Uses of Herbs and Drug Interactions in Cardiovascular Patients

More and more consumers are taking herbal supplements as an alternative treatment for their diseases.  It is estimated that more than 15 million people in the US consume herbal remedies or high-dose vitamins, and the total number of visits to the complementary medicine providers far exceeds those to primary physicians. 

Lack of efficacy and adverse effects associated with prescription medicines lead many patients to explore herbal medicines.  Uses of herbal medicines, however, are not without any risks.  Although most of these herbal medicines have good safety profile, some herbal medicines have not been shown to be efficacious.  Some even interact with western medicines, leading to life-threatening consequences. (Table 1)

The purpose of this paper is to equip cardiovascular patients with the latest uses of commonly used herbal medicines and the potential interaction of these herbal medicines with prescription medicines.  Patients are advised to inform their primary care physicians and their specialists of the herbal supplements they are taking and to limit the use of herbal medicines to a shorter time period.

A) Aconite (烏頭草)

Uses

Traditional Chinese practitioners use aconite for pain relief caused by trigeminal and intercostal neuralgia, rheumatism, migraine, and general debilitation.

Drug interaction

Long term use might increase the risk of atrial or ventricular fibrillation. 

B) Black cohosh (黑參麻)

Uses

Black cohosh has been used to relief symptoms of menopause, pre-menstrual tension and other gynecologic problems.

Drug interaction

Black cohosh should not be used with estrogen replacement therapy (ERT) since the combination of black cohosh and ERT has been shown to increase the risk of cardiovascular events and breast cancer.  Pregnant and lactating women should avoid taking black cohosh.

C) Danshen (丹參)

Uses

Danshen is used in traditional Chinese medicine for the treatment of coronary artery disease and menstrual abnormalities.

Drug interaction

Danshen reduces the elimination of warfarin and increases the bleeding risk associated with warfarin.  It also interferes with digoxin essay.

D) Echinacae (紫錐花)

Uses

Echinacae is used to strengthen the immune system to prevent infections.  Side effects of Echinacae include nausea, dizziness, dyspnea, rash, and dermatitis.

Drug interaction

Long term use may increase the liver toxicity of other medications (e.g., statins(Zocor, Lipitor, Crestor), fibrates (Bezalip, Lopid and Tricor), niacins (niaspan), or amiodarone(codarone)).

E) Ginseng (人蔘)

Uses

Ginseng is advertised as an immune system stimulant that increases vigor, sexual potency and longevity.   It is also used to treat myocardial infarction, congestive heart failure (CHF), angina pectoris and hyperglycemia in diabetic patients. 

Drug interaction

Concomitant use of ginseng and warfarin results in an increase in bleeding time while use of ginseng and digoxin causes an increase in digoxin level.  Pregnant women or women receiving hormone replacement therapy are advised not to use Ginseng since ginseng contains ingredients similar to estrogen.  Also, long use of ginseng might result in reduced responsiveness to loop diuretics.

F) Ginkgo (銀杏)

Uses

Ginkgo is used for cardiovascular disease, cerebrovascular or peripheral vascular insufficiency, importance, inner ear dysfunction, retinopathy, pre-menstrual syndrome, stress, depression, and dementia.

Drug interaction

The concurrent use of ginkgo with antiplatelet (aspirin, Plavix, Effient, Aggrrastat and ReoPro), anticoagulant (warfarin) or antithrombotic agents (Streptase) increases the risk of bleeding.  In clinical trials, ginkgo has also been shown to reduce the effectiveness of antihypertensive nicardipine (Cardene).

G) Garlic (大蒜)

Uses

Garlic has been used to treat infectious conditions since 1550 BC, due to its antimicrobial and immune-enhancing properties.  Garlic has also been promoted to prevent cardiovascular disease because of its cholesterol-lowering, antihypertensive, antiplatelet and fibrinolytic properties.

Drug Interaction

Patients taking anticoagulant or antiplatelet agents should avoid taking garlic supplements since garlic increase the risk of bleeding.  Patients taking aspirin, warfarin and garlic supplements are advised to discontinue the garlic supplements for at least 10 days before elective therapy

H) Grapefruit juice (西柚)

Uses

Grapefruit juice is used as a dietary intervention to lose weight and to improve cardiovascular health. 

Drug interaction

Grapefruit juice increases the blood level of calcium-channel blockers (Norvasc, Plendil, Cardif and Cardene), cyclosporine (Sandimmune, Neoral, Cicloral and Gengraf), statins (Lipitor, Zocor, Crestor), midazolam (Dormicum, Versed and Hypnovel), estrogen and terazoin (Hytrin). 

I) Gynura (白子菜,雞菜)

Uses

Gynura is used widely in Chinese medicine to improves microcirculation and relieve pain.

Drug interaction

Gynura interacts with angiotensin-converting enzyme drugs (e.g. Vasotec, Altace, Accupril, Zestril, Prinivil, Lotensin, Cozaar, Diovan, Benicar, Avapro and Micardis ).  Long term use has been associated with hepatic toxicity.

J) Hawthorn (山楂)

Uses

Hawthorn extract is used mostly to treat angina, CHF, bradyarrhythmia and cerebral insufficiency.

Drug interaction

Hawthorn enhances the effect of digitalis (Digoxin) and increases the risk of bleeding in patients taking antiplatelet or anticoagulant agents.  Patients who take digitalis, antiplatelet, anticoagulant and Hawthorn need to monitor for potential toxic effects.

K) Licorice (甘草)

Uses

Licorice is used as an expectorant.  Long term use might result in pseudoaldosteronism, hypokalemia, hypertension, ventricular arrhythmia, hyperglycemia and edema.

Drug interaction

Licorice increases the effects of spironolactone (Aldactone) and digoxin.  It also interacts with antiplatelet, anticoagulant and antidiabetes agents (e.g. Lantus, Amaryl, Januvia, Metformin, Diamicron, Actos, Glucophage, Byetta and Advandia), rendering these agents less effective.

L) Motherwort (益母草)

Uses

Motherwort is use in both European and Asian traditional medicine to treat cardiac weakness, rapid heart beat, anxiety, insomnia, hypertension, amenorrhea, and edema.

Drug interaction

When taken with benzodiazepines for insomnia, motherwort increases the sedative effect of benzodiazepines and might result in coma.

M) Saw Palmetto  (鋸棕櫚)

Uses

Saw Palmetto is used for the treatment of benign prostatic hypertrophy (BPH), hypertension and urinary infections.

Drug interaction

Saw Palmetto increases the risk of bleeding in patients taking warfarin.  When use in long term, saw palmetto might increase in the risk of cholestatic hepatitis, acute pancreatitis and intro-operative floppy iris syndrome.

N) St. John’s wort (聖約翰草)

Uses

St. John’s wort is typically used to treat depression, anxiety, sleep disorders, common cold, herpes, ulcerative colitis, pain and the human immunodeficiency virus.

Drug interaction

Since St. John’s wort decreases the prothrombin time of warfarin and increase the risk of stroke, people taking warfarin who have a history of stroke, thrombosis, atrial fibrillation or prosthetic cardiac valves should avoid the use of St. John’s wort.  

Also, patients who take ethinyl estradiol, indinavir (Crixivan), cyclosporine, statins and digoxin will have the level and efficacy of these drugs reduced.

Lastly, patients who take antidiabetes agents and St. John’s wort should watch out for hypoglycemia since St. John’s wort potentiate the glycemic effects of antidiabetes agents.

O) Tetrandrine (粉防己鹼)

Uses

In Chinese medicine, tetrandrine is used to treat hypertension and angina.

Drug interaction

Tetrandrine lower glucose level and might cause hypoglycemia in diabetic patients.  Long term use might cause hepatotoxicity and renal toxicity.

P) Yohimbine (育亨賓)

Uses

Yohimbine is used for the treatment of sexual disorders and exhaustion.

Drug interaction

Yohimbine reduces the efficacy of antihypertensive and diuretics.  Yohimbine is contraindicated in patients with hypertension, angina, and renal impairment.

Conclusions

Use of herbal remedies is widespread and is increasing dramatically.  These remedies, however, are not subjected to the same regulations as prescription drugs.  Thus, the purity, efficacy and safety of herbal products are not always known and some products may not even contain the amount of active ingredients listed on the label.  Furthermore, some of these herbal remedies posses serious drug interaction with prescription medicines. 

Cardiovascular patients who are taking prescription medicines with narrow therapeutic index such as digoxin and warfarin are advised to consult their physicians before taking any herbal medicines and to take these herbal medicines for a short period of time.

Table 1.  Herb-Drug Interactions 

Herb	Drug or Drug Class	Interaction or Other Comments
Comfrey	Phenobarbital	Increases metabolism of comfrey, producing a lethal metabolite from pyrolizidine that results in severe hepatotoxicity
Danshen(丹參)	Anticoagulant or antiplatelet agentsDigoxin	Increases bledding due to additive effectsIncreases side effects of digoxin
Echinacea(紫錐花)	Amiodarone or ibutilideStatins, fibrates, niacin	Increases QT intervalIncreases risk o hepatotoxic effects
Ephedra	Antidiabetes drugsClass IA and class III antiarrhythmicsBeta-blockers Monoamine oxidase inhibitors	Increases blood glucoseDecreases effectiveness of oral hypoglycemic agentsIncreases QT interval Decreases effects of beta-blockers, leading to hypertension and tachycardia Hypertension
Evening primrose oil (月見草油)	Phenobarbital	Decreases seizure threshold
Garlic(大蒜)	Aspirin, clopidogrel, warfarin or heparinoid drugs	Increases bleeding risk
Ginkgo biloba(銀杏)	Antidiabetes drugsAspirinWarfarin	Increases hypoglycemiaIncreases bleedingInhibits PAF hemorrhage
Ginseng(人蔘)	Antidiabetes drugsDigoxinWarfarin Pheneizine sulfate	Increases hypoglycemiaInterferes with digoxin assay, leading to falsely increased levelsDecreases effectiveness of warfarin Headache Irritability Insomnia
Hawthorn(山楂)	DigoxinCalcium-channel blockers or nitrates	Increases effects of digoxinIncreases vasodilatory effects
Kava	Alprazolam	Increases CNS depressionIncreases effects of alcohol
Licorice(甘草)	Spironolactone	Increases effects of spironolactone
Saw palmetto(鋸棕櫚)	Anticoagulant or antiplatelet agents	Increases bleeding
Soy milk (豆奶)	Warfarin	Decreases effectiveness of warfarin
St. John’s wort (聖約翰草)	DigoxinClopidogrelWarfarin Simvasatin Paroxetine Class IA and III antiarrhythmic agents Clyclosporine Theophyllline Indinavir	Decreases serum digoxin concentrationIncreases activity of clopidogrelIncreases bleeding Decreases warfarin bioavailability and effectiveness Decreases effectiveness of simavastatin Nausea Lethargy Incoherence Decreases effectiveness (precipitating arrhythmias Decreases cyclosporine concentration due to increased clearance (transplant rejection) Decreases serum concentration Decreases serum concentration (treatment failure in HIV patients)
Yohimbine (育亨賓)	Clonidine, GuanabenzCNS stimulants (e.g. amphetamines)ACE Inhibitors Beta-blockers	Decreases blood pressure reduction effect of centrally active agentsRisk of hypertensive crisis due to its monoamine oxidase inhibitor activityDecreases effectiveness of ACE inhibitors Hypertension Decreases effectiveness of beta-blockers Hypertension Increases heart rate

 

Drug Class and Brand Names

Angiotensin-converting enzyme drugs = Vasotec, Altace, Accupril, Zestril, Prinivil, Lotensin, Cozaar, Diovan, Benicar, Avapro and Micardis

Anticoagulant = warfarin

Antidiabetes agents = Lantus, Amaryl, Januvia, Metformin, Diamicron, Actos, Glucophage, Byetta and Advandia

Antiplatelet = aspirin, Plavix, Effient, Aggrrastat and ReoPro

Antithrombotic agents = Streptase

Calcium-channel blockers = Norvasc, Plendil, Cardif and Cardene

Cyclosporine = Sandimmune, Neoral, Cicloral and Gengraf

Digitalis = Digoxin = Lanoxin

Indinavir = Crixivan

Midazolam = Dormicum, Versed and Hypnovel

Spironolactone = Aldactone

Statins = Lipitor, Zocor, Crestor

Terazoin = Hytrin

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