are classified as?
DNA gyrase inhibitors
Quinolones block bacterial DNA synthesis by inhibiting?
bacterial topoisomerase II (DNA gyrase) and topoisomerase IV
Inhibition of
DNA gyrase prevents?
prevents the relaxation of positively supercoiled DNA
that is required for normal transcription and replication
Inhibition
of topoisomerase IV interferes with?
separation of replicated chromosomal
DNA into the respective daughter cells during cell division
Earlier quinolones such as nalidixic acid did not achieve systemic
antibacterial levels and were useful only in the treatment of?
lower
urinary tract infections
the least
active of the fluoroquinolones against both gram-negative and
gram-positive organisms, with minimum inhibitory concentrations
(MICs) fourfold to eightfold higher than those of ciprofloxacin
Norfloxacin
comprise a second group of quinolones possessing
excellent gram-negative activity and moderate to good activity
against gram-positive bacteria
Ciprofloxacin, enoxacin, lomefloxacin, levofloxacin, ofloxacin, and
pefloxacin
MICs of second group of quinolones for gram-negative cocci and bacilli, including Enterobacter sp, P aeruginosa , Neisseria meningitidis, H aemophilus sp, and Campylobacter jejuni?
1–2 mcg/mL and often less
Ciprofloxacin is the
most active agent of this group against gram-negative organisms, ____ in particular.
P aeruginosa
the L-isomer of ofloxacin,
has superior activity against gram-positive organisms, including
Streptococcus pneumoniae
levofloxacin
make up a third
group of fluoroquinolones with improved activity against grampositive
organisms, particularly S pneumoniae and some staphylococci
Gatifloxacin, gemifloxacin, and moxifloxacin
During fluoroquinolone therapy, resistant organisms emerge in
about one of every ____, especially among staphylococci,
P aeruginosa , and Serratia marcescens
10^7 –10^9 organisms
Resistance is due to one
or more point mutations in the quinolone binding region of the
target enzyme or to a change in the permeability of the organism. More recently
two types of plasmid-mediated resistance have been described. These are?
The
first type utilizes Qnr proteins, which protect DNA gyrase from the
fluoroquinolones. The second is a variant of an aminoglycoside
acetyltransferase capable of modifying ciprofloxacin
Resistance to one
fluoroquinolone, particularly if it is of high level, generally confers
cross-resistance to all other members of this class. True or false?
True
After oral administration, the fluoroquinolones are well absorbed
(bioavailability of?)
80 - 90%
Oral absorption of quinolones is impaired by
divalent and trivalent cations, including those
in antacids
oral fluoroquinolones should be taken 2
hours before or 4 hours after any products containing these cations
Dosage adjustment
for renal failure is not necessary for which quinolone?
moxifloxacin
Nonrenally cleared fluoroquinolones are relatively contraindicated in patients with?
hepatic failure
Quinolone not effective against UTIs?
Moxifloxacin
Fluoroquinolones (except _____, which does not achieve adequate systemic concentrations)
have been used in infections of soft tissues, bones, and joints
and in intra-abdominal and respiratory tract infections, including
those caused by multidrug-resistant organisms such as Pseudomonas
and Enterobacter .
norfloxacin
drug of choice for prophylaxis
and treatment of anthrax
Ciprofloxacin
Quinolones effective in treating
chlamydial urethritis or cervicitis
Ciprofloxacin and levofloxacin
occasionally used for treatment of tuberculosis and atypical mycobacterial infections
Ciprofloxacin, levofloxacin,
or moxifloxacin
agents that may be suitable
for eradication of meningococci from carriers or for prophylaxis
of infection in neutropenic cancer patient
Ciprofloxacin, levofloxacin,
or moxifloxacin
so-called respiratory fluoroquinolones effective and used
increasingly for treatment of upper and lower respiratory tract
infections
levofloxacin, gatifloxacin, gemifloxacin, and moxifloxacin
With enhanced gram-positive activity and activity against
atypical pneumonia agents (chlamydiae, Mycoplasma , and Legionella
levofloxacin, gatifloxacin, gemifloxacin, and moxifloxacin
Fluoroquinolones are generally well tolerated. The most common
effects are?
nausea, vomiting, and diarrhea
Photosensitivity has been reported with which quinolones?
lomefloxacin and
pefloxacin
ECG change that occurs with gatifloxacin, levofloxacin,
gemifloxacin, and moxifloxacin
QTc prolongation
gatifloxacin, levofloxacin,
gemifloxacin, and moxifloxacin, should be avoided or used with caution in patients with which cardiac conditions?
QT c interval prolongation uncorrected hypokalemia those receiving class IA (eg, quinidine or procainamide) or class III antiarrhythmic agents (sotalol, ibutilide, amiodarone) patients receiving other agents known to increase the QT c interval (eg, erythromycin, tricyclic antidepressants)
Quinolone associated with hyperglycemia
in diabetic patients and with hypoglycemia in patients
also receiving oral hypoglycemic agents
Gatifloxacin
Fluoroquinolones may damage growing cartilage and cause an
arthropathy. Thus, these drugs are not routinely recommended for?
patients under 18 years of age.
a rare complication
that has been reported in adults using quinolones
tendonitis
Fluoroquinolones are considered safe for pregnancy. True or false?
False
