Gout Medications

Gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or "gout flare," followed later by chronic deforming arthritis. Gout medications include antiinflammatory and urate-lowering medications. Colchicine is an antiinflammatory medication that can be used for acute gout flares. The urate-lowering drug classes include the xanthine oxidase inhibitors, uricosuric agents, and uricases. These medications are beneficial for the prevention of gout exacerbations and work through a variety of mechanisms. Xanthine oxidase inhibitors are the most commonly used urate-lowering therapy; these work by inhibiting the enzyme necessary for the conversion of purines to uric acid. Uricosuric agents reduce reabsorption of uric acid by the proximal tubule, thereby increasing renal excretion. Lastly, the urases are recombinant enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body's constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes that metabolize uric acid to allantoin. In addition to gout, urate-lowering treatment can also be used for other indications, such as the prevention of tumor lysis syndrome Tumor lysis syndrome Tumor lysis syndrome is a potentially lethal group of metabolic disturbances that occurs when large numbers of cancer cells are killed rapidly. The lysed cells release their intracellular contents into the bloodstream, resulting in the development of hyperkalemia, hyperuricemia, hyperphosphatemia, hypocalcemia, and acute kidney injury. Tumor Lysis Syndrome and uric acid nephrolithiasis Nephrolithiasis Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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Overview

Gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or "gout flare," followed later by chronic deforming arthritis. Gout pathophysiology

  • Gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or "gout flare," followed later by chronic deforming arthritis. Gout is a metabolic disease associated with: 
    • ↑ Serum uric acid levels (> 6.8 mg/dL) 
    • Abnormal deposits of monosodium urate in tissues
  • Uric acid:
    • Produced from purine compounds (synthesized in the body or comes from foods)
    • Excreted mainly through the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys
  • Hyperuricemia is due to overproduction and/or underexcretion of uric acid → supersaturation → deposition of monosodium urate crystals in the tissues
  • Monosodium urate crystals:
    • Can erode the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones and damage other tissues, such as tendons and cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage
    • Cause recurrent monoarticular arthritis and chronic deforming arthritis 
  • The precise relationship between hyperuricemia and gout is unclear:
    • The majority (90%) of people with hyperuricemia do not have gout.
    • Normal or low serum uric acid levels do not rule out gout.
    • All individuals with gout will have hyperuricemia at some point, although levels may fluctuate.

Management options

  • Antiinflammatory therapies:
    • NSAIDs
    • Glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids
    • Colchicine
  • Urate-lowering therapies:
    • ↓ Uric acid production: xanthine oxidase inhibitors
    • ↑ Uric acid excretion: uricosuric agents
    • ↑ Uric acid metabolism: uricases

Colchicine

Chemistry

Colchicine is an alkaloid extracted from Colchicum autumnale (autumn crocus).

Mechanism of action

  • Antiinflammatory
  • Inhibits microtubule polymerization by binding to tubulin
  • Effects:
    • Inhibits cell mitosis
    • Prevents neutrophil:
      • Migration
      • Activation
      • Degranulation

Pharmacokinetics

Absorption:

  • Rapid oral absorption
  • Food consumption does not affect rate of absorption. 

Distribution: 

  • Concentrates in:
    • Leukocytes
    • Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver
    • Kidneys
    • Spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen
  • Protein binding: approximately 40%

Metabolism: 

  • Hepatic
  • Cytochrome P450 system (CYP3A4)
  • Glucuronidation 

Excretion: 

  • Urine
  • Bile
  • Enterohepatic recirculation is possible.

Indications

Gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or "gout flare," followed later by chronic deforming arthritis. Gout:

  • Treatment of acute flares (primarily used by individuals who are unable to take NSAIDs)
  • Prevention of recurrent flares

Other indications include:

  • Calcium pyrophosphate crystal arthritis
  • Acute pericarditis Pericarditis Pericarditis is an inflammation of the pericardium, often with fluid accumulation. It can be caused by infection (often viral), myocardial infarction, drugs, malignancies, metabolic disorders, autoimmune disorders, or trauma. Acute, subacute, and chronic forms exist. Pericarditis
  • Behçet syndrome
  • Sweet syndrome
  • Familial Mediterranean fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
    • ↓ Frequency of attacks
    • ↓ Risk of amyloidosis Amyloidosis Amyloidosis is a disease caused by abnormal extracellular tissue deposition of fibrils composed of various misfolded low-molecular-weight protein subunits. These proteins are frequently byproducts of other pathological processes (e.g., multiple myeloma). Amyloidosis

Adverse effects

  • GI:
    • Nausea
    • Vomiting
    • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea 
    • Abdominal cramping/ pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
    • Hepatotoxicity
  • Hematologic: 
    • DIC DIC Disseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. Disseminated Intravascular Coagulation 
    • Leukopenia
    • Granulocytopenia
    • Thrombopenia
    • Aplastic anemia Aplastic Anemia Aplastic anemia (AA) is a rare, life-threatening condition characterized by pancytopenia and hypocellularity of the bone marrow (in the absence of any abnormal cells) reflecting damage to hematopoietic stem cells. Aplastic anemia can be acquired or inherited, however, most cases of AA are acquired and caused by autoimmune damage to hematopoietic stem cells. Aplastic Anemia 
  • Neuromuscular: rhabdomyolysis Rhabdomyolysis Rhabdomyolysis is characterized by muscle necrosis and the release of toxic intracellular contents, especially myoglobin, into the circulation. Rhabdomyolysis 
  • Genitourinary:
    • Azoospermia
    • Oligospermia
  • Dermatologic: 
    • Alopecia Alopecia Alopecia is the loss of hair in areas anywhere on the body where hair normally grows. Alopecia may be defined as scarring or non-scarring, localized or diffuse, congenital or acquired, reversible or permanent, or confined to the scalp or universal; however, alopecia is usually classified using the 1st 3 factors. Alopecia 
    • Maculopapular rash 
  • Nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. General Structure of the Nervous System: peripheral neuropathy

Precautions

Caution should be used in individuals with:

  • Severe renal impairment
  • Severe hepatic impairment 
  • Bone marrow suppression

Drug interactions

The following could lead to increased levels of colchicine:

  • P-glycoprotein (efflux transporter) inhibitors:
    • Cyclosporine
    • Ranolazine 
  • CYP3A4 inhibitors:
    • Clarithromycin and erythromycin
    • Itraconazole, fluconazole, and ketoconazole
    • Ritonavir
    • Diltiazem and verapamil
    • Grapefruit juice

Xanthine Oxidase Inhibitors

Chemistry

  • Allopurinol: purine analog (of hypoxanthine, a substrate of xanthine oxidase)
  • Febuxostat: nonpurine

Mechanism of action

  • Normal action of xanthine oxidase:
    • Converts hypoxanthine to xanthine
    • Then converts xanthine to uric acid
  • Allopurinol:
    • Competitive inhibitor of xanthine oxidase
    • Its metabolite, oxypurinol, is a noncompetitive inhibitor. 
  • Febuxostat:
    • Occupies a channel in xanthine oxidase
    • Impairs access to the active site → inhibits enzyme function
  • Overall: both prevent uric acid synthesis → ↓ plasma uric acid concentration → prevent hyperuricemia
Xanthine oxidase inhibitors preventing conversion into uric acid

The xanthine oxidase inhibitors, allopurinol and febuxostat, prevent the conversion of hypoxanthine and xanthine to uric acid.

Image by Lecturio.

Pharmacokinetics

Table: Pharmacokinetics of the xanthine oxidase medications
Medication Absorption Distribution Metabolism Excretion
Allopurinol Well absorbed orally Negligible protein-binding
  • Hepatic and xanthine oxidase
  • Active metabolites
Urine and feces
Febuxostat Highly protein-bound
  • Hepatic
  • Cytochrome P450 system
  • Active metabolites

Indications

Allopurinol:

  • Gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or "gout flare," followed later by chronic deforming arthritis. Gout
    • Preferred urate-lowering medication
    • Can be initiated during an acute flare with concurrent antiinflammatory therapy
    • Useful in treating: 
      • Gouty arthritis
      • Skin tophi
      • Uric acid nephropathy
  • Hyperuricemia secondary to malignancy and tumor lysis syndrome Tumor lysis syndrome Tumor lysis syndrome is a potentially lethal group of metabolic disturbances that occurs when large numbers of cancer cells are killed rapidly. The lysed cells release their intracellular contents into the bloodstream, resulting in the development of hyperkalemia, hyperuricemia, hyperphosphatemia, hypocalcemia, and acute kidney injury. Tumor Lysis Syndrome
  • Prevention of calcium oxalate or uric acid nephrolithiasis Nephrolithiasis Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis

Febuxostat:

  • Gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or "gout flare," followed later by chronic deforming arthritis. Gout
    • Used for those who are not able to tolerate allopurinol or who have significant renal impairment
    • Can be initiated during an acute flare with concurrent antiinflammatory therapy.
  • Hyperuricemia
  • Prevention of tumor lysis syndrome Tumor lysis syndrome Tumor lysis syndrome is a potentially lethal group of metabolic disturbances that occurs when large numbers of cancer cells are killed rapidly. The lysed cells release their intracellular contents into the bloodstream, resulting in the development of hyperkalemia, hyperuricemia, hyperphosphatemia, hypocalcemia, and acute kidney injury. Tumor Lysis Syndrome

Adverse effects

Allopurinol:

  • Acute gout flare (↓ serum uric acid → mobilization of uric acid crystals from joints and tophi)
  • Hypersensitivity:
    • Pruritus 
    • Fever 
    • Erythematous or maculopapular eruption 
    • Stevens-Johnson syndrome Stevens-Johnson syndrome Stevens-Johnson syndrome (SJS) is a cutaneous, immune-mediated hypersensitivity reaction that is commonly triggered by medications, including antiepileptics and antibiotics. The condition runs on a spectrum with toxic epidermal necrolysis (TEN) based on the amount of body surface area (BSA) involved. Stevens-Johnson Syndrome or toxic epidermal necrolysis 
    • Drug reaction with eosinophilia and systemic symptoms (DRESS)
  • GI:
    • Nausea
    • Abdominal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
    • Anorexia
    • Ageusia
    • Hepatotoxicity
  • Hematologic:
    • Neutropenia Neutropenia Neutrophils are an important component of the immune system and play a significant role in the eradication of infections. Low numbers of circulating neutrophils, referred to as neutropenia, predispose the body to recurrent infections or sepsis, though patients can also be asymptomatic. Neutropenia
    • Thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia
    • Aplastic anemia Aplastic Anemia Aplastic anemia (AA) is a rare, life-threatening condition characterized by pancytopenia and hypocellularity of the bone marrow (in the absence of any abnormal cells) reflecting damage to hematopoietic stem cells. Aplastic anemia can be acquired or inherited, however, most cases of AA are acquired and caused by autoimmune damage to hematopoietic stem cells. Aplastic Anemia

Febuxostat:

  • Acute gout flare
  • GI: 
    • Nausea
    • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea 
    • ↑ Transaminases
  • Dermatology: rash 
  • Neuromuscular:
    • Headache
    • Arthralgia

Contraindications

  • Allopurinol: individuals with HLA-B5801 allele → ↑ risk of severe hypersensitivity reactions
  • Febuxostat: individuals with cardiovascular disease → ↑ risk of heart-related death

Drug interactions

Xanthine oxidase inhibitors can lead to an increased concentration of 6-mercaptopurine and azathioprine (which are metabolized by xanthine oxidase).

Uricosuric Drugs

Mechanism of action

  • Normal physiology:
    • Uric acid is filtered at the glomerulus.
    • 90% is reabsorbed in the proximal tubule.
    • Only a small amount is excreted in the urine.
  • Uricosuric medications: ↑ excretion of uric acid in the urine → ↓ serum uric acid
    • Probenecid:
      • Competitively inhibits the transporter responsible for uric acid reabsorption
      • Probenecid is reabsorbed, not uric acid.
    • Lesinurad: similar mechanism of action

Pharmacokinetics

Table: Pharmacokinetics of the uricosuric medications
Medication Absorption Distribution Metabolism Excretion
Probenecid Rapid, well absorbed Highly protein-bound Hepatic Urine
Lesinurad Hepatic, cytochrome P450 Urine and feces

Indications

Uricosuric agents are uncommonly used for the treatment of hyperuricemia and chronic gout.

  • Used in individuals whose conditions have not appropriately responded to monotherapy with xanthine oxidase inhibitors
  • Probenecid: 
    • Can be used as monotherapy
    • May be ineffective in moderate to severe chronic kidney disease Chronic Kidney Disease Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease
  • Lesinurad is used in combination with a xanthine oxidase inhibitor.

Adverse effects

Probenecid:

  • Acute gout flare (similar to xanthine oxidase inhibitors)
  • GI: 
    • Nausea and vomiting
    • Anorexia
    • Dyspepsia 
  • CNS:
    • Dizziness 
    • Headache 
  • Genitourinary:
    • Polyuria
    • Nephrotic syndrome Nephrotic syndrome Nephrotic syndrome is characterized by severe proteinuria, hypoalbuminemia, and peripheral edema. In contrast, the nephritic syndromes present with hematuria, variable loss of renal function, and hypertension, although there is sometimes overlap of > 1 glomerular disease in the same individual. Nephrotic Syndrome
  • Hematologic:
    • Hemolytic anemia Hemolytic Anemia Hemolytic anemia (HA) is the term given to a large group of anemias that are caused by the premature destruction/hemolysis of circulating red blood cells (RBCs). Hemolysis can occur within (intravascular hemolysis) or outside the blood vessels (extravascular hemolysis). Hemolytic Anemia
    • Aplastic anemia Aplastic Anemia Aplastic anemia (AA) is a rare, life-threatening condition characterized by pancytopenia and hypocellularity of the bone marrow (in the absence of any abnormal cells) reflecting damage to hematopoietic stem cells. Aplastic anemia can be acquired or inherited, however, most cases of AA are acquired and caused by autoimmune damage to hematopoietic stem cells. Aplastic Anemia

Lesinurad:

  • Acute gout flare
  • CNS: headache
  • GI: gastroesophageal reflux disease Gastroesophageal Reflux Disease Gastroesophageal reflux disease (GERD) occurs when the stomach acid frequently flows back into the esophagus. This backwash (acid reflux) can irritate the lining of the esophagus, causing symptoms such as retrosternal burning pain (heartburn). Gastroesophageal Reflux Disease
  • Genitourinary:
    • Acute renal failure 
    • Nephrolithiasis

Contraindications

  • Severe renal impairment
  • Kidney transplantation
  • Probenecid: uric acid nephrolithiasis Nephrolithiasis Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis
  • Lesinurad: tumor lysis syndrome Tumor lysis syndrome Tumor lysis syndrome is a potentially lethal group of metabolic disturbances that occurs when large numbers of cancer cells are killed rapidly. The lysed cells release their intracellular contents into the bloodstream, resulting in the development of hyperkalemia, hyperuricemia, hyperphosphatemia, hypocalcemia, and acute kidney injury. Tumor Lysis Syndrome

Drug interactions

The following drug interactions are associated with probenecid:

  • ↓ Urinary excretion of: 
    • Penicillin
    • Cephalosporins Cephalosporins Cephalosporins are a group of bactericidal beta-lactam antibiotics (similar to penicillins) that exert their effects by preventing bacteria from producing their cell walls, ultimately leading to cell death. Cephalosporins are categorized by generation and all drug names begin with "cef-" or "ceph-." Cephalosporins
    • Methotrexate 
  • Salicylates → ↓ probenecid effect

Uricases

Medications in this class

  • Pegloticase
  • Rasburicase

Chemistry

These medications are classified as recombinant urate oxidases (uricases).

Mechanism of action

The uricases metabolize uric acid to allantoin, which is: 

  • More soluble than uric acid
  • Unlikely to precipitate

Indications

Pegloticase:

  • Used for advanced or chronic gout that is refractory to other therapies
  • Not used for asymptomatic hyperuricemia
  • Should not to be used in combination with other urate-lowering agents

Rasburicase:

  • Used to treat hyperuricemia related to malignancy and tumor lysis syndrome Tumor lysis syndrome Tumor lysis syndrome is a potentially lethal group of metabolic disturbances that occurs when large numbers of cancer cells are killed rapidly. The lysed cells release their intracellular contents into the bloodstream, resulting in the development of hyperkalemia, hyperuricemia, hyperphosphatemia, hypocalcemia, and acute kidney injury. Tumor Lysis Syndrome
  • Not FDA-approved for treatment of gout

Adverse effects

  • GI: 
    • Nausea and vomiting
    • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea 
    • Constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation
  • Dermatologic: 
    • Rash 
    • Urticaria Urticaria Urticaria is raised, well-circumscribed areas (wheals) of edema (swelling) and erythema (redness) involving the dermis and epidermis with associated pruritus (itch). Urticaria is not a single disease but rather is a reaction pattern representing cutaneous mast cell degranulation. Urticaria (Hives) 
  • Immunologic:
    • Development of antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins to the medication
    • Anaphylaxis
  • Cardiovascular:
    • Peripheral edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
    • Supraventricular arrhythmia

Contraindications

The uricases should not be used for individuals with glucose-6-phosphatase dehydrogenase (G6PD) deficiency (can precipitate severe hemolysis).

References

  1. Cleveland Clinic. (n.d.). Gout: what is it, symptoms, causes, treatment. Retrieved October 1, 2021, from https://my.clevelandclinic.org/health/diseases/4755-gout
  2. CDC. (2020). Gout, arthritis. https://www.cdc.gov/arthritis/basics/gout.html
  3. Hilal-Dandan, R., et al. (2014). Goodman and Gilman’s Manual of Pharmacology and Therapeutics. Open WorldCat, http://accesspharmacy.mhmedical.com/book.aspx?bookid=1810.
  4. Rang, H.P., Dale, M.M. (Eds.). (2016). Rang and Dale’s Pharmacology, 8th ed. Elsevier, Churchill Livingstone.
  5. Johns Hopkins Arthritis Center. Gout treatment : medications and lifestyle adjustments to lower uric acid. Retrieved October 1, 2021, from https://www.hopkinsarthritis.org/arthritis-info/gout/gout-treatment/
  6. Perez-Ruiz, F. (2020). Pharmacologic urate-lowering therapy and treatment of tophi in patients with gout. UpToDate. Retrieved October 1, 2021, from https://www.uptodate.com/contents/pharmacologic-urate-lowering-therapy-and-treatment-of-tophi-in-patients-with-gout 
  7. Sadiq, N.M., Robinson, K.J., Terrell, J.M. (2021). Colchicine. StatPearls. Retrieved October 10, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK431102/
  8. Gerriets, V., Jialal, I. (2021). Febuxostat. StatPearls. Retrieved October 10, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK544239/
  9. Qurie, A., Banal, P., Goyal, A., Musa, R. (2021). Allopurinol. StatPearls. Retrieved October 10, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK499942/
  10. First, D.E., Ulrich, R.W., Prakash, S. (2012). Nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, nonopioid analgesics, and drugs used in gout. In Katzung, B.G., Masters, S.B., and Trevor, A.J. (Eds.), Basic & Clinical Pharmacology, 12th ed. McGraw-Hill, pp. 635–657. https://pharmacomedicale.org/images/cnpm/CNPM_2016/katzung-pharmacology.pdf

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