Brandon ends up in the emergency room where he presents withcough, severe abdominal pain, nausea, low blood pressure,

and fever. Cameron says that one disease cannot cause all of these symptoms. After Brandon's kidneys begin to fail, Foreman suggests that he has a viral heart infection. House disagrees, saying that simultaneous development

ofhypothyroidism and a sinus infection is more likely. Foreman and House argue that each of their respective diagnoses more closely conforms to Occam's razor. Unexpectedly, Brandon's white blood cell count drops, indicating House and Foreman were both wrong. Brandon's damaged immune system leaves him vulnerable to the simplest infections. At the clinic pharmacy, House develops a new theory that Brandon's cough medicine was accidentally replaced with the gout medicine, colchicine. House explains that colchicine poisoning accounts for all of Brandon's symptoms save onehis cough. However, a visit to Brandon's pharmacy appears to rule out the cough medicine as the source of the colchicine. Undeterred, House pulls out some of Brandon's hair, which House claims as further support for his theory. House orders treatment for colchicine overdose, and Brandon recovers. House then raids the clinic pharmacy looking for a form of colchicine that would explain Brandon's overdose. Chase and Cameron discover from Brandon that his old "cough medicine" tablets did not have letters on them, while the genuine cough medicine they provide does. As this scene plays out, House discovers a colchicine pill in the pharmacy that looks similar to Brandon's old "cough medicine" and compares it to the real one with the letter.

Colchicine/Probenecid

All medicines may cause side effects, but many people have no, or minor, side effects.Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Colchicine/Probenecid: Diarrhea; dizziness; flushing; hair loss; headache; loss of appetite; nausea; sore gums; stomach pain; vomiting. Seek medical attention right away if any of these SEVERE side effects occur when using Colchicine/Probenecid: Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); blood in the urine; dark urine; decreased or increased urination; fever, chills, or persistent sore throat; lower back, lower stomach, genital, or inner thigh pain; muscle pain, tenderness, or weakness; numbness, burning, or tingling; severe diarrhea; severe or persistent nausea or vomiting; unusual bleeding or bruising; unusual tiredness or weakness; unusually pale skin; worsening gout; yellowing of the eyes or skin. This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA. Side Effects by Body System - for Healthcare Professionals Gastrointestinal Gastrointestinal side effects have included diarrhea, nausea, vomiting, and abdominal pain in nearly 80% of treated patients, and can be indicative of acute colchicine toxicity. Anorexia, electrolyte disturbance, pancreatitis, and paralytic ileus may also occur, and steatorrhea and enzyme inhibition have been reported in patients on long-term colchicine prophylaxis.

Hematologic A case of fatal pancytopenia developed in a patient treated with 10 mg of colchicine over a 5 day period.

Thrombocytopenia is a rare side effect and is usually associated with myelotoxicity. Hematologic side effects have included thrombocytopenia, pancytopenia, leukopenia, agranulocytosis, bone marrow failure, bone marrow depression, disseminated intravascular coagulation, and aplastic anemia in patients on longterm therapy and are most common in cases of overdose or intoxication. Heinzbody hemolytic anemia has been reported in 3 cases. Nervous system Colchicine-induced neuromyopathy often presents with a pattern of general muscle weakness, elevated creatinine phosphokinase, a diffuse myositic pattern on EMG, and noninflammatory vacuolar changes on muscle biopsy. Nervous system side effects have rarely included myopathy, seizures, mental status changes, and neuropathy in patients with impaired renal function, and are sometimes reversible with drug discontinuation. Neuromyopathy occurrence has been reported with or without elevated muscle enzymes. Renal Acute renal failure with a fatal outcome has been reported in a 78-old-man after a 10 day course of colchicine 0.5 mg three times a day.

Chronic renal failure has been reported in two Sepharad patients after 20 years of appropriate colchicine therapy for familial Mediterranean fever.

Renal side effects have included acute renal failure and rare cases of rapid progressive glomerulonephritis. Chronic renal failure and acute renal failure with a fatal outcome following colchicine toxicity have been reported. Dermatologic Dermatologic side effects have included urticaria, alopecia after intoxication or long-term usage, toxic epidermal necrolysis with concomitant ethanol use, fixed drug eruption, dermatitis, and purpura. Genitourinary A case of reversible azoospermia has been reported in a patient treated with colchicine. The patient's sperm count returned to normal when colchicine was discontinued, and decreased on reintroduction of the drug. The patient fathered two apparently normal children while not receiving the drug. One study of six patients treated with colchicine showed moderate oligospermia in two patients, but no effect in any of the treated patients. Genitourinary side effects have rarely included azoospermia. Hepatic Hepatic side effects have occasionally been reported. Respiratory Respiratory side effects including adult respiratory distress syndrome have been reported. Musculoskeletal Musculoskeletal side effects have been reported the most frequently. These have included myopathy, manifested as weakness, neuropathy, and paralysis.

Pharmacology [edit]Mechanism of Action Colchicine inhibits microtubule polymerization by binding to tubulin, one of the main constituents of microtubules. Availability of tubulin is essential tomitosis, and therefore colchicine effectively functions as a "mitotic poison" or spindle poison.[10] The mitosis inhibiting function of colchicine has been of great use in the study of cellular genetics. To see the chromosomes of a cell under a light microscope, it is important that they be viewed near the point in the cell cycle in which they are most dense. This occurs near the middle of mitosis, so mitosis must be stopped before it completes. Adding colchicine to a culture during mitosis is part of the standard procedure for doing karyotype studies. Apart from inhibiting mitosis (a process heavily dependent on cytoskeletal changes), colchicine also inhibits neutrophil motility and activity, leading to a netanti-inflammatory effect. [edit]Indications Colchicine has a relatively low therapeutic index. In August 2009, colchicine won Food and Drug Administration (FDA) approval in the United States as a stand-alone drug for the treatment of acute flares of gout and familial Mediterranean fever.[11][12] It had previously been approved as an ingredient in an FDA-approved combination product for gout. The approval was based on a study in which two doses an hour apart were effective at combating the condition.[11] It is also used as an anti-inflammatory agent for long-term treatment of Behet's disease.[13]

[edit]Use in cancer treatment Since one of the defining characteristics of cancer cells is a significantly increased rate of mitosis, this means that cancer cells are significantly more vulnerable to colchicine poisoning than are normal cells. However, the therapeutic value of colchicine against cancer is (as is typical

with chemotherapy agents) limited by its toxicity against normal cells. [edit]Off-label uses The British drug development company Angiogene is developing a prodrug of a colchicine congener, ZD6126[14] (also known as ANG453) as a treatment for cancer. Colchicine is "used widely" off-label by naturopaths for a number of treatments, including the treatment of back pain.[15] Colchicine is also used for constipation-predominant irritable bowel syndrome in women,[16] and for treatment of severe or persistent aphthous stomatitis (canker sores).[17] [edit]Contraindications Long-term (prophylactic) regimens of oral colchicine are absolutely contraindicated in patients with advanced renal failure (including those on dialysis). Ten to 20% of a colchicine dose is excreted unchanged by the kidneys. Colchicine is not removed by hemodialysis. Cumulative toxicity is a high probability in this clinical setting. A severe neuromyopathy may result. The presentation includes a progressive onset of proximal weakness, elevated creatine kinase, and sensorimotor polyneuropathy. Colchicine toxicity can be potentiated by the concomitant use of cholesterol-lowering drugs (statins, fibrates). This neuromuscular condition can be irreversible (even after drug discontinuation). Accompanying dementia has been noted in advanced cases. It may culminate in hypercapnic respiratory failure and death. (Minniti-2005)

[edit]Side-effects Side-effects include gastrointestinal upset and neutropenia. High doses can also damage bone marrow and lead to anemia and also cause hair loss. All of these side-effects can result from hyperinhibition of mitosis.[citation needed] A main side-effect associated with all mitotic inhibitors is peripheral neuropathy, which is a numbness or tingling in the hands and feet due to peripheral nerve damage that can becomes so severe that reduction in dosage or complete cessation of the drug may be required. Microtubules are involved in vesicular transport. Peripheral nerves are among the longest in the body. Brownian motion is not significant enough in these peripheral nerves to allow vesicles to reach their destination. Thus, they are susceptible to microtubule toxins.[citation needed] [edit]Toxicity Colchicine poisoning has been compared to arsenic poisoning; symptoms start 2 to 5 hours after the toxic dose has been ingested and include burning in the mouth and throat, fever, vomiting, diarrhea,abdominal pain, and kidney failure. These symptoms may set in as many as 24 hours after the exposure. Onset of multiple-system organ failure may occur within 24 to 72 hours. This includeshypovolemic shock due to extreme vascular damage and fluid loss through the GI tract, which may result in death. In addition, sufferers may experience kidney damage, resulting in low urine output and bloody urine; low white blood cell counts (persisting for several days); anemia; muscular weakness; and respiratory failure. Recovery may begin within 6 to 8 days. There is no specific antidote for colchicine, although various treatments do exist.[18] Certain common inhibitors of CYP3A4 and/or P-gp, including grapefruit juice, may increase the risk of colchicine toxicity