Thomas Y. K. Chan

Relationship Between Patients’ Warfarin Knowledge and Anticoagulation Control:

OBJECTIVE To evaluate patients’ knowledge of warfarin and its relationship to anticoagulation control. METHODS From January to March 1999, 122 patients attending the warfarin clinic of the Prince of Wales Hospital in Hong Kong were interviewed. Their knowledge of warfarin therapy and adherence to medical advice were tested by 9 questions. A score (maximum 1.0) was calculated for each patient. The number of international normalized ratios (INRs) that was within the target range in the 4 most recent clinic visits was noted. RESULTS Fifty-six men and 66 women participated in the study (mean ± SD age 58.0 ± 13.0, duration of treatment 43.1 ± 39.8 mo). Patients’ warfarin knowledge was poor, with an overall score of 0.48 ± 0.18. Participants generally knew the colors of their warfarin tablets and took them regularly. They almost always informed their physicians and dentists of their warfarin therapy. Only 40–45% of patients knew the strengths of their warfarin tablets, the reason for taking warfarin, and its effect on the body. Their deficiencies in knowledge were even more obvious with respect to the possible consequences of under- or over-anticoagulation, drugs and medicated oils that might interact with warfarin, and management of a missed dose. Knowledge was related to age (r −0.43; p < 0.001) and duration of therapy (r 0.18; p = 0.044). Sixty patients (49.2%) had read the information booklet on warfarin and had better knowledge than those who had not (0.53 ± 0.20 vs. 0.42 ± 0.20; p < 0.001). Illiteracy was the main reason for not reading the booklet. There was a positive correlation between patients’ warfarin knowledge and the number of INR values that was within the target range in the 4 most recent clinic visits (r 0.20; p = 0.024). CONCLUSIONS Patients’ warfarin knowledge, a determinant of anticoagulation control, was generally poor. More attention should be given to the education of elderly and illiterate patients.

Chinese herbal medicines revisited: a Hong Kong perspective

Chinese herbal medicines (CHM) and Chinese proprietary medicines (CPM) are widely used by people of Chinese origin throughout the world. Although the use of these medicinal materials rarely causes significant toxic effects, cases of severe and even fatal poisoning have occurred after medication with herbs containing aconitine, podophyllin, and anticholinergic substances. Furthermore, CHM and CPM are often adulterated with substituted herbs, heavy metals, and western medicines; such contamination can have important clinical consequences. In Hong Kong, surveillance and legislation are required to control the use of some of these herbal preparations. In other countries, medical practitioners should also be aware of the possibility that these herbal-medicine-related remedies may cause significant clinical problems in their Chinese patients.

Interaction between Warfarin and Danshen (Salvia Miltiorrhiza)

OBJECTIVE: To discuss the potential for an adverse interaction between the Chinese herb danshen, the dry root and rhizome of Salvia miltiorrhizaBge, and warfarin. DATA SOURCES: A MEDLINE search was performed (from January 1966 through October 2000) using the key words danshen and Salvia miltiorrhiza. All articles written in English or with an English extract were considered for review. STUDY SELECTION AND DATA EXTRACTION: All studies of antithrombotic effects of danshen or interaction between danshen and warfarin were evaluated. Previous case reports of an adverse interaction between danshen and warfarin were reviewed. DATA SYNTHESIS: Danshen is commonly used in mainland China for the treatment of atherosclerosis-related disorders such as cardiovascular and cerebrovascular diseases. Danshen can affect hemostasis in several ways, including inhibition of platelet aggregation, interference with the extrinsic blood coagulation, antithrombin III—like activity, and promotion of fibrinolytic activity. Single-dose and steady-state studies in rats indicated that danshen increased the absorption rate constants, AUCs, maximum concentrations, and elimination half-lives, but decreased the clearances and apparent volume of distribution of both R- and S-warfarin. Consequently, the anticoagulant response to warfarin was exaggerated. Three cases have previously been published reporting gross overanticoagulation and bleeding complications when patients receiving chronic warfarin therapy also took danshen. CONCLUSIONS: Because of both pharmacokinetic and pharmacodynamic interactions, danshen should be avoided in patients taking warfarin.

Toxicity of Complementary Therapies: An Eastern Perspective

Chinese traditional medicine is used extensively in Chinese populations, and other Asian countries employ similar therapies. Herbal treatments have a major role in these systems, and although most have a well‐established safety record, occasional adverse effects are seen. Problems arise when toxic herbs are used in excessive doses, with improper preparation, or when they are substituted erroneously. There may also be adulteration with Western drugs or heavy metals, and interactions between herbs and Western drugs may also occur. It is always prudent to obtain a complete history of the use of herbal medications during any clinical assessment, particularly in Asian patients.

Usage and adverse effects of Chinese herbal medicines

The great majority of Chinese herbal preparations are safe, and in the past, some useful Western drugs have been derived from these herbs. Nearly all serious poisonings are due to the few preparations containing aconitine, podophyllin or anti cholinergics or else proprietary preparations containing dangerous Western drugs or heavy metals. Both medical professionals and the general public should be alerted to the potential toxicity of herbal remedies. There should be frequent monitoring of Chinese herbal medicines or their derivatives, such as some Chinese proprietary medicines, for undeclared Western drugs and heavy metals. Mothers should be discouraged from treating their children with herbal or proprietary medicines. There should be con tinuing efforts to collect safety information on these widely used products.

Adverse Interactions Between Warfarin and Nonsteroidal Antiinflammatory Drugs: Mechanisms, Clinical Significance, and Avoidance

Objective: To review the mechanisms and clinical significance of adverse interactions between warfarin and nonsteroidal antiinflammatory drugs (NSAIDs) and discuss how these interactions can be avoided. Data Sources: Previous studies of interactions between warfarin and NSAIDs or reports of adverse interactions were identified from a MEDLINE search (1976 to present) and from the reference lists of pertinent articles. Study Selection And Data Extraction: All articles were considered for inclusion in the review. Pertinent information was selected for discussion. Data Synthesis: All NSAIDs can prolong bleeding time by inhibiting platelet function. High-dose aspirin has a direct hypoprothrombinemic effect. Phenylbutazone and its analogs enhance the hypoprothrombinemic effect of warfarin through a pharmacokinetic interaction by inhibiting the hepatic metabolism of warfarin. Mefenamic acid also enhances the anticoagulant effect of warfarin, but the mechanism is not known. The clinical relevance of protein binding displacement in the interaction between warfarin and NSAIDs has been overstated, although a significant one may be more likely in the presence of high concentrations of NSAIDs in patients with slow elimination of warfarin (e.g., those with severe heart failure or impaired liver function). NSAIDs can induce gastrointestinal bleeding, which is likely to be more severe if warfarin is also given. Conclusions: The combined use of warfarin and NSAIDs is generally discouraged because of the increased risk of bleeding in these patients. In patients receiving warfarin who also require NSAIDs, phenylbutazone and its analogs, high-dose aspirin, mefenamic acid, excessive use of topical methyl salicylate, and NSAIDs that are associated with a higher risk of bleeding peptic ulcers should be avoided. Patients should be closely monitored for anticoagulant control and bleeding complications during the combined use of warfarin and NSAIDs.

Drug-induced syndrome of inappropriate antidiuretic hormone secretion : Causes, diagnosis and management

SummaryHyponatraemia is common among the elderly, and may be caused by physiological changes, disease processes or drugs. About half of elderly patients with hyponatraemia have features typical of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). It is important to establish whether drugs are the cause, as this is easily remediable.The clinical manifestations of SIADH are predominantly attributable to hyponatraemia and serum hypo-osmolality. The severity of the signs and symptoms depends on the degree of hyponatraemia and the rapidity with which the syndrome develops.Although a growing number of drugs have been reported to produce SIADH, most published reports concern vasopressin and its analogues, thiazide and thiazide-like diuretics, chlorpropamide, carbamazepine, antipsychotics, antidepressants and nonsteroidal anti-inflammatory drugs. Old age is a risk factor for SIADH following the use of many of these drugs. The use of these drugs in combination, excessive fluid intake and other underlying conditions that limit free water excretion increase the risk.Drug-induced SIADH usually resolves following cessation of the offending agent(s). Additional measures are required in patients with symptomatic hyponatraemia, including fluid restriction and intravenous sodium chloride and/or furosemide (frusemide) therapy. Careful monitoring is essential, with particular attention paid to the rate and extent of correction of the hyponatraemia.

Antihypertensive and anti-albuminuric effects of losartan potassium and felodipine in Chinese elderly hypertensive patients with or without non-insulin-dependent diabetes mellitus

After a 4-week placebo baseline period, 29 Chinese elderly hypertensive patients were randomized, double-blind, to 12 weeks of treatment with either losartan potassium (n = 19), an angiotensin II antagonist at the AT1 receptor, or felodipine (n = 10), a calcium channel blocking agent. Of these 29 patients 12 had coexisting non-insulin-dependent diabetes mellitus. At week 12, the mean reductions (95% confidence intervals) in mean arterial pressure were similar in both groups: losartan -18 (range -22 to -14) mm Hg; felodipine -19 (range -25 to -11) mm Hg. In the whole group, the 24-hour urinary albumin excretion was reduced by 27% with losartan as compared with no change in the felodipine-treated group (p = 0.03; analysis of variance). In the diabetic group, losartan treatment reduced the urinary albumin excretion by 24% as compared with 11% in the felodipine-treated group. In the non-diabetic patients, the urinary albumin excretion fell by 29% in the losartan-treated group, but increased by 14% in the felodipine-treated group (p < 0.001; repeated-measures analysis of variance). Plasma sodium increased to a similar extent in both groups. The fasting plasma triglyceride level declined by 25% (p < 0.001 within group) with losartan, but was not significantly reduced in the felodipine-treated group. For comparable reductions in blood pressure, a greater reduction in albuminuria was seen with losartan than with felodipine treatment in Chinese hypertensive patients with or without non-insulin-dependent diabetes mellitus. Long-term studies are required to examine whether these antiproteinuric effects of losartan can be translated to renoprotection.

The Efficacy and Tolerability of Adjunctive Alternative Herbal Medicine (Salvia miltiorrhiza and Pueraria lobata) on Vascular Function and Structure in Coronary Patients

BACKGROUND Danshen and gegen (D&G) have long been used in treatment of angina and other cardiac symptoms in Chinese materia medica. Recent pharmacological studies suggest their therapeutic values. We aimed to evaluate the efficacy and safety of Salvia miltiorrhiza (danshen) and Pueraria lobata (gegen) in secondary prevention. METHODS One hundred (100) consecutive coronary patients (mean age 58 +/- 8 years) were randomized to adjunctive treatment with D&G combination (3 g) or placebo (6 capsules) for 24 weeks in double-blind parallel fashion, followed by optional open-label D&G (1.5 g/day) for 6 more months. Brachial flow-mediated dilation (FMD) and carotid intima-media thickness (IMT) were measured using ultrasound. RESULTS Baseline characteristics were similar between the 2 groups. After 24 weeks and compared with baseline, there were no significant changes in blood pressures, blood hematological and biochemical profiles, or folate and homocysteine levels in both groups, but there was a mild decrease in low density lipoprotein (LDL) cholesterol in both groups (p < 0.05). Brachial FMD improved during D&G (p < 0.001) and less so during placebo treatment (p < 0.05), while improvement in carotid IMT was observed only in the D&G group (p < 0.05). After open-label D&G treatment for 6 more months (n = 45), further improvement in both brachial FMD (p < 0.0001) and carotid IMT (p < 0.0001) was observed. Eight (8) adverse events were reported-6 during placebo and 2 during D&G treatment-requiring treatment termination in 2 patients (on placebo). CONCLUSIONS D&G adjunctive treatment in coronary patients was well tolerated and effective in improving vascular function and structure. These two herbs may become a novel agent for secondary prevention.

Monitoring the Safety of Herbal Medicines

SummaryExtremely limited knowledge about the ingredients in herbal medicines and their effects in humans, the lack of stringent quality control and the heterogenous nature of herbal medicines all necessitate the continuous monitoring of the safety of these products. In Hong Kong, safety information on herbal medicines has come from the enquiries and reports received by our Drug and Poisons Information Service, on-going surveillance of patients treated in a large general teaching hospital and review of reports from the medical literature. Circumstances under which poisonings have occurred are also analysed in order to devise preventive measures. Once collected, this information is then distributed to health professionals in Hong Kong and abroad. WHO projects and pilot studies in Europe are also under way to promote and facilitate reporting of adverse reactions to herbal medicines.