Adverse and Paradoxical Reactions to Herbs and Pharmaceuticals: Seven Case Studies by M.M. Van Benschoten, OMD
OAdverse responses to pharmaceuticals and Chinese herbal formulas are complex issues that require immediate action. Side effects from prescription medications should be managed by having the patient contact the prescribing MD for instructions on dose reduction or discontinuation. Herbal formulas causing side effects should be stopped, with reexamination and reformulation of the prescription with different ingredients. If this is not an option, after all adverse symptoms resolve, the prescription may be restarted at one half the original dose. If a lower dose is not tolerated, reformulation is in order.
In our experience, food poisoning can sensitize patients to their herbal prescription, which explains initial tolerance followed by gastrointestinal side effects weeks later. This observation coincides with the traditional restriction on raw and cold foods, which are more likely to have bacterial contamination.
In clinical practice, acupuncturists routinely treat the aftermath of extensive pharmaceutical interventions. Drug resistance is common in many diseases, and side effects of prescription medications may persist long after they are discontinued. The case studies below illustrate common conditions seen in the clinic.
Case 1
Mr. A is an 87 year old with stage 4 prostate cancer and hypertension maintained on antihormonal therapy and Terazosin, an alpha adrenergic receptor blocker. After twenty years of treatment with Chinese herbal extracts, his last two prescriptions have caused increased blood pressure, even though the ingredients are antihypertensive and are taken at least one hour apart from the pharmaceuticals.
Several ingredients in both prescriptions activate the pregnane X receptor, which induces the hepatic drug metabolism enzymes CYP 3A1, 3A2, and 3A4. This increases metabolism of the antihypertensive medication, and this effect is not compensated for by the hypotensive action of the herbal formula. The herbal prescriptions were stopped immediately, and the patient’s blood pressure monitored daily to ensure a return to normal values.
Prescription 1 - cynanchum atratum (bai wei), ilex pubescens (mao dong qing), cnidium (chuan xiong), crataegus (shan zha), scute (huang qin), astragalus seed (sha yuan zi), gastrodia (tian ma), acorus (shi chang pu), eleutherococcus (ci wu jia), siegesbeckia (xi xian cao), coriolus (yun zhi), vitex (man jing zi)
Prescription 2 - angelica sinensis (dang gui), curcuma longa (jiang huang), pueraria (ge gen), prunella (xia gu cao), gambir (gou teng), chrysanthemum (ju hua)
Hypotensive/Pregnane X receptor activate
angelica sinensis (dang gui), cnidium (chaun xiong), coptis (huang lian), curcuma longa (jiang huang), epimedium (yin yang huo), gardenia (shan zhi zi), salvia (dan shen), schizandra (wu wei zi)
Pregnane X receptor activate
angelica sinensis (dang gui), artemisia scoparia (yin chen hao), citrus (chen pi), clove (ding xiang), cnidium (chuan xiong), coptis (huang lian), curcuma longa (jiang huang), epimedium (yin yang huo), gardenia (shan zhi zi), ginkgo leaf (jin xing ye), licorice (gan cao), lycium bark and fruit (di gu pi, gou ji zi), ophiopogon (mai men dong), paeony (bai shao), polygonum cuspidatum (hu zhang), polygonum multiflorum (he shou wu), rehmannia cooked (sheng di huang), salvia (dan shen), schizandra (wu wei zi), silybum (shui fei ji), trichosanthes (tian hua fen)
CYP3A1 induce
atractylodes lancea (cang zhu), atractylodes macrocephala (bai zhu), curcuma (jiang huang), gingko leaf (jin xing ye), pueraria (ge gen), sophora root (ku shen)
Case 2
Mr. B is an 24 yr old post kidney transplant. Increasing his dosage of Prograf, an antirejection drug, increases his creatinine, a measure of kidney function. At the dose that is considered therapeutic by laboratory test results, toxic effects of the drug on the transplanted kidney are reflected by an elevation in creatinine. This case illustrates the need to consider individual differences in drug tolerance and dosing. The following herbs are prescribed to protect the kidney from drug toxicity and to lower the creatinine levels.
Prescription - bidens (xian feng cao), lindera (wu yao), physalis (pao zai cao), salvia (dan shen), moutan (mu dan pi), paeony (bai shao)
Bidens and lindera reduce creatinine. Lindera inhibits glomerular cell fibrosis and apoptosis. Physalis suppresses graft versus host reactions and T cell activation. Salvia lowers angiotensin II, inhibits TGF beta, and increases glomerular filtration rate. Moutan and paeony reduce monocyte chemotactic protein, an inflammatory pathway in renal autoimmune disease
Case 3
Ms. C is a 53 yr old post menopause. Hormone replacement therapy including estrogen, progesterone, testosterone, and DHEA results in alopecia. Conversion of testosterone to 5DHT is the most likely cause for this reaction. Herbs to enhance hair growth and inhibit the conversion of testosterone via 5-alpha reductase type I and II are administered to reverse the alopecia.
Prescription - angelica sinensis (dang gui), cuscuta (tu su zi), sophora root (ku shen), drynaria (gu sui bu), eclipta (han lian cao), pueraria flower (ge hua)
Angelica sinensis, cuscuta, sophora root inhibit testosterone 5-alpha reductase. Drynaria, eclipta, and pueraria flower enhance hair growth.
Case 4
Mr. D is a 61 yr old with atrial fibrillation. After a few days on Diltiazem, a calcium channel blocker, he has severe erectile dysfunction. This is a common side effect of antihypertensive medications. Herbs to increase the intracavernous pressure and cause vasodilation of the corpus cavernosum are prescribed to address the adverse reaction.
Prescription - lotus embryo (lian zi xin), lycium fruit (gou ji zi), rubus (fu pen zi), tribulus (bai ji li)
Lotus embryo and tribulus induce relaxation of the corpus cavernosum. Lycium fruit, rubus, and tribulus increase intracavernous pressure. Tribulus increases expression of the androgen receptor.
Case 5
Ms. E is a 85 yr old with recent gastric bleeding from anticoagulant therapy, chronic sinusitis, head injury with hematoma, urinary tract infection with agitation, sleep apnea, and anemia. Previous medications included Coumadin, Plavix, and aspirin. Laser coagulation via endoscopy was performed to stop the bleeding, and aspirin and Plavix were discontinued.
Prescription - magnolia bark (hou pu), lindera (wu yao), chrysanthemum (ju hua), aucklandia (mu xiang), plantago (che qian zi), gastrodia (tian ma), pyrossia (shi wei), thlaspi (bai jiang cao), cuscuta (tu su zi), lycium fruit (gou ji zi)
Magnolia bark has antiulcer effects. Lindera stops bleeding. Chrysanthemum, aucklandia, plantago have antibacterial and antifungal actions for the chronic sinusitis. Gastrodia is neuroprotective and anticonvulsant for the head injury. Pyrossia and thlaspi are antibacterial for the urinary tract infection. Cuscuta and lycium fruit increase nerve growth factors to help address the sleep apnea.
Case 6
Ms. F has concentration, memory, mood, sleep, verbal processing disorder, and muscle twitching which are related to previous Prozac use. Her history includes partial hysterectomy and post traumatic stress from verbal abuse in prior relationships and in the current workplace. She has chronic sinusitis causing nasal crusting, fatigue, and hypoglycemia, and is two years overdue for routine dental cleaning. Coffee intolerance aggravates her insomnia and anxiety.
Prescription - acorus (shi chang pu), bupleurum (chai hu), gambir (gou teng), zizyphus spinosa (suan cao ren), salvia (dan shen), schefflera (qi yi lian), lotus seed (lian zi), hibiscus (fu rong), phragmites (lu gen), crataegus (shan zha), perilla leaf (su ye), codonopsis (dang shen)
Acorus, bupleurum, gambir, zizyphus spinosa, salvia, schefflera, and lotus seed have antianxiety, antidepressant, anticonvulsant, and sedative effects to counteract the negative response to Prozac. Hibiscus, phragmites, and crataegus are antibacterial and antibiofilm for the chronic sinusitis. Perilla leaf and codonopsis stabilize blood sugar to address the hypoglycemia.
Case 7
Mr. F is a 3 yr old with a history of premature birth, autism spectrum diagnosis, allergies, asthma, nosebleeds, dairy intolerance, and a breakthrough reaction to the chicken pox vaccine. The current scientific literature refutes vaccination as a causative factor, however the immune dysfunction that is characteristic of autism may contribute to adverse reactions from immunization. Streptococcal infections can trigger autoimmune inflammation of the central nervous system in the syndrome known as PANDAS, pediatric neuropsychiatric disorders associated with streptococcus. The presence of nosebleeds is often an indication of chronic strep infection.
Prescription - chrysanthemum indicum (ye ju hua), platycodon (jie geng), prunella (xia gu cao), eclipta (han lian cao), acorus (shi chang pu), gambir (gou teng), siler (fang feng), thlaspi (bai jiang cao), curcuma longa (jiang huang), cnidium (chuan xiong), corydalis (yan hu suo), magnolia bark (hou pu)
Chrysanthemum indicum, platycodon, prunella, and eclipta are antistreptococcal and stop bleeding. Curcuma longa, prunella, thlaspi are antiherpesvirus. Acorus, gambir are anticonvulsant, sedative, and neuroprotective. Corydalis, magnolia bark, and siler interact with calcium channels and have sedative and muscle relaxing effects. Cnidium improves mitochondrial function.