Page 1152 - Basic _ Clinical Pharmacology ( PDFDrive )

1138 SECTION X Special Topics

(ie, stimulated pituitary-adrenocortical system, agonist at glu- have been reported in patients using high doses (>3 g/d) of
cocorticoid receptor); analgesia (inhibited substance P); vaso- P ginseng. Methylxanthines found in the ginseng plant may con-
regulatory effects (increased endothelial nitric oxide, inhibited tribute to this effect. Vasoregulatory effects have not been found
prostacyclin production); cardioprotective activity (reduced ven- to be clinically significant.
tricular remodeling and cardiac hypertrophy in animal models
of myocardial ischemia); antiplatelet activity; improved glucose Drug Interactions & Precautions
homeostasis (reduced cell death in pancreatic beta cells; increased
insulin release, number of insulin receptors, and insulin sensi- Irritability, sleeplessness, and manic behavior have been reported
tivity); and anticancer properties (reduced tumor angiogenesis, in psychiatric patients using ginseng in combination with other
increased tumor cell apoptosis). Such extensive claims naturally medications (phenelzine, lithium, neuroleptics). Ginseng should
evoke skepticism and require careful replication. be used cautiously in patients taking any psychiatric, estrogenic,
or hypoglycemic medications. Ginseng has antiplatelet properties
Clinical Trials and should not be used in combination with warfarin. Cytokine
stimulation has been claimed for both P ginseng and P quinque-
Ginseng is most often claimed to help improve physical and men- folium in vitro and in animal models. In a randomized, double-
tal performance or to function as an “adaptogen,” an agent that blind, placebo-controlled study, P ginseng significantly increased
helps the body to return to normal when exposed to stressful or natural killer cell activity versus placebo with 8 and 12 weeks
noxious stimuli. However, the clinical trials evaluating ginseng for of use. Immunocompromised individuals, those taking immune
these indications have shown few, if any, benefits. Some random- stimulants, and those with autoimmune disorders should use
ized controlled trials evaluating “quality of life” and “cognition” ginseng products with caution.
have claimed significant benefits in some subscale measures of
behavior, cognitive function, or quality of life but rarely in overall Dosage
composite scores using P ginseng. Better results have been observed
with P quinquefolium and P ginseng in lowering postprandial A dose of 1–2 g/d of the crude P ginseng root or its equivalent is
glucose indices in subjects with and without diabetes. This was considered standard dosage. Two hundred milligrams of standard-
the subject of a systematic review in which 15 studies (13 random- ized P ginseng extract are equivalent to 1 g of the crude root. The
ized and 2 nonrandomized) were evaluated. Nine of the studies trademarked preparation Ginsana has been used as a standardized
reported significant reductions in blood glucose. Some random- extract in some clinical trials and is available in the USA.
ized, placebo-controlled trials have reported immunomodulating
benefits of P quinquefolium and P ginseng in preventing upper MILK THISTLE (SILYBUM MARIANUM)
respiratory tract infections. Use of ginseng for 2–4 months in
healthy seniors may reduce the risk of acquiring the common cold Chemistry
as well as the duration of symptoms. Because of heterogeneity
in these trials, however, the findings are insufficient to warrant a The fruit and seeds of the milk thistle plant contain a lipophilic
recommendation of ginseng for cold prevention. To assess effects mixture of flavonolignans known as silymarin. Silymarin comprises
on cardiovascular health, a systematic review and meta-analysis 2–3% of the dried herb and is composed of three primary isomers:
of 17 randomized controlled trials involving predominantly silybin (also known as silybinin or silibinin), silychristin (sili-
P ginseng (12 studies) and P quinquefolium (5 studies) species in christin), and silydianin (silidianin). Silybin is the most prevalent
persons with and without hypertension was performed. Over a and potent of the three isomers and accounts for 50–70% of the
mean time period of 9 weeks, no significant effect was observed silymarin complex. Products should be standardized to contain
of ginseng on SBP, DBP, and mean arterial pressure compared 70–80% silymarin.
with controls. Finally, two case-control studies and a cohort study
suggest a non-organ-specific cancer-preventive effect with long- Pharmacologic Effects
term administration of P ginseng. Significant benefits in some 1. Liver disease—In animal models, milk thistle purportedly
cancer-related fatigue symptoms have been observed in both a limits hepatic injury associated with a variety of toxins, including
dose-finding study and a multisite, double-blind, randomized trial Amanita mushrooms, galactosamine, carbon tetrachloride, acet-
using P quinquefolium, 2 g daily, versus placebo over a 2-month aminophen, radiation, cold ischemia, and ethanol. In vitro studies
period. In summary, the strongest support for use of P ginseng or and some in vivo studies indicate that silymarin reduces lipid per-
P quinquefolium currently relates to its effects in cold prevention, oxidation, scavenges free radicals, and enhances glutathione and
lowering postprandial glucose, nonspecific cancer prevention, and superoxide dismutase levels. This may contribute to membrane
alleviating cancer-related fatigue.
stabilization and reduce toxin entry.
Milk thistle appears to have anti-inflammatory properties. In
Adverse Effects vitro, silybin strongly and noncompetitively inhibits lipoxygenase

Vaginal bleeding and mastalgia have been described in case activity and reduces leukotriene formation. Inhibition of leukocyte
reports, suggesting possible estrogenic effects. Central nervous migration has been observed in vivo and may be a factor when
system stimulation (eg, insomnia, nervousness) and hypertension acute inflammation is present. Silymarin inhibits nuclear factor