Sickle Cell Anemia Medication

Updated: Jul 27, 2017
  • Author: Joseph E Maakaron, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Medication

Medication Summary

The goals of pharmacotherapy are to reduce and prevent complications. The drugs used in treatment of sickle cell disease (SCD) include antimetabolites, analgesics, antibiotics, vaccines, and nutritional agents.

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Antimetabolites

Class Summary

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 (Droxia, Hydrea)

Hydroxyurea inhibits deoxynucleotide synthesis. Its myelosuppressive effects last a few days to a week and are easier to control than those of alkylating agents.

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Opioid Analgesics

Class Summary

Opioid analgesics are used to control acute crisis and chronic pain.

Oxycodone and aspirin (Percodan)

This drug combination is indicated for the relief of moderate to severe pain. Oxycodone binds to opiate receptors in the CNS inhibiting the ascending pain pathways, altering pain response and perception. Aspirin inhibits platelet aggregation; has analgesic and anti-inflammatory properties.

Methadone (Dolophine, Methadose)

Methadone is used in the management of severe pain. It inhibits ascending pain pathways, diminishing the perception of and response to pain.

Morphine sulfate (Duramorph, Infumorph, MorphaBond ER, MS Contin, Kadian)

An opioid analgesic, morphine interacts with endorphin receptors in the CNS, inhibiting the pain pathways, altering pain response and perception.

Oxycodone and acetaminophen (Percocet, Endocet, Xartemis XR, Primlev)

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.

Fentanyl (Sublimaze, Duragesic, Abstral, Actiq, Fentora)

A synthetic opioid analgesic that is primarily a mu receptor agonist, fentanyl is 50-100 times more potent than morphine. Unlike morphine, fentanyl is not commonly associated with histamine release.

Nalbuphine

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

Codeine binds to opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering perception and response to pain.

Codeine/acetaminophen (Tylenol with Codeine #3,Tylenol with Codeine #4 )

This combination is a mild narcotic analgesic. Acetaminophen believed to inhibit the synthesis of prostaglandins in the CNS, and peripherally block pain impulse generation. Codeine binds to in the CNS; causing inhibition of ascending pain pathways, altering pain perception and response.

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Nonsteroidal Analgesics

Class Summary

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

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 (Ecotrin, Ascriptin, Bayer Aspirin, St. Joseph Adult Aspirin, Durlaza)

Aspirin treats mild to moderate pain. It inhibits prostaglandin synthesis, which prevents formation of platelet-aggregating thromboxane A2.

Acetaminophen (Tylenol, Aspirin-Free Anacin, Acephen, Cetafen Extra, Ofirmev)

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.Acetaminophen is believed to work peripherally to block pain impulse generation.

Ibuprofen (Advil, Genpril, I-Prin, Motrin IB, Addaprin)

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.

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Tricyclic Antidepressants

Class Summary

Tricyclic antidepressants (TCAs) increase the levels of certain brain chemicals which improve mood and regulate pain signals. Low doses of TCAs relieve pain, although its mechanism is still unknown.

Amitriptyline (Elavil)

Amitriptyline inhibits presynaptic reuptake of serotonin and norepinephrine and blocks cholinergic, adrenergic, histaminergic, and sodium channels.

Nortriptyline (Pamelor)

Nortriptyline may increase the synaptic concentration of serotonin and/or norepinephrine in the CNS by reuptake inhibition via the presynaptic neuronal membrane; inhibits the activity of histamine, 5-hydroxytryptamine, and acetylcholine. It increases the pressor effect of norepinephrine but blocks the pressor response of phenethylamine.

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Vitamins

Class Summary

Supplemental folic acid replenishes the depleted folate stores necessary for erythropoiesis.

Folic acid (FA-8)

Folic acid is necessary for proper nucleotide metabolism. It is an important cofactor for enzymes used in production of RBCs.

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Nutritionals

Class Summary

Severe anemia and vaso-occlusive processes results in incapacitating complications. Glutamine reduces acute complications (eg acute chest syndrome) associated with SCD.

Glutamine (Endari)

Glutamine is an amino acid oral powder for acute complications associated with SCD. The precise mechanism of action is unknown. Sickle RBCs are more susceptible to oxidative damage than normal RBCs, which may contribute to chronic hemolysis and vaso-occlusive events associated with SCD. Pyridine nucleotides, NAD+ and its reduced form NADH, regulates and prevents oxidative damage in RBCs. Glutamine is believed to improve the NAD redox potential in sickle RBCs by increasing reduced glutathione’s availability.

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Antibiotics

Class Summary

The absence of a spleen inhibits immunological functions of clearing bacteria from the blood and synthesizing antibodies leading to an increased frequency of infetion. These agents are used for treatment of suspected or confirmed infections.

Cefuroxime (Ceftin, Zinacef)

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.

Amoxicillin and clavulanate (Augmentin, Augmentin XR, Augmentin ES-600)

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.

Penicillin VK

Penicillin inhibits the biosynthesis of cell wall mucopeptide.

Cefixime (Suprax)

Cefixime inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs); thus inhibiting cell wall biosynthesis. Bacteria lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.

Ceftriaxone

A third-generation cephalosporin, inhibits bacterial cell wall synthesis by binding to one or more PBPs; downstream inhibits cell wall biosynthesis via inhibition the final steps of peptidoglycan synthesis along the bacterial cell walls.

Azithromycin (Zithromax, Zmax)

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.

Cefaclor

A second-generation cephalosporin, cefaclor is indicated for infections caused by susceptible gram-positive cocci and gram-negative rods.

Clarithromycin (Biaxin, Biaxin XL)

Clarithromycin exerts its antibacterial action by binding to 50S ribosomal subunit resulting in inhibition of protein synthesis. The 14-OH clarithromycin metabolite is twice as active as the parent compound against certain organisms.

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Phosphodiesterase Type 5 Inhibitors

Class Summary

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 (Revatio)

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.

Tadalafil (Adcirca)

Inhibits PDE-5 in smooth muscle of pulmonary vasculature where PDE-5 is responsible for the degradation of cyclic guanosine monophosphate (cGMP). Increased cGMP concentration results in pulmonary vasculature relaxation; vasodilation in the pulmonary bed and the systemic circulation may occur.

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Endothelin Receptor Antagonists

Class Summary

These agents are used for pulmonary hypertension associated with sickle cell disease.

Bosentan (Tracleer)

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.

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Iron Chelators

Class Summary

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 mesylate (Desferal)

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 (Exjade, Jadenu)

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 (Ferriprox)

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.

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Antiemetics

Class Summary

These agents are useful in the treatment of symptomatic nausea.

Promethazine (Phenergan, Phenadoz, Promethegan)

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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Adrenergic Agonists

Class Summary

These agents have been used successfully for priapism, possibly due to their sympathomimetic vasopressor activity.

Pseudoephedrine (Nexafed, Sudafed, Zephrex-D, Genaphed, SudoGest)

Pseudoephedrine promotes vasoconstriction by directly stimulating alpha-adrenergic receptors.

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Vaccines

Class Summary

It is recommended to maintain an up-to-date immunization schedule for pneumococcal, haemophilus influenzae and meningococcal vaccine

Pneumococcal vaccine 13-valent (Prevnar 13)

The pneumococcal 13-valent vaccine contains capsular antigens extracted from Streptococcus pneumoniae and are used to stimulate active immunity to pneumococcal infection.

Pneumococcal vaccine polyvalent (Pneumovax 23)

Pneumococcal polysaccharide polyvalent is an inactive bacterial vaccine that induces active immunization to the 23 pneumococcal serotypes contained in the vaccine.

Haemophilus influenzae type b vaccine (ActHIB, Hiberix, PedvaxHIB)

The vaccine consists of Haemophilus influenzae type b capsular polysaccharide (polyribosyl-ribitol-phosphate, PRP). IgG acts as an anti-capsular PRP antibody, demonstrating bactericidal activity against H influenzae type b.

Meningococcal A C Y and W-135 diphtheria conjugate vaccine (Menactra, Menveo)

The vaccine induces bactericidal antibody production specific to the capsular polysaccharides (eg, serogroups A, C, Y and W-135). The presence of anti-capsular meningococcal antibodies are associated with protecting against invasive meningococcal diseases.

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