Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anagrelide hydrochloride (Agrylin, Roberts Pharmaceutical Corp.) is an oral imidazoquinazoline agent that has been shown to reduce elevated platelet counts and the risk of thrombosis in patients with thrombocythaemia in various myeloproliferative disorders (MPD). It is currently approved by the FDA as oral treatment for essential thrombocythaemia (ET) and thrombocythaemia associated with polycythaemia vera (PV). Anagrelide selectively suppresses bone marrow megakaryocytes by interfering with the maturation process and decreasing platelet production without affecting the erythroid and myeloid progenitor cells. Other medications indicated for the treatment of thrombocythaemia, including interferon alpha (IFN-alpha), alkylating agents and hydroxyurea, suppress all cell lines. Anagrelide is known to inhibit platelet cyclic adenosine monophosphate (cAMP) phosphodiesterase at concentrations that exceed those achieved at doses used to treat ET. Anagrelide is extensively metabolised in the liver and its metabolites are primarily excreted in the urine. Adverse effects associated with the use of anagrelide are primarily caused by the drugs' direct vasodilating and positive inotropic effects. These include headache, hypotension and diarrhoea. It has also been known to cause fluid retention, tachycardia, nausea, abdominal pain and arrhythmias. The starting dose of anagrelide ranges from 0.5 mg q.i.d. to 1 mg b.i.d. with a maximum dose of 2.5 mg q.i.d. Adequate responses have been maintained with a median dose of 2-2.5 mg/day. Platelet counts begin to decrease in 7-10 days, however, they return to pre-treatment levels within 4-8 days if therapy is stopped. Anagrelide 2 mg/day for one year costs approximately US$6439, and treatment must continue indefinitely [1].
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PMID:Anagrelide: a novel agent for the treatment of myeloproliferative disorders. 1124 36

Essential thrombocythaemia (ET), the most often occurring myeloproliferative disorder is a clonal malignant disorder arising from stem cell. The course of the disease is complicated by some severe thrombotic events and far less commonly by haemorrhagic phenomena. Treatment of ET consist of antiplatelet drugs (e.g. aspirin) and lowering platelet count (hydroxyurea or interferon alpha). Anagrelide (anagrelide hydrochloride) is an imidazoquinazoline derivative which lowers platelet count probably by inhibiting thrombopoiesis and reduces platelet aggregation. The aim of the study was to evaluate the efficacy and side effects of anagrelide in patients with ET refractory to prior treatment with hydroxyurea. Anagrelide (Agrylin or Thromboreductin) was used in 40 patients with ET from Jan. 1999 to June. 2003. Out of 40 patients, there were 29 females and 11 males, (median age 52.0 +/- 14.25 years; range, 21-72). Median follow up was 23 months (range, 8 to 54 months). Anagrelide in the average dose of 2,0 mg (range, 1,0-3,5 mg) reduced platelet count in all patients. Median time of response was 3-4 weeks. Complete remission (platelet count < or =450 G/l) achieved 22 persons (55%) and partial remission 17 persons, and only one patient had platelet count slightly above 600 G/l (627 G/l). There was a significant (p < 0.05) reduction in platelet count from a mean of 1136.05 +/- 295.09 G/l to 480.98 +/- 72.26 G/l (56%) Despite platelet count reduction <500 G/l in 3 patients reappeared symptoms of low extremities deep venous thrombosis and in one transient ischaemic cerebral stroke was found. Hemoglobin level in a single case was lower than 12 g/dL (10.8 g/dL), and neither leukopenia nor disturbances of hepatic or renal function were observed. During the first two months of treatment with anagrelide some mild and transient side effects were noticed, eg. headache in 10 (25%), fluid retention in 8 (20%), palpitations in 4 (10%), and diarrhoea in 2 (5%) patients, but all of them continued therapy. Achieved platelet count reduction allowed in 2 ET patients safe performance of planned surgery (cholecystectomy, partial thyroidectomy) and in 1 balloon coronary angioplasty. Anagrelide proved to be an effective drug for of ET patients refractory to hydroxyurea.
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PMID:[Anagrelide in the treatment of thrombocythemia essential (ET)]. 1596 9