Module 9 14 Sulfonamide Antibiotics and Trimethoprim Flashcards
1
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Question
A
Answer
2
Q
What role did sulfonamides play in the treatment of bacterial infections when first introduced in the 1930s?
A
Sulfonamides significantly reduced morbidity and mortality from susceptible infections when first introduced in the 1930s.
3
Q
What led to the decline in the use of sulfonamides over time?
A
The development of penicillin and newer antibiotics resulted in a significant decline in the use of sulfonamides.
4
Q
What are the primary uses of sulfonamides today?
A
Sulfonamides, especially in combination with trimethoprim, are commonly used for treating urinary tract infections (UTIs).
5
Q
Are sulfonamides typically bacteriostatic or bactericidal?
A
Sulfonamides are typically bacteriostatic, meaning they inhibit bacterial growth.
6
Q
Why are sulfonamides considered as a group rather than focusing on individual prototypes in discussions?
A
The similarities among sulfonamides are more significant than the differences, making it more practical to discuss them as a group.
7
Q
What are sulfonamides structurally related to, and how does this relate to their antimicrobial action?
A
Sulfonamides are structurally related to para-aminobenzoic acid (PABA), a component of folate. Their antimicrobial action is based on this structural similarity to PABA.
8
Q
How do sulfonamides inhibit bacterial growth?
A
Sulfonamides inhibit bacterial growth by blocking the synthesis of tetrahydrofolate, which is a derivative of folate. This disruption prevents bacteria from synthesizing essential components like DNA, RNA, and proteins.
9
Q
Why do sulfonamides not harm mammalian cells?
A
Sulfonamides do not harm mammalian cells because of the difference in how bacteria and humans acquire folate.
10
Q
What is the consequence of blocking tetrahydrofolate synthesis in bacteria?
A
Blocking tetrahydrofolate synthesis in bacteria leads to their inability to produce essential components like DNA, RNA, and proteins, ultimately inhibiting their growth.
11
Q
How does the mode of folate acquisition by bacteria and mammalian cells explain the selective action of sulfonamides?
A
Bacteria must synthesize folate, while mammalian cells acquire it directly from the diet. Sulfonamides target the folate synthesis pathway, making them effective against bacteria without harming human cells.
12
Q
What types of bacteria are susceptible to sulfonamides?
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Sulfonamides are effective against gram-positive cocci, including methicillin-resistant Staphylococcus aureus (MRSA), and gram-negative bacilli.
13
Q
Which other microorganisms are sensitive to sulfonamides?
A
Sulfonamides also target Listeria monocytogenes, actinomycetes (e.g., Nocardia), chlamydiae (e.g., Chlamydia trachomatis), some protozoa (e.g., Toxoplasma species, plasmodia, Isospora belli), and two fungi: Pneumocystis jirovecii and Paracoccidioides brasiliensis.
14
Q
What is the status of bacterial resistance to sulfonamides?
A
Many bacterial species have developed resistance to sulfonamides.
15
Q
Among which bacterial species is resistance to sulfonamides particularly high?
A
High resistance is observed among gonococci, meningococci, streptococci, and shigellae.
16
Q
What are the principal mechanisms of bacterial resistance to sulfonamides?
A
The main resistance mechanisms are reduced sulfonamide uptake, sufficient synthesis of PABA to overcome inhibition, and alteration in the structure of dihydropteroate synthetase to reduce binding and inhibition by sulfonamides.
17
Q
How can resistance to sulfonamides be acquired?
A
Resistance may be acquired through spontaneous mutation or via the transfer of plasmids that carry antibiotic resistance genes, known as R factors.
18
Q
What was the historical use of sulfonamides in medicine?
A
Sulfonamides were once widely used for treating bacterial infections.
19
Q
Why are the applications of sulfonamides now limited?
A
The limited use of sulfonamides today is primarily due to the introduction of less toxic bactericidal antibiotics and the emergence of sulfonamide resistance.
20
Q
What is the main medical indication for sulfonamides in the present day?
A
The principal indication for sulfonamides is the treatment of urinary tract infections (UTIs).
21
Q
What is the primary medical application of sulfonamides like sulfamethoxazole?
A
Sulfonamides, especially sulfamethoxazole, are often the preferred drugs for the treatment of acute urinary tract infections (UTIs).
22
Q
Which bacterium is the leading cause of UTIs, and how does it usually respond to sulfonamides?
A
Escherichia coli is the most common cause of UTIs, and it typically shows sensitivity to sulfonamides.
23
Q
Why is sulfamethoxazole, often in combination with trimethoprim, favored for UTI treatment?
A
Sulfamethoxazole is favored for UTI treatment due to its good solubility in urine and its ability to achieve effective concentrations within the urinary tract.
24
Q
For which infections is sulfonamides like sulfamethoxazole used as a valuable treatment?
A
Sulfonamides are useful for nocardiosis, Listeria species infections, and Pneumocystis jirovecii infections.
25
What are the alternative treatments provided by sulfonamides for Chlamydia trachomatis infections, and which specific infections do they target?
Sulfonamides serve as alternatives to doxycycline and erythromycin for infections caused by Chlamydia trachomatis, including trachoma, inclusion conjunctivitis, urethritis, and lymphogranuloma venereum.
26
In what protozoal infections are sulfonamides, in combination with pyrimethamine, effective treatments?
Sulfonamides, when combined with pyrimethamine, are used to treat toxoplasmosis and malaria caused by chloroquine-resistant Plasmodium falciparum.
27
What is the role of topical sulfonamides in medical practice, and where are they applied?
Topical sulfonamides are used to treat superficial eye infections and to prevent bacterial colonization in burn patients.
28
How does sulfasalazine, a specific sulfonamide, contribute to the treatment of ulcerative colitis, and is its effect based on inhibiting microbial growth?
Sulfasalazine is used to treat ulcerative colitis, but its therapeutic benefits in this condition are not related to inhibiting microbial growth.
29
How well are sulfonamides absorbed when administered orally?
Sulfonamides are well absorbed after oral administration.
30
Where are sulfonamides effectively distributed within the body, and what can be the concentration in various body fluids compared to the blood?
Sulfonamides are distributed to various body tissues and fluids, with concentrations in fluids like pleural, peritoneal, ocular, and similar fluids reaching as high as 80% of the concentration in the blood.
31
Do sulfonamides cross the placental barrier, and what are the implications of this capability?
Yes, sulfonamides can cross the placental barrier, resulting in sufficient drug levels in the fetus. This can lead to both antimicrobial effects and potential toxicity in the developing fetus.
32
What is the peak concentration time for sulfadiazine, a sulfonamide antibiotic?
The peak concentration for sulfadiazine is reached 3 to 6 hours after administration.
33
What is the protein binding percentage of sulfadiazine?
Sulfadiazine has a protein binding of 38% to 48%.
34
How is sulfadiazine metabolized?
Sulfadiazine is metabolized through acetylation.
35
What is the half-life of sulfadiazine, and how is it primarily eliminated?
The half-life of sulfadiazine is approximately 10 hours, and it is primarily eliminated through urine.
36
What is the peak concentration time for trimethoprim?
The peak concentration for trimethoprim is reached within 1 to 4 hours after administration.
37
What is the protein binding percentage of trimethoprim?
Trimethoprim has a protein binding of 44%.
38
How is trimethoprim metabolized?
Trimethoprim is metabolized through demethylation, oxidation, and hydroxylation.
39
What are the half-lives of sulfamethoxazole and trimethoprim in combination products like Bactrim?
Sulfamethoxazole has a half-life of 9 to 12 hours, while trimethoprim has a half-life of 8 to 10 hours.
40
How are sulfamethoxazole and trimethoprim primarily eliminated in the body?
Both sulfamethoxazole and trimethoprim are primarily eliminated through urine.
41
What is the typical initial dose and subsequent dose for adults taking Sulfadiazine, an oral sulfonamide?
Adults typically receive an initial dose of 2-4 grams, followed by 2-4 grams every 24 hours in divided doses.
42
How is the dosing regimen different for children over 2 months receiving Sulfadiazine?
Children over 2 months receive an initial dose of 75 mg/kg per day divided into 4-6 doses, followed by a maintenance dose of 150 mg/kg per day (up to 6 grams) in divided doses.
43
Why is it recommended to avoid taking oral sulfonamides like Sulfadiazine with vitamin C or acidifying drinks?
Avoiding vitamin C and acidifying drinks helps reduce the risk of crystalluria.
44
What is the dosing regimen for adults taking Sulfamethoxazole (+ trimethoprim) like Bactrim?
Adults take 800 mg SMZ/160 mg TMP tablets every 12-24 hours.
45
How is the dosing regimen different for children over 2 months receiving Sulfamethoxazole (+ trimethoprim)?
Children initially take 4 mg TMP/kg every 12 hours, which may be increased to 20 mg TMP/kg per day.
46
What precautions should be taken when using Silver sulfadiazine (Silvadene) topically?
It should not be used on the face to prevent blue-green or gray discoloration.
47
How should Mafenide (Sulfamylon) be applied topically?
A thin layer should be applied to the affected skin 1-2 times per day, and the cream should cover the burned area.
48
What is the dosing regimen for Sulfacetamide ophthalmic (Bleph-10, Diosulf, Sodium Sulamyd)?
For the solution, 1-2 drops are administered every 2-3 hours. For the ointment, it is applied every 3-4 hours, with increased time intervals when tapering off.
49
What is the dosing regimen for adults taking Trimethoprim (Primsol)?
Adults take 100 mg every 12 hours or 200 mg every 24 hours.
50
How should Trimethoprim be administered to children over 2 months?
Children receive 4-12 mg/kg per day divided into two 12-hour doses and should be administered with food or milk.
51
What are some of the adverse effects associated with sulfonamides?
Adverse effects of sulfonamides include hypersensitivity reactions, blood dyscrasias, and kernicterus in newborns.
52
What is hypersensitivity in the context of sulfonamides?
Hypersensitivity refers to an overreaction of the immune system to sulfonamide drugs, resulting in allergic reactions.
53
What are blood dyscrasias in the context of sulfonamides?
Blood dyscrasias are abnormal changes in blood components, such as red blood cells, white blood cells, and platelets, which can occur as an adverse effect of sulfonamide use.
54
Who is at risk of developing kernicterus due to sulfonamide exposure?
Kernicterus is a condition that primarily affects newborns, and it can be associated with sulfonamide exposure. It involves the accumulation of bilirubin in the brain, leading to neurological damage.
55
What percentage of patients may experience hypersensitivity reactions to sulfonamides?
Approximately 3% of patients may experience hypersensitivity reactions to sulfonamides.
56
What are some mild hypersensitivity reactions associated with sulfonamide use?
Mild hypersensitivity reactions can include rash, drug fever, and photosensitivity.
57
How can patients minimize the risk of photosensitivity reactions when taking sulfonamides?
To reduce the risk of photosensitivity reactions, patients should:Avoid prolonged exposure to sunlight.Wear protective clothing.Apply sunscreen to exposed skin.
58
What advice should be given to patients taking sulfonamides regarding the prescribed course of treatment?
Patients should complete the full prescribed course of treatment, even if their symptoms improve before the course is finished.
59
Why is it recommended that patients taking oral sulfonamides drink at least 8 to 10 glasses of water or noncaffeinated fluids per day?
This is advised to reduce the risk of crystalluria. Caffeine can be consumed in addition to these fluids.
60
What precautions should patients take to prevent photosensitivity reactions while using sulfonamides?
Patients should:Avoid prolonged exposure to sunlight. Wear protective clothing. Apply sunscreen to exposed skin. Avoid tanning beds.
61
Why is it important for patients to report signs of hypersensitivity, such as a rash?
Reporting hypersensitivity signs promptly is essential to address any adverse reactions.
62
In which cases are topical sulfonamides still used, and why have they become less common?
Topical sulfonamides are now less commonly used due to the high frequency of hypersensitivity reactions. They are generally reserved for ophthalmic infections, burns, and bacterial vaginosis caused by Gardnerella vaginalis and a mixed population of anaerobic bacteria.
63
What is the most severe hypersensitivity response to sulfonamides, and what is its mortality rate?
The most severe hypersensitivity reaction to sulfonamides is Stevens-Johnson syndrome, with a mortality rate of about 25%.
64
What are the symptoms of Stevens-Johnson syndrome?
Symptoms include widespread skin and mucous membrane lesions, fever, malaise, and toxemia.
65
Why were long-acting sulfonamides banned in the United States?
Long-acting sulfonamides were banned due to their higher likelihood of inducing Stevens-Johnson syndrome.
66
Can short-acting sulfonamides also cause Stevens-Johnson syndrome, and how common is this?
Short-acting sulfonamides may rarely cause the syndrome, but the incidence is low.
67
What action should be taken if any type of skin rash is observed in a patient taking sulfonamides?
Sulfonamides should be immediately discontinued if any type of skin rash is observed.
68
Who should not be given sulfonamides, and why?
Patients with a history of severe hypersensitivity to chemically related drugs should not be given sulfonamides, although the risk of cross-reactivity with these agents is probably low.
69
What is the common feature among various drugs listed under "Other Sulfonamide Drugs"?
The common feature is that they contain sulfonamide groups in their chemical structure.
70
Name some therapeutic classes or medical conditions for which sulfonamide drugs are used.
Sulfonamide drugs are used in various therapeutic classes and medical conditions, including alpha1 blockers, anticonvulsants, antidiabetic agents (sulfonylureas), antidysrhythmic drugs, antimigraine drugs, diuretics (carbonic anhydrase inhibitors, loop diuretics, thiazide and thiazide-related diuretics), protease inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), and urocosuric drugs.
71
Can you provide examples of specific drugs in the "Other Sulfonamide Drugs" category?
Some examples include Tamsulosin, Topiramate, Glimepiride, Furosemide, Celecoxib, and Probenecid.
72
What medical conditions or diseases are these sulfonamide drugs used to treat?
These drugs are used to treat a wide range of medical conditions, including benign prostatic hyperplasia, epilepsy, diabetes, cardiac arrhythmias, migraines, glaucoma, and HIV infection, among others.
73
What genetic condition makes individuals more susceptible to hemolytic anemia caused by sulfonamides?
Glucose-6-phosphate dehydrogenase (G6PD) deficiency, an inherited trait, can make individuals more susceptible to hemolytic anemia when exposed to sulfonamides.
74
Who is most commonly affected by G6PD deficiency?
G6PD deficiency is more common among people of African and Mediterranean origin.
75
What are the symptoms of hemolytic anemia caused by sulfonamides?
Hemolysis can lead to symptoms such as fever, pallor, and jaundice.
76
Besides hemolytic anemia, what other blood-related complications can sulfonamides cause?
Sulfonamides can also lead to agranulocytosis, leukopenia, thrombocytopenia, and, rarely, aplastic anemia.
77
What precaution is recommended when sulfonamides are used over an extended period?
Regular blood tests should be conducted to monitor for potential adverse effects, especially when sulfonamides are used for an extended duration.
78
What is kernicterus, and what causes it in newborns?
Kernicterus is a disorder in newborns caused by the deposition of bilirubin in the brain. It results in severe neurologic deficits and potential death.
79
How is bilirubin normally prevented from entering the central nervous system (CNS) in infants?
Bilirubin is typically tightly bound to plasma proteins in infants' blood, preventing it from entering the CNS.
80
How do sulfonamides contribute to the risk of kernicterus in infants?
Sulfonamides can displace bilirubin from plasma proteins, making it free and able to access the brain.
81
Why are infants particularly vulnerable to kernicterus when exposed to sulfonamides?
Infants are vulnerable to kernicterus because their blood-brain barrier is poorly developed, allowing bilirubin to enter the brain more easily.
82
What is the recommended precaution to avoid the risk of kernicterus in infants?
Sulfonamides should not be administered to infants younger than 2 months to prevent the risk of kernicterus.
83
Who else should avoid sulfonamide use due to the potential risk of kernicterus in infants?
Pregnant patients beyond 32 weeks of gestation and breastfeeding individuals should also avoid sulfonamide use to protect newborns from kernicterus.
84
Why should infants younger than 2 months not be given sulfonamides?
Infants younger than 2 months should avoid sulfonamides to prevent the risk of kernicterus, a potentially fatal condition.
85
What should pregnant women be cautious about when it comes to systemic sulfonamides?
Pregnant women should exercise caution with systemic sulfonamides, as they may cause birth defects, especially if taken during the first trimester. Near the end of pregnancy, sulfonamides can lead to kernicterus in the infant.
86
Why should breastfeeding women on sulfonamides be warned about breastfeeding infants younger than 2 months?
Sulfonamides are secreted in breast milk. Breastfeeding women on sulfonamides should be warned that breastfeeding an infant younger than 2 months can cause kernicterus.
87
What are the patient care concerns for older adults taking sulfonamides?
Older adults are more susceptible to adverse effects from sulfonamides, and these effects are more likely to be severe. Life-threatening effects, including neutropenia, Stevens-Johnson syndrome, and toxic epidermal necrolysis, occur more frequently in older adults.
88
Why did older sulfonamides pose a risk to the urinary system?
Older sulfonamides had low solubility, which could lead to the formation of crystalline aggregates in the urinary system, causing irritation, obstruction, and potentially life-threatening complications.
89
How has the risk of renal damage been reduced with today's sulfonamides?
Today's sulfonamides are more water-soluble, which has reduced the risk of renal damage compared to older formulations.
90
How can adults minimize the risk for renal damage when taking sulfonamides?
Adults should maintain a daily urine output of at least 1200 mL by drinking 8 to 10 glasses of water each day.
91
Who are sulfonamides contraindicated for?
Sulfonamides are contraindicated for patients with severe renal disease.
92
What should providers do when prescribing sulfonamides for patients with a creatinine clearance (CrCl) of 15 to 30 mL/minute?
Providers should prescribe 50% of the typical recommended dose for patients with a CrCl in the range of 15 to 30 mL/minute.
93
How can sulfonamides affect the effects of certain drugs like warfarin, phenytoin, and sulfonylurea-type oral hypoglycemics?
Sulfonamides can intensify the effects of these drugs.
94
What is the main mechanism behind the interaction between sulfonamides and these drugs?
The inhibition of hepatic metabolism by sulfonamides is the main mechanism.
95
What might happen when warfarin, phenytoin, and sulfonylurea-type oral hypoglycemics are combined with sulfonamides?
These drugs may become more potent, potentially leading to toxicity.
96
What should be considered to prevent toxicity when these drugs are taken with sulfonamides?
A reduction in the dosage of these drugs may be necessary to prevent toxicity when combined with sulfonamides.
97
Is there a concern about cross-sensitivity to other drugs with a sulfonamide component in people hypersensitive to sulfonamide antibiotics?
There's a theoretical concern, but it depends on the specific drugs.
98
What does current evidence suggest about sensitivity to sulfonamide antibiotics and nonantibiotic sulfonamides?
Current evidence indicates shared sensitivity among sulfonamide antibiotics but not cross-sensitivity to nonantibiotic sulfonamides.
99
Can you give an example of a drug that contains sulfonamide and may raise concern?
An example is sulfasalazine, an anti-inflammatory drug that breaks down into sulfapyridine, which is an antibiotic.
100
Why do experts recommend caution for severe hypersensitivity reactions to sulfonamide antibiotics?
Precaution is recommended to ensure patient safety and avoid potential adverse reactions.
101
What is typically found in the product labeling for drugs containing sulfonamide components?
Product labeling usually includes warnings and precautions related to potential hypersensitivity reactions.
102
What should be considered when deciding to use drugs with a sulfonamide component?
A careful evaluation of the benefits versus the risks should be considered when prescribing these drugs.
103
How are sulfonamide antibiotics categorized?
Systemic sulfonamides are categorized into two major groups: systemic sulfonamides and topical sulfonamides.
104
Which category of sulfonamides is used more frequently?
Systemic sulfonamides are more commonly used.
105
How are systemic sulfonamides classified based on their action?
Systemic sulfonamides are categorized into two groups: short-acting and intermediate-acting.
106
What distinguishes short-acting sulfonamides from intermediate-acting ones?
The primary difference is the dosing interval, which is much shorter for short-acting sulfonamides.
107
What is the unique feature of sulfamethoxazole among sulfonamides?
Sulfamethoxazole is the only intermediate-acting sulfonamide.
108
How can the risk of renal damage from crystalluria be minimized when using sulfamethoxazole?
Maintaining adequate hydration can reduce the risk.
109
Is sulfamethoxazole available as a single medication, or is it typically combined with another drug?
Sulfamethoxazole is not available as a standalone medication; it is commonly found in combination with trimethoprim.
110
What type of sulfonamide is sulfadiazine?
Sulfadiazine is a short-acting sulfonamide.
111
How does the risk of crystalluria in sulfadiazine compare to sulfamethoxazole?
Sulfadiazine is more likely to cause crystalluria than sulfamethoxazole.
112
What is the key measure to avoid renal damage when using sulfadiazine?
Maintaining a high urine flow is essential to prevent renal damage.
113
What is the risk associated with most topical sulfonamides?
Most topical sulfonamides have a high incidence of hypersensitivity reactions.
114
Are the preparations discussed in the text associated with a high or low incidence of hypersensitivity?
The preparations discussed in the text have a relatively low incidence of hypersensitivity.
115
What is sulfacetamide (Bleph-10) commonly used for?
Sulfacetamide (Bleph-10) is widely used for superficial eye infections (conjunctivitis, corneal ulcer) and dermatologic disorders.
116
What are some side effects associated with the use of sulfacetamide in the eyes?
Side effects may include blurred vision, sensitivity to bright light, headaches, brow ache, and local irritation.
117
Why should sulfacetamide not be used by patients with certain medical histories?
Sulfacetamide should not be used by patients with a history of severe hypersensitivity to sulfonamides, sulfonylureas, or thiazide or loop diuretics.
118
In what forms is sulfacetamide available for treating skin conditions?
Sulfacetamide is available in lotions, gels, washes, and shampoos, typically as a 10% solution, for treating seborrheic dermatitis, acne vulgaris, and bacterial skin infections.
119
What are mafenide (Sulfamylon) and silver sulfadiazine commonly used for?
They are used to prevent bacterial colonization in patients with second- and third-degree burns.
120
What is the mechanism of action for mafenide (Sulfamylon)?
Mafenide works similarly to other sulfonamides.
121
Is the application of mafenide or silver sulfadiazine typically painful?
The application of mafenide is often painful, while silver sulfadiazine application is usually pain-free.
122
What systemic effect can mafenide have, and how should patients be monitored for this?
Mafenide can cause acidosis, so patients should be monitored for their acid–base status.
123
What skin discoloration issue can be associated with silver sulfadiazine, and where should its application be avoided?
Silver sulfadiazine can cause a blue-green or gray skin discoloration, and its application should be avoided on the face.
124
What is the target of trimethoprim in bacteria?
Trimethoprim inhibits dihydrofolate reductase, an enzyme that converts dihydrofolate to its active form.
125
How does trimethoprim affect bacterial synthesis of DNA, RNA, and proteins?
Trimethoprim suppresses the bacterial synthesis of DNA, RNA, and proteins, similar to sulfonamides.
126
Can trimethoprim be both bactericidal and bacteriostatic, and what determines this?
Yes, trimethoprim can be either bactericidal (kills bacteria) or bacteriostatic (inhibits bacterial growth), depending on the conditions at the infection site.
127
What makes trimethoprim selectively toxic to bacteria and not harmful to host cells?
Trimethoprim is selectively toxic to bacteria because bacterial dihydrofolate reductase differs in structure from mammalian dihydrofolate reductase, allowing trimethoprim to inhibit the bacterial enzyme at concentrations about 40,000 times lower than those required to inhibit the mammalian enzyme.
128
Which types of bacteria are targeted by trimethoprim?
Trimethoprim is effective against most enteric gram-negative bacteria, including E. coli, Klebsiella pneumoniae, Proteus mirabilis, Serratia marcescens, and Salmonella and Shigella species.
129
Besides gram-negative bacteria, what other types of microorganisms are susceptible to trimethoprim?
Trimethoprim is also active against some gram-positive bacteria like Corynebacterium diphtheriae and Listeria monocytogenes, as well as the protozoan parasite Toxoplasma gondii and the fungus Pneumocystis jirovecii.
130
How do bacteria develop resistance to trimethoprim?
Bacteria can become resistant to trimethoprim by increasing the production of dihydrofolate reductase, altering the structure of dihydrofolate reductase to reduce its affinity for trimethoprim, or by reducing their cellular permeability to the drug.
131
What are the two main mechanisms by which bacteria can modify dihydrofolate reductase to resist trimethoprim?
Bacteria can either produce increased amounts of dihydrofolate reductase or create an altered form of the enzyme with reduced binding affinity for trimethoprim.
132
How can bacterial resistance to trimethoprim emerge?
Bacterial resistance can arise through spontaneous genetic mutations or through the transfer of resistance factors (R factors) from one bacterium to another. However, such resistance is relatively uncommon in the United States.
133
What is the approved use of trimethoprim in treating urinary tract infections (UTIs)?
Trimethoprim is approved for the initial therapy of acute, uncomplicated UTIs caused by susceptible bacteria, which may include E. coli, P. mirabilis, K. pneumoniae, Enterobacter species, and specific Staphylococcus species, such as S. saprophyticus.
134
In addition to its use in UTIs, what can extend the applications of trimethoprim?
When combined with sulfamethoxazole, trimethoprim can be used to treat a wider range of infections and conditions.
135
What should patients be informed about when taking trimethoprim regarding the early signs of blood dyscrasias?
Patients should be informed about recognizing early signs of blood dyscrasias, including symptoms like a sore throat, fever, or pallor. They should also be instructed to report these symptoms promptly if they occur.
136
What are the common adverse effects of trimethoprim?
Common adverse effects of trimethoprim include itching and rash.
137
What are the gastrointestinal reactions that can occur occasionally with trimethoprim?
Gastrointestinal reactions such as epigastric distress, nausea, vomiting, glossitis, and stomatitis can occur occasionally with trimethoprim.
138
What is the sensitivity of mammalian dihydrofolate reductase to trimethoprim?
It is relatively insensitive to trimethoprim.
139
What are the rare side effects of trimethoprim related to?
Rare side effects of trimethoprim are related to reduced tetrahydrofolate production.
140
When do megaloblastic anemia, thrombocytopenia, and neutropenia typically occur with trimethoprim use?
They occur in individuals with preexisting folic acid deficiency.
141
When should caution be exercised when administering trimethoprim?
Caution is needed when giving trimethoprim to patients who are at risk of folate deficiency, such as those with excessive alcohol intake, pregnant women, or debilitated patients.
142
What should be done if early signs of bone marrow suppression appear in patients taking trimethoprim?
Complete blood counts should be performed.
143
What is the recommended action if a significant reduction in blood cell counts is observed in patients on trimethoprim?
Trimethoprim should be discontinued.
144
What can be administered to restore normal hematopoiesis in patients experiencing blood cell count reduction due to trimethoprim?
Leucovorin, a reduced form of folic acid.
145
How can trimethoprim contribute to hyperkalemia?
Trimethoprim suppresses the kidney's ability to excrete potassium.
146
Who is at greater risk of developing hyperkalemia due to trimethoprim use?
Individuals taking high trimethoprim doses, those with kidney problems, and those on medications that raise potassium levels, such as ACEIs, ARBs, potassium-sparing diuretics, aldosterone antagonists, and potassium supplements.
147
Why are patients over 65 years taking ACEIs or ARBs at a higher risk of hyperkalemia with trimethoprim?
They are at a higher risk because of the combination of these medications with trimethoprim.
148
How can the risk of hyperkalemia when using trimethoprim be reduced?
By monitoring serum potassium levels, preferably around 4 days after starting treatment, as hyperkalemia often develops within 5 days.
149
What is the effect of large doses of trimethoprim on fetal development in animals?
They have caused fetal malformations.
150
Have developmental abnormalities due to trimethoprim been observed in humans?
No, developmental abnormalities have not been observed in humans.
151
Why is it generally advisable to avoid routine use of trimethoprim during pregnancy?
Trimethoprim readily crosses the placenta, and there is a potential risk of exacerbating pregnancy-related folate deficiency.
152
How does trimethoprim affect breastfeeding women and their infants?
Trimethoprim is excreted in breast milk and can interfere with folic acid utilization by nursing infants, so it should be administered with caution to breastfeeding women.
153
What are the two components combined in the fixed-dose combination product known as TMP/SMZ?
Trimethoprim (TMP) and sulfamethoxazole (SMZ).
154
What is the primary purpose of TMP/SMZ as an antimicrobial preparation?
It inhibits sequential steps in the synthesis of tetrahydrofolate in microorganisms.
155
How does TMP/SMZ achieve its antimicrobial effect?
TMP and SMZ work in concert to inhibit steps in tetrahydrofolate synthesis, which is essential for nucleic acid and protein production in microorganisms.
156
Can you name some trade names for the combination of TMP and SMZ?
Bactrim, Protrin, Septra, and Trisulfa.
157
What is the main mechanism of action of TMP/SMZ, a combination of trimethoprim and sulfamethoxazole?
Inhibiting consecutive steps in the synthesis of tetrahydrofolate, crucial for nucleic acid and protein production in microorganisms.
158
Which component of TMP/SMZ acts first in the inhibition of tetrahydrofolate synthesis?
Sulfamethoxazole (SMZ) inhibits the incorporation of PABA into folate.
159
What is the role of trimethoprim (TMP) in the antimicrobial effect of TMP/SMZ?
TMP inhibits dihydrofolate reductase, the enzyme that converts dihydrofolate into tetrahydrofolate.
160
How do TMP and SMZ potentiate each other's antimicrobial effects in TMP/SMZ?
By blocking two critical reactions in tetrahydrofolate synthesis, they make the combination more powerful than the sum of the effects of TMP alone and SMZ alone.
161
Why is TMP/SMZ selectively toxic to microbes and not harmful to mammalian cells?
Mammalian cells use preformed folic acid and are not affected by SMZ. Also, dihydrofolate reductases in mammalian cells are relatively insensitive to TMP inhibition.
162
What range of bacteria is TMP/SMZ effective against?
TMP/SMZ is active against both gram-positive and gram-negative bacteria.
163
Why is TMP/SMZ effective against a broad spectrum of bacteria?
Because both trimethoprim (TMP) and sulfamethoxazole (SMZ) are broad-spectrum antimicrobial drugs on their own.
164
What percentage of urinary tract pathogens are susceptible to TMP/SMZ?
Approximately 80% of urinary tract pathogens are susceptible.
165
Can you name some specific bacteria that are consistently susceptible to TMP/SMZ?
E. coli, P. mirabilis, L. monocytogenes, S. aureus (including methicillin-resistant isolates), C. trachomatis, Salmonella typhi, Shigella species, Vibrio cholerae, Haemophilus influenzae, and Yersinia pestis.
166
Besides bacteria, what other microorganisms are susceptible to TMP/SMZ?
TMP/SMZ is also active against Nocardia species, certain protozoa like T. gondii, and two fungi, P. jirovecii and P. brasiliensis.
167
Is resistance to TMP/SMZ more or less common than resistance to TMP or SMZ used individually?
Resistance to TMP/SMZ is less common than resistance to TMP or SMZ used separately.
168
What explains the lower resistance to TMP/SMZ?
The reduced likelihood of an organism developing resistance to both TMP and SMZ compared to developing resistance to just one of them.
169
What is TMP/SMZ's role in the treatment of infectious diseases?
TMP/SMZ is a preferred or alternative medication for various infectious diseases.
170
Which infections is TMP/SMZ especially valuable for treating?
TMP/SMZ is particularly valuable for urinary tract infections (UTIs), otitis media, bronchitis, shigellosis, and pneumonia caused by Pneumocystis jirovecii.
171
What is the primary purpose of TMP/SMZ in the context of infection?
TMP/SMZ is used for the treatment of uncomplicated urinary tract infections (UTIs).
172
Which bacterial strains is TMP/SMZ effective against in UTIs?
It is effective against susceptible strains of E. coli, Klebsiella and Enterobacter species, P. mirabilis, Proteus vulgaris, and Morganella morganii.
173
For which type of infections is TMP/SMZ particularly useful?
TMP/SMZ is particularly useful for treating chronic and recurrent infections.
174
What is TMP/SMZ the preferred treatment for?
TMP/SMZ is the preferred treatment for infections caused by Pneumocystis jirovecii, an opportunistic fungus.
175
In which individuals is Pneumocystis jirovecii infection commonly observed?
It is commonly observed in immunocompromised individuals, such as cancer patients, organ transplant recipients, and individuals with AIDS.
176
Why can the use of TMP/SMZ be limited in AIDS patients?
TMP/SMZ often leads to a high incidence of adverse effects in AIDS patients, which can restrict its use in this group.
177
What type of infections is TMP/SMZ a preferred treatment for, involving gram-negative bacilli?
TMP/SMZ is a preferred treatment for infections caused by several gram-negative bacilli, including Yersinia enterocolitica and Aeromonas species.
178
What is TMP/SMZ the drug of choice for when treating shigellosis?
TMP/SMZ is the drug of choice for shigellosis, particularly when caused by susceptible strains of Shigella flexneri and S. sonnei.
179
What infections can TMP/SMZ be used to treat when they are caused by susceptible strains of H. influenzae or Streptococcus pneumoniae?
TMP/SMZ can be used for the treatment of otitis media and acute exacerbations of chronic bronchitis.
180
For which infections is TMP/SMZ effective in cases of urethritis and pharyngeal infection caused by penicillinase-producing Neisseria gonorrhoeae?
TMP/SMZ is effective against urethritis and pharyngeal infections caused by penicillinase-producing Neisseria gonorrhoeae.
181
Name some other infections that can be treated with TMP/SMZ.
Other treatable infections include whooping cough, nocardiosis, brucellosis, melioidosis, listeriosis, and chancroid.
182
How can TMP/SMZ be administered?
TMP/SMZ can be administered orally or by intravenous infusion.
183
Where in the body are therapeutic concentrations of TMP and SMZ achieved?
Therapeutic concentrations are achieved in various tissues and body fluids, including vaginal secretions, cerebrospinal fluid, pleural effusions, bile, and aqueous humor.
184
Can both trimethoprim (TMP) and sulfamethoxazole (SMZ) cross the placenta and enter breast milk?
Yes, both TMP and SMZ can cross the placenta and enter breast milk.
185
What is the ideal ratio of TMP to SMZ in plasma for optimal antibacterial effects?
The ideal ratio is 1:20 in plasma.
186
How should TMP and SMZ be administered to maintain the 1:20 ratio in plasma?
To maintain the 1:20 ratio, TMP and SMZ must be administered in a ratio of 1:5.
187
What is the typical content of standard TMP/SMZ tablets to achieve the 1:5 ratio?
Standard tablets contain 80 mg of TMP and 400 mg of SMZ.
188
Do TMP and SMZ have similar plasma half-lives, and how does this affect their ratio in the body?
Yes, TMP and SMZ have similar plasma half-lives (10 hours for TMP and 11 hours for SMZ). Their levels decline in parallel, maintaining the 1:20 ratio as they are eliminated.
189
Is TMP/SMZ usually well-tolerated, and how often does toxicity occur with routine use?
Yes, TMP/SMZ is generally well-tolerated, and toxicity from routine use is rare.
190
What are some common adverse effects associated with TMP/SMZ?
Common adverse effects of TMP/SMZ include nausea, vomiting, and rash.
191
Can serious toxicities occur with TMP/SMZ, similar to sulfonamides and trimethoprim used alone?
Yes, serious toxicities associated with sulfonamides and trimethoprim can occur with TMP/SMZ, although they are infrequent.
192
What are some adverse effects that TMP/SMZ can cause, similar to sulfonamides?
TMP/SMZ, like sulfonamides, can cause hypersensitivity reactions (including Stevens-Johnson syndrome), blood dyscrasias (hemolytic anemia, agranulocytosis, leukopenia, thrombocytopenia, aplastic anemia), kernicterus in neonates, and renal damage.
193
What are some adverse effects that TMP/SMZ can cause, similar to trimethoprim?
Like trimethoprim, TMP/SMZ can lead to megaloblastic anemia (but only in patients who are folate deficient), hyperkalemia (especially in certain patient groups), and birth defects (especially during the first trimester).
194
Are there any adverse effects related to the central nervous system (CNS) associated with TMP/SMZ?
Yes, TMP/SMZ may cause adverse CNS effects, including headache, depression, and hallucinations.
195
Which patient group is unusually susceptible to TMP/SMZ toxicity, and what is the approximate incidence of adverse effects in this group?
Patients with AIDS are unusually susceptible to TMP/SMZ toxicity, and the incidence of adverse effects (rash, recurrent fever, leukopenia) in this group is about 55%.
196
How can the risk of crystalluria be reduced in patients taking TMP/SMZ?
Crystalluria can be avoided by maintaining adequate hydration.
197
What is the purpose of periodic blood tests in patients receiving TMP/SMZ?
Periodic blood tests allow for the early detection of hematologic disorders.
198
Why should TMP/SMZ be withheld from certain patient groups to avoid kernicterus?
TMP/SMZ should be withheld from pregnant patients near term, nursing mothers, and infants younger than 2 months to prevent kernicterus.
199
When should TMP/SMZ be withheld to prevent possible birth defects?
TMP/SMZ should be withheld during the first trimester of pregnancy to avoid possible birth defects.
200
How can the risk of megaloblastic anemia be reduced in patients taking sulfonamides?
The risk of megaloblastic anemia can be reduced by withholding sulfonamides from individuals likely to be folate deficient, such as debilitated patients, pregnant patients, and patients with excessive alcohol intake.
201
What patient history should be considered to minimize hypersensitivity reactions to TMP/SMZ?
To minimize hypersensitivity reactions, avoid TMP/SMZ in patients with a history of hypersensitivity to sulfonamides or chemically related drugs, including thiazide diuretics, loop diuretics, and sulfonylurea-type oral hypoglycemics.
202
How can injury from hyperkalemia be reduced in patients taking TMP/SMZ?
Injury from hyperkalemia can be reduced by checking serum potassium levels and exercising caution in patients taking other drugs that can elevate potassium.
203
Which component of TMP/SMZ primarily interacts with other drugs, leading to potential interactions?
The interactions of TMP/SMZ with other drugs are primarily due to the presence of sulfamethoxazole (SMZ).
204
How can SMZ in TMP/SMZ affect the effects of drugs like warfarin, phenytoin, and sulfonylurea-type oral hypoglycemics (e.g., glipizide)?
SMZ can intensify the effects of drugs like warfarin, phenytoin, and sulfonylurea-type oral hypoglycemics, much like sulfonamides used alone.
205
What may be necessary when these drugs are combined with TMP/SMZ to avoid potential interactions?
When these drugs are combined with TMP/SMZ, a reduction in their dosage may be needed to avoid interactions.
206
How can TMP/SMZ affect bone marrow suppression in patients receiving methotrexate?
TMP/SMZ may intensify bone marrow suppression in patients receiving methotrexate.
207
What risk can drugs that raise potassium levels pose when combined with TMP/SMZ?
Drugs that raise potassium levels can increase the risk of hyperkalemia when taking TMP/SMZ.
208
What is the therapeutic goal when using TMP/SMZ for treatment?
The therapeutic goal is to achieve the absence of infection.
209
What baseline data should be collected before starting TMP/SMZ treatment for suspected urinary tract infections (UTIs)?
For suspected UTIs, perform urinalysis with culture and sensitivity.
210
When is it recommended to obtain a complete blood count (CBC) with white cell differential before starting TMP/SMZ treatment?
Obtain a CBC if it's indicated or if the treatment is expected to be prolonged.
211
In what situations should renal function be checked before initiating TMP/SMZ treatment?
Check renal function if there are concerns about kidney health.
212
What should be monitored in patients using TMP/SMZ if they develop signs or symptoms of blood disorders?
Monitor CBC if signs or symptoms of blood disorders develop.
213
For patients with HIV infection, what should be monitored in addition to CBC?
For patients with HIV, monitor CD4+ count.
214
What signs and symptoms should be assessed during TMP/SMZ treatment to monitor its effectiveness?
Assess signs and symptoms of hypersensitivity reactions and resolution of infection.
215
When is it important to check potassium levels when using trimethoprim in TMP/SMZ treatment?
If hyperkalemia is suspected due to trimethoprim use, check potassium levels 4 days after starting treatment.
216
Which groups of patients are sulfonamides contraindicated for?
Sulfonamides are contraindicated for nursing mothers, pregnant women in the first trimester, those near term, and infants younger than 2 months.
217
What should be done for patients with G6PD deficiency in terms of antibiotic choice?
Alternative antibiotics should be chosen for patients with G6PD deficiency.
218
What precautions should be taken when prescribing sulfonamides for patients with renal impairment?
Caution should be exercised, and in patients with renal impairment (creatinine clearance of 15–30 mL/min), the dosage should be decreased by 50%. If creatinine clearance falls below 15 mL/min, sulfonamide use must be discontinued.
219
What is the contraindication for trimethoprim, and when should it be avoided?
Trimethoprim is contraindicated in patients with folate deficiency (manifested as megaloblastic anemia) and should be avoided during pregnancy and lactation when possible.
220
What is the recommended action for patients with renal dysfunction when taking trimethoprim?
Patients with renal dysfunction require a reduced dosage of trimethoprim.
221
When should trimethoprim be avoided, and in which patient groups?
Trimethoprim should be avoided in patients with likely folate deficiency, such as those with alcoholism or debilitation, and in pregnant women.
222
How can you evaluate the therapeutic effect of TMP/SMZ treatment?
The therapeutic effect is achieved when there is no evidence of infection, which can be indicated by negative urinalysis, white cell differential returning to normal, and the resolution of signs and symptoms.
