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An     herbal   overdose

11/12/2015

1 Comment

 
36 year old male with PMHx of IDDM and depression was prescribed a new drug by his psychiatrist for psychogenic erectile dysfunction. He presented to the hospital 16 hours after taking 350mg of this drug. He was drowsy and confused on presentation with a BP of 130/80 and HR of 150 with atrial fibrillation, which he had no history of. He was having rigors and retrosternal pain. He had no other co-ingestions. His rectal temperature was 35.5C. He was well-perfused peripherally. His laboratory studies were otherwise unremarkable. He was admitted for altered mental status and for new atrial fibrillation, which spontaneously resolved within 24 hours.
Picture

  • Yohimbe extract is an indole alkaloid derived from the bark of a West African evergreen (Pausinystalia yohimbe) - Active ingredient is yohimbine
  • Grows primarily in west Africa and Congo
  • Past studies show possible usefulness in vascular, diabetic and psychogenic impotence[1] 
  • ‘Street uses’ include as an aphrodisiac, hallucinogen, and dietary supplement (to be used for “fast weight-loss” and “body-building supplementation”).
  • Available by prescription (Yocon, Aphrodyne, Testomar) or over the counter


Pharmacology/Uses:
  • Predominantly alpha-2-antagonist - Increases release of norepinephrine and dopamine by blocking the pre and post-synaptic alpha-2-adrenoceptors, therefore acting as a CNS stimulant
  • Effects are somewhat opposite of clonidine (alpha-2-agonist) & can be synergistic with co-ingestants (e.g. caffeine). 
  • Also has moderate affinity to alpha-1-adrenoceptors
  • Use in dieting/bodybuilding: Promotes sympathetic activity by central and peripheral mechanisms; therefore, administration prior to exercise boosts lipolysis and serum FFA levels[6].


Use in erectile dysfunction: 
  • FDA-approved drug as of 1995 for treatment of impotence.
  • Previously widely used in veterinary medicine for treatment of impotent breeding stallions
  • Alpha-2 adrenoceptors mediate erection-inhibiting impulses in CNS
  • Also believed to enhance central sexual impulse by blocking the alpha-2-adrenoceptors in the locus ceruleus in the brain[8].
  • Also shown to have relaxant effect on corpus cavernosum/increase in NO content in dose-dependent manner in rats, however, more recent studies in rabbits did not show benefit from yohimbine.
  • Meta-analysis in 1998 of seven clinical trials did show superiority over placebo for treatment of ED, however, not used routinely in urological practices.
  • Recommended dosing is 16mg a day taken in 3 divided doses, suggested treatment period is no longer than 10 weeks. [10]


Pharmacokinetics:
  • Rapidly absorbed and maximum plasma concentrations are achieved in less than 1 hour of oral administration. Metabolized by liver and kidneys. Crosses blood-brain barrier.
  • Average oral dose of 5-15mg produces a therapeutic whole blood level range of 40-400 ng/mL
  • Plasma half-life of roughly 35 minutes[2], however, latency in response of about 2-3 weeks after initiation of treatment of erectile dysfunction.
  • Overdoses leading to neurotoxic effects seen up to 5,000 ng/mL
  • Case report of 37-year-old bodybuilder who ingested 5000mg of yohimbine during a competition and presented with malaise, vomiting, and repeated seizures secondary to it’s neurotoxic effects in acute ingestion.


Clinical toxicity:
  • Nausea, GI irritation, agitation, anxiety, hypertension, diaphoresis, mydriasis, priapism[9] and bronchospasm due to central adrenergic activity.
  • Symptoms begin to show around 20-30mg yohimbine. LD50 is around 40mg/kg.
  • MAOi effect
  • Contraindicated in hypotension, diabetes, heart/liver/kidney disease and schizophrenia
  • Case report of atrial fibrillation secondary to severe toxicity, likely due to noradrenergic blockade in CNS [4].
  • Thought to cause peripheral alpha-1-blockade at higher doses, leading to peripheral vasodilation and hypothermia[3, 4].


Treatment:
  • Supportive care and benzodiazepines as needed
  • Clonidine can be used to treat yohimbine-associated hypertension[5].

References
  1. Morales et al. The effectiveness of yohimbine in the treatment of organic impotence J Urol 1987
  2. Owen et al. The pharmacokinetics of yohimbine in man. Eur J Clin Pharmcol 1987
  3. Starke K et al. Preferential blockade of presynaptic alpha receptors by yohimbine. Eur J Pharmacol 1975.
  4. Varkey S. Overdose of Yohimbine. BMJ 1992.
  5. Anderson C et al. Case Study: Two fatal case reports of acute yohimbine intoxication. J Anal Toxicol 2013.
  6. McCarty MF. Pre-exercise administration of yohimbine may enhance the efficacy of exercise training as a fat loss strategy by boosting lipolysis. Med Hypotheses 2002.
  7. Saad MA et al. Potential effects of yohimbine and sildenafil on erectile dysfunction in rats. Eur J Pharmacol 2013.
  8. Corazza O et al. Sexual Enhancement Products for Sale Online: Raising Awareness of the Psychoactive Effects of Yohimbine, Maca, Horny Goat Weed, and Ginkgo biloba. BioMed Research Intl 2014.
  9. Myers A et al. Refractory Priapism Associated with Ingestion of Yohimbe Extract. J Med Toxicol 2009.
  10. FDA guidelines on yohimbe bark extract / yohimbine

Other sources used include Goldfrank’s 10th edition, Haddad’s 3rd edition, and The Poison Review (www.thepoisonreview.com)
​
Authored by: Dr. Michael Mollo M.D.
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