Ginkgo biloba

Introduction

An ornamental tree & the oldest species of tree. Medicinal use has been traced back to the Chinese Materia Medica from 2800 BC. The German physician Engelbert Kaempfer was the 1st European to catalog Ginkgo in the late 17th century. It was brought to the US in 1784. Ginkgo is the most resistant of all trees to infection & pollution.

Uses

Current uses:

• symptomatic treatment of cognitive impairment* due to organic brain disease
  • Alzheimer's disease
    • no benefit in prevention of Alzheimer's disease
  • multi-infarct dementia
  • prevention of cognitive decline post ischemic stroke
• peripheral arterial disease*
• headache
• vertigo
• asthma
• tinnitus
• macular degeneration
• no memory benefit for healthy elderly*
• anxiety (GRS9); not FDA-approved

* of questionable benefit for cognitive impairment peripheral arterial disease (data conflicting)

Contraindications

Caution:

• discontinue use prior to surgery (1-2 weeks prior)
• avoid in patients with bleeding disorder
• avoid in patients with seizure disorder

Dosage

• standard extract is 24% flavonoid glycosides
  • cognitive impairment:
    • 120 to 240 mg of dry leaf extract in 2-3 doses
  • peripheral arterial disease
    • 120 to 1600 mg of dry leaf extract in 2-3 doses
  • prevention of cognitive decline post ischemic stroke 450 mg QD
• capsules 40 mg
• usual dose 40 mg TID
• range 80-240 mg/day
• gingi fluid extract 1:1, 25% alcohol: 1-2 mL TID
• start with low dose & titrate upward to avoid headache
• discontinue 36 hours before surgery

Pharmacokinetics

• at least 8 weeks of treatment for cognitive impairment
• at least 6 weeks of treatment for peripheral vascular disease
• Ginkgo probably induces CYP2C19

Adverse effects

• increase risk for bleeding
  • case reports of subarachnoid hemorrhage & hyphemas
• GI distress (common)
  • nausea
  • diarrhea
• headache (common)
  • use a low dose & titrate upward
• no data on safety during pregnancy
• no toxicity reported with leaf
• skin contact with fruit can cause a poison ivy type syndrome
• seizures (case reports); reduces seizure threshold
• anxiety; used for anxiety (GRS9)

Drug interactions

• potential interaction with anticoagulants*
  • warfarin (coumadin)
  • heparin
• potential interactions with antiplatelet agents*
  • non-steroidal anti-inflammatory agents (NSAIDs)
  • SSRI (fluoxetine)
• anticonvulsive agents
• possible interaction with drugs that lower seizure threshold
  • antipsychotics, antidepressants, cholinesterase inhibitors, decongestants, sedating antihistamines, systemic steroids, methylphenidate, fentanyl, theophylline, cyclosporine
• tricyclic antidepressants (TCA)
• trazodone (Desyrel) in combination may cause CNS depression by overstimulation of GABA receptors
• diminished levels of drugs metabolized by CYP2C19
  • ginkgo decreases omeprazole levels & probably other proton pump inhibitors
• MAO inhibitors increase effect & toxicity of ginkgo
• possible interactions with alprazolam, buspirone, efavirenz

* discontinue 36 hours before surgery

• drug interaction(s) of ginko biloba with proton pump inhibitors

Mechanism of action

• active ingredients:
  • Ginkgo flavone glycosides & heterosides
    • quercetin
    • kaempferol
    • isorhamnetine
  • terpenes
  • organic acids
  • the leaves are extracted with acetone:water, the organic solvent removed & the extract dried & processed
• membrane stabilizing
• free radical scavenger
• enhances cellular uptake & utilization of glucose & O2
• make enhance action of Na+/K+ ATPase
• vasodilation via nitric oxide & prostacyclin
• may enhance venous tone
• inhibits platelet activation, adhesion & degranulation due to direct membrane & antioxidant effects
• increased synthesis of prostacyclin
• antagonist of platelet activating factor (PAF)
• improved rheological properties of blood
• improvement of hypoxic tolerance

More general terms

• pharmaceutical herb; medicinal herb; herbal supplement