Anti-Coagulant/Anti-Thrombotic

Angelica -- Derived from the root of Angelica archangelica and related species.  Known popularly as angelica root, angelica radix, and dong quai.

Active Constituents -- Coumarins (angelicin, osthol, bergaptan and several other coumarins), ferulic acid, chalcones (xanthoagnelol), and numerous terpenes, alcohols, esters, lactones, and polysaccharides.

Reported Uses -- menopause, menstrual discomfort, aneamia, poor circulation, headache, osteoporosis, hay fever, asthma.  Current recommendations are primarily for peripheral vascular disease, GI disorders, and cancer.

Pharmacologic Actions -- The primary effect of angelica is inhibition of platelet aggregation, which has been shwon both in vitro and in vivo.  (This may be the result of either thromboxane synthesis inhibition or prostacyclin synthesis promotion.)  Other effects observed in laboratory settings include stimulation of haematopoiesis (mice), reduced myocardial injury and arrhythmias (cultured cells), anti-tumour effects (mice -- may increase TNF-alpha), anti-inflammatory/analgesic effects (mice), anti-bacterial actions (in vitro) and uterine contraction/tracheal relaxation (mice).

Clinical Trials -- No human trials have been performed using angelica alone.

Doses -- Little aggreement exists on recommended doses.

Side effects -- photodermatitis, phototoxicity, other allergic reactions, hypotension.

Drug interactions -- anti-coagulants, anti-thrombotics

Contra-indications -- pregnancy, breast feeding, diabetes, bleeding disorders.

Clinical Considerations -- monitor for bleeding, avoid sunlight, potentially carcinogenic.

Although angelica possesses pharmacologic activity that may be beneficial, lack of human data discourages its recommendation.

Horse Chestnut -- Derived from the seed of AEsculus hippocastanum, a tree native fo North Central Asia.

Active Constituents -- aescin (escine).  Marketed under the tradenames Venostatin Retard^R and Venostat^R.  The extracts also contain various flavonoids (quercetin, kaempferol, astragalin, and rutin), coumarins (aesculetin, scopolin), and phytosterols.

Reported Uses -- varicose veins, diarrhoea, fever, phlebitis, haemorrhoids, prostatic hypertrophy.

Pharmacologic actions -- Horse chestnut has been reported in the scientific literature to possess anti-inflammatory activity, to reduce transcapillary filtration, to increase levels of prostaglandin F2 alpha, to stabilise lysosomal membranes, and to have anti-viral and anti-diarrhoeal actions.

Clinical Trials -- Human studies have been performed examining the efficacy of horse chestnut.  The stabilisation of lysosomal membranes has been associated with a reduction of enzymes that are responsible for varicose formation.  Three separate trials indicated improvement in vascular insufficiency with reduced lower leg oedema, mean lower leg volume, heaviness, tenseness, fatigue, and paraesthesias.

Dose -- Most clinical trials have emplyed 100-200 mg aescin in one to two doses daily.

Side effects -- nuscle spasms, nausea and vomiting, nephropathy, hepatotoxicity, pruritus, urticaria, hypersensitivity.

Drug Interactions -- Increased incidence of bleeding with anti-coagulants and anti-thrombotics.

Contra-indications -- pregnancy, breastfeeding, patients taking anti-coagulants and anti-thrombotics, bleeding disorders.

Clinical Considerations -- Patients should be monitored for bleedings, nephrotoxicity, and hepatotoxicity.  Horse chestnut may discolour the urine red.  Self administration of raw plant materials should be discouraged, since the fruit, leaves, and older bark is poisonous.  Additionally, the buckeye, also locally referred to as horse chestnut, should not be confused with true horse chestnut.

Summary -- The clinical evidence for efficacy in the treatment of varicose veins is supported and the basis is greater than many claims for other herbal therapies.  However, additional research is required and indiscriminate use should be discouraged.

Grapeseed and Pinebark (Vitis coigneti, V. vinifera and Pinus maritima, P. nigra; respectively)

Active consituents for both plants are proanthocyandins, marketed under the trade name and commonly referred to as Pycnogenol^R.

Reported Uses -- atherosclerosis, inflammation, cardiac and cerebral hypoxia, varicose veins, cancer

Pharmacologic Actions -- The proanthocyanidins have been shown to have anti-oxidant effects (especially inhibiting lipid peroxidation), inhibit xanthine oxidase, inhibit nucleotidase activity (found in many snake venoms), and to inhibit enzyme (collagenase, elastase, hyaluronidase) activity involved in skin turnover.

Rat studies have demonstrated both hepatoprotective and hepatotoxic actions.  Cell regenerations has been shown in rats and decreased skin degredation in rabbits.

Clinical Trials -- Human trials have shown decreased pain, limb heaviness, and swelling in patients with peripheral vascular disease, however these trials have been poorly controlled.

Doses -- 25-300 mg daily for 3 days followed by 40-80 mg daily maintenance.

There are no reported side effects or drug interactions for the proanthocyanidins.

Caffeine -- The diuretic action of caffeine is similar in response to that seen with the thiazides (increased excretion of sodium, potassium, and chloride).  However, its mechanism is probably due to increased renal blood flow and subsequent increased glomerular filtration.  Antagonism of the adenosine at the renal nephron (which would alter the renin/angiotensin/aldosterone response) may also contribute to the diuretic actions of caffeine.

Nettle (Urtica dioica) -- Stinging nettle.  Both leaves and roots are used.

Constituents -- histamine, serotonin, choline, formic acid, scopoletin, glycosides, and sterols.

Current Uses -- hypertension, heart failure, renal dysfunction.  Older uses include asthma, cough, epistaxis, gout, wound healing.

Pharmacologic actions -- Nettle has been shown to have diuretic properties in laboratory animals (mechanism unknown), stimulate uterine contractions, immunostimulant (lectin protein component) and anti-inflammatory (scopoletin) actions, and to inhibit BPH in mice.

Clinical Trials -- Human studies have demonstrated a reduction in residual urine, reductions in post-operative blood loss and inflammation, and improvement in symptoms of allergic rhinitis.

Doses used -- 150-300 mg capsules as needed; 1-2 teaspoonfuls of dried herb for tea, and 1/4 to 1 tespoonful of tincture.

Side Effects -- contact dermatitis, diarrhoea, oedema, GI irritation.

Drug Interactions -- additive electrolyte loss with diuretics

Contraindications -- Pregnancy, children, geriatrics.

Clinical Considerations -- Cutaneous exposure to the plant may cause intense burning for 12 hours or longer.

The FDA considers nettle to be of undefined safety.

Goldenseal -- Hydrastis canadensis, Jaundice root, yellow root, Indian tumeric.

Active Constituents -- alkaloids (hydrastine, berberine, hydrastinine, canadine) and numerous other constituents.

Proposed Uses -- Diuresis, often recommended as an aid to mask drug use in urine drug tests.

Pharmacologic Actions -- Uterine contractile effects and (paradoxically) other smooth muscle relaxant effects), anticoagulant effects, cardiotonic (low doses) and cardiodepressant (high doses), antipyretic, antimuscarinic, antihistaminic, hypotensive, and hypertensive effects have all been reported in the literature.  Obviously many of these effects are opposing.  This may reflect individual component actions.

Clincial Trials -- Very few have been performed.  Berberine has been shown to be a more effective antipyretic than aspirin in one old trial.  Most trials have been small but have shown effects including reductions in post-partum haemorrhage, improvements in biliary flow, decreases in diarrhoea, but NO effects on urine output.

Doses -- 250 mg of the liquid extract or 1/2 to 1 G of the dried root, t.i.d.

Side Effects -- bradycardia, asystole, heart block, CNS depression, paraesthesias, seizures, paralysis, respiratory depression, GI cramping, leucocytosis, and mouth ulcers have all been reported.

Contraindications -- cardiovascular disease, pregnancy.

Drug Interactions -- CNS depressants, antihypertensives, anti-coagulants.  Also inhibits B vitamin absorption.

Clinical Considerations -- There is no scientific or clinical basis for the ability of goldenseal to mask urine drug tests (these studies have specifically been performed).

Bearberry -- Arctostaphylos uva-ursi, a low, evergreen shrub.  The leaves are the active part.  Most well known as uva ursi

Constituents -- arbutin (a hydroquinone) and numerous other constituents.

Proposed uses -- as a mild diuretic and mild urinary antiseptic

Pharmacologic properties -- The hydroquinone has been shown to have antiseptic and astringent activity and the triterpene ursolic acid and the flavonoid isoquecetin have both demonstrated diuretic actions.  Other actions include attenuation of weight loss in diabetic mice and enhancement of NSAID and steroidal anti-inflammatory effects.

Clincial Trials -- No controlled, human studies have been performed.

Doses -- range from 1 to 10 G daily.  Anecdotal evidence indicates that as much as 20 G may be taken without adverse effect and as little as 1 G may cause toxicity in sensitive individuals.

Adverse Effects -- Cyanosis, green urine, nausea, vomiting, and at high doses tinnitus, seizures, cardiovascular collapse.

Drug Interactions -- Diuretics (additive) and urinary acidifiers (may inactive the antiseptic effect of uva ursi).

Contraindications -- Pregnancy

Summary -- Evidence does exist for potential diuretic actions of uva ursi, but the potential toxicities outweigh its preference over the existing diuretics.

Buchu -- Barosma betulina (Agathosma betulina) -- The leaves of this South African shrub are used.

Constituents -- Volatile oils, diosphenol (buchu camphor), pulegone, flavonoids, and terpenes.

Proposed uses -- diuretic and UTIs.

Pharmacologic Actions -- NONE identified other than mild anti-inflammatory actions in rats.

Clinical Trials -- NONE performed.

Doses -- 1 oz of dried leaves (tea) or 1-2 ml of tincture, t.i.d. to q.i.d.

Side Effects -- Diarrhoea, nausea, vomiting, (volative oil) and hepatotoxicity, hypermenorrhoea, spontaneous abortion (pulegone)

Drug Interactions -- anti-coagulants/thrombotics (enhanced effects)

Contraindications -- pregnancy, renal disease, liver disease.

Clinical considerations -- any patient taking buchu should be monitored for potential hepatotoxicity and nephrotoxicity.

There is no evidence for the use of buchu as a diuretic.  Its potential toxicity outweighs any potential benefit.