FDA Approved Tobacco Dependence Rx · 2016-09-13 · E-Cigarettes • Invented in 2003 by Hon Lik, ... • At 6 and 12 months, no significant difference in tobacco use (smoking) between

P-1

American Osteopathic College of Occupational and Preventive MedicineOMED 2016 Didactic Sessions.

Put That in Your Pipe and Smoke It

Brian Kloss, DO, JD, PA-C

SUNY Upstate Medical University

Syracuse, NY

Cigarette Use in US

• 19% of people in US are active cigarette users.• 69% of smokers want to quit.• 52% tried to quit between 2009-2010.1

FDA Approved Tobacco Dependence Rx2

• Replacements: gum, inhaler, lozenge, nasal spray,transdermal patch.

• Bupropion SR and Varenicline.• Abstinence rates remain 19-33% at best.

E-Cigarettes

• Invented in 2003 by Hon Lik, a Chinese Pharmacistseeking a non-combusted nicotine delivery deviceand introduced to the US in 2004.3, 4

• 40-75% of adults in US have heard of E-Cigs. 3

• About 8% of adults have used them. 3

• 21% of US smokers have tried them. 3

• 1% of Americans are frequent users. 3

• Use by adolescents has doubled from 2011-2012. 3

• 4.7% of middle school students, 10% HS studentshave used them at least once. 3

FDA Statistics on “ENDS”

• More than 3 million middle and high school studentswere current users of e-cigarettes in 2015, up from anestimated 2.46 million in 2014.1, 2

• Sixteen percent of high school and 5.3 percent ofmiddle school students were current users of e-cigarettes in 2015, making e-cigarettes the mostcommonly used tobacco product among youth for thesecond consecutive year.1

• During 2011-2015, e-cigarette use rose from 1.5percent to 16.0 percent among high school studentsand from 0.6 percent to 5.3 percent among middleschool students.1

FDA Statistics on “ENDS”

• In 2013-2014, 81% of current youth e-cigarette userscited the availability of appealing flavors as the primaryreason for use.3

• In 2014, 12.6% of U.S. adults had ever tried an e-cigarette, and about 3.7% of adults used e-cigarettesdaily or some days.4

1. Centers for Disease Control and Prevention. Tobacco Use Among Middle and High School Students –United States, 2011 -2015. Morbidity and Mortality Weekly Report 2016; 65(14): 361-367.2. Centers for Disease Control and Prevention. Tobacco Product Use Among Middle and High School Students –United States, 2011 -2014. Morbidity and Mortality Weekly Report 2015; 64: 381-5.3. Villanti AC, Johnson AL, Ambrose BK, et al. Use of flavored tobacco products among U.S. youth and adults;findings from the first wave of the PATH Study (2013-2014).

4. Schoenborn CA, Gindi RM. Electronic cigarette use among adults: United States, 2014.NCHS data brief, no. 217. Hyattsville, MD: National Center for Health Statistics, 2015.

P-2


Popularity of E-Cigs

• Experimentation

• Smoking Cessation

• Perceived Safety

• Lower Costs

• Variety of Flavors

• Indoor use/use in Public

• Fashionable/Look Cool

E-Cigs/Vaping in Movies

Dennis Quaid - Beneath the DarknessRobert De Nero - HeistHBO True Detective – Season 2

John Cusack – Drive Hard

Johnny Depp – The Tourist

Kevin Spacey – House of Cards

Hollywood Stars E-Cigs/Vaping

Leo!

Simon

Jack!

Catherine Zeta Jones

Anatomy of E-Cig

• Lithium battery – power source• Atomizing device/heater• Liquid-filled cartridge – with or without nicotine

3 Main Categories3

• First Gen: “Cigalikes” – resemble cigarettes• Second Gen: eGos – larger models with refillable

fluid tanks• Third Gen: Mods – a modified version combining

elements the of above models

Anatomy of E-Cig

"Components of a MiniCiggy e-cigarette" by Horsten at English Wikipedia. Licensed under CC BY-SA 3.0 via Wikimedia Commons –

http://commons.wikimedia.org/wiki/File:Components_of_a_MiniCiggy_e-cigarette.jpg#/media/File:Components_of_a_MiniCiggy_e-cigarette.jpg

A: LED Light Cover C: Atomizer (Heating Element)B: Battery D: Cartridge (Mouth Piece)

First Generation

cartomizer

P-3


First Generation

• Single piece = disposable – 200-500 puffs

• Rechargeable with replaceable cartridges

• Can have push button or is activated withinhalation pressure sensors

• User doesn’t handle nicotine fluid

Second Generation

Second Generation

• Larger, more colorful units

• Larger batteries

• Atomizer and fluid tanks are separate

• Customizable

• Refillable e-liquid chamber

Third Generation: Mods

Third Generation: Mods

• Modified Mint tins (Altoids) , Atari 2600joystick, metal or wooden boxes, etc.

• Can have larger batteries, larger e-fluid tanks,variable voltage settings

• Changing resistance settings, adding/alteringcoils, adjusting voltage affects fluid atomized,cloud size, throat hit, etc.

http://www.vapor4life.com/blog/odd-mods-5-strangest-modified-e-cigs/

Vapor4Life: Odd Mods

P-4


Speaking of Ghostbusters E-Cig MP3 Player & Telephone

SuperSmoker Club

VapeFest Vape Magazines

E-Fluid

• Propylene glycol or glycerin

• Nicotine mg/ml

• Flavoring – tobacco, mint, cherry, fruits

← 18mg nico�ne/ml

Nicotine Comparison Chart

P-5


E-Fluid Health Risks

• Flavoring can contain cytotoxins.

• Cinnamaldehyde flavor is cytotoxic.

• Diethylene glycol is a toxic carcinogen.

• Diacetyl and acetyl propionyl are respiratoryirritants.

• FDA Reported Events: headache, chest pain,nausea, CHF, tachycardia, seizure, lipidpneumonia.

• Nicotine is a potent poison.

E-Cig Laws: US

• FDA attempted to regulate E-Cigs claimingviolation of Federal Food Drug and CosmeticAct, but lost because E-Cigs were notconsidered drug delivery devices.2

• 2013 FDA proposed a rule to include e-cigs inthe statutory definition of “tobacco products”to gain regulatory authority under the TobaccoControl Act.2

E-Cig Laws: US

• 2014 Report by US Surgeon General onTobacco recommends further research onrisk/benefit to user and bystanders. 2

• Several states including: Delaware, NJ, MD, NHhave banned their sale and use. 2

• NYC banned public and indoor use inDecember 2013. 2

E-Cig Laws: EU, Canada

• Canada: electronic nicotine delivery systemscan not be imported or manufactured withoutbeing approved as a new drug.4

• EU: October 2013, law passed allowing e-cigswith less than 30 mg/ml nicotine, must carryhealth warnings and can not be sold to thoseunder 18. Ingredients must be listed andpackages carry health warnings.4

E-Cig Laws: US

• May 5, 2016 – FDA will regulate E-Cigs startingin 90 days (To take effect August 2016).

• Lawsuits challenging regulations to be filed.

• Includes vape shops mixing own fluids.

• Will this make big tobacco stronger?

• ENDS “Electronic Nicotine Delivery Systems”

P-6


Caponnetto, et al Study

• 12 month randomized trial of 300 adults not seeking toquit smoking

• Randomized to 1 of 3 groups:

1) 12 weeks of 7.2 mg cartridges

2) 6 weeks of 7.2 mg cartridges → 6 weeks 5.4mg carts

3) 12 weeks of nicotine free cartridges

Caponnetto, et al Study

• At 12 weeks there was a decrease in number ofcigarettes per day and exhaled CO levels in all 3 groups

• Percent reduction of daily cigarette use: 26%, 20%, 21%

• Abstinence rates at 12 weeks: 11%, 17%, 4%

• At 6 and 12 months, no significant difference in tobaccouse (smoking) between the three groups.

Bullen et al Study

• 657 adult smokers, all looking to quit, were randomized to1 of 3 groups:

1) 16 mg e-cigs

2) 21 mg nicotine patches

3) nicotine free e-cigs

• Participants used e-cigs freely or daily patch for 1 weekprior to quitting and for 12 weeks after quit date.

• Participants could continue their intervention longer afterthe 12 weeks if they chose to do so.

Bullen et al Study

• 29% of nicotine e-cig users, 35% of placebo users(nicotine free e-cig) and 8% patch users continued theirassigned intervention after 12 weeks.

• Abstinence rates at 6 months were as follows:

1) 7.3% - 16 mg e-cig users

2) 5.8% - 21 mg nicotine patch users

3) 4.1% - nicotine free e-cigs (placebo) users

• Study was underpowered to prove statistical significance.No significant adverse effects in any of the 3 groups.

Teens Who Use E-Cigs More Likely toSmoke Combustible Cigarettes

• Adam Leventhal, PhD - JAMA August 18, 2015

• 2530 14-year-olds who never smokedcombustible cigs followed up at 6 or 12 months.

• Baseline e-cig users had more frequent use ofcombustible cigarettes in past 6 months (30.7% vs8.1% 6-month cohort) and (25.2% vs 9.3% 12-month cohort).

Recommendations3

• AHA: clinicians should not recommend as ameans to quit smoking, if actively using, suggest apredetermined quit date

• Not demonstrably superior to FDA approvedmedications for smoking cessation

• May lead to dual use of cigarettes and e-cigs

• E-cigs are not FDA approved

• Short-term safety risks: airway irritation

• Long-term safety risks: unknown

• No regulatory oversight

P-7


Nicotine Overdose

21mg/ml = 210mg6mg/ml = 60mg

10 ml bottles

Nicotine Overdose

• 1-year-old toddler died in Fort Plain, NY from anunintentional nicotine overdose on December 9, 2014.

• First documented death from ingestion of E-fluid in US.

• Number of calls to poison control centers for exposurehas steadily increased over the past few years:

2011: 271

2013: 1543

2014: 3783

2015: 3067American Association Poison Control Centers

Nicotine Overdose

• Nicotine is found in tobacco plants and products

• Green Tobacco Sickness – poisoning from harvesting wettobacco plants

Some Variation in Estimates of Toxicity• Lower limits adult lethal dose 0.5 - 1mg/kg

• Child lethal dose 0.1 mg/kg (based on rats/mice)

• Newer estimates: 6.5-13mg/kg lethal dose for adults

Nicotine Sources

• Cigarette: 9 mg (1 mg absorbed when smoked)

• Chew/Dip: 4mg-14 mg

• 1 can snuff = 4 packs cigarettes nicotine

• 30 minutes chew = 3 cigarettes nicotine

• Nicotine Inhaler: 10mg per cartridge

• Nicotine Patches: 7mg, 14 mg, 21mg

• Nicotine Gum: 2-4 mg

• Nicotine Fluid – 60ml of 25mg/ml = $60.00

(Highly concentrated nicotine = 1500mg/60ml)

Hypothetical Pediatric Overdose

21mg/ml x10 = 210mg

Lethal Dose:6.5mg/kg

To Kill a 22 pound childyou need:65 mg nicotine

65mg/210 = 3 ml

Nicotine Overdose

Symptoms

• Headache

• Lightheadedness

• Dizziness/Ataxia

• Nausea and Vomiting

• Stomach Pain

• Pallor

• Tacchycardia

• Salivation

• Hypertension

P-8


Nicotine Overdose

• Biphasic Response

• Later symptoms include bradycardia,hypotension, weakness, dyspnea, seizures,cardiac dysrhythmia, coma and death.

• Initial response is nicotinic receptorstimulation in sympathetic, parasympatheticand neuromuscular junction.

• Similar to cholinergic overdose.

Nicotine OD

• Excessive stimulation ofnicotinic cholinergic receptorsONLY.

• Carbamate and OP overdosestimulates BOTH nicotinic andmuscarinic receptors.

• Toxidromes are similar, but notidentical.

• Nicotine is biphasic:

Tachycardia → Bradycardia

Hypertension → Hypotension

Treatment

• Call Poison Control Center

• Supportive

• A, B, C’s

• Seizure/Agitation = Benzos

• Bradycardia/Excessive Cholinergic = Atropine

• Hypotension: Fluids, Levophed/Norepi

Exploding E-Cigs

Exploding E-Cigs Exploding E-Cigs

P-9


Butane Hash Oil

Butane Hash Oil

• BHO, 710 OIL, shatter, glass, honey, bees wax,wax, hashish oil, budder, dabs

• Potent form of THC and cannabinoids extractedfrom plant material using pressurized butane.

• May contain up to 60-85% THC.

• Smoked in small aliquots known as “dabs” usinga vaporizer or blowtorch heated water pipe.

• Water pipe may be referred to as an “OIL Rig”

Butane Hash Oil

• Can cause explosions when beingmanufactured/extracted.

• Sells for $10-$40 gram in Green States, $100elsewhere.

• Reportedly no odor when vaped.

• Commercial vaporizers sold/marketedspecifically for this purpose.

BHO Use

P-10


BHO Fails BHO Aftermath

Hookah & Tobacco Waterpipes

Waterpipe Use in US

• Waterpipe tobacco is centuries old and hasorigins linked to southwest Asia and north Africa

• Waterpipe: hookah, narghile, shisha

• Tobacco: maassel, shisha

• 10-20% of some young adult populations users

• Very popular around college campuses

• 200-300 hookah cafes opened in US since 1999

P-11


Waterpipe vs Cigarettes

Cigarette

• 5 minutes of smoking

• 10-13 puffs – 50 ml smoke

• Total smoke: 650 ml (0.65 L)

Waterpipe

• 60 minutes of smoking

• 200 puffs – 500 ml smoke

• Total smoke: 90 - 100 liters

½ Carton

Waterpipe Facts

• 44% US users report hookah use >60 minutes

• 411 Johns Hopkins Freshmen - 15% reporteduse in last 30 days.

• 744 Virginia Commonwealth Universitystudents – 20.3% reported use in last 30 days.

• 1671 Arab American teens – 26.6% reporteduse at least once, many before age 14, somebefore age 10.

Cobb, C. Ward, K. et al. Waterpipe Tobacco Smoking: An Emerging Health Crisis in the United StatesAm Journal Health Behavior 2010;34(3):275-285

How Far to Nearest Hookah Lounge? 9 Hookah Options w/i 1 Mile Radius!

References

1) Centers for Disease Control. Quitting smoking among adults –United States, 2001-2010. MMWR Morb Mortality Wkly Rep.2011; 60(44):1513-9.

2) Hagstrom, K., Gannon, D., Sobieraj, D. Electronic Cigarettes forSmoking Cessation. Drug Information Update: Hartford Hospital.Vol 78, No 7: 435. August 2014.

3) Ebbert, J., Agunwamba, A., Rutten, L. Counseling of Patients andthe Use of Electronic Cigarettes. Concise Review for Clinicians.Mayo Clinic. Jan 2015:90(1):128-134

4) Harrell, P., et al. Electronic Nicotine Delivery Systems (E-Cigarettes): Review of Safety and Smoking Cessation Efficacy.Otolaryngology – Head and Neck Surgery 2014, Vol. 151(3) 381-393.

Clinical Studies Referenced

• Bullen C, Howe C, Laugesen, et al. Electroniccigarettes for smoking cessation: arandomized controlled trial. Lancet. 2013;382(9905):1629-37

• Caponnetto P, Campagna D, Cibella F, et al.Efficiency and safety of an electronic cigarette(ECLAT) as tobacco cigarettes substitutes: aprospective 12-month randomized controldesign study. Plos One. 2013; 8(6):e66317

P-12


Additional E-Cig Reading

Beaglehole R, Bonita R, Yach D, Mackay J, Reddy KS. A tobacco-free world: acall to action to phase out the sale of tobacco products by 2040. Lancet. 2015Mar 14;385(9972):1011-8. doi: 10.1016/S0140-6736(15)60133-7. Review. PubMed PMID:25784348.

Ebbert JO, Agunwamba AA, Rutten LJ. Counseling patients on the use ofelectronic cigarettes. Mayo Clin Proc. 2015 Jan;90(1):128-34. doi:10.1016/j.mayocp.2014.11.004. Review. PubMed PMID: 25572196.

Collaco JM, Drummond MB, McGrath-Morrow SA. Electronic cigarette use andexposure in the pediatric population. JAMA Pediatr. 2015 Feb;169(2):177-82. doi:10.1001/jamapediatrics.2014.2898. Review. PubMed PMID: 25546699.


McRobbie H, Bullen C, Hartmann-Boyce J, Hajek P. Electronic cigarettes forsmoking cessation and reduction. Cochrane Database Syst Rev. 2014;12:CD010216.doi: 10.1002/14651858.CD010216.pub2. Epub 2014 Dec 17. Review. PubMed PMID:25515689.

Oh AY, Kacker A. Do electronic cigarettes impart a lower potential diseaseburden than conventional tobacco cigarettes? Review on E-cigarette vapor versustobacco smoke. Laryngoscope. 2014 Dec;124(12):2702-6. doi: 10.1002/lary.24750.Epub 2014 Oct 9. Review. PubMed PMID: 25302452.

Hagstrom K, Gannon D, Sobieraj D. Electronic cigarettes for smoking cessation.Conn Med. 2014 Aug;78(7):435-9. Review. PubMed PMID: 25195313.12: Harrell PT, Simmons VN, Correa JB, Padhya TA, Brandon TH. Electronic nicotinedelivery systems ("e-cigarettes"): review of safety and smoking cessationefficacy. Otolaryngol Head Neck Surg. 2014 Sep;151(3):381-93. doi:10.1177/0194599814536847. Epub 2014 Jun 4. Review. PubMed PMID: 24898072; PubMedCentral PMCID: PMC4376316.


Callahan-Lyon P. Electronic cigarettes: human health effects. Tob Control.2014 May;23 Suppl 2:ii36-40. doi: 10.1136/tobaccocontrol-2013-051470. Review.PubMed PMID: 24732161; PubMed Central PMCID: PMC3995250.

Drummond MB, Upson D. Electronic cigarettes. Potential harms and benefits.Ann Am Thorac Soc. 2014 Feb;11(2):236-42. doi: 10.1513/AnnalsATS.201311-391FR.Review. PubMed PMID: 24575993.

• Website: www.klossandbruce.com

• Twitter: @EM_PEARLS

• Facebook: Kloss and Bruce

• YouTube: Kloss and Bruce (Toxicology Videos)

• E-Mail: [email protected]

If You Like My Style, Invite Me Back!

Documents

FDA Approved Tobacco Dependence Rx · 2016-09-13 · E-Cigarettes • Invented in 2003 by Hon Lik, ... • At 6 and 12 months, no significant difference in tobacco use (smoking) between