Drugs for UTIs

Question 1

Antibiotics for UTIs include:

Answer 1

1. Sulfonamides
2. Trimethoprim, SMZ-TMP
3. Cephalosporins
4. Fluroquinolones

Question 2

What is an example of a urinary tract antiseptic?

Answer 2

Nitrofurantoin

Question 3

What were the first drugs available for the systemic treatment of bacterial infections?

Answer 3

Sulfonamides

Question 4

What are sulfonamides primarily used for?

Answer 4

Primarily used against UTIs

Question 5

What do sulfonamides do to suppress bacterial growth?

Answer 5

suppress bacterial growth by inhibiting synthesis of tetrahydrofolate, a derivative of folate.

Question 6

What is folate used for?

Answer 6

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.

Question 7

If all cells require folate, why don’t sulfonamides harm us?

Answer 7

Bacteria and mammalian cells acquire folate differently

Question 8

How do bacteria get folate?

Answer 8

Bacteria are unable to take up folate from their environment, so they must synthesize this from precursors.

Question 9

How do mammalian cells acquire folate?

Answer 9

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.

Question 10

Sulfonamides are bacteriostatic, what does this mean for us?

Answer 10

adequate host defenses are essential for the elimination of infection.

Question 11

Pharmacokinetics: Absorption of sulfonamides

Answer 11

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.

Question 12

Pharmacokinetics: Distribution of sulfonamides

Answer 12

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.

Question 13

How are sulfonamides metabolized and excreted?

Answer 13

Metabolized in liver and excreted by kidneys thru half-lives

Question 14

What are adverse effects of sulfonamides?

Answer 14

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.

Question 15

What are included in hypersensitivity reactions to sulfonamides?

Answer 15

Mild reactions, such as rash, drug fever and photosensitivity, are relatively common.

Question 16

What is the most severe hypersensitivity reaction to sulfonamides?

Answer 16

The most severe hypersensitivity response to sulfonamides is Stevens-Johnson syndrome, a rare reaction with a mortality rate of about 25%.

Question 17

Sulfonamides can cause hemolytic anemia in what kind of patients?

Answer 17

Sulfonamides can cause hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Question 18

Hematological effects of sulfonamides include:

Answer 18

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.

Question 19

When sulfonamides are used for a long time, what should be done?

Answer 19

Monitor CBC for agranulocytosis, leukopenia, thrombocytopenia, aplastic anemia

When sulfonamides are used for a long time, periodic blood tests should be obtained.

Question 20

Kernicterus

Answer 20

Kernicterus is a disorder in newborns caused by the deposition of bilirubin in the brain.

Question 21

What does bilirubin do in cases of kernicterus?

Answer 21

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.

Question 22

Who should not receive sulfonamides? Why?

Answer 22

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.

Question 23

Due to their low solubility, how did sulfonamides come out of the urine?

Answer 23

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.

Question 24

To minimize risk of renal damage with sulfonamide use, what should be done?

Answer 24

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.

Question 25

What increases the risk of sulfa crystals?

Answer 25

Factors such as high drug concentration in urine, urinary stasis, and low urine pH increase this risk

Question 26

Sulfonamides can intensify the effects of what:

Answer 26

Sulfonamides can inten-sify the effects of warfarin, phenytoin, and sulfonylurea-type oral hypoglycemics (e.g., glipizide, glyburide).

Question 27

What is a worry about sulfonamides?

Answer 27

people who are hypersensitive to sulfonamide antibiotics may be cross-hypersensitive to other drugs that contain a sulfonamide moiety

Question 28

Trimethoprim/Sulfamethoxazole (TMP/SMZ): What spectrum is it?

Answer 28

Broad spectrum

Question 29

How to TMP/SMZ potentiate each others effects?

Answer 29

By inhibiting two reactions required for synthesis of tetrahydrofolate

Question 30

TMP/SMZ
Pharmacokinetics: Absorption

Answer 30

TMP/SMZ may be administered orally or by IV infusion.

Question 31

TMP/SMZ
Pharmacokinetics: Distribution

Answer 31

Both components of TMP/SMZ are well distributed throughout the body.

Question 32

Pharmacokinetics: Excretion of TMP-SMZ

Answer 32

excreted by the kidneys (both agents are
concentrated in the urine)

Question 33

COmmon Adverse Drug Reactions to TMP/SMZ

Answer 33

The most common adverse effects are nausea, vomiting, and rash.

Question 34

Serious adverse reactions to TMP/SMZ:

(because of sulfonamides)

Answer 34

*Hypersensitivity reactions (including Stevens-Johnson syndrome)
*Blood dyscrasias (hemolytic anemia, agranulocytosis, leukopenia, thrombocytopenia, aplastic anemia)
*Kernicterus in neonates
*Renal damage

Question 35

Serious adverse reactions to TMP/SMZ:

(because of trimethoprim)

Answer 35

*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)

Question 36

UT antiseptics- what do they do?

Answer 36

These drugs become concentrated in the urine and are active against the common urinary tract pathogens.

Question 37

What is the mode of action of nitrofurantoin?

Answer 37

Nitrofurantoin injures bacteria by damaging DNA.

Question 38

What kind of effects do nitrofurantoin have at high doses and low?

Answer 38

is a broad-spectrum antibacterial drug, producing bacteriostatic effects at low concentrations and bactericidal effects at high concentrations.

Question 39

What is nitrofurantoin used for?

Answer 39

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.

Question 40

Adverse Drug Reactions: Nitrofurantoin?

Answer 40

GI effects

Pulmonary reactions

Hematologic effects

Peripheral neuropathy

Hepatotoxicity

Birth defects - may or may nor

Question 41

GI effects of Nitrofurantoin? How can it me minimized?

Answer 41

Nv, diarrhea

These can be minimized by administering nitrofurantoin with milk or with meals, by reducing the dosage, and by using the macrocrystalline formulations.

Question 42

Pulmonary reactions to Nitrofurantoin?

Answer 42

Acute reactions, which are most common, manifest as dyspnea, chest pain, chills, fever, cough, and alveolar infiltrates.

Some patients, permanent lung damage may occur.

Question 43

Peripheral neuropathy associated with Nitrofurantoin

Answer 43

Damage to sensory and motor nerves is a serious concern. Demyelinization and nerve degeneration can occur and may be irreversible.