Drugs for UTIs Flashcards
Exam 1- you are an idiot and fail at everything
Antibiotics for UTIs include:
- Sulfonamides
- Trimethoprim, SMZ-TMP
- Cephalosporins
- Fluroquinolones
What is an example of a urinary tract antiseptic?
Nitrofurantoin
What were the first drugs available for the systemic treatment of bacterial infections?
Sulfonamides
What are sulfonamides primarily used for?
Primarily used against UTIs
What do sulfonamides do to suppress bacterial growth?
suppress bacterial growth by inhibiting synthesis of tetrahydrofolate, a derivative of folate.
What is folate used for?
Folate is required by all cells to make DNA, RNA, and proteins; therefore in the absence of tetrafolate, bacteria are unable to synthesize DNA, RNA, and proteins.
If all cells require folate, why don’t sulfonamides harm us?
Bacteria and mammalian cells acquire folate differently
How do bacteria get folate?
Bacteria are unable to take up folate from their environment, so they must synthesize this from precursors.
How do mammalian cells acquire folate?
In contrast to bacteria, mammalian cells do not manufacture their own folate. Instead, they simply take up folate obtained from the diet, using a specialized transport system for uptake.
Sulfonamides are bacteriostatic, what does this mean for us?
adequate host defenses are essential for the elimination of infection.
Pharmacokinetics: Absorption of sulfonamides
Sulfonamides are well absorbed after oral administration.
When applied topically to the skin or mucous membranes, these drugs may be absorbed in amounts sufficient to cause systemic effects.
Pharmacokinetics: Distribution of sulfonamides
Sulfonamides are well distributed to all tissues.
Sulfonamides readily cross the placenta
Concentrations in pleural, peritoneal, ocular, and similar body fluids may be as much as 80% of the concentration in blood.
How are sulfonamides metabolized and excreted?
Metabolized in liver and excreted by kidneys thru half-lives
What are adverse effects of sulfonamides?
Prominent among these are hypersensitivity reactions, blood dyscrasias, and kernicterus, which occurs in newborns.
Renal damage from crystalluria was a problem with older sulfonamides but is less common with the sulfonamides used today.
What are included in hypersensitivity reactions to sulfonamides?
Mild reactions, such as rash, drug fever and photosensitivity, are relatively common.
What is the most severe hypersensitivity reaction to sulfonamides?
The most severe hypersensitivity response to sulfonamides is Stevens-Johnson syndrome, a rare reaction with a mortality rate of about 25%.
Sulfonamides can cause hemolytic anemia in what kind of patients?
Sulfonamides can cause hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.
Hematological effects of sulfonamides include:
Red cell lysis can produce fever, pallor, and jaundice; patients should be observed for these signs.
In addition to hemolytic anemia, sulfonamides can cause agranulocytosis, leukopenia, thrombocytopenia, and, rarely, aplastic anemia.
When sulfonamides are used for a long time, what should be done?
Monitor CBC for agranulocytosis, leukopenia, thrombocytopenia, aplastic anemia
When sulfonamides are used for a long time, periodic blood tests should be obtained.
Kernicterus
Kernicterus is a disorder in newborns caused by the deposition of bilirubin in the brain.
What does bilirubin do in cases of kernicterus?
Bilirubin is neurotoxic and can cause severe neurologic deficits and even death.
Sulfonamides promote kernicterus by displacing bilirubin from plasma proteins. Because the blood-brain barrier of infants is poorly developed, the newly freed bilirubin has easy access to sites within the brain.
Who should not receive sulfonamides? Why?
Because of the risk for kernicterus, sulfonamides should not be administered to infants younger than 2 months.
Sulfonamides should not be given to pregnant patients after 32 weeks of gestation or to those who are breast-feeding.
Due to their low solubility, how did sulfonamides come out of the urine?
Because of their low solubility, older sulfonamides tended to come out of solution in the urine, forming crystalline aggregates in the kidneys, ureters, and bladder.
To minimize risk of renal damage with sulfonamide use, what should be done?
adults should maintain a daily urine output of at least 1200mL. This can be accomplished by consuming 8 to 10 glasses of water each day.
What increases the risk of sulfa crystals?
Factors such as high drug concentration in urine, urinary stasis, and low urine pH increase this risk
Sulfonamides can intensify the effects of what:
Sulfonamides can inten-sify the effects of warfarin, phenytoin, and sulfonylurea-type oral hypoglycemics (e.g., glipizide, glyburide).
What is a worry about sulfonamides?
people who are hypersensitive to sulfonamide antibiotics may be cross-hypersensitive to other drugs that contain a sulfonamide moiety
Trimethoprim/Sulfamethoxazole (TMP/SMZ): What spectrum is it?
Broad spectrum
How to TMP/SMZ potentiate each others effects?
By inhibiting two reactions required for synthesis of tetrahydrofolate
TMP/SMZ
Pharmacokinetics: Absorption
TMP/SMZ may be administered orally or by IV infusion.
TMP/SMZ
Pharmacokinetics: Distribution
Both components of TMP/SMZ are well distributed throughout the body.
Pharmacokinetics: Excretion of TMP-SMZ
excreted by the kidneys (both agents are
concentrated in the urine)
COmmon Adverse Drug Reactions to TMP/SMZ
The most common adverse effects are nausea, vomiting, and rash.
Serious adverse reactions to TMP/SMZ:
(because of sulfonamides)
*Hypersensitivity reactions (including Stevens-Johnson syndrome)
*Blood dyscrasias (hemolytic anemia, agranulocytosis, leukopenia, thrombocytopenia, aplastic anemia)
*Kernicterus in neonates
*Renal damage
Serious adverse reactions to TMP/SMZ:
(because of trimethoprim)
*Megaloblastic anemia (but only in patients who are folate deficient)
*Hyperkalemia (especially in patients on high doses, in those with renal impairment, and in those taking other drugs that can raise potassium levels)
*Birth defects (especially during the first trimester)
UT antiseptics- what do they do?
These drugs become concentrated in the urine and are active against the common urinary tract pathogens.
What is the mode of action of nitrofurantoin?
Nitrofurantoin injures bacteria by damaging DNA.
What kind of effects do nitrofurantoin have at high doses and low?
is a broad-spectrum antibacterial drug, producing bacteriostatic effects at low concentrations and bactericidal effects at high concentrations.
What is nitrofurantoin used for?
Nitrofurantoin is indicated for acute infections of the lower urinary tract caused by susceptible organisms
In addition, the drug can be used for prophylaxis of recurrent lower UTI.
Adverse Drug Reactions: Nitrofurantoin?
GI effects
Pulmonary reactions
Hematologic effects
Peripheral neuropathy
Hepatotoxicity
Birth defects - may or may nor
GI effects of Nitrofurantoin? How can it me minimized?
Nv, diarrhea
These can be minimized by administering nitrofurantoin with milk or with meals, by reducing the dosage, and by using the macrocrystalline formulations.
Pulmonary reactions to Nitrofurantoin?
Acute reactions, which are most common, manifest as dyspnea, chest pain, chills, fever, cough, and alveolar infiltrates.
Some patients, permanent lung damage may occur.
Peripheral neuropathy associated with Nitrofurantoin
Damage to sensory and motor nerves is a serious concern. Demyelinization and nerve degeneration can occur and may be irreversible.
