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, subdural 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)
    • increases risk of bleeding independent of INR
  • 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; botanical