HERBAL SUPPLEMENT & MARIJUANA USE PRE- & POST-TRANSPLANT - - PowerPoint PPT Presentation

HERBAL SUPPLEMENT & MARIJUANA USE PRE- & POST-TRANSPLANT

Mariesa Cote, PharmD Clinical Pharmacist – Solid Organ Transplant Massachusetts General Hospital October 4th, 2018

STATEMENT OF DISCLOSURE

• I have no conflicts of interest

OBJECTIVES

• Identify the risks associated with herbal supplement use pre-transplant
• Identify major drug interactions with herbal supplements
• Explain the risks of marijuana use post-transplant

ALTERNATIVE MEDICINE

• Form of medical therapy used as a substitute for conventional medicine
• Naturopathic medicine
• Homeopathic medicine
• Chinese medicine
• Aromatherapy
• Massage therapy
• Use of a special diet or herbal remedy to cure or alleviate the symptoms
• f a condition

Kaye, et al. Anesthesiology Clin Am. 2004

HISTORY OF HERBAL THERAPY

• Ancient middle-eastern civilizations used herbal therapy extensively
• Herbal gardens were created to grow medicinal plants for medical schools
• Early colonial days relied on herbal therapy to provide medical care in

the home

• Herbal therapy re-emerged in the U.S. in the 1960s
• The Office of Alternative Medicines by the National Institutes of

Health was established in 1992

Kaye, et al. Anesthesiology Clin Am. 2004

REGULATIONS

• Dietary Supplement Health and Education Act (DSHEA) of 1994
• Defines dietary supplements as “a product to supplement the diet”
• Considered food, not drugs
• No requirements for safety & efficacy testing
• Food and Drug Administration (FDA)
• Included in the “supplement” category, not classified as a drug
• Manufacturers exempt from approval by FDA
• No protocol for standardization of these herbal supplements
• Lack of standard regulations and good manufacturing practice (GMP) leads

to products available of variable quality and content

Kaye, et al. Anesthesiology Clin Am. 2004 Gabardi S, et al. Clin J Am Soc Nephrol. 2007. Ang-Lee MK, et al. JAMA. 2001.

DIETARY SUPPLEMENTS Vitamins Minerals Herbs Amino acids Enzymes Organ tissues Metabolites

Kaye, et al. Anesthesiology Clin Am. 2004

FORMULATIONS

Extracts Concentrates Tablets Capsules Gelcaps Liquids Powders Oils

Kaye, et al. Anesthesiology Clin Am. 2004

HERBAL THERAPY & DIETARY SUPPLEMENTS

• There are >20,000 nutraceuticals available in the United States
• Approximately 36% of the population use nutraceuticals in conjunction

with prescription drugs

• Majority of patients report utilizing these products to “cure” chronic

conditions

• Misconception that these products are “natural” so they must be safe
• Only 12% of supplement users seek care from a physician or licensed

complementary and alternative medicine provider

Kaye, et al. Anesthesiology Clin Am. 2004 Gabardi S, et al. Clin J Am Soc Nephrol. 2007.

HERBAL THERAPY & DIETARY SUPPLEMENTS

• 70% of patients failed to disclose their herbal supplement use
• Rationale:
• Thoughts that physicians are not knowledgeable about herbal supplements
• Patient’s fear admitting to providers their use of non-standard therapy
• Thoughts that herbal supplement use is unrelated to their medical care
• Herbal supplements not considered medications that require reporting

Providers should seek out a history of herbal supplement use!

Ang-Lee MK, et al. JAMA. 2001

TOP 10 BEST SELLING HERBAL PRODUCTS

Cranberry Saw palmetto Soy Garlic Gingko Echinacea Milk Thistle Black cohosh

• St. John's Wort

Ginseng

https://www.takingcharge.csh.umn.edu/explore-healing-practices/botanical-medicine/10-top-best-selling-botanicals-what-they-do

PERI-OPERATIVE USE

SURGICAL CONCERNS

• Applicable to both organ donors and recipients
• Decreased platelet aggregation or inhibition of clotting  Bleeding
• Central nervous system (CNS) depression  Potentiation of

anesthesia

• American Society of Anesthesiologists recommends that patients

discontinue use of herbal supplements 2-3 weeks before surgery

Kaye, et al. Anesthesiology Clin Am. 2004

BLEEDING RISK

Herbal Indication Perioperative considerations Recommendation

Garlic (Allium sativum) Vasodilatory effect ↓cholesterol ↑ bleeding risk through platelet dysfunction & ↑ fibrinolytic activity D/C 7 days prior to surgery Ginger (Zingiber

• ffcinale)

N/V, motion sickness, vertigo Potent inhibitor of thromboxane; ↑ bleeding risk D/C 14 days prior to surgery Avoid w/ use of antiplatelets, anticoagulants & NSAIDs Gingko biloba Antioxidant, circulatory stimulant, dementia Inhibits platelet activating factor; ↑ bleeding risk; gingko toxin D/C 2 days prior to surgery Avoid w/ use of antiplatelets, anticoagulants & NSAIDs Avoid with anticonvulsants

Kaye, et al. Anesthesiology Clin Am. 2004 Wong A, et al. Continuing Education in Anaesthesia, Critical Care & Pain. 2011

BLEEDING RISK

Herbal Indication Perioperative considerations Recommendation

Ginseng Mood enhancer, Immunomodulation, Hypoglycemic activity Irreversible platelet inhibition  ↑bleeding ↓blood glucose ↑blood pressure D/C 7 days prior to surgery Avoid w/ use of antiplatelets, anticoagulants & NSAIDs Turmeric Anti-infective, analgesic, anti- inflammatory and anti-

• xidant effects

Antiplatelet effects D/C 14 days prior to surgery

Kaye, et al. Anesthesiology Clin Am. 2004 Wong A, et al. Continuing Education in Anaesthesia, Critical Care & Pain. 2011 Natural Medicines Database

DRUG-DRUG INTERACTIONS

Herbal Indication Perioperative considerations Recommendation

• St. John’s

Wort (Hypericum perforatum) Antidepressant Inducer of CYP3A4 & 2C9 Sedative effects D/C 5 days prior to surgery Drug interactions! Echinacea Immunostimulatory properties Potential for anaphylaxis Inhibits CYP3A4 D/C 14 days prior to surgery Drug interactions!

Kaye, et al. Anesthesiology Clin Am. 2004 Wong A, et al. Continuing Education in Anaesthesia, Critical Care & Pain. 2011

SEDATIVE EFFECTS

Herbal Indication Perioperative Complications Recommendation

Kava kava (Piper methysticum) Anxiolytic/sedative Potentiation of the effects of anesthesia/sedatives D/C 24 hours prior to surgery Valerian Anxiolytic/sedative Potentiation of the effects of anesthesia/sedatives D/C 2 weeks prior to surgery Melatonin Sedative Potentiation of the effects of anesthesia/sedatives No general consensus for when to D/C - recommend D/C 7-14 days prior to surgery

Kaye, et al. Anesthesiology Clin Am. 2004 Wong A, et al. Continuing Education in Anaesthesia, Critical Care & Pain. 2011 Natural Medicines Database

RECOMMENDATION

• Providers should seek out a history of herbal supplement use
• Patients utilizing herbal supplements can be referred to pharmacy for

consult

• All herbal supplements should be held at least 2 weeks prior to

surgery

POST-TRANSPLANT USE

POST-TRANSPLANT CONSIDERATIONS

• Modulation of the immune system through “boosting” of the immune

system

• Drug-drug interactions through alterations in cytochrome P450

metabolism and P-glycoprotein (P-gp) transporter function

• Direct toxic effects on the transplanted organ

IMMUNOMODULATION

Herbal Indication Post-Transplant Concerns Recommendation

Ginseng Mood enhancer, Immunomodulation, Hypoglycemic activity Stimulates the immune function by increasing T cell proliferation that may interfere with immunosuppressive therapy. AVOID Echinacea Immunostimulatory properties Stimulates immune function through activation of complement pathway increasing activity of T cells potentially interfering immunosuppressive therapy AVOID Melatonin Sedative Stimulates immune function through secretion of cytokines potentially interfering immunosuppressive therapy Case reports of autoimmune hepatitis AVOID

Kaye, et al. Anesthesiology Clin Am. 2004 Wong A, et al. Continuing Education in Anaesthesia, Critical Care & Pain. 2011 Natural Medicines Database Kang S, et al. J Ginseng Res. 2012. Carrillo-Vico A, et alInternational Journal of Molecular Sciences. 2013.

DRUG-DRUG INTERACTIONS

Herbal Indication Post-Transplant Concerns Recommendation

• St. John’s Wort

(Hypericum perforatum) Antidepressant Inducer of CYP3A4 & 2C9 Sedative effects AVOID Drug interactions! ↓immunosuppression levels  rejection Echinacea Immunostimulatory properties Inhibits CYP3A4 AVOID Drug interactions! ↑immunosuppression levels  toxicity Turmeric Anti-infective, analgesic, anti-inflammatory and anti-oxidant effects Inhibits CYP3A4 AVOID ↑immunosuppression levels  toxicity

Kaye, et al. Anesthesiology Clin Am. 2004 Wong A, et al. Continuing Education in Anaesthesia, Critical Care & Pain. 2011 Natural Medicines Database

FRUIT JUICES

Fruit Juice Post-Transplant Concerns Recommendation

Pomegranate Case report of elevated tacrolimus levels in a heart transplant patient consuming 1-2 pomegranate popsicles per day (51g each) CAUTION – may result in increased tacrolimus levels Clementine Case report of elevated tacrolimus levels in a renal transplant patient consuming >1 kg/day of clementines; tacrolimus levels returned to normal with discontinuation Recommend use in moderation Grapefruit Case report of elevated tacrolimus levels in a liver transplant patient consuming 250ml of grapefruit juice four times per day for 3 days CAUTION – effect on tacrolimus level was delayed, peaking ~1 week after grapefruit ingestion Cranberry No significant difference in cyclosporine levels when 1 glass of cranberry juice consumed. Recommend use in moderation

Khuu T, et al. The Journal of Heart and Lung Transplantation 2013. Theile D, et al. European Journal of Pharmaceutical Sciences. 2017. Julie G, et al. Clinical Pharmacology & Therapeutics. 2006. Fukatsu S et al. Drug Metabolism and Pharmacokinetics. 2006.

HEPATOTOXIC DIETARY SUPPLEMENTS

• Bee pollen
• Birch oil
• Blessed thistle
• Borage
• Butterbur
• Cascara Sagrada
• Celandine
• Chaparral
• DHEA
• Echinacea
• Ephedra
• Green tea
• Kava
• Mistletoe
• Periwinkle
• Sassafras
• Turmeric
• Valerian
• Vitamin E

Gabardi S, et al. Clin J Am Soc Nephrol. 2007.

HEPATOTOXIC DIETARY SUPPLEMENTS

• Echinacea
• Used as an immunostimulant to fight a variety of infections
• Multiple case reports of acute cholestatic hepatitis
• Consumption of echinacea root extract 600mg-1500mg daily for 5-14 days
• Green Tea
• Polyphenols are thought to be associated with the anti-oxidant properties of

green tea

• Data in animals showing acute tubular necrosis & hepatotoxicity with green

tea supplement use

Natural Medicines Database Gabardi S, et al. Clin J Am Soc Nephrol. 2007.

HEPATOTOXIC DIETARY SUPPLEMENTS

• Valerian
• Used to manage insomnia and restlessness
• Multiple case reports of hepatotoxicity with a variety of doses utilized
• Long-term effect of valerian on liver function is unknown
• Vitamin E
• Used for cancer prevention and wound healing
• Immunostimulatory properties are undesirable post-transplant
• Deleterious effects seen in patients taking more than 1000mg per day

Natural Medicines Database Gabardi S, et al. Clin J Am Soc Nephrol. 2007. Neff GW, et al. Liver Transpl. 2004.

HEPATOTOXIC DIETARY SUPPLEMENTS

• Turmeric
• Multiple case reports of autoimmune hepatitis in a patients taking turmeric

dietary supplements

• LFT abnormalities resolved with discontinuation of supplements
• Ramelteon/Melatonin
• Case reports of autoimmune hepatitis
• Immunostimulatory effects of melatonin through T
• cell and B-cell

modulation, potentiating autoimmune hepatitis

Funk J, et al. The FASEB Journal. 2017 Lulefahr AL, et al. BMF Case Reports. 2018. Fourman LT, et al. J Clin Gastroenterol. 2013. Hong YG, et al. J Clin Gastroenterol. 1997.

NEPHROTOXIC DIETARY SUPPLEMENTS

Direct Nephrotoxicity

• Chromium
• Creatine
• L-Lysine
• Yohimbe
• Willow Bark
• Cat's Claw
• Turmeric
• Ginger
• Green

T ea Nephrolithiasis

• Vitamin C
• Ephedra
• Cranberry

Rhabdomyolysis

• Wormwood Oil
• Creatine
• Licorice
• Red

Yeast Rice

Gabardi S, et al. Clin J Am Soc Nephrol. 2007.

NEPHROTOXIC DIETARY SUPPLEMENTS

• Chromium
• Used for weight loss, glucose control and hyperlipidemia
• Multiple case reports of ATN related to chromium use
• Amount consumed varied from 600mcg/day to 2400mcg/day for 2 weeks to 6 months
• Creatine
• Used for muscle enhancement or “body building”
• T

wo case reports of ATN & 5 cases of rhabdomyolysis following creatine use

• One patient ingested 5g/day for 4 weeks and the second ingested 15g/day for 1 week

followed by 2g/day for 12 weeks

• After stopping creatine, serum creatinine normalized

Gabardi S, et al. Clin J Am Soc Nephrol. 2007.

NEPHROTOXIC DIETARY SUPPLEMENTS

• L-Lysine
• Used to promote wound healing/treat oral ulcers/cold sores
• Reported to cause Fanconi Syndrome and tubulointerstitial nephritis
• Single case report of patient consuming 3000mg/day for 5 years
• Ginger
• Theoretical risk based on known mechanisms
• Used to treat inflammation and inhibit cyclooxygenase (COX)
• Inhibition of prostaglandins leading to vasoconstriction & renal failure

Gabardi S, et al. Clin J Am Soc Nephrol. 2007.

NEPHROTOXIC DIETARY SUPPLEMENTS

• Turmeric
• Theoretical risk based on known mechanisms
• Used to treat inflammation and inhibit cyclooxygenase (COX)
• Inhibition of prostaglandins leading to vasoconstriction & renal failure
• Green Tea
• Polyphenols are thought to be associated with the anti-oxidant properties of

green tea

• Data in animals showing acute tubular necrosis & hepatotoxicity with green

tea supplement use

Gabardi S, et al. Clin J Am Soc Nephrol. 2007. Lambet JD, et al. Chem Res Toxicol. 2007.

NEPHROTOXIC DIETARY SUPPLEMENTS

• Vitamin C
• Used to promote wound healing & prevent cancer and heart disease
• Metabolized to oxalate leading nephrolithiasis secondary to oxaluria
• Immunostimulatory properties are undesirable post-transplant
• Seen in patients utilizing 60g/day of

Vitamin C

• Cranberry
• Used to acidify the urine and prevent urinary tract infections
• Contains oxalate leading to nephrolithiasis secondary to oxaluria
• Case reports of nephrolithiasis following administration of cranberry

concentrate tablets and >1L of juice per day

Gabardi S, et al. Clin J Am Soc Nephrol. 2007.

NEPHROTOXIC DIETARY SUPPLEMENTS

• Licorice
• Potent diuretic associated with severe hypokalemia
• FDA Warning in October 2017 regarding risk of arrhythmia associated with

black licorice use

• Age 40 or older and consuming 2 ounces per day for at least two weeks

Gabardi S, et al. Clin J Am Soc Nephrol. 2007. https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm277152.htm

RESOURCES

• Natural Medicines

https://naturalmedicines- therapeuticresearch- com.ezproxymcp.flo.org/

• National Center for

Complementary and Integrative Health https://nccih.nih.gov/

MARIJUANA USE

MARIJUANA

• Extract of Cannabis sativa (Indian hemp)

plant

• Classified as a Schedule 1 containing

substances with high abuse potential

• Consists of 60 pharmacologically active

cannabinoids

• Two most described cannabinoids are

delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD)

Oberbarnscheidt, T. J Addict Res Ther. 2016.

MECHANISM OF ACTION

• Cannabinoid receptors are present in the brain and spinal cord
• CB1 receptors are primarily in the nervous system
• Antagonism of these receptors leads to mental & behavioral effects
• Alters perceptions & mood, affects memory and learning
• Leads to impaired judgement
• CB2 receptors primarily in the periphery on cells in the immune

system

• Possible immunosuppressive activity of cannabis
• Inhibition of neurotransmitter release (acetylcholine & glutamate)

Oberbarnscheidt, T. J Addict Res Ther. 2016.

MECHANISM OF ACTION

• CBD does not have psychoactive

effects & appears to block the effects

• f THC through antagonism at the

CBD receptor

• Marijuana has become significantly

more potent

• Newer forms of marijuana available

with higher THC content

Oberbarnscheidt, T. J Addict Res Ther. 2016. ElSohly MA, et al. Biol Psychiatry. 2016.

FORMULATIONS

• Natural Form
• Consists of THC & CBD
• Active component is THC which is sought after for psychoactive effects
• Marijuana or “Medical Marijuana”

Oberbarnscheidt, T. J Addict Res Ther. 2016.

FORMULATIONS

• Synthetic Forms
• Consist of THC
• Two FDA-approved forms: Marinol (Dronabinol) & Cesamet (Nabilone)
• Street Forms: K2, Spice, Joker, Black Mamba, Kush, and Kronic

Oberbarnscheidt, T. J Addict Res Ther. 2016. Synthetic Cannabinoids. NIDA. 2018.

FORMULATIONS

Marinol (dronabinol) Cesamet (nabilone) Schedule CIII substance CII substance Indication Indicated for the treatment of:

• Anorexia in AIDS patients
• N/V associated with cancer

chemotherapy Indicated for the treatment of:

• N/V associated with cancer

chemotherapy Dosing Initial dose: 2.5mg BID Initial dose: 1-2mg BID, 1-3 hours prior to chemotherapy Adverse Effects May cause psychiatric and cognitive effects and impair mentation May cause psychiatric and cognitive effects and impair mentation Dose adjustment None May increase LFTs (≤1%) None Drug Interactions Substrate of 2C9 & 3A4 **Cyclosporine/Tacrolimus None

• Marinol. FDA. 2017.
• Cesamet. FDA. 2013.

FORMULATIONS

• Semi-Synthetic Forms
• Combination of THC & CBD
• Sativex (Nabiximols) – Not available in U.S.

Oberbarnscheidt, T. J Addict Res Ther. 2016.

FORMULATIONS

• Epidiolex (cannabidiol) was approved

by the FDA in June 2018

• CBD oral solution for management of

Lennox-Gastaut syndrome and Dravet syndrome

• Three randomized, controlled trials

showed significantly greater reductions in seizure activity compared to placebo

• Mild increases in liver transaminases

were noted but raising the possibility

• f more severe injury

https://www.thecannabist.co/2018/04/18/gw-pharmaceuticals-epidiolex-cbd-justin-grover/103667/ Epidiolex (Cannabidiol) in Treatment Resisntant Epilepsy.

PHARMACOKINETICS - ABSORPTION

Route Absorption Peak Concentration Bioavailability Inhalation/smoking Rapid drug delivery to the brain 22 min Varies, 2-56% Oral Slow 1-2hr but can be delayed to 8hr 10-20% Sublingual Fast 30 min 10-20% Rectal Fast 15min 20-40% Transdermal Slow 2hr; maintained for 48hr 10%

Oberbarnscheidt, T. J Addict Res Ther. 2016.

PHARMACOKINETICS - DISTRIBUTION

• Highly lipophilic which allows it to be easily taken up into the tissues
• THC and metabolites are formed with prolonged exposure, allowing for

accumulation of these substances in tissues

• Half-life varies based on frequency of use
• Infrequent users: 1.3 days
• Frequent users: 5-13 days
• THC has a large volume of distribution (Vd) with slow elimination from

the body

• Crosses the placenta & accumulates in breast milk

Oberbarnscheidt, T. J Addict Res Ther. 2016.

PHARMACOKINETICS - METABOLISM

• THC is metabolized in the liver by hydroxylation and oxidation by

CYP450 enzymes

• CYP2C9, 2C19, 3A4
• Certain metabolizing enzymes are decreased in cirrhosis
• CYP1A and CYP3A are reduced
• CYP2C, 2A and 2B are unaltered
• Equipotent active metabolite of THC is 11-OH-THC
• Possible extra-hepatic sites in the brain, intestine and lung

Oberbarnscheidt, T. J Addict Res Ther. 2016. Elbekai RH, er al. Curr Drug Metab. 2004.

PHARMACOKINETICS - ELIMINATION

• Rate of excretion varies based on gender
• Women - clearance rate: 11.8 ±3 L/hr
• Men - clearance rate: 14.9 ±3.7 L/hr
• 65% feces; 20% urine

Oberbarnscheidt, T. J Addict Res Ther. 2016.

USE PRE-TRANSPLANT

USE PRE-TRANSPLANT

• Over 25 states have legalized medical marijuana with another 4 states

legalizing recreational use

• Marijuana use has been considered a relative contraindication to

transplant listing in some centers

• Transplant guidelines do not provide a recommendation regarding

marijuana use pre-transplant

• There are 7 states with current laws that prohibit transplant centers

from denying transplant listing based solely on a patient’s use of medical marijuana

Allen LA, et al. Circ Heart Fail. 2016.

CURRENT LAWS

• Current legislature includes the following statement regarding

marijuana use and transplant listing:

• “For the purposes of medical care, including organ transplants, a registered

qualifying patient's authorized use of cannabis in accordance with this Act is considered the equivalent of the authorized use of any other medication used at the direction of a physician, and may not constitute the use of an illicit substance or otherwise disqualify a qualifying patient from needed medical care.”

• Wash. Rev. Code. § 69.51A.110 (2011). 410 Ill. Comp. Stat. § 130/40(a)(2) (2015).
• Del. Code. Ann. tit. 16, § 4905A(a)(2) (2015). Ariz. Rev. Stat. § 36–2813(c) (2015).

R.I. Gen. Laws § 21-28.6-4(p) (2015). N.H. Rev. Stat. Ann. § 126-X:2VII (2013).

• Minn. Stat. § 152.32(b) (2014).

AB 258 (Act to add Cal. Health & Safety Code Section 7151.36) Feb. 9, 2015

CONCERNS POST-TRANSPLANT

1. Infection risk 2. Bleeding risk 3. Drug interactions 4. Cannabinoid Hyperemesis Syndrome 5. Impaired cognition 6. Cardiovascular effects 7. Abuse/Addiction potential

INFECTION

• Aspergillus species found in soil, air and vegetable matter, including

tobacco

• Marijuana smoking may subject immunocompromised patients to

serious & lethal opportunistic fungal infections

• Multiple case reports and at least 2 cases at BIDMC of invasive fungal

infections related to smoking marijuana

Hamadeh R, et al. CHEST. 1988 Marks WH, et al. Transplantation. 1996.

INFECTION

• Use of a water pipe has been

associated with severe infection

• Case report of Pseudomonas

aeruginosa necrotizing pneumonia secondary to water pipe usage

• Heating of cannabis buds is not

sufficient for sterilization

• Vaping does not reach high enough

temperatures to kill fungal spores

• Autoclaves have been used to sterilize

marijuana

• Temperatures as high as 150ºC/300ºF

were utilized

Kumar AN, et al. Respirol Case Rep. 2018.

BLEEDING

• Synthetic cannabinoids have been recently linked to serious,

unexplained bleeding in numerous states

• Over 94 people presented to the hospital with life-threatening

coagulopathy secondary to brodifacoum

• Brodifacoum is used in a commercial product used for killing rodents

and pests

• Synthetic cannabinoid product samples tested positive for brodifacoum

Synthetic Cannabis Laced With Poison Linked to Severe Bleeding, CDC Warns. Medscape. 2018.

DRUG-DRUG INTERACTIONS

• Exogenous cannabinoids are potent

inhibitors of CYP3A and P-gp transporter

• CYP2C9, 3A4 and 2C19 inhibitors

increase plasma concentration of THC & CBD

• Multiple case reports of elevated

CNI levels

• Tacrolimus level of 45.8ng/mL when

previously at goal – patient using marijuana gummies

• Cyclosporine level of 500ng/mL following

marijuana brownie use

Hauser N, et al. Case Reports in Transplantation. 2016 Horn JR, et al. Pharmacy Times. 2014.

CANNABINOID HYPEREMESIS SYNDROME

• Cyclical vomiting without other identifiable cause seen in patients with

chronic cannabis use

• Most commonly seen in patients with prolonged, high-dose cannabis

use

• Most cases are refractory to usual antiemetic agents with patients

reporting relief only from long, hot showers

• Concerning post-transplant if patients are unable to take

immunosuppression consistently

Hickey JL, Witsil JC, Mycyk MB. Am J Emerg Med. 2013.

IMPAIRED COGNITION

• Classified as a hallucinogen
• Impairs coordination, perception of time/surroundings, comprehension and

cognition

• Develop psychotic symptoms including hallucinations, paranoia and

delusions

• Post-transplant medication regimen consists of 15+ medications
• Patient must be able to make frequent dose adjustments, administer

medications multiple times per day and ensure timing of administration is accurate

Oberbarnscheidt, T. J Addict Res Ther. 2016.

CARDIOVASCULAR EFFECTS

• Dose dependent tachycardia and increase cardiac workload
• Evidence suggest marijuana users are at a 5-fold increased risk of an

acute cardiac event

• Increased risk of ischemia due to a reduction in blood flow to the

brain

• Marijuana use can lead to vasodilation of peripheral blood vessels

leading to orthostatic hypotension & syncope

Oberbarnscheidt, T. J Addict Res Ther. 2016.

ABUSE/ADDICTION POTENTIAL

• High potential for abuse, affecting the same reward system in the brain

as alcohol and opioids

• Tolerance can develop over time, requiring an increase in the amount
• f cannabis to produce the same effect
• With discontinuation of use or between uses, withdrawal symptoms

can occur including anxiety, depression, irritability and insomnia

• Withdrawal can occur within 1-3 days, peaks within 2-6 days and can

last up to 4-14 days depending on frequency of use

Oberbarnscheidt, T. J Addict Res Ther. 2016.

CONCLUSION

• Marijuana consists of 60 pharmacologically active cannabinoids and is

available as many formulations

• Some centers consider marijuana use a relative contraindication to

transplant listing

• There is a potential for drug interactions with immunosuppression and

marijuana may increase the risk for post-transplant complications, including infection

• Patients utilizing marijuana should be educated on the risks of

marijuana use pre- & post-transplant

QUESTION 1

ST is scheduled for kidney donation in 3 weeks. When reviewing her medications, she reports taking gingko biloba and ginseng supplements daily at home. Which of the following is the correct recommendation in regards to herbal supplement use prior to surgery? a) She should hold gingko biloba & ginseng 1 week prior to surgery b) She does not need to hold gingko biloba & ginseng prior to surgery c) She should hold gingko biloba & ginseng 2 weeks prior to surgery

QUESTION 2

MJ is s/p liver transplant 2 months prior and is maintained on tacrolimus, mycophenolate and prednisone. He is inquiring about turmeric supplements given their anti-infective and anti-oxidant properties and wants to know if they interact with his transplant medications. Which of the following is correct? a) Turmeric is a CYP3A4 inducer, potential leading to a reduction in immunosuppression levels b) Turmeric is a CYP3A4 inhibitor, leading to an increase in immunosuppression levels c) Turmeric does not impact CYP3A4 and is safe to take post-transplant

QUESTION 3

Which of the following risks may be associated with marijuana use post- transplant? a) Infection b) Cardiovascular effects c) Bleeding d) A&B only e) All of the above

QUESTIONS?

EMAIL: MCOTE@MGH.HARVARD.EDU

REFERENCES

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