The drugs used in treatment of sickle cell disease (SCD) include antimetabolites, analgesics, antibiotics, and vaccines.
Hydroxyurea affects DNA, resulting in increased production of Hb F, which inhibits sickling. Considerable effort is being expended to identify agents whose ultimate effect interferes with the sickling process and prevents the many complications of sickle cell disease.
Hydroxyurea inhibits deoxynucleotide synthesis. Its myelosuppressive effects last a few days to a week and are easier to control than those of alkylating agents.
Opioid analgesics are used to control acute crisis and chronic pain.
This drug combination is indicated for the relief of moderate to severe pain.
Methadone is used in the management of severe pain. It inhibits ascending pain pathways, diminishing the perception of and response to pain.
An opioid analgesic, morphine interacts with endorphin receptors in the CNS.
This drug combination is indicated for the relief of moderate to severe pain. It is the drug of choice for patients who are hypersensitive to aspirin.
A synthetic opioid analgesic that is primarily a mu receptor agonist, fentanyl is 50-100 times more potent than morphine. It has short duration of action (1-2 h) and minimal cardiovascular effects, such as hypotension. Respiratory depression is uncommon, but this effect lasts longer than its analgesic effect. Fentanyl is frequently used in patient-controlled analgesia for relief of pain. Unlike morphine, fentanyl is not commonly associated with histamine release.
An opioid agonist/antagonist, nalbuphine stimulates kappa opioid receptor in the CNS, which causes inhibition of ascending pain pathways. An antagonist at the opioid mu receptors, it is useful for moderate-to-severe pain in sickle cell disease.
Codeine binds to opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering perception and response to pain.
This combination is a mild narcotic analgesic. Provide the family with a small supply for use when pain severity is greater than can be managed with acetaminophen alone. Counsel parents to use for severe pain only, not as the first medication for each symptom.
Acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) add to the effects of opioids during painful crisis. This allows use of lower doses of narcotics.
Ketorolac is an intravenously administered NSAID and a very powerful analgesic. It inhibits prostaglandin synthesis by decreasing activity of the enzyme cyclooxygenase, which results in decreased formation of prostaglandin precursors. In turn, this results in reduced inflammation.
Aspirin treats mild to moderate pain. It inhibits prostaglandin synthesis, which prevents formation of platelet-aggregating thromboxane A2.
Acetaminophen is the drug of choice for pain in patients with documented hypersensitivity to aspirin or NSAIDs, with upper GI disease, or who are taking oral anticoagulants.
Ibuprofen is usually the drug of choice for treatment of mild to moderate pain, if no contraindications exist. It inhibits inflammatory reactions and pain by decreasing the activity of the enzyme cyclo-oxygenase, resulting in inhibition of prostaglandin synthesis.
Folate is necessary for erythropoiesis. Supplemental folic acid replenishes depleted folate stores secondary to hemolysis.
Folic acid is nnecessary for proper nucleotide metabolism. It is an important cofactor for enzymes used in production of RBCs.
These agents are used for treatment of suspected or confirmed infections.
Cefuroxime is a second-generation cephalosporin that maintains the gram-positive activity of first-generation cephalosporins and adds activity against Proteus mirabilis, Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, and Moraxella catarrhalis. The condition of the patient, severity of infection, and susceptibility of the microorganism should determine proper dose and route of administration.
This drug combination extends the antibiotic spectrum of this penicillin to include bacteria normally resistant to beta-lactam antibiotics. It is indicated for skin and skin structure infections caused by beta-lactamase-producing strains of Staphylococcus aureus. Administer treatment for a minimum of 10 d.
Penicillin inhibits the biosynthesis of cell wall mucopeptide.
A third-generation cephalosporin, ceftriaxone is the most common antibiotic used in the management of fever in patients with sickle cell disease in the acute care/ED setting. This agent is widely distributed throughout the body, including gallbladder, lungs, bone, bile, and cerebrospinal fluid (CSF); ceftriaxone diffuses into the CSF at higher concentrations when the meninges are inflamed.
Azithromycin is a macrolide antibiotic that is useful for treatment of
community-acquired pneumonia in sickle cell disease, as an adjunct to a cephalosporin to cover Chlamydia or Mycoplasma infections.
A second-generation cephalosporin, cefaclor is indicated for infections caused by susceptible gram-positive cocci and gram-negative rods.
Phosphodiesterase Type 5 Inhibitors
Phosphodiesterase type 5 (PDE5) inhibitors are used to treat pulmonary hypertension associated with sickle cell disease. These agents are also used to prevent priapism associated with sickle cell disease.
Sildenafil promotes selective smooth muscle relaxation in lung vasculature, possibly by inhibiting PDE5. This results in a subsequent reduction of blood pressure in pulmonary arteries and an increase in cardiac output.
Endothelin Receptor Antagonists
These agents are used for pulmonary hypertension associated with sickle cell disease.
Bosentan improves pulmonary arterial hemodynamics by competitively binding to ET-1 receptors endothelin-A and endothelin-B in pulmonary vascular endothelium and pulmonary vascular smooth muscle. This leads to a significant increase in cardiac index associated with a significant reduction in pulmonary artery pressure, pulmonary vascular resistance, and mean right atrial pressure.
Iron overload is a consequence of the numerous transfusions required and may lead to complications such as heart or liver failure. Iron chelators help maintain hemoglobin levels within the desired range.
Deferoxamine helps prevent damage to the liver and bone marrow from iron deposition by promoting renal and hepatic excretion in urine and bile in feces. It readily chelates iron from ferritin and hemosiderin but not from transferrin. It does not affect iron in the cytochromes or hemoglobin. This agent is most effective when administered by continuous infusion. It gives urine a red discoloration.
Deferasirox is an orally administered iron chelation agent that has been shown to reduce the liver iron concentration in adults and children who receive repeated RBC transfusions. It binds iron with high affinity in a 2:1 ratio.
Deferiprone (1,2 dimethyl-3-hydroxypyridine-4-one) is a member of a family of hydroxypyridine-4-one (HPO) chelators that requires 3 molecules to fully bind iron (III), each molecule providing 2 coordination sites (bidentate chelation). It is designated as an orphan drug in the United States.
These agents are useful in the treatment of symptomatic nausea.
Phenergan is used for symptomatic treatment of nausea in vestibular dysfunction. Antidopaminergic agent effective in the treatment of emesis. It blocks postsynaptic mesolimbic dopaminergic receptors in the brain and reduces stimuli to the brainstem reticular system.
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- Approach Considerations
- Baseline Blood Study Abnormalities
- Suggested Routine Clinical Laboratory Evaluations
- Laboratory Studies in the Ill Child
- Additional Tests
- Magnetic Resonance Imaging
- Nuclear Medicine Scans
- Transcranial Doppler Ultrasonography
- Abdominal Ultrasonography
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- Approach Considerations
- Hydroxyurea Therapy
- Management of Ophthalmic Manifestations
- Vaso-Occlusive Crisis Management
- Control of Acute Pain
- Treatment of Acute Chest Syndrome
- Control of Chronic Pain
- Management of Chronic Anemia
- Prevention and Treatment of Infections
- Treatment of Gallstones
- Treatment of Priapism
- Treatment of Leg Ulcers
- Stroke Prevention
- Treatment of Pulmonary Hypertension
- Sickle Cell Nephropathy
- Treatment of Other Complications
- Stem Cell Transplantation
- Diet and Activity Restrictions
- Investigational Treatments
- Long-Term Monitoring
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