Details of the Drug

General Information of Drug (ID: DMVPUQI)

Drug Name
Hydroflumethiazide
Synonyms
Bristab; Bristurin; Dihydroflumethazide; Dihydroflumethiazide; Diucardin; Diuredemina; Diurometon; Elodrin; Elodrine; Enjit; Finuret; Flutizide; Glomerulin; HFZ; Hidroalogen; Hidroflumetiazid; Hidroflumetiazida; Hydol; Hydrenox; Hydroflumethazide; Hydroflumethiazidum; Hydroflumethizide; Idroflumetiazide; Leodrine; Metflorylthiazidine; Metforylthiadiazin; Metforylthiazidin; Methforylthiazidine; NaClex; Olmagran; Rivosil; Robezon; Rodiuran; Rontyl; Saluron; Sisuril; Spandiuril; Trifluoromethylhydrazide; Trifluoromethylhydrothiazide; Vergonil; Component of Salutensin; Idroflumetiazide [DCIT]; SB01887; Di-ademil; Di-adenil; Hidroflumetiazida [INN-Spanish]; Hydroflumethiazidum [INN-Latin]; Naciex (glaxo); Saluron (TN); Hydroflumethiazide [INN:BAN:JAN]; Hydroflumethiazide (JAN/USP/INN); Ethyl-2H-1,2, 4-benzothiadiazine-7-sulfonamide 1,1-dioxide; Fluoromethyl-3, 4-dihydro-1,2,4-benzothiadiazine 1,1-dioxide; 1,1-dioxo-6-(trifluoromethyl)-3,4-dihydro-2H-1; 2H-1,2, 4-Benzothiadiazine-7-sulfonamide, 3, 4-dihydro-6-(trifluoromethyl)-, 1,1-dioxide; 2H-1,2,4-Benzothiadiazine-7-sulfonamide, 3,4-dihydro-6-(trifluoromethyl)-, 1,1-dioxide; 3, 4-Dihydro-6-trifluorom; 3, 4-Dihydro-6-trifluoromethyl-7-sulfamoylbenzo-1,2,4-thiadiazine 1, 1-dioxide; 3,4-Dihydro-6-(trifluoromethyl)-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide; 3,4-Dihydro-6-trifluoromethyl-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide; 3,4-Dihydro-6-trifluoromethyl-7-sulfamoylbenzo-1,2,4-thiadiazine 1,1-dioxide; 3,4-Dihydro-7-sulfamoyl-6-trifluoromethyl-2H-1,2, 4-benzothi; 3,4-Dihydro-7-sulfamoyl-6-trifluoromethyl-2H-1,2,4-benzothiadiazine 1,1-dioxide; 3,4-Dihydro-7-sulfamyl-6-trifluoromethyl-2H-1,2,4-benzothiadiazine 1,1-dioxide; 6-(Trifluoromethyl)-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide; 6-Trifluoromethyl-3, 4-dihydro-7-sulfamoyl-2H-1,2,4-benzothiadiazine 1,1-dioxide; 6-Trifluoromethyl-3,4-dihydro-7-sulfamoyl-2H-1,2,4-benzothiadiazine 1,1-dioxide; 6-Trifluoromethyl-7-sulfamoyl-3,4-dihydro-1,2, 4-benzothiadiazine-1,1-dioxide; 6-Trifluoromethyl-7-sulfamoyl-3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxide; 6-Trifluoromethyl-7-sulfamyl-3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxide; 7-Sulfamoyl-6-tri; 7-Sulfamoyl-6-trifluoromethyl-3,4-dihydro-1,2,4-benzothiadiazine 1,1-dioxide; 7-Sulfamyl-6-trifluoromethyl-3,4-dihydro-1,2,4-benzothiadiazine 1, 1-dioxide; 7-Sulfamyl-6-trifluoromethyl-3,4-dihydro-1,2,4-benzothiadiazine 1,1-dioxide
Indication
Disease Entry ICD 11 Status REF
Congestive heart failure BD10 Approved [1], [2], [3]
Therapeutic Class
Diuretics
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 331.3
Topological Polar Surface Area (xlogp) 0.4
Rotatable Bond Count (rotbonds) 1
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 10
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [4]
Clearance
The drug present in the plasma can be removed from the body at the rate of 9.7 mL/min/kg [5]
Elimination
90% of drug is excreted from urine in the unchanged form [4]
Half-life
The concentration or amount of drug in body reduced by one-half in 2 hours [5]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 10.0515 micromolar/kg/day [6]
Vd
Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 2.2 L/kg [5]
Water Solubility
The ability of drug to dissolve in water is measured as 0.3 mg/mL [4]
Chemical Identifiers
Formula
C8H8F3N3O4S2
IUPAC Name
1,1-dioxo-6-(trifluoromethyl)-3,4-dihydro-2H-1lambda6,2,4-benzothiadiazine-7-sulfonamide
Canonical SMILES
C1NC2=C(C=C(C(=C2)C(F)(F)F)S(=O)(=O)N)S(=O)(=O)N1
InChI
InChI=1S/C8H8F3N3O4S2/c9-8(10,11)4-1-5-7(2-6(4)19(12,15)16)20(17,18)14-3-13-5/h1-2,13-14H,3H2,(H2,12,15,16)
InChIKey
DMDGGSIALPNSEE-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
3647
ChEBI ID
CHEBI:5784
CAS Number
135-09-1
DrugBank ID
DB00774
TTD ID
D00WAM
VARIDT ID
DR01030

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Solute carrier family 12 member 1 (SLC12A1) TTS087L S12A1_HUMAN Blocker [7]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Hydroflumethiazide
DDI Drug Name DDI Drug ID Severity Mechanism Disease REF
Carvedilol DMHTEAO Moderate Increased risk of hypertriglyceridemia by the combination of Hydroflumethiazide and Carvedilol. Heart failure [BD10-BD1Z] [16]
Bumetanide DMRV7H0 Moderate Increased risk of fluid/electrolyte loss by the combination of Hydroflumethiazide and Bumetanide. Heart failure [BD10-BD1Z] [17]
Digitoxin DMWVIGP Moderate Increased risk of hypokalemia by the combination of Hydroflumethiazide and Digitoxin. Heart failure [BD10-BD1Z] [18]
Coadministration of a Drug Treating the Disease Different from Hydroflumethiazide (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Dronedarone DMA8FS5 Major Increased risk of ventricular arrhythmias by the combination of Hydroflumethiazide and Dronedarone. Angina pectoris [BA40] [19]
Rabeprazole DMMZXIW Moderate Increased risk of hypomagnesemia by the combination of Hydroflumethiazide and Rabeprazole. Bacterial infection [1A00-1C4Z] [20]
Cariprazine DMJYDVK Moderate Additive hypotensive effects by the combination of Hydroflumethiazide and Cariprazine. Bipolar disorder [6A60] [21]
Phenylbutazone DMAYL0T Moderate Antagonize the effect of Hydroflumethiazide when combined with Phenylbutazone. Chronic pain [MG30] [22]
Ketoprofen DMRKXPT Moderate Antagonize the effect of Hydroflumethiazide when combined with Ketoprofen. Chronic pain [MG30] [22]
Levomilnacipran DMV26S8 Moderate Increased risk of hyponatremia by the combination of Hydroflumethiazide and Levomilnacipran. Chronic pain [MG30] [23]
Sertraline DM0FB1J Moderate Increased risk of hyponatremia by the combination of Hydroflumethiazide and Sertraline. Depression [6A70-6A7Z] [23]
Vilazodone DM4LECQ Moderate Increased risk of hyponatremia by the combination of Hydroflumethiazide and Vilazodone. Depression [6A70-6A7Z] [23]
Selegiline DM6034S Moderate Additive hypotensive effects by the combination of Hydroflumethiazide and Selegiline. Depression [6A70-6A7Z] [24]
Vortioxetine DM6F1PU Moderate Increased risk of hyponatremia by the combination of Hydroflumethiazide and Vortioxetine. Depression [6A70-6A7Z] [23]
Isocarboxazid DMAF1NB Moderate Additive hypotensive effects by the combination of Hydroflumethiazide and Isocarboxazid. Depression [6A70-6A7Z] [24]
Milnacipran DMBFE74 Moderate Increased risk of hyponatremia by the combination of Hydroflumethiazide and Milnacipran. Depression [6A70-6A7Z] [23]
Escitalopram DMFK9HG Moderate Increased risk of hyponatremia by the combination of Hydroflumethiazide and Escitalopram. Depression [6A70-6A7Z] [23]
Desvenlafaxine DMHD4PE Moderate Increased risk of hyponatremia by the combination of Hydroflumethiazide and Desvenlafaxine. Depression [6A70-6A7Z] [23]
OPC-34712 DMHG57U Moderate Additive hypotensive effects by the combination of Hydroflumethiazide and OPC-34712. Depression [6A70-6A7Z] [21]
Phenelzine DMHIDUE Moderate Additive hypotensive effects by the combination of Hydroflumethiazide and Phenelzine. Depression [6A70-6A7Z] [24]
Mepenzolate DM8YU2F Minor Altered absorption of Hydroflumethiazide due to GI dynamics variation caused by Mepenzolate. Digestive system disease [DE2Z] [25]
Oxybutynine DMJPBAX Minor Altered absorption of Hydroflumethiazide due to GI dynamics variation caused by Oxybutynine. Discovery agent [N.A.] [25]
Eslicarbazepine DMZREFQ Moderate Increased risk of hyponatremia by the combination of Hydroflumethiazide and Eslicarbazepine. Epilepsy/seizure [8A61-8A6Z] [26]
Ethacrynic acid DM60QMR Moderate Increased risk of fluid/electrolyte loss by the combination of Hydroflumethiazide and Ethacrynic acid. Essential hypertension [BA00] [17]
Nadolol DMW6GVL Moderate Increased risk of hyperglycemia by the combination of Hydroflumethiazide and Nadolol. Essential hypertension [BA00] [16]
Mefenamic acid DMK7HFI Moderate Antagonize the effect of Hydroflumethiazide when combined with Mefenamic acid. Female pelvic pain [GA34] [22]
Solifenacin DMG592Q Minor Altered absorption of Hydroflumethiazide due to GI dynamics variation caused by Solifenacin. Functional bladder disorder [GC50] [25]
Tolterodine DMSHPW8 Minor Altered absorption of Hydroflumethiazide due to GI dynamics variation caused by Tolterodine. Functional bladder disorder [GC50] [25]
Propantheline DM2EN6G Minor Altered absorption of Hydroflumethiazide due to GI dynamics variation caused by Propantheline. Gastric ulcer [DA60] [25]
Dexlansoprazole DM1DBV5 Moderate Increased risk of hypomagnesemia by the combination of Hydroflumethiazide and Dexlansoprazole. Gastro-oesophageal reflux disease [DA22] [20]
Metipranolol DMJMVKI Moderate Increased risk of hyperglycemia by the combination of Hydroflumethiazide and Metipranolol. Glaucoma [9C61] [16]
Levobunolol DMTNFCQ Moderate Increased risk of hyperglycemia by the combination of Hydroflumethiazide and Levobunolol. Glaucoma [9C61] [16]
Procarbazine DMIK367 Moderate Additive hypotensive effects by the combination of Hydroflumethiazide and Procarbazine. Hodgkin lymphoma [2B30] [24]
Acebutolol DM0TI4U Moderate Increased risk of hyperglycemia by the combination of Hydroflumethiazide and Acebutolol. Hypertension [BA00-BA04] [16]
Captopril DM458UM Moderate Additive hypotensive effects by the combination of Hydroflumethiazide and Captopril. Hypertension [BA00-BA04] [27]
Nebivolol DM7F1PA Moderate Increased risk of ventricular arrhythmias by the combination of Hydroflumethiazide and Nebivolol. Hypertension [BA00-BA04] [16]
Pindolol DMD2NV7 Moderate Increased risk of hyperglycemia by the combination of Hydroflumethiazide and Pindolol. Hypertension [BA00-BA04] [16]
Perindopril DMOPZDT Moderate Additive hypotensive effects by the combination of Hydroflumethiazide and Perindopril. Hypertension [BA00-BA04] [27]
Quinapril DMR8H31 Moderate Additive hypotensive effects by the combination of Hydroflumethiazide and Quinapril. Hypertension [BA00-BA04] [27]
Belladonna DM2RBWK Minor Altered absorption of Hydroflumethiazide due to GI dynamics variation caused by Belladonna. Infectious gastroenteritis/colitis [1A40] [25]
Meclofenamic acid DM05FXR Moderate Antagonize the effect of Hydroflumethiazide when combined with Meclofenamic acid. Inflammatory spondyloarthritis [FA92] [22]
Propiomazine DMKY8V1 Moderate Additive hypotensive effects by the combination of Hydroflumethiazide and Propiomazine. Insomnia [7A00-7A0Z] [28]
ITI-007 DMUQ1DO Moderate Additive hypotensive effects by the combination of Hydroflumethiazide and ITI-007. Insomnia [7A00-7A0Z] [21]
Dicyclomine DMZSDGX Minor Altered absorption of Hydroflumethiazide due to GI dynamics variation caused by Dicyclomine. Irritable bowel syndrome [DD91] [25]
Arsenic trioxide DM61TA4 Major Increased risk of ventricular arrhythmias by the combination of Hydroflumethiazide and Arsenic trioxide. Mature B-cell lymphoma [2A85] [29]
Ozanimod DMT6AM2 Moderate Additive hypotensive effects by the combination of Hydroflumethiazide and Ozanimod. Multiple sclerosis [8A40] [24]
Promethazine DM6I5GR Moderate Additive hypotensive effects by the combination of Hydroflumethiazide and Promethazine. Nausea/vomiting [MD90] [21]
Sibutramine DMFJTDI Moderate Increased risk of hyponatremia by the combination of Hydroflumethiazide and Sibutramine. Obesity [5B80-5B81] [23]
Naproxen DMZ5RGV Moderate Antagonize the effect of Hydroflumethiazide when combined with Naproxen. Osteoarthritis [FA00-FA05] [22]
Diflunisal DM7EN8I Moderate Antagonize the effect of Hydroflumethiazide when combined with Diflunisal. Pain [MG30-MG3Z] [22]
Ibuprofen DM8VCBE Moderate Antagonize the effect of Hydroflumethiazide when combined with Ibuprofen. Pain [MG30-MG3Z] [22]
Flavoxate DMKV4NL Minor Altered absorption of Hydroflumethiazide due to GI dynamics variation caused by Flavoxate. Pain [MG30-MG3Z] [25]
Safinamide DM0YWJC Moderate Additive hypotensive effects by the combination of Hydroflumethiazide and Safinamide. Parkinsonism [8A00] [24]
Rasagiline DM3WKQ4 Moderate Additive hypotensive effects by the combination of Hydroflumethiazide and Rasagiline. Parkinsonism [8A00] [24]
Biperiden DME78OA Minor Altered absorption of Hydroflumethiazide due to GI dynamics variation caused by Biperiden. Parkinsonism [8A00] [25]
Methylscopolamine DM5VWOB Minor Altered absorption of Hydroflumethiazide due to GI dynamics variation caused by Methylscopolamine. Peptic ulcer [DA61] [25]
Bromfenac DMKB79O Moderate Antagonize the effect of Hydroflumethiazide when combined with Bromfenac. Postoperative inflammation [1A00-CA43] [22]
Levomepromazine DMIKFEL Moderate Additive hypotensive effects by the combination of Hydroflumethiazide and Levomepromazine. Psychotic disorder [6A20-6A25] [28]
Meloxicam DM2AR7L Moderate Antagonize the effect of Hydroflumethiazide when combined with Meloxicam. Rheumatoid arthritis [FA20] [22]
Oxaprozin DM9UB0P Moderate Antagonize the effect of Hydroflumethiazide when combined with Oxaprozin. Rheumatoid arthritis [FA20] [22]
Quetiapine DM1N62C Moderate Additive hypotensive effects by the combination of Hydroflumethiazide and Quetiapine. Schizophrenia [6A20] [21]
Mesoridazine DM2ZGAN Moderate Increased risk of ventricular arrhythmias by the combination of Hydroflumethiazide and Mesoridazine. Schizophrenia [6A20] [30]
Aripiprazole DM3NUMH Moderate Additive hypotensive effects by the combination of Hydroflumethiazide and Aripiprazole. Schizophrenia [6A20] [21]
Iloperidone DM6AUFY Moderate Increased risk of ventricular arrhythmias by the combination of Hydroflumethiazide and Iloperidone. Schizophrenia [6A20] [30]
Paliperidone DM7NPJS Moderate Increased risk of ventricular arrhythmias by the combination of Hydroflumethiazide and Paliperidone. Schizophrenia [6A20] [30]
Perphenazine DMA4MRX Moderate Increased risk of ventricular arrhythmias by the combination of Hydroflumethiazide and Perphenazine. Schizophrenia [6A20] [30]
Molindone DMAH70G Moderate Additive hypotensive effects by the combination of Hydroflumethiazide and Molindone. Schizophrenia [6A20] [21]
Thiothixene DMDINC4 Moderate Additive hypotensive effects by the combination of Hydroflumethiazide and Thiothixene. Schizophrenia [6A20] [21]
Trifluoperazine DMKBYWI Moderate Increased risk of ventricular arrhythmias by the combination of Hydroflumethiazide and Trifluoperazine. Schizophrenia [6A20] [30]
Amisulpride DMSJVAM Moderate Increased risk of ventricular arrhythmias by the combination of Hydroflumethiazide and Amisulpride. Schizophrenia [6A20] [30]
Asenapine DMSQZE2 Moderate Additive hypotensive effects by the combination of Hydroflumethiazide and Asenapine. Schizophrenia [6A20] [21]
Pimozide DMW83TP Major Increased risk of ventricular arrhythmias by the combination of Hydroflumethiazide and Pimozide. Schizophrenia [6A20] [31]
Methdilazine DMAUHQX Moderate Additive hypotensive effects by the combination of Hydroflumethiazide and Methdilazine. Vasomotor/allergic rhinitis [CA08] [28]
Trimeprazine DMEMV9D Moderate Additive hypotensive effects by the combination of Hydroflumethiazide and Trimeprazine. Vasomotor/allergic rhinitis [CA08] [28]
Amiodarone DMUTEX3 Major Increased risk of ventricular arrhythmias by the combination of Hydroflumethiazide and Amiodarone. Ventricular tachyarrhythmia [BC71] [32]
⏷ Show the Full List of 71 DDI Information of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7197).
2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
3 FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 088850.
4 BDDCS applied to over 900 drugs
5 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
6 Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
7 DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6.
8 Nongenomic effect of aldosterone on ion transport pathways of red blood cells. Cell Physiol Biochem. 2008;22(1-4):269-78.
9 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
10 Update of diuretics in the treatment of hypertension. Am J Ther. 2007 Mar-Apr;14(2):154-60.
11 Nerve Terminal GABAA Receptors Activate Ca2+/Calmodulin-dependent Signaling to Inhibit Voltage-gated Ca2+ Influx and Glutamate Release. J Biol Chem. 2009 Mar 27;284(13):8726-37.
12 Na-K-Cl cotransport regulates intracellular volume and monolayer permeability of trabecular meshwork cells. Am J Physiol. 1995 Apr;268(4 Pt 1):C1067-74.
13 Genetic variation in the renal sodium transporters NKCC2, NCC, and ENaC in relation to the effects of loop diuretic drugs. Clin Pharmacol Ther. 2007 Sep;82(3):300-9.
14 Function and regulation of epithelial sodium transporters in the kidney of a salt-sensitive hypertensive rat model. J Hypertens. 2007 May;25(5):1065-72.
15 The 45-year story of the development of an anti-aldosterone more specific than spironolactone. Mol Cell Endocrinol. 2004 Mar 31;217(1-2):45-52.
16 Dean S, Kendall MJ, Potter S, Thompson MH, Jackson DA "Nadolol in combination with indapamide and xipamide in resistant hypertensives." Eur J Clin Pharmacol 28 (1985): 29-33. [PMID: 3987783]
17 Leary WP, Reyes AJ "Drug interactions with diuretics." S Afr Med J 65 (1984): 455-61. [PMID: 6701709]
18 Semple P, Tilstone WJ, Lawson DH "Furosemide and urinary digoxin clearance." N Engl J Med 293 (1975): 612-3. [PMID: 902451]
19 Product Information. Multaq (dronedarone). sanofi-aventis , Bridgewater, NJ.
20 FDA. U.S. Food and Drug Administration "FDA Drug Safety Communication: Low magnesium levels can be associated with long-term use of proton pump inhibitor drugs (PPIs).".
21 Aronowitz JS, Chakos MH, Safferman AZ, Lieberman JA "Syncope associated with the combination of clozapine and enalapril." J Clin Psychopharmacol 14 (1994): 429-30. [PMID: 7884028]
22 Muller FO, Schall R, Devaal AC, Groenewoud G, Hundt HKL, Middle MV "Influence of meloxicam on furosemide pharmacokinetics and pharmacodynamics in healthy volunteers." Eur J Clin Pharmacol 48 (1995): 247-51. [PMID: 7589049]
23 Product Information. Savella (milnacipran). Forest Pharmaceuticals, St. Louis, MO.
24 Ban TA "Drug interactions with psychoactive drugs." Dis Nerv Syst 36 (1975): 164-6. [PMID: 1116424]
25 Beermann B, Groschinsky-Grind M "Enhancement of the gastrointestinal absorption of hydrochlorothiazide by propantheline." Eur J Clin Pharmacol 13 (1978): 385-7. [PMID: 668798]
26 Product Information. Aptiom (eslicarbazepine). Sunovion Pharmaceuticals Inc, Marlborough, MA.
27 Burnakis TG, Mioduch HJ "Combined therapy with captopril and potassium supplementation: a potential for hyperkalemia." Arch Intern Med 144 (1984): 2371-2. [PMID: 6391404]
28 Product Information. Clozaril (clozapine). Novartis Pharmaceuticals, East Hanover, NJ.
29 Ohnishi K, Yoshida H, Shigeno K, et al. "Prolongation of the QT interval and ventricular tachycardia in patients treated with arsenic trioxide for acute promyelocytic leukemia." Ann Intern Med 133 (2000): 881-5. [PMID: 11103058]
30 Cerner Multum, Inc. "Australian Product Information.".
31 Product Information. Orap Tablets (pimozide). Gate Pharmaceuticals, Sellersville, PA.
32 Antonelli D, Atar S, Freedberg NA, Rosenfeld T "Torsade de pointes in patients on chronic amiodarone treatment: contributing factors and drug interactions." Isr Med Assoc J 7 (2005): 163-5. [PMID: 15792261]