187: Dapsone Flashcards
1
Q
What is the primary mechanism by which dapsone acts as a bacteriostatic antibiotic?
A
Dapsone acts as a bacteriostatic antibiotic by interfering in the folate biosynthetic pathway. It inhibits the synthesis of dihydrofolic acid by competing with para-aminobenzoic acid for the active site of dihydropteroate synthetase.
2
Q
What are the anti-inflammatory properties of dapsone and how does it compare to NSAIDs?
A
Dapsone has anti-inflammatory potential comparable to NSAIDs, although its exact mechanism remains unknown. It inhibits neutrophil migration to areas of inflammation, chemotaxis, and the release of inflammatory mediators, making it effective in treating dermatologic disorders.
3
Q
What are the clinical uses of dapsone in immunocompromised patients?
A
Dapsone is used for the treatment of Hansen disease, toxoplasmosis, and as prophylaxis for Pneumocystis pneumonia (PCP) in immunocompromised patients, often in combination with pyrimethamine and leucovorin.
4
Q
What is the absorption and peak serum concentration timeline for dapsone?
A
Dapsone is absorbed from the gut with a bioavailability exceeding 86%. Peak serum concentrations are attained within 2 to 8 hours after administration.
5
Q
What are the significant side effects associated with dapsone therapy?
A
Significant side effects of dapsone include hemolysis and methemoglobinemia, which are particularly concerning in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.
6
Q
How does dapsone function as an anti-inflammatory agent?
A
Dapsone exhibits anti-inflammatory properties by inhibiting neutrophil chemotaxis, migration to areas of inflammation, and the release of inflammatory mediators. It also inhibits myeloperoxidase activity, which is involved in the oxidative burst of neutrophils.
7
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A
Dapsone has a bioavailability exceeding 86% when absorbed from the gut, with peak serum concentrations attained within 2 to 8 hours after administration, which is crucial for its therapeutic effectiveness.
8
Q
What is the role of dapsone in treating dermatitis herpetiformis?
A
Dapsone is used for its anti-inflammatory effects in dermatitis herpetiformis, providing prompt relief from pruritus and controlling skin lesions, often leading to a rapid and dramatic response that can serve as a diagnostic test for the disease.
9
Q
What is the FDA approval status of dapsone for acne treatment?
A
In 2016, the U.S. FDA approved a 7.5% dapsone gel for once-daily application for acne vulgaris, which is an advancement over the previously used 5% formulation that required twice-daily application.
10
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A
Dapsone inhibits the migration of neutrophils to inflammation sites by blocking chemotactic signals and preventing their adherence to skin-localized IgA and endothelium, thereby modulating the inflammatory response.
11
Q
What is the importance of monitoring patients on dapsone therapy?
A
Monitoring is crucial for patients on dapsone therapy to detect potential side effects such as hemolysis and methemoglobinemia, especially in those with G6PD deficiency, ensuring safe and effective treatment.
12
Q
What are the implications of dapsone’s classification in pregnancy?
A
Dapsone is classified as a Category C drug in pregnancy, indicating that risk cannot be ruled out, and its use should be carefully considered against potential benefits in pregnant patients.
13
Q
What are the primary metabolic pathways of dapsone in the liver?
A
Dapsone is metabolized primarily through acetylation by N-acetyltransferase to monacetyl-dapsone (MADDS) and through hydroxylation by cytochrome P-450 enzymes, resulting in the generation of dapsone hydroxylamine (DDS-NOH).
14
Q
What is the distribution of dapsone in the body?
A
Dapsone is distributed in virtually all organs and retained in the skin, muscle, kidneys, and liver. It can also be found in sweat, saliva, sputum, tears, and bile. Trace concentrations can be seen up to 3 weeks after discontinuation of treatment.
15
Q
What are the implications of dapsone crossing the blood-brain barrier and placenta?
A
Dapsone crosses the blood-brain barrier and placenta, which can lead to cases of neonatal hemolysis and cyanosis if the mother is treated with dapsone during pregnancy.
16
Q
What are the common drug interactions that increase blood levels of dapsone?
A
The common drug interactions that increase blood levels of dapsone include: Probenecid (Increases levels), Trimethoprim (Increases levels).
17
Q
What is the significance of dapsone hydroxylamine in terms of side effects?
A
Dapsone hydroxylamine is a potent oxidant responsible for the development of methemoglobinemia, hemolysis, and liver damage. Reduced levels of enzymes that reduce dapsone hydroxylamine have been detected in patients who developed symptomatic methemoglobinemia.
18
Q
What is the recommended use of topical dapsone gel?
A
Topical dapsone gel, approved in 2005 for the treatment of acne vulgaris, can be applied twice daily on up to 22% of patients’ body surface area, resulting in systemic levels that are 100-fold less than oral dapsone at therapeutic doses, with a favorable safety profile.
19
Q
What are the medical indications for dapsone?
A
Dapsone is primarily used for: Leprosy (Commonly used in combination with rifampicin and clofazimine), PCP Prevention (Treats and prevents Pneumocystis pneumonia in immunocompromised hosts), Toxoplasmosis (Used in patients unable to tolerate trimethoprim with sulfamethoxazole).
20
Q
A patient with renal dysfunction is prescribed dapsone. What precautions should be taken?
A
Dapsone should be avoided in patients with significant renal dysfunction. Renal function should be checked before prescribing dapsone.
21
Q
What is the clinical significance of the FDA’s removal of the requirement for G6PD testing before topical dapsone treatment?
A
In 2008, the FDA removed the requirement for pretreatment G6PD testing for dapsone, indicating that the risk of hemolytic anemia in G6PD-deficient patients is lower than previously thought when using topical dapsone.
22
Q
What are the effects of rifampicin on dapsone levels in the body?
A
Rifampicin reduces dapsone blood levels by upregulating the P-450 system, which can lead to decreased effectiveness of dapsone therapy.
23
Q
How can cimetidine and omeprazole affect dapsone therapy?
A
Cimetidine and omeprazole block the N-hydroxylation of dapsone, which can mitigate some side effects associated with dapsone therapy.
24
Q
What are the therapeutic indications for dapsone?
A
Dapsone is indicated for: Infectious diseases (Hansen disease, malaria, leishmaniasis, nocardiosis, PCP prophylaxis), Anti-inflammatory (Dermatitis herpetiformis, erythema elevatum diutinum, linear IgA dermatosis), Adjunctive treatment (Granuloma annulare), Neutrophilic dermatoses (Subcorneal pustular dermatosis). See Table 187-2.
25
What is the recommended starting dose of dapsone to minimize adverse effects?
The recommended starting dose of dapsone is between 50 mg to 100 mg/day to minimize potential pharmacologic adverse effects, particularly hemolysis.
26
What are the adverse reactions associated with dapsone?
Adverse reactions of dapsone include: Hemolysis, Methemoglobinemia, Toxic hepatitis, Exfoliative dermatitis, Urticaria, Gastrointestinal upset.
27
What is the clinical significance of topical dapsone for acne vulgaris?
Topical dapsone (5% gel) is FDA approved for treating acne vulgaris in adults and adolescents up to 12 years old. It can reduce the mean total lesion count by 39% to 49%.
28
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The likely diagnosis is bullous eruption of systemic lupus erythematosus. Management includes discontinuation of dapsone and appropriate treatment for lupus.
29
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Dapsone is indicated for treating autoimmune blistering diseases such as bullous pemphigoid, pemphigus vulgaris, linear IgA dermatosis.
30
How should the dose of dapsone be adjusted after a successful therapeutic trial?
After a successful therapeutic trial, the dose of dapsone should be decreased to a point at which lesions recur to ensure that the improvement was indeed caused by dapsone.
31
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Potential adverse reactions of dapsone include: Hemolysis, Methemoglobinemia, Exfoliative dermatitis, Fatigue, Insomnia.
32
What are the potential adverse reactions associated with dapsone therapy?
Potential adverse reactions of dapsone include:
- Hemolysis
- Methemoglobinemia
- Exfoliative dermatitis
- Urticaria
- Erythema nodosum
- Fatigue
- Insomnia
- Psychosis
- Peripheral neuropathy
- Motor neuropathy
- Life-threatening side effects such as Stevens-Johnson syndrome and toxic epidermal necrolysis.
33
What is the clinical response time for dapsone in treating generalized granuloma annulare?
The clinical response to dapsone in treating generalized granuloma annulare is typically observed within 24 to 48 hours.
34
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Topical dapsone (5% gel) is FDA approved for the treatment of acne vulgaris in adults and adolescents aged up to 12 years old.
35
What precautions should be taken when using topical dapsone with benzoyl peroxide?
When using topical dapsone with benzoyl peroxide, it may cause yellow-orange discoloration of the skin, which is washable but may stain clothing.
36
What is the therapeutic dose range for dapsone?
The therapeutic dose of dapsone varies from 25 mg to 200 mg/day, usually administered in a single dose.
37
What role does dapsone play in the treatment of systemic lupus erythematosus?
Dapsone may be effective in treating bullous eruptions associated with systemic lupus erythematosus, particularly as a second-line or steroid-sparing agent.
38
What is the significance of granulocytes in diseases treated with dapsone?
In diseases treated with dapsone, granulocytes (neutrophils or eosinophils) are often the predominant infiltrating cells, especially early in the pathologic process, which may influence the response to therapy.
39
What is the most common side effect of dapsone and what condition can it lead to?
The most common side effect of dapsone is dose-related hemolysis, which may lead to hemolytic anemia and methemoglobinemia. Approximately 20% of patients develop hemolysis.
40
What should be ruled out before initiating dapsone therapy in patients?
G6PD deficiency should be ruled out before initiating dapsone therapy in all patients, as the side effect of hemolysis is more common and severe in those with G6PD deficiency.
41
What are the signs and symptoms of methemoglobinemia caused by dapsone?
Signs and symptoms of methemoglobinemia include cyanosis, headache, shortness of breath, chest pain, and fatigue. Symptoms usually occur with methemoglobin levels of 20% to 30%.
42
What dietary supplement has been suggested to lower methemoglobin levels in dapsone-treated patients?
Lipoic acid, a dietary supplement with antioxidant properties, has been suggested to lower methemoglobin levels in dapsone-treated patients, with a recommended dosage of 90 mg/day.
43
What is the incidence of dapsone hypersensitivity syndrome in treated patients?
The incidence of dapsone hypersensitivity syndrome is between 0.2% to 5% of treated patients.
44
What are the common manifestations of dapsone hypersensitivity syndrome?
Dapsone hypersensitivity syndrome commonly manifests with a rash, fever, jaundice, and eosinophilia. It typically occurs within the first 6 weeks of therapy.
45
What is the most frequent cause of death associated with dapsone hypersensitivity syndrome?
The most frequent cause of death associated with dapsone hypersensitivity syndrome is hepatic coma.
46
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Serious adverse effects of dapsone include nausea, headache, ufatigue, insomnia, psychosis, and peripheral neuropathy. Neurologic side effects can include distal motor neuropathy.
47
A patient with G6PD deficiency is prescribed dapsone. What complications should you anticipate, and how would you manage them?
Patients with G6PD deficiency are at higher risk for hemolysis when taking dapsone. Hemolysis is more profound at the initiation of therapy and may be accompanied by compensatory reticulocytosis. Management includes ruling out G6PD deficiency before initiating therapy and monitoring for signs of hemolysis. If hemolysis occurs, discontinuation of dapsone and supportive care may be required.
48
A patient develops cyanosis and fatigue after starting oral dapsone. What is the likely diagnosis, and how would you confirm it?
The likely diagnosis is methemoglobinemia, caused by dapsone hydroxylamine generating reactive oxygen species. Confirmation involves pulse oximetry as a screening test, followed by direct methemoglobin determination if an abnormal value is found.
49
A patient on dapsone therapy presents with fever, rash, and jaundice within the first 6 weeks. What is the likely condition, and how should it be managed?
The patient likely has dapsone hypersensitivity syndrome, which manifests with rash, fever, jaundice, and eosinophilia. Management includes immediate discontinuation of dapsone and corticosteroid therapy, such as methylprednisolone followed by a prednisone taper.
50
A patient on dapsone therapy develops peripheral neuropathy. What is the likely cause, and how should it be managed?
Peripheral neuropathy is a neurologic side effect of dapsone, often reversible with dose reduction or discontinuation.
51
A patient on dapsone therapy develops photosensitivity. How should this be managed?
Dapsone-induced photosensitivity is rare and usually not dose-dependent. Management includes avoiding sun exposure and using protective measures.
52
A patient on dapsone therapy develops Stevens-Johnson syndrome. What is the management approach?
Management includes immediate discontinuation of dapsone and supportive care, including corticosteroids if indicated.
53
A patient on dapsone therapy develops a rash and fever after 3 weeks. What is the likely diagnosis, and what is the prognosis?
The likely diagnosis is dapsone hypersensitivity syndrome. Early discontinuation of dapsone is associated with a better prognosis.
54
A patient on dapsone therapy develops hemolysis. What laboratory findings would confirm this, and how should it be managed?
Laboratory findings include a drop in hemoglobin and elevated reticulocyte counts. Management includes discontinuation of dapsone and supportive care.
55
A patient on dapsone therapy develops eosinophilia and lymphadenopathy. What is the likely condition?
The likely condition is dapsone hypersensitivity syndrome, which often includes eosinophilia and lymphadenopathy.
56
A patient on dapsone therapy develops a distal motor neuropathy. What is the management approach?
Management includes dose reduction or discontinuation of dapsone. Monitoring distal motor strength at follow-up visits is recommended.
57
A patient on dapsone therapy develops nausea and psychosis. What is the likely cause, and how should it be managed?
These are neurologic side effects of dapsone. Management includes dose reduction or discontinuation.
58
A patient on dapsone therapy develops erythema nodosum. What is the management approach?
Management includes discontinuation of dapsone and supportive care.
59
A patient on dapsone therapy develops exfoliative dermatitis. What is the management approach?
Management includes discontinuation of dapsone and supportive care, including corticosteroids if indicated.
60
A patient on dapsone therapy develops a morbilliform rash. What is the likely cause, and how should it be managed?
The likely cause is a hypersensitivity reaction to dapsone. Management includes discontinuation of dapsone and supportive care.
61
A patient on dapsone therapy develops a scarlatiniform exanthema. What is the management approach?
Management includes discontinuation of dapsone and supportive care.
62
A patient on dapsone therapy develops urticaria. What is the likely cause, and how should it be managed?
The likely cause is a hypersensitivity reaction to dapsone. Management includes discontinuation of dapsone and supportive care.
63
A patient on dapsone therapy develops erythema multiforme. What is the management approach?
Management includes discontinuation of dapsone and supportive care.
64
A patient on dapsone therapy develops toxic hepatitis. What is the management approach?
Management includes discontinuation of dapsone and supportive care, including corticosteroids if indicated.
65
A patient on dapsone therapy develops cholestatic jaundice. What is the likely cause, and how should it be managed?
The likely cause is dapsone-induced liver toxicity. Management includes discontinuation of dapsone and supportive care.
66
A patient on dapsone therapy develops a rash and fever. What is the likely diagnosis, and how should it be managed?
The likely diagnosis is dapsone hypersensitivity syndrome. Management includes discontinuation of dapsone and corticosteroid therapy.
67
A patient on dapsone therapy develops lymphadenopathy. What is the likely cause, and how should it be managed?
The likely cause is dapsone hypersensitivity syndrome. Management includes discontinuation of dapsone and corticosteroid therapy.
68
A patient on dapsone therapy develops eosinophilia. What is the likely cause, and how should it be managed?
The likely cause is dapsone hypersensitivity syndrome. Management includes discontinuation of dapsone and corticosteroid therapy.
69
A patient on dapsone therapy develops a rash and fever after 4 weeks. What is the likely diagnosis, and what is the prognosis?
The likely diagnosis is dapsone hypersensitivity syndrome. Early discontinuation of dapsone is associated with a better prognosis.
70
A patient on dapsone therapy develops a rash and fever after 6 weeks. What is the likely diagnosis, and what is the prognosis?
The likely diagnosis is dapsone hypersensitivity syndrome. Early discontinuation of dapsone is associated with a better prognosis.
71
What is the most common side effect of dapsone and how does it relate to G6PD deficiency?
The most common side effect of dapsone is hemolysis, which may lead to hemolytic anemia and methemoglobinemia. Approximately 20% of patients develop hemolysis, and this side effect is more severe in individuals with G6PD deficiency. Hemolysis is more profound at the initiation of therapy and is often accompanied by a compensatory reticulocytosis.
72
What are the signs and symptoms of methemoglobinemia caused by dapsone?
Signs and symptoms of methemoglobinemia caused by dapsone include:
- Cyanosis
- Headache
- Shortness of breath
- Chest pain
- Fatigue
Symptoms usually occur with methemoglobin levels of 20% to 30% and symptomatic methemoglobinemia is rare.
73
How can cimetidine and lipoic acid be used in the management of dapsone-induced methemoglobinemia?
Cimetidine can be used to block the hydroxylation of dapsone, intentionally lowering methemoglobin levels in dapsone-treated patients by 27% to 60%. Additionally, lipoic acid, a dietary supplement with antioxidant properties, has been shown to decrease methemoglobin formation, with a suggested dosage of 90 mg/day for dapsone-treated patients.
74
What liver-related adverse effects are associated with dapsone?
Dapsone can cause toxic hepatitis and cholestatic jaundice. Hepatitis and jaundice may also occur as part of the dapsone hypersensitivity reaction. Dapsone is metabolized by the cytochrome P450 system, and its metabolites are associated with the methemoglobinemia side effect of the drug.
75
What skin reactions can occur due to dapsone use?
Skin reactions associated with dapsone include:
- Exfoliative dermatitis
- Erythema multiforme
- Urticaria
- Erythema nodosum
- Morbilliform and scarlatiniform exanthema
- Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Dapsone-induced photosensitivity is rare but usually not dose-dependent, and topical dapsone can cause mild skin irritation, redness, dry skin, burning, and itching.
76
What is the incidence and clinical presentation of dapsone hypersensitivity syndrome?
The incidence of dapsone hypersensitivity syndrome is between 0.2% to 5% of treated patients. This syndrome manifests with a rash, fever, jaundice, and eosinophilia within the first 6 weeks of therapy. Symptoms may be ameliorated by corticosteroid therapy, and the maximum latency for symptoms can be up to 20 weeks.
77
What are the hematologic changes associated with dapsone hypersensitivity syndrome?
Hematologic changes associated with dapsone hypersensitivity syndrome include:
- Leucocytosis in 56.6% of patients
- Eosinophilia in 43.8% of patients. These changes can indicate the severity of the reaction and may require monitoring and management.
78
What is the most frequent cause of death associated with dapsone hypersensitivity syndrome?
The most frequent cause of death associated with dapsone hypersensitivity syndrome is hepatic coma. Nearly 10% of patients may have a fatal outcome, highlighting the importance of early recognition and discontinuation of dapsone therapy.
79
What is the recommended management for dapsone-induced hepatic dysfunction?
Management of dapsone-induced hepatic dysfunction may include:
1. Withdrawal of dapsone and possibly steroid therapy.
2. Corticosteroids have proven helpful, with dosages up to 1g/day of methylprednisolone for 3 days, followed by a taper over 4 to 6 weeks.
3. Monitoring liver function tests and hematologic parameters to assess recovery.
80
What are the potential viral reactivations associated with dapsone therapy?
Dapsone therapy can lead to reactivation of latent viruses such as human herpesvirus 6 (HHV6), cytomegalovirus, and Epstein-Barr virus. These reactivations typically develop between 2 and 7 weeks after initiation and may present with the triad of fever, rash, and hepatitis.
81
What are important concepts to consider in hemolysis and methemoglobinemia in the setting of dapsone therapy?
- Acute methemoglobinemia: Rarely occurs, can lead to dyspnea, anemia, vascular collapse, and serious cases may result in death.
- Heinz bodies: Oxidized hemoglobin becomes microscopically visible as Heinz bodies, which target RBCs for removal by the spleen.
- Symptomatic anemia: Occurs in about 10% of patients, higher in certain populations such as solid organ allograft recipients (23%).
- If dapsone therapy is efficacious but hemolysis is limiting therapy, coadministration of darbepoetin may allow continuation of drug at therapeutic doses
82
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Monitoring should include:
1. Targeted history and physical examination: To screen for significant preexisting anemia, cardiopulmonary disease, and peripheral neuropathy.
2. Laboratory tests: CBC and reticulocyte counts to determine baseline white blood cell count, hemoglobin, and reticulocytes.
3. G6PD deficiency: Should be ruled out, along with significant hepatic or renal dysfunction.
83
What monitoring is recommended during the initiation of dapsone therapy?
Monitoring should include:
1. Targeted history and physical examination to screen for significant preexisting anemia, cardiopulmonary disease, and peripheral neuropathy.
2. Laboratory tests: CBC and reticulocyte counts to determine baseline white blood cell count, hemoglobin, and reticulocytes.
3. G6PD deficiency should be ruled out, along with significant hepatic or renal dysfunction.
4. Ongoing monitoring: After therapy begins, obtain a white blood cell count with differential and hemoglobin levels and reticulocyte count weekly for the first month, then twice a month for the next two months.
84
What are the symptoms and risks associated with agranulocytosis in patients receiving dapsone therapy?
Symptoms of agranulocytosis include:
- Fever
- Pharyngitis
- Dysphagia
- Oral ulcerations
Agranulocytosis is estimated to occur in 0.2% to 0.4% of treated patients, usually during the first three months of therapy. It is typically reversible within days upon stopping therapy but may be fatal due to superseding infections.
85
What should patients be informed about regarding the potential adverse effects of dapsone therapy?
Patients should be made aware of:
- The risk of agranulocytosis and dapsone hypersensitivity syndrome, which is highest during the first three months of therapy.
- The importance of seeking medical attention for significant symptoms such as:
- Fever
- Pharyngitis
- Dysphagia
- Swollen lymph nodes
- Oral ulcerations
- Rash
They should also carry a medication card indicating they are on dapsone therapy to inform emergency physicians of the potential risks.
86
A patient on dapsone therapy develops Heinz bodies in their erythrocytes. What is the underlying mechanism?
Heinz bodies are caused by the oxidation of hemoglobin into methemoglobin by dapsone hydroxylamine, a potent oxidant. This labels RBCs as senescent, targeting them for removal by the spleen.
87
A patient on dapsone therapy develops agranulocytosis. What are the symptoms, and how can recovery be expedited?
Symptoms include fever, pharyngitis, dysphagia, and oral ulcerations. Recovery can be expedited using recombinant granulocyte colony-stimulating factor.
88
A patient on dapsone therapy develops aplastic anemia. What is the prognosis and management?
Aplastic anemia is rare but can be fatal. Management includes discontinuation of dapsone and supportive care.
89
A patient on dapsone therapy develops a mixed hepatocellular and cholestatic picture. What is the likely cause?
The likely cause is dapsone-induced hepatitis, which may occur as part of the hypersensitivity reaction.
90
A patient on dapsone therapy develops dyspnea and vascular collapse. What is the likely diagnosis, and what is the treatment?
- Acute methemoglobinemia.
- Methylene blue, 1% solution, 1 to 2 mg/kg slow IV (to decrease degree od methemoglobinemia)
- Ascorbic acid 1000 mg IV Q12 hours (increase methemoglobin reductase activity)
G6PD-deficient patients should not be given methylene blue because they may have insufficient NADPH, and unreduced methylene blue is its own direct hemolytic agent.
91
A patient on dapsone therapy develops hemophagocytic syndrome. What is the management approach?
Management includes discontinuation of dapsone and supportive care.
92
A patient on dapsone therapy develops a mixed hepatocellular and cholestatic picture. What is the management approach?
Management includes discontinuation of dapsone and supportive care, including corticosteroids if indicated.
93
What are the potential hematologic adverse effects associated with dapsone therapy?
The potential hematologic adverse effects associated with dapsone therapy include:
- Hemolysis: Caused by dapsone hydroxylamine, leading to methemoglobinemia and Heinz body formation.
- Agranulocytosis: Estimated to occur in 0.2% to 0.4% of treated patients, usually during the first 3 months of therapy.
- Aplastic Anemia: Rare but can be fatal, leading to significant white blood cell formation abnormalities.
94
How does G6PD deficiency affect patients undergoing dapsone therapy?
Patients with G6PD deficiency are less tolerant of pharmacologic oxidative stress and are at risk for substantial hemolysis when treated with dapsone. There are two types of G6PD deficiency screened for, with 'A-type' being milder and more common in African Americans. Baseline anemia should be assessed before starting dapsone therapy, especially since symptomatic anemia occurs in about 10% of patients.
95
What monitoring is recommended during the first few months of dapsone therapy?
During the first few months of dapsone therapy, the following monitoring is recommended:
1. CBC and reticulocyte counts: Weekly for the first month, then twice a month for the next 2 months.
2. G6PD deficiency: Should be ruled out before starting therapy.
3. Monitoring for symptoms: Patients should be educated to seek medical attention for significant fever, pharyngitis, dysphagia, swollen lymph nodes, oral ulcerations, and rash.
4. Hemoglobin levels: A drop of 1 to 2 g/dL should be anticipated, but in the absence of symptoms, it should not prompt drug discontinuation.
96
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Clinical manifestations of agranulocytosis in patients on dapsone include:
- Fever
- Pharyngitis
- Dysphagia
- Oral ulcerations
These symptoms usually occur during the first 3 months of therapy and can be fatal if not addressed promptly.
97
What is the significance of monitoring reticulocyte counts in patients receiving dapsone?
Monitoring reticulocyte counts in patients receiving dapsone is significant because:
- A profoundly elevated reticulocyte count suggests that erythropoiesis is at its maximum, indicating that further dose increases may not be well tolerated.
- It provides an estimation of the adequacy of compensation for hemolysis, helping to assess the patient's response to therapy and the risk of adverse effects.
98
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Patients should be informed that during the first 3 months of dapsone therapy, the risk of agranulocytosis and hypersensitivity syndrome is highest. They should be educated to seek immediate medical attention for symptoms such as:
- Significant fever
- Pharyngitis
- Dysphagia
- Swollen lymph nodes
- Oral ulcerations
- Rash
Awareness of these symptoms is crucial for timely intervention.
99
What is the role of darbepoetin in the context of dapsone therapy?
Darbepoetin may be coadministered with dapsone therapy if hemolysis is limiting treatment efficacy. It can help maintain therapeutic doses of dapsone by stimulating erythropoiesis, thus allowing continued treatment despite the risk of hemolysis.
100
What laboratory tests should be performed before initiating dapsone therapy?
Before initiating dapsone therapy, the following laboratory tests should be performed:
1. Glucose-6-phosphate dehydrogenase (G6PD) test to rule out deficiency.
2. Complete Blood Count (CBC) to assess baseline white blood cell count, hemoglobin, and reticulocytes.
3. Hepatic function tests to check for liver dysfunction.
4. Renal function tests to rule out renal dysfunction.
101
What are the potential consequences of untreated methemoglobinemia in patients on dapsone?
Untreated methemoglobinemia in patients on dapsone can lead to serious consequences, including:
- Dyspnea
- Anemia
- Vascular collapse
- In severe cases, it may result in death due to lack of oxygen delivery to tissues.
102
How should patients be educated about the signs of hemolysis while on dapsone therapy?
Patients should be educated to recognize the signs of hemolysis while on dapsone therapy, which may include:
- Fatigue
- Pallor
- Jaundice
- Dark urine
- Shortness of breath
They should be advised to report these symptoms immediately to their healthcare provider for further evaluation and management.
103
What should patients with diabetes be aware of when taking dapsone?
Dapsone can cause falsely low hemoglobin A1c values due to accelerated RBC turnover. Monitoring fructosamine levels can help avoid this potential confounder.
104
In which conditions should dapsone be used with caution?
Dapsone should be used with caution in the following conditions:
1. G6PD deficiency
2. Methemoglobinemia reductase deficiency
3. Severe hepatopathy
4. Cardiac insufficiency or heart failure
5. Pulmonary diseases
6. Comedication with methemoglobinemia-inducing drugs or compounds.
105
What is the role of activated charcoal in dapsone overdose management?
Activated charcoal is administered to reduce drug levels by removing dapsone from the gut, which is important due to dapsone's enterohepatic recirculation.
106
What is the use of methylene blue in the context of dapsone treatment?
Methylene blue, at a concentration of 1% solution, can be used to decrease the degree of methemoglobinemia. It acts as a cofactor for methemoglobin reductase after being reduced by cellular stores of NADPH.
107
What is the effect of ascorbic acid in the treatment of methemoglobinemia related to dapsone?
Ascorbic acid, administered at 1000 mg IV every 12 hours, can be used until G6PD status is reviewed. Its effect is due to its ability to increase methemoglobin reductase activity.
108
A patient on dapsone develops shortness of breath and chest pain. What is the potential adverse effect, and what treatment options are available?
The patient may have symptomatic methemoglobinemia. Treatment options include methylene blue (1% solution, 1-2 mg/kg slow IV) or ascorbic acid (1000 mg IV Q12 hours) if G6PD status is uncertain.
109
A patient with diabetes is prescribed dapsone. What specific monitoring should be done to avoid misinterpretation of glycemic control?
Dapsone causes falsely low hemoglobin A1c values due to accelerated RBC turnover. Monitoring fructosamine levels avoids this potential confounder.
110
A patient on dapsone therapy develops severe anemia. What are the contraindications and precautions for continuing therapy?
Dapsone is contraindicated in patients with severe anemia. Precautions include ruling out G6PD deficiency, methemoglobinemia reductase deficiency, severe hepatopathy, cardiac insufficiency, and pulmonary diseases.
111
A patient overdoses on dapsone. What are the key steps in managing this situation?
Management includes repeated dialysis to remove the unbound portion of dapsone, administration of activated charcoal to reduce drug levels, and methylene blue (1-2 mg/kg slow IV) to decrease methemoglobinemia. G6PD-deficient patients should not receive methylene blue.
112
A patient on dapsone therapy develops optic ischemic injury. What could be the underlying cause, and how should it be addressed?
Massive intravascular hemolysis seen in dapsone overdose has been linked to optic ischemic injury. Management includes addressing the overdose with dialysis and activated charcoal.
113
What is the recommended management for patients with mild symptoms of anemia or methemoglobinemia taking dapsone?
Patients should take cimetidine 400 mg TID and lipoic acid 90 mg/day, and their symptoms should be observed to determine if dapsone administration can continue.
114
In which conditions is dapsone contraindicated?
Dapsone is contraindicated in patients who are allergic to the drug and should not be administered to patients with severe anemia.
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Dapsone must be used with caution in patients with G6PD deficiency due to the risk of hemolysis.
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Activated charcoal can reduce drug levels by removing dapsone from the gut, which is important in managing overdose cases.
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Methylene blue acts as a cofactor for methemoglobin reductase, helping to decrease the degree of methemoglobinemia after being reduced by cellular stores of NADPH.
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Ascorbic acid can be administered to increase methemoglobin reductase activity until G6PD status is reviewed, allowing for safe administration of methylene blue.
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Adverse effects include hemolysis, methemoglobinemia, and hypersensitivity reactions, which may manifest as rash, fever, jaundice, and eosinophilia.
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A drop in hemoglobin of 1 to 2 g/dL should be anticipated, and in the absence of symptoms, it should prompt drug discontinuation.
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Hemolysis is a common adverse effect of dapsone, occurring in a significant percentage of patients, though the exact percentage is not specified in the text.
