Page 1150 - Basic _ Clinical Pharmacology ( PDFDrive )

1136 SECTION X Special Topics

needed by these microbes. A Cochrane review studying the effect The active constituents in ginkgo are flavone glycosides and
of garlic on cold prevention and treatment found a significant terpenoids including ginkgolides A, B, C, and J, and bilobalide.
reduction in total number of colds using a garlic supplement
(with 180 mg allicin content) once daily for 12 weeks. Limited
conclusions can be drawn regarding the effects observed, however, Pharmacologic Effects
because only one trial met inclusion criteria. Given the availability 1. Cardiovascular effects—In animal models and some
of safe and effective prescription antimicrobials, the usefulness of human studies, ginkgo has been shown to increase blood flow,
garlic in this area appears limited. reduce blood viscosity, and promote vasodilation, thus enhanc-
ing tissue perfusion. Enhancement of endogenous nitric oxide
4. Antineoplastic effects—In rodent studies, garlic inhibits effects (see Chapter 19) and antagonism of platelet-activating
procarcinogens for colon, esophageal, lung, breast, and stomach factor have been observed in animal models.
cancer, possibly by detoxification of carcinogens and reduced Ginkgo biloba has been studied for its effects on mild to
carcinogen activation. Several epidemiologic case-control studies moderate occlusive peripheral arterial disease. Among 11 random-
demonstrate a reduced incidence of stomach, esophageal, and ized, placebo-controlled studies involving 477 participants using
colorectal cancers in persons with high dietary garlic consump- standardized ginkgo leaf extract (EGb761) for up to 6 months, a
tion. Current anticancer studies are focused on specific organosul- nonsignificant trend toward improvements in pain-free walking
fur garlic compounds in in vivo animal models of cancer and in distance (increase of 64.5 meters) was observed (P = .06). The
vitro effects on human cancer cell lines.
authors concluded that the standardized extract lacked benefit for
this indication.
Adverse Effects The Ginkgo Evaluation of Memory (GEM) study and the
recently published GuidAge study evaluated cardiovascular out-
Following oral ingestion, adverse effects of garlic products may
include nausea (6%), hypotension (1.3%), allergy (1.1%), and comes as well as incidence and mean time to Alzheimer’s demen-
bleeding (rare). Breath and body odor have been reported with an tia associated with the long-term use of ginkgo for 5–6 years
incidence of 20–40% at recommended doses using enteric-coated in approximately 3000 elderly (age ≥70) adults with normal
powdered garlic formulations. Contact dermatitis may occur with cognition or mild cognitive impairment. Daily use of 240 mg/d
the handling of raw garlic. EGb761 did not affect the incidence of hypertension or reduce
blood pressure among persons with hypertension or prehyperten-
sion. No significant effects in cardiovascular disease mortality,
Drug Interactions & Precautions ischemic stroke or events, or hemorrhagic stroke were observed.
Because of reported antiplatelet effects, patients using anticlotting
medications (eg, warfarin, aspirin, ibuprofen) should use garlic 2. Metabolic effects—Antioxidant and radical-scavenging prop-
cautiously. Additional monitoring of blood pressure and signs erties have been observed for the flavonoid fraction of ginkgo as
and symptoms of bleeding is warranted. Garlic may reduce the well as some of the terpene constituents. In vitro, ginkgo has been
bioavailability of saquinavir, an antiviral protease inhibitor, but it reported to have superoxide dismutase-like activity and superoxide
does not appear to affect the bioavailability of ritonavir. anion- and hydroxyl radical-scavenging properties. The flavonoid
fraction has also been observed to have antiapoptotic properties.
In some studies, it has also demonstrated a protective effect in lim-
Dosage iting free radical formation in animal models of ischemic injury

Dried, powdered garlic products should be standardized to and in reducing markers of oxidative stress in patients undergoing
contain 1.3% alliin (the allicin precursor) or have an allicin- coronary artery bypass surgery.
generating potential of 0.6%. Enteric-coated formulations are
recommended to minimize degradation of the active substances. 3. Central nervous system effects—In aged animal models,
A daily dose of 600–900 mg/d of powdered garlic is most com- chronic administration of ginkgo for 3–4 weeks led to modifica-
mon. This is equivalent to one clove of raw garlic (2–4 g) per day. tions in central nervous system receptors and neurotransmitters.
A garlic bulb can contain up to 1.8% alliin. Doses of AGE most Receptor densities increased for muscarinic, α 2 , and 5-HT recep-
1a
often range from 600 to 1800 mg/d, but doses up to 7200 mg tors, and decreased for β adrenoceptors. Increased serum levels of
daily have been safely used in clinical trials for up to 6 months. acetylcholine and norepinephrine and enhanced synaptosomal
reuptake of serotonin and dopamine have also been reported.
Additional possible effects include inhibition of amyloid-beta
GINKGO (GINKGO BILOBA) fibril formation and protective effects of Egb761 on hippocampal
neurons against cell death induced by beta-amyloid.
Ginkgo has been used to treat cerebral insufficiency and
Chemistry dementia of the Alzheimer type. The term cerebral insufficiency,

Ginkgo biloba extract is prepared from the leaves of the ginkgo however, includes a variety of manifestations ranging from poor
tree. The most common formulation is prepared by concentrat- concentration and confusion to anxiety and depression as well as
ing 50 parts of the crude leaf to prepare one part of extract. physical complaints such as hearing loss and headache. For this