Page 1151 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 64 Dietary Supplements & Herbal Medications 1137

reason, studies evaluating cerebral insufficiency tend to be more was combined with efavirenz, sedation when combined with tra-
inclusive and difficult to assess than trials evaluating dementia. zodone, priapism when combined with risperidone, and seizure
A meta-analysis of ginkgo for cognitive impairment or dementia when combined with valproic acid and phenytoin; all warrant
was performed by the Cochrane Collaboration. They reviewed 36 further pharmacokinetic studies before firm conclusions can be
randomized, double-blind, placebo-controlled trials ranging in drawn. Seizures have been reported as a toxic effect of ginkgo,
length from 3 to 52 weeks. Significant improvements in cognition most likely related to seed contamination in the leaf formulations.
and activities of daily living were observed at 12 but not 24 weeks. Uncooked ginkgo seeds are epileptogenic due to the presence of
Significant improvements in clinical global assessment however, ginkgotoxin. Ginkgo formulations should be avoided in individu-
were observed at 24 but not 12 weeks. The authors concluded als with preexisting seizure disorders.
that the effects of ginkgo in the treatment of cognitive impairment
and dementia were unpredictable and unlikely to be clinically Dosage
relevant. However, recent meta-analyses of randomized controlled
trials, 22–26 weeks in duration, using EGb761 that limited inclu- Ginkgo biloba dried leaf extract is usually standardized to contain
sion criteria to patients with dementia of the Alzheimer type (in 24% flavone glycosides and 6% terpene lactones. The daily dose
eight studies), vascular or mixed dementia type (in six studies), or most commonly studied and associated with a benefit in clinical
dementia with neuropsychiatric features (in four studies) showed trials of dementia is 240 mg daily of the dried extract in two divided
favorable results. Significant improvements in cognition and doses.
activities of daily living were observed for ginkgo compared to
placebo. Clinical global assessment of improvement also was sig-
nificantly improved when EGb761 doses of 240 mg/d were used, GINSENG
but not doses of 120 mg/d. Because of the stricter inclusion crite-
ria used, the overall methodologic quality of the studies was higher Chemistry
than that of the Cochrane review, when determining a benefit in Ginseng may be derived from any of several species of the genus
patients with dementia. This suggests that patients with a diagno- Panax. Of these, crude preparations or extracts of Panax ginseng, the
sis of dementia are more likely to benefit than patients with more Chinese or Korean variety, and P quinquefolium, the American vari-
mild cognitive impairment. In the GEM and GuidAge studies ety, are most often available to consumers in the United States. The
that included persons with normal or mild cognitive impairment, active principles appear to be the triterpenoid saponin glycosides
the effects of ginkgo as a prophylactic agent to prevent progression called ginsenosides or panaxosides, of which there are approximately
to dementia were assessed. No benefit was observed with 5–6 years 30 different types. It is recommended that commercial P ginseng
of ginkgo treatment. formulations be standardized to contain 4–10% ginsenosides.
Other plant materials are commonly sold under the name
4. Miscellaneous effects—Ginkgo has been studied for its ginseng but are not from Panax species. These include Siberian
effects in schizophrenia, tardive dyskinesia, allergic and asthmatic ginseng (Eleutherococcus senticosus) and Brazilian ginseng (Pfaffia
bronchoconstriction, short-term memory in healthy, nonde- paniculata). Of these, Siberian ginseng may be more widely avail-
mented adults, erectile dysfunction, tinnitus and hearing loss, and able in the USA. Siberian ginseng contains eleutherosides but no
macular degeneration. Preliminary data from eight randomized, ginsenosides. Currently, there is no recommended standardization
double-blind, placebo-controlled trials suggest that EGb761 can for eleutheroside content in Siberian ginseng products.
significantly reduce the symptoms of chronic schizophrenia when
used in combination with standard treatment (eg, clozapine,
haloperidol, olanzapine). These trials were conducted in China, so Pharmacologic Effects
firm conclusions about benefit in a broader population are lack- An extensive literature exists on the potential pharmacologic
ing. There is insufficient evidence to warrant clinical use for the effects of ginsenosides. Unfortunately, the studies differ widely in
other conditions listed. the species of Panax used, the ginsenosides studied, the degree of
purification applied to the extracts, the animal species studied, the
Adverse Effects doses or concentrations involved, and the measurements used to
Adverse effects of ginkgo have been reported with a frequency com- evaluate the responses. Reported beneficial pharmacologic effects
parable to that of placebo. These include nausea, headache, stomach include modulation of immune function (induced mRNA expres-
upset, diarrhea, allergy, anxiety, and insomnia. A few case reports sion for interleukins-2 and -1α, interferon-γ, and granulocyte-
noted bleeding complications in patients using ginkgo. In some of macrophage colony-stimulating factor; activated B and T cells,
these cases, the patients were also using either aspirin or warfarin. natural killer cells, and macrophages). Central nervous system
effects included increased proliferating ability of neural progeni-
Drug Interactions & Precautions tors and increased central levels of acetylcholine, serotonin, nor-
epinephrine, and dopamine in the cerebral cortex. Miscellaneous
Ginkgo may have antiplatelet properties and should not be used effects included antioxidant activity; anti-inflammatory effects
in combination with antiplatelet or anticoagulant medications. (inhibited tumor necrosis factor-α, interleukin-1β, and vascu-
Other single case reports noted virologic failure when ginkgo lar and intracellular cell adhesion molecules); antistress activity