Single-dose pharmacokinetics of paracetamol and its conjugates in Chinese non-insulin-dependent diabetic patients with renal impairment.

OBJECTIVE: A single oral dose of paracetamol (20 mg.kg-1) was given to 38 Chinese patients with non-insulin-dependent diabetes mellitus (NIDDM) who had either normal renal function or varying degrees of renal impairment, with creatinine clearances ranging from 4 to 123 ml.min-1.1.73 m-2. The plasma and urinary concentrations of paracetamol and its major metabolites were measured by high-performance liquid chromatography (HPLC). RESULTS: The absorption and elimination of paracetamol were unaffected by renal impairment. However, the area under the plasma concentration time curve and the elimination half-life of paracetamol metabolites increased significantly with worsening renal insufficiency. Mean renal clearances of paracetamol and its conjugates were significantly reduced in these subjects. There was no evidence of altered metabolic activation with renal impairment. CONCLUSION: The results demonstrate that paracetamol disposition is minimally affected by diabetic nephropathy; however, extensive accumulation of conjugates may occur.

Acute effects of the potent lacrimator o-chlorobenzylidene malononitrile (CS) tear gas.

1. The use of tear gas to control civil unrest is accepted practice by government authorities worldwide. It is rarely used in Hong Kong but during a recent riot at a Vietnamese detention centre large quantities were used and this was cause for some concern. 2. All patients presenting to the British Red Cross Clinic after the incident were seen by one of the authors. To establish if exposure to tear gas had serious effects on the health of the detainees, the case records of the 184 patients with symptoms consistent with CS exposure were reviewed 2 months later. 3. The most common complaints were burns (52%), cough (38%), headache (29%), shortness of breath (21%), chest pain (19%), sore throat (15%) and fever (13%). However, the only common findings on examination by a physician were burns (52%) and an inflamed throat (27%). All burns could be categorised as "minor' according to the American Burns Association classification and all were consistent with CS gas exposure. 4. Some patients complained of other symptoms that had not been previously reported in the literature, such as haemoptysis (8%) and haematemesis (4%), but these were only confirmed in one patient. 5. The majority of patients had recovered within 2 weeks of exposure although one asthmatic patient complained of shortness of breath lasting for 33 days and a sore throat lasting for 38 days after the incident. She had abnormally low peak expiratory flow readings, but had a clinical history of asthma. 6. No serious sequelae were encountered, but the incidence of burns in these patients was higher than would be expected from a review of the literature. However, very little data on the effects of tear gas in a riot situation has been published. There have been reports of high concentrations of CS gas causing reactive airways dysfunction but this was not seen in our group of patients.

Use of antidiabetic and antihypertensive drugs in hospital and outpatient settings in Hong Kong.

OBJECTIVE: To investigate the usage patterns of antidiabetic and antihypertensive drugs and to identify any discordance between recommended management guidelines and clinical practice in two study locations. DESIGN: Prescription survey. SETTING: A government- operated general outpatient clinic (GOPC) and a medical/geriatric specialist clinic (SC) affiliated with a regional hospital in the same district. PATIENTS: Patients presenting with a prescription during the study period at the respective pharmacy were classified as having diabetes if at least one antidiabetic agent was prescribed and as having hypertension if a cardiovascular drug was prescribed in a hypotensive dosage. MAIN OUTCOME MEASURE: The pattern of use of antidiabetic and antihypertensive drugs. RESULTS: One thousand one hundred forty-four consecutive prescriptions were collected in the GOPC, and 1523 in the SC. Of 9.4% (n = 107) of patients were classified as having diabetes in the GOPC and 20.4% (n = 310) in the SC (p<0.001). Most patients with diabetes were taking oral hypoglycemic agents (98.1% in GOPC vs. 84.5% in SC). Glibenclamide was the sufonylurea used most often as monotherapy in both settings (50.5% in GOPC vs. 40.6% in SC). The combined use of a sulfonylurea with metformin was common in both settings (22.4% in GOPC vs. 28.4% in SC). Metformin monotherapy (1.9% in GOPC vs. 2.6% in SC) and combination treatment of insulin with an oral agent (0% in GOPC vs. 2.6% in SC) were rarely prescribed. In the GOPC, 24.5% (n = 280) of patients were prescribed an antihypertensive drug compared with 47.1% (n = 717) in the SC (p< 0.001). In the GOPC, the use of antihypertensive drugs was more prevalent in those with diabetes (53.5%) than in the remaining patients without diabetes (21.5%, p<0.001). In the SC, 51% of patients with diabetes were receiving antihypertensive drugs, but 40% of patients without diabetes were also receiving three treatments. In the GOPC, diuretics (indapamide 14.3% other 59%) and methyldopa (9.5%) were the most frequent choices of antihypertensive drugs when used as monotherapy in subjects without diabetes. In the SC, apart from diuretics (indapamide 12.9%, other 20.3%), beta-blockers (29%) also were prescribed frequently. If treated with only one antihypertensive drug, most patients with diabetes in the GOPC were prescribed indapamide (72.7%), and patients in the SC were treated mainly with angiotensin-converting enzyme inhibitors (35%) indapamide (22.5%), or calcium-channel blockers (13.8%). CONCLUSIONS: In this prescription-based survey, diabetes mellitus and hypertension were found to be common diseases in general practice and in a hospital SC. Oral hypoglycemic agents were the main from of antidiabetic therapy in both settings, with glibenclamide being the most commonly prescribed sulfonylurea. The types of antihypertensive drugs used were different in the two locations and varied according to the coexistence of type II diabetes mellitus. Despite some potential limitations, prescription-based surveys are an easy and economical method for surveying the occurrence of some common medical problems and the pattern of drug use in a fairly large number of patients in health institutions.

Use and abuse of benzodiazepines in Hong Kong 1990-1993--the impact of regulatory changes.

To control benzodiazepine abuse in Hong Kong, the Government's Pharmacy and Poisons Board reclassified benzodiazepines as Dangerous Drugs in October 1990. Apart from formal prescriptions, detailed records were then required for the supply and dispensing of these drugs. These regulations were applied initially only to brotizolam, triazolam and flunitrazepam, and were extended in January 1992 to include all benzodiazepines. The impact of these regulatory changes on benzodiazepine use has been studied by analyzing the sales patterns of seven benzodiazepines between 1990-1993. In 1991, the sales of flunitrazepam and triazolam fell, but the sales of five unrestricted benzodiazepines increased. In 1992-1993, the sales of all but one of the benzodiazepines fell. Comparing 1993 to 1990, the fall in sales was particularly marked for triazolam, chlordiazepoxide and flunitrazepam. A regulation requiring the use of proper prescriptions and detailed records for the supply and dispensing of benzodiazepines, appears to have curbed, at least partially, their abuse in Hong Kong.

Self-medication among university students in Hong Kong.

Five hundred and sixty-three university students were interviewed to survey the practice of self-medication which was found to be very prevalent (94.0%). The most commonly used items included remedies for cough and cold, antipyretics and analgesics. Topical preparations and Chinese herbal medicines were also frequently consumed. Self-medication items were mostly obtained from home medicine cabinets and pharmacy shops (not necessarily staffed by registered pharmacists) and they also relied heavily on family members and previous illness experience for information on the medications they took. The healthcare professionals only played a minor role in the provision of drug information. Nevertheless, the concept of self-medication is well-established among these university students as they recognised that minor illness could be cared for without seeing a doctor. Healthcare professionals should assume more active roles in the provision of drug information and counselling so that a good self-care programme could be established.

The estimation of paracetamol and its major metabolites in both plasma and urine by a single high-performance liquid chromatography assay.

Many analytical methods exist for the assay of paracetamol in biological fluids, including colorimetry with chemical derivatization, direct spectrophotometry, chromatographic methods and immunoassays. Their development has been largely driven by the needs of clinical toxicology requiring the rapid, reliable and highly specific estimation of paracetamol in plasma samples to determine the need for antidote therapy. However, for in vivo metabolism studies, a specific assay method which can provide measurements of paracetamol and its metabolites in both plasma and urine is desired. A reversed-phase HPLC method with UV detection at 254 nm was developed to fulfil these requirements. The assay involves minimum sample preparation with a relatively short run time. The solvent system involves a simple isocratic elution with a composition of 0.1 M potassium dihydrogen orthophosphate-acetic acid-propan-2-ol, (100:0.1:0.75, v/v/v). The reproducibility of the assay was high with an inter-assay RSD of 0.2-1.7% for urinary paracetamol concentrations of 5-500 micrograms ml-1 and 0.1-3.3% for plasma concentrations between 5 and 25 micrograms ml-1. A similarly high degree of precision was found for the glucuronide, sulphate, cysteine and mercapturate metabolites of paracetamol. The same assay can be used to analyse both plasma and urine samples and thus was employed for studies on the metabolism of paracetamol in healthy subjects and in patients with various diseases.

Gastric emptying in the postpartum period.

We measured gastric emptying, using the technique of paracetamol absorption, in eight women on their first and third postpartum day. Gastric emptying was rapid and there was no difference between the first and third day in the time to peak plasma concentration of paracetamol. Six women returned after six weeks for a further study. Gastric emptying was still rapid but the metabolism of paracetamol appeared to be slower than that found during the immediate postpartum period. These findings suggest that fluid fasting guidelines in patients more than one day postpartum need not be different from those in non-pregnant patients.