CAM+Case+Studies+Answers

=CAM Case Studies Answers=

**Echinacea (//Echinacea purpurea, Echinacea pallida, Echinacea augustifolia//) **
//Richard, a 40 ‐  year  ‐  old man presents to your pharmacy, and asks for advice about Echinacea. He has heard that it is a natural remedy for treating and preventing the common cold. He explains that he, his wife and two young children experienced a number of colds last winter because the children attend childcare and are “always bringing germs home”. He is thinking they should try Echinacea to prevent them from getting so many colds this year. He asks your advice about the effectiveness of ////Echinacea and whether it would be safe for all the family to use.// **Orally, echinacea is used for treating and preventing the common cold and other upper respiratory infections.
 * • What are some of the common uses of Echinacea?

 • What information could be collected from this customer that would assist you in making your recommendations? ** Allergic reactions seem to be uncommon, but some people are more likely to be sensitive. For example, atopic individuals, people with a genetic tendency toward allergic conditions, are at increased risk for allergic reactions to echinacea. Individuals sensitive to the Asteraceae/Compositae plant family might also be more likely to experience an allergic reaction to echinacea. Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs.
 * • What system of traditional medicine was Echinacea first used in? What were some of its traditional uses?

Do not take echinacea if:
 * You are pregnant or breast-feeding.
 * You have a skin condition called pemphigus vulgaris.
 * You have an immune system disorder such as multiple sclerosis (MS), lupus (systemic lupus erythematosus, SLE), rheumatoid arthritis (RA), or other immune system conditions called "autoimmune disease."

Echinacea seems to increase plasma concentrations of caffeine by 30%. This is likely due to inhibition of cytochrome P450 1A2 (CYP1A2) by echinacea.

Echinacea appears to inhibit CYP1A2 enzymes in humans. Theoretically, echinacea might increase levels of drugs metabolized by CYP1A2. Some drugs metabolized by CYP1A2 include acetaminophen (Tylenol), amitriptyline (Elavil), clopidogrel (Plavix), clozapine (Clozaril), diazepam (Valium), estradiol, olanzapine (Zyprexa), ondansetron (Zofran), propranolol (Inderal), ropinirole (Requip), tacrine (Cognex), theophylline, verapamil (Calan, Covera-HS, Isoptin, Verelan), warfarin (Coumadin), and others.

o The effectiveness of Echinacea for the treatment of the common cold; **Taking some echinacea preparations seems to modestly reduce symptom severity and duration, possibly by about 10% to 30% Echinacea seems to be most effective if started when symptoms are first noticed and continued for 7-10 days. Not all research is positive. Some studies show no benefit for treating the common cold in adults. Echinacea studies have used different echinacea species and a wide variety of preparation methods. Studies have also used different patient populations and study designs. Due to these discrepancies among studies, it's not surprising that different studies have different results. The best evidence appears to be for preparations of the Echinacea purpurea species. Other preparations that have been used include a variety of extracts of the herbs and root parts of Echinacea pallida and Echinacea angustifolia species. Echinacea teas and fixed combination herbal preparations containing echinacea have also been used.
 * • What advice or information could you give to the customer about:

**Taking echinacea prophylactically to prevent the development of a cold does not seem to be effective
 * <span style="font-size: 10pt; font-family: 'Arial','sans-serif'">o The effectiveness of Echinacea for preventing the common cold;

** Echinacea seems to activate chemicals in the body that decrease inflammation, which might reduce cold and flu symptoms. Laboratory research suggests that echinacea can stimulate the body's immune system, but there's no evidence that this occurs in people. Echinacea also seems to contain some chemicals that can attack yeast and other kinds of fungus directly. <span style="font-size: 10pt; font-family: 'Arial','sans-serif'"> The applicable parts of echinacea are the roots and the above ground parts. The composition of each of the three commonly used echinacea species is similar, with some variation in the amounts of active constituents. Although these species are often used interchangeably, there is very little research comparing them. Echinacea is used for upper respiratory tract infections such as the common cold and influenza infections because it is reported to have antiviral and immune system stimulatory effects; however, there are no reports that it has activity against respiratory viruses. Echinacea increases phagocytosis and increases lymphocyte activity, possibly by promoting the release of tumor necrosis factor (TNF), interleukin-1 (IL-1), and interferon. Several constituents of echinacea seem to be involved in stimulating this non-specific immune response. **Likely safe when used orally and appropriately, short-term. Several formulations of echinacea have been used safely in trials lasting up to 12 weeks There is insufficient reliable evidence about the safety of echinacea when used long-term. **Possibly safe when used orally, short-term. There is some evidence that an Echinacea purpurea juice extract is safe in children aged 2-11 years when used for up to 10 days. However, echinacea might increase the risk of rash in some children
 * <span style="font-size: 10pt; font-family: 'Arial','sans-serif'">o The mechanism by which Echinacea is thought to work
 * <span style="font-size: 10pt; font-family: 'Arial','sans-serif'">o Adverse or unwanted effects of Echinacea;
 * <span style="font-size: 10pt; font-family: 'Arial','sans-serif'">o Safety and effectiveness of Echinacea in children?

A study in children aged 2-11 years also suggests that taking an Echinacea purpurea juice extract 7.5-10 mL/day (Madaus AG, Germany) for up to 10 days also does not significantly decrease cold symptoms

The best evidence appears to be for preparations of the Echinacea purpurea species. Other preparations that have been used include a variety of extracts of the herbs and root parts of Echinacea pallida and Echinacea angustifolia species. Echinacea teas and fixed combination herbal preparations containing echinacea have also been used.
 * <span style="font-size: 10pt; font-family: 'Arial','sans-serif'">• Several types of echinacea preparations are available in the market. What <span style="font-size: 10pt; font-family: 'Arial','sans-serif'">information is available about which type of echinacea preparation has the greatest ** <span style="font-size: 10pt; font-family: 'Arial','sans-serif'">**body of evidence?**

**<span style="font-size: 10pt; font-family: 'Arial','sans-serif'">2. Ginkgo (//Ginkgo biloba//) **
//<span style="font-size: 10pt; font-family: 'Arial','sans-serif'">Mavis Brown, a regular customer in your pharmacy, comes in with her 89 yo husband Tom. She is ////<span style="font-size: 10pt; font-family: 'Arial','sans-serif'">very concerned as Tom has been doing some unusual things – he wakes in the middle of the night ////<span style="font-size: 10pt; font-family: 'Arial','sans-serif'">and thinks it is day, he doesn’t recognise people he knows well and is very forgetful. Tom’s doctor ////<span style="font-size: 10pt; font-family: 'Arial','sans-serif'">has diagnosed dementia with no reversible cause. Tom has had a mitral valve replacement and is on ////<span style="font-size: 10pt; font-family: 'Arial','sans-serif'">warfarin. Mavis has read in the Readers Digest that ginkgo is good for dementia and asks whether ////<span style="font-size: 10pt; font-family: 'Arial','sans-serif'">Tom should be trying it. //

Possibly effective: Taking ginkgo leaf orally seems to modestly improve symptoms of Alzheimer's, vascular, or mixed dementias. Studies lasting from 3 months to a year show that ginkgo leaf extract can stabilise or improve some measures of cognitive function and social functioning in patients with multiple types of dementia. Although there are conflicting findings, the majority of evidence indicates that ginkgo leaf extract can be modestly helpful for treating dementia. Some researchers estimate that the improvement seen in patients using ginkgo leaf extract is roughly equivalent to a 6-month delay in disease progression. However, outcome studies have not yet verified ginkgo's effects on disease progression.
 * <span style="font-size: 10pt; font-family: 'Arial','sans-serif'">• What benefits may ginkgo have in dementia? What is the evidence is available to support its <span style="font-size: 10pt; font-family: 'Arial','sans-serif'">use in this condition? **

Ginkgo has also been evaluated for prevention of dementia. Epidemiologic research suggests that taking ginkgo is not associated with a decreased risk of developing dementia in elderly patients with memory impairment; however, it might be associated with a decreased risk of overall mortality.

Most clinical studies have not compared ginkgo to conventional drugs such as the cholinesterase inhibitors. However, in a preliminary comparative trial, a specific ginkgo leaf extract (EGb 761, Tanakan) 160 mg daily seems to be comparable to donepezil 5 mg daily for mild to moderate Alzheimer's dementia after 24 weeks of treatment. Indirect comparisons suggests that ginkgo might be less effective than the conventional drugs donepezil (Aricept), tacrine (Cognex), and other cholinesterase inhibitors.

Most of the clinical studies on the effectiveness of ginkgo leaf for dementia have used the standardized extracts EGb 761 (Tanakan) and LI 1370 (Lichtwer Pharma). These two extracts are similar and prepared to contain approximately 24% to 25% flavone glycosides and 6% terpene lactones. Products with similar ingredients include Ginkai (Lichtwer Pharma), Ginkgo 5 (Pharmline), Ginkgold and Ginkgo (Nature's Way), and Quanterra Mental Sharpness (Warner-Lambert).

**Orally, ginkgo is used for dementia, including Alzheimer's, vascular, and mixed dementia. Ginkgo leaf is also used orally for conditions associated with cerebral vascular insufficiency, especially in the elderly, including memory loss, headache, tinnitus, vertigo, dizziness, difficulty concentrating, mood disturbances, and hearing disorders.
 * <span style="font-size: 10pt; font-family: 'Arial','sans-serif'">• What other conditions is ginkgo used for?

**Most of the clinical studies on the effectiveness of ginkgo leaf for dementia have used the standardized extracts EGb 761 (Tanakan) and LI 1370 (Lichtwer Pharma).
 * <span style="font-size: 10pt; font-family: 'Arial','sans-serif'"> <span style="font-size: 10pt; font-family: 'Arial','sans-serif'">• Some standardised products of ginkgo are available. What components are ginkgo products <span style="font-size: 10pt; font-family: 'Arial','sans-serif'">commonly standardised to?

Ginkgo interacts with anticoagulant/antiplatelet drugs ** [|**Interaction Rating**] = ** Major ** Do not use this combination [|Severity] = High • [|Occurrence] = Probable • [|Level of Evidence] = [|**D**] Ginkgo leaf has been shown to decrease platelet aggregation and might increase the risk of bleeding when combined with antiplatelet or anticoagulant drugs. It is thought that the ginkgo constituent, ginkgolide B, displaces platelet-activating factor (PAF) from its binding sites, decreasing blood coagulation. Short-term use of ginkgo leaf might not significantly reduce platelet aggregation and blood clotting. One study shows that healthy men who took a specific ginkgo leaf extract (EGb 761) 160 mg twice daily for 7 days did not have reduced prothrombin time. Also, a single dose of ginkgo plus clopidogrel (Plavix) does not seem to significantly increase bleeding time. However, single doses of ginkgo plus cilostazol (Pletal) does seem to prolong bleeding time. It has been suggested that ginkgo has to be taken for at least 2-3 weeks to have a significant effect on platelet aggregation. Use ginkgo cautiously or avoid in patients who are taking antiplatelet or anticoagulant drugs. Some of these drugs include aspirin, clopidogrel (Plavix), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, indomethacin (Indocin), ticlopidine (Ticlid), warfarin (Coumadin), and others.
 * <span style="font-size: 10pt; font-family: 'Arial','sans-serif'">• Would you have any concerns about the use of Ginkgo in Tom’s situation. Why?

<span style="font-size: 10pt; font-family: 'Arial','sans-serif'">**• What advice would you give to Tom and Mavis?** Avoid use of gingko as it can increase the risk of bleeding. Possibly try another complementary medicine such as acetyl-L-carnitine, huperzine A and vitamin E.

//<span style="font-size: 10pt; font-family: 'Arial','sans-serif'">Mary, a 28 year old woman, comes to your pharmacy to ask your advice about St John’s Wort. She ////<span style="font-size: 10pt; font-family: 'Arial','sans-serif'">purchased a St John’s Wort (SJW) containing product from a supermarket hoping it might provide ////<span style="font-size: 10pt; font-family: 'Arial','sans-serif'">relief for some moderate depression and anxiety she has been experiencing. he noticed a warning ////<span style="font-size: 10pt; font-family: 'Arial','sans-serif'">on the packet “St John’s Wort affects the way that some prescription medicines work”. She asks if ////<span style="font-size: 10pt; font-family: 'Arial','sans-serif'">you can explain what this means and which prescription medicines are affected. Her doctor has given ////<span style="font-size: 10pt; font-family: 'Arial','sans-serif'">her a prescription for an SSRI for her depression and she is not sure whether to use it. She has also ////<span style="font-size: 10pt; font-family: 'Arial','sans-serif'">taken the oral contraceptive pill for the last three years. //<span style="font-size: 10pt; font-family: 'Arial','sans-serif'"> Orally, St. John's Wort is used for depression, dysthymia, anxiety, heart palpitations, mood disturbances associated with menopause, attention deficit-hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), and seasonal affective disorder (SAD).
 * <span style="font-size: 10pt; font-family: 'Arial','sans-serif'">3. St John’s Wort (//Hypericum perforatum//) **
 * • What conditions is St John’s commonly used for?**

<span style="font-size: 10pt; font-family: 'Arial','sans-serif'">**•** <span style="font-size: 10pt; font-family: 'Arial','sans-serif'">**What were its uses in traditional** **<span style="font-size: 10pt; font-family: 'Arial','sans-serif'">medicine?

<span style="font-size: 10pt; font-family: 'Arial','sans-serif'">• What are the mechanisms by which St John’s wort may produce interactions with <span style="font-size: 10pt; font-family: 'Arial','sans-serif'">prescription medicines? Which types of prescription medicines are of particular concern? **<span style="font-size: 10pt; font-family: 'Arial','sans-serif'">St <span style="font-size: 10pt; font-family: 'Arial','sans-serif'"> John's Wort can increase serotonin levels: triptans, MAOIs, antidepressants Induce CYP3A4 enzymes: alpralozam, amitryptyline, SSRIs, cyclosporin Induce 1A2, 2C9, 3A4 (responsible for metabolism of oestrogens and progestins): oral contraceptives (use additional protection) Induce 1A2: celecoxib, diclofenac, fluvastatin, glipizide, ibuprofen, irbesartan, losartan, phenytoin, piroxicam, tamoxifen, tolbutamide, torsemide, and S-warfarin Induce 3A4: calcium channel blockers (diltiazem, nicardipine, verapamil), chemotherapeutic agents (etoposide, paclitaxel, vinblastine, vincristine, vindesine), antifungals (ketoconazole, itraconazole), glucocorticoids, cisapride, alfentanil, fentanyl, losartan, fluoxetine, midazolam, omeprazole, ondansetron, propranolol, fexofenadine, and numerous others Lowers levels of digoxin <span style="font-size: 10pt; font-family: 'Arial','sans-serif'">• What advice could you give to Mary about the use of SJW with her other medications? **Concomitant use with antidepressants can lead to increased adverse effects and increase the risk of serotonergic side effects, including serotonin syndrome. Although this effect has only been reported with nefazodone, paroxetine, and sertraline, it might also occur with other antidepressants. Use of St. John's Wort with other antidepressants should only be done with close supervision. Also, concurrent use might theoretically cause cerebral vasoconstriction disorders such as Call-Fleming syndrome.
 * <span style="font-size: 10pt; font-family: 'Arial','sans-serif'">

St. John's Wort can decrease norethindrone and ethinyl estradiol levels by 13% to 15%, resulting in breakthrough bleeding, irregular menstrual bleeding, or unplanned pregnancy. Bleeding irregularities usually occur within a week of starting St. John's wort and regular cycles usually return when St. John's Wort is discontinued. Unplanned pregnancy has occurred with concurrent use of oral contraceptives and St. John's Wort extract. St. John's Wort is thought to induce the cytochrome P450 1A2 (CYP1A2), 2C9 (CYP2C9), and 3A4 (CYP3A4) enzymes, which are responsible for metabolism of progestins and estrogens in contraceptives. Women taking St. John's Wort and oral contraceptives concurrently should use an additional or alternative form of birth control. <span style="font-size: 10pt; font-family: 'Arial','sans-serif'">• What is the evidence to support the use of SJW for <span style="font-size: 10pt; font-family: 'Arial','sans-serif'">a) depression? ** St. John's Wort extracts are more effective than placebo, likely as effective as low-dose tricyclic antidepressants, and likely as effective as the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, sertraline, and paroxetine. Taking St. John's Wort extracts improves mood, decreases anxiety and somatic symptoms, and decreases insomnia related to mild to severe major depression. Short-term response rates to St. John's Wort appear to between 65% and 100%; however, long-term, the response rates appear to be lower, 60% to 69%.
 * <span style="font-size: 10pt; font-family: 'Arial','sans-serif'">

Most studies have used St. John's Wort extracts based on hypericin content, but extracts standardized based on hyperforin also seem to be effective. Most studies have evaluated St. John's Wort in adults, however, there is also some evidence it might be effective for depression in children 6 to 16 years old.

The effectiveness of St. John's Wort for depression has been called into question based on equivocal findings of two studies in psychiatric care settings. But the overwhelming majority of evidence in primary care settings shows that St. John's Wort is effective for most patients. Patients in primary care settings may have less severe depression than patients seeking psychiatric care.

Clinical guidelines from the American College of Physicians-American Society of Internal Medicine suggest that St. John's Wort can be considered an option along with conventional antidepressants for short-term treatment of mild depression. However, since St. John's Wort has not been shown to be more effective or significantly better tolerated than conventional antidepressants; and since St. John's Wort causes many drug interactions, it might not be an appropriate choice for many patients, particularly those who take other conventional drugs.

Taking St. John's Wort extracts improves mood, decreases anxiety and somatic symptoms, and decreases insomnia related to mild to severe major depression.
 * <span style="font-size: 10pt; font-family: 'Arial','sans-serif'">b) anxiety? **

//<span style="font-size: 10pt; font-family: 'Arial','sans-serif'">Mary asks if there are any side effects when taking St John’s Wort and how these might <span style="font-size: 10pt; font-family: 'Arial','sans-serif'">compare with the prescription medicine (SSRI) that her doctor has prescribed. // **Orally, St. John's Wort is usually well tolerated. Side effects can include insomnia, vivid dreams, restlessness, anxiety, agitation, irritability, gastrointestinal (GI) discomfort, diarrhea, fatigue, dry mouth, dizziness, and headache. St. John's wort can also cause skin rash, paresthesia, and hypoglycemia. Insomnia can often be alleviated by decreasing the dose or taking St. John's wort in the morning. In clinical trials, the incidence of adverse effects in patients treated with St. John's Wort is similar to placebo and less than conventional antidepressants.
 * <span style="font-size: 10pt; line-height: 115%; font-family: 'Arial','sans-serif'">What advice could you give her?