Health Effects of Substance Use

Health Effects of Substance Use

September 2nd, 2021

CSAM Review Course in Addiction Medicine

Jonathan Watson, MD

Orange County Correctional Health Services, Physician

Beit T’Shuvah, Medical Director

CONFLICT OF INTEREST DISCLOSURE

I, Jonathan Watson, have nothing to disclose, and I will not be discussing “off label” use of drugs or devices in this presentation.

OH JEEZ….Sinus tachycardiaAtrial fibrillationVentricular tachycardiaVentricular fibrillationAcute HypertensionChronic HypertensionHemorrhagic StrokeIschemic StrokeHIVHep BHep BChronic BronchitisOral CancerEsophageal cancerLung cancerStomach CancerCellulitisAbscessGastritisEndocarditisVenous StasisThrombophlebitisTalc granulomatosisProctitisSeizureQT prolongationMalignant hyperthermiaRhabdomyolysisAortic dissection

Cognitive impairmentCOPDPneumoniaCataractsNeuropathyMacrocytic anemiaRenal injurySleep disturbancesDilated cardiomyopathyHypertrophic cardiomyopathyPneumoniaMalory Weiss tearsBoerhaave syndromePeriodontitisMalnutritionOsteopeniaOsteoporosisCataractsBotulismConstipationIschemic bowelCoagulopathyVasculitisSubmucosal FibrosisNicotinic stomatitisPulmonary hypertensionPulmonary edemaPulmonary hemorrhage Erectile dysfunction

Anoxic brain injuryBronchitits

BurnsAortic dissectionCoronary artery vasospasmPeriodic leg movementsTicChoreaCompartment syndromeFractureMicronutrient deficiencyLeukoencephalopathyRespiratory failureBronchiolitis ObliteransEosinophilic PneumonitisAnginaMycotic aneurysmCentral pontine myelinosisWithdrawal deliriumWithdrawal seizureDelirium TremensWernicke Korsakoff

https://www.nytimes.com/2016/08/08/business/media/this-is-your-brain-on-drugs-tweaked-for-todays-parents.html

EDUCATIONAL OBJECTIVES After attending this presentation, participants will be able to describe how a person’s health is affected by:

SOCIAL DETERMINANTS OF HEALTH OF PWUD

SOCIAL DETERMINANTS OF HEALTH OF PWUD

• Bias and stigma in healthcare

• Nearly all participants endorsed

• Explicit Judgement, Minimizing, Stereotyped, Involvement of hospital security

• Poor pain control and denial of controlled medications that were prescribed

outpatient (benzos)

• Inadequate withdrawal management

• Restrictions, not being able to leave the floor (reminiscent of incarceration

SOCIAL DETERMINANTS OF HEALTH OF PWUD• Incarceration

Evelyn J. Patterson, 2013: The Dose–Response of Time Served in Prison on Mortality: New York State, 1989–2003 American Journal of Public Health 103, 523_528, https://doi.org/10.2105/AJPH.2012.301148

“2-year decline in life expectancy for each year served in prison”

SOCIAL DETERMINANTS OF HEALTH OF PWUD• Drugs effect on motivation

• Hygiene (dental, wound care)

• Preventative health maintenance

• Interactions with healthcare

• “No-Showed” for showing up late

• Cravings can be a factor in hospital AMA discharges

• Malnutrition

• Difficulty affording food

• May not feel hungry

• Ethanol itself is calorie dense (7.1 kCal per gram)

• May lead to complications

• Refeeding syndrome

SOCIAL DETERMINANTS OF HEALTH OF PWUD• Infectious Disease

• Housing related (ex. Tuberculosis)

• STDs/HIV

• Inconsistent condom use

• Impairment

• Motivation

• Rape, sexual assault, coercion, and exploitation

• A study of female sex workers found that substance use

was linked with violence and coercive condom negotiation

from clients

SOCIAL DETERMINANTS OF HEALTH OF PWUD• Traumatic injury

• MVA – in 2015 29% of MVA fatalities were alcohol related

• Violence

• Substances don’t “cause” violence; most PWUD are non-violent

• Things like disinhibition, paranoia, psychosis, may play a role in

violence

ROUTES OF ADMINISTRATION - INSUFFLATION

ROUTES OF ADMINISTRATION - INSUFFLATION

• Nasal injury

• Cocaine: vasoconstriction leading to tissue necrosis

By Dr.J.S.Bhandari, India - Own work, CC BY-SA 3.0,https://commons.wikimedia.org/w/index.php?curid=6736314

Blanksma, C & Brand, H.. (2006). Cocaine abuse: Orofacial manifestations and implications for dental

treatment. International dental journal. 55. 365-9. 10.1111/j.1875-595X.2005.tb00047.x.

ROUTES OF ADMINISTRATION - INHALATION• Toxic Leukoencephalopathy

• “Smoking” Heroin off of foil (chasing the dragon)

• Chemical process is pyrolysis; the heroin pyrolysate is inhaled

• Spongiform Leukoencephalopathy – myelin sheath develops

intracytoplasmic vacuoles → neuronal loss and gliosis

• Symptoms can progress over hours to weeks (or months)

• Ataxia and speech difficulties → EPS, spastic paresis, hyperreflexia,

~25% will progress to mutism, extensor posturing, fever, coma, death

• Wide variety in prognosis (improvement is possible)

http://www.emdocs.net/toxcard-chasing-the-dragon/

http://neuropathologyblog.blogspot.com/2012/07/chasing-dragon-cause-of-toxic.html

Cerebellum, posterior limb of internal capsule and posterior cerebrum, corticospinal

tracks, anterior thalami,, splenium of corpus callosum, posterior corona radiata,

occipital, parietal, posterior temporal, posterior frontal lobes

Sparing of suborctical white matter, anterior limb of internal capsule, dentate nuclei,

grey matter

MRI changes may progress over months (even w/ clinical improvement)

ROUTES OF ADMINISTRATION - INHALATION• Toxic Leukoencephalopathy

• MRI T2 and T2 flair shows hyperintense white matter of the :

Bartlett E, Mikulis DJ. Chasing “chasing the dragon” with MRI: Leukoencephalopathy in drug abuse. Br J Radiol. 2005;78(935):997-1004. doi:10.1259/bjr/61535842

Achamallah N, Wright RS, Fried J. Chasing the wrong dragon: A new presentation of heroin-induced toxic leukoencephalopathy mimicking anoxic brain injury. J Intensive Care Soc. 2019;20(1):80-85. doi:10.1177/1751143718774714

ROUTES OF ADMINISTRATION - SUBLINGUAL

• Oral Submucous Fibrosis

• Areca nut and tobacco products

• Fibrosis of the lamina propria → stiffness of the oral mucosa

• 1.9% - 9% of cases undergo malignant transformation

Rao NR, Villa A, More CB, Jayasinghe RD, Kerr AR, Johnson NW. Oral submucous fibrosis: A contemporary narrative review with a proposed inter-professional approach for an early diagnosis and clinical management. J

Otolaryngol - Head Neck Surg. 2020;49(1):1-11. doi:10.1186/s40463-020-0399-7

• Prevalence of OSMF n India

• 0.2 – 2.3% of males

• 1.2 – 4.6% of females18

Can make it hard to eat, open

mouth; decreased tongue movement

Symptoms may include burning pain,

ulceration

https://www.downtoearth.org.in/news/gutkha-ban-has-reduced-consumption-of-tobacco-in-india-who-47868

By Thamizhpparithi Maari - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=17755273

Gutkha

• Areca nut acts as mild stimulant17

• Paan (“tobacco, seeds, quenched lime, spices, areca nut enfolded in

betal quid”) and Gutkha (“over three decades ago, a tobacco industry

emerged in India producing gutkha, which consists of slaked lime,

areca nut, chewing tobacco, spices, catechu packed in tins or

pouches”)17 are sold in South and Southeast Asia and in the diaspora

(10 – 20% of worlds population consumes areca nut)

ROUTES OF ADMINISTRATION - ORAL

• Erosive Esophagitis, Gastritis

• Direct toxic effect of ETOH + acetaldehyde

• Liver Injury

• Oral formulations of anabolic steroids have 17-alpha-alkylation

• Metabolized more slowly than IM formulations →↑ Hepatotoxicity

https://commons.wikimedia.org/wiki/File:Peliosis_hepatis.png

Transaminitis

Acute cholestasis

Peliosis hepatis (large blood sinuses/cavities that develop

in the liver paranchyma) – rare – can rupture →

hemodynamic collapse

Hepatic tumors (adenoma, HCC)

QUESTION!!!

You are wrapping up notes at the end of your shift in the emergency

department when your colleague enters the work-room and shouts in

exasperation, “Mr. S is back again!! He’s high as a kite and demanding

pain meds. Well too bad, buddy!”

Mr. S is a 53 y/o African American cis male with T2DM, HTN, and BPH. He

uses heroin and methamphetamine intravenously and has started using

the veins on his feet as other became harder to find. On admission to the

ED he endorses 10/10 right lower extremity pain. His exam includes:

QUESTION!!!

Mr. S is a 53 y/o African American cis male with T2DM, HTN, and BPH. He

uses heroin and methamphetamine intravenously and has started using

the veins on his feet as other became harder to find. On admission to the

ED he endorses 10/10 right lower extremity pain. His exam includes:

Vitals: T39.4, 105/65, p130, RR24. O2sat 91%

Right lower leg is tender and edematous with poorly defined erythema

that has extended several centimeters beyond the line drawn by the nurse

one hour ago. There is no crepitus or fluctuance, however there is a 4cm

dusky, insensate patch over the dorsum of the foot

QUESTION!!!

Vitals: T39.4, 105/65, p130, RR24. O2sat 91%

Extremities: Right lower leg is tender and edematous with poorly defined

erythema that has extended several centimeters beyond the line drawn by

the nurse one hour ago. There is no crepitus or fluctuance, however there

is a 4cm dusky, insensate patch over the dorsum of the foot

Initial management of this patient should include:

A. Pain control, IVF + Vancomycin, reevaluate in one hour

B. CT Pulmonary Angiogram

C. MRI Foot w/ and w/o contrast

D. Urgent Vascular Surgery Consult

ROUTES OF ADMINISTRATION – INJECTION

• Infectious

• Cellulitis

• Abscess

• Necrotizing Fasciitis

In PWID

1. Most common is staph aureus and strep pyogenes (group A)

2. Clostridium is more common in PWID than in gen population

Symptoms: localized pain out of proportion

Signs: bullae, dusky/purple skin, crepitus; gas on XR; fever, hemodynamic instability

https://wikem.org/wiki/File:CTNecrotizingFasciitis.png

https://www.embeds.co.uk/2020/11/28/necrotising-fasciitis/

Raquel García-Tarriño, José Ballesteros-Betancourt, Alex Soriano-Viladomiu, Jose Ríos-Guillermo, Manuel Llusá-Pérez, Andrés Combalia,

Necrotizing fasciitis: Usefulness of the LRINEC score in a third-level hospital, Injury, 2021, ISSN 0020-1383,

May not have all the symptoms, refer to surgeon if at all concerned

1. In PWID, should include Vascular Surgeon

Life threatening, rapidly progressing

1. One study of 37 cases had avg 30% mortality (>60% of patients older than 60)

a. Some studies quote as high as 73%

• Can mimic cellulitis in early stages

• Bacteria release toxins → promote inflammation → multiorgan failure

QUESTION!!!

Vitals: T39.4, 105/65, p130, RR24. O2sat 91%

Extremities: Right lower leg is tender and edematous with poorly defined

erythema that has extended several centimeters beyond the line drawn by

the nurse one hour ago. There is no crepitus or fluctuance, however there

is a 4cm dusky, insensate patch over the dorsum of the foot

Initial management of this patient should include:

A. Reassurance, fluids, Start IV Vancomcin, with plans reevaluate

B. CT Pulmonary Angiogram

C. MRI Foot w/ and w/o contrast

D. Urgent Vascular Surgery Consult


• Infectious

• Cellulitis

• Abscess

• Necrotizing Fasciitis

• Osteomyelitis

• Endocarditis

• Septic Arthritis

• Epidural Abscess

• Hep C

• HIV


• Vein sclerosis

• Talc granulomatosis

• Lung

• Liver

• Spleen

• Retina

• Skin

• Pancreas

• Kidney

• Bone marrow

• Lymph nodes

Staloch, D. A., & Hedley, J. S. (2017). Pulmonary Foreign-Body Granulomatosis. New England Journal of Medicine, 377(13), 1273–1273. https://doi.org/10.1056/nejmicm1701787

Soliman, M.K., Sarwar, S., Hanout, M. et al. High-resolution adaptive optics findings in talc retinopathy. Int J Retin Vitr 1, 10 (2015). https://doi.org/10.1186/s40942-015-0009-4

1. Talc is used as a bulking agent in pills;

2. Sometimes used to add weight to cocaine

3. When injected, talk particles get trapped in fine capillary beds

4. When trapped it causes a foreign body reaction → granuloma, interstitial fibrosis

ROUTES OF ADMINISTRATION –RECTAL• Chemical Proctocolitis

• Solution administered w/ syringe or soaked up with a tampon which is

then inserted

• Bleeding, mucosal edema,

Seki T, Fukushima H. Self-administered alcohol enema causing chemical proctocolitis. Open Access Emerg Med. 2019;11:129-132. doi:10.2147/OAEM.S208214

TOXIC EFFECTS OF DRUGS THEMSELVES

TOXIC EFFECTS OF DRUGS THEMSELVES

• Stimulants

• Meth

• Cocaine

STIMULANTS – PULMONARY• Pulmonary Hypertension

• Patients with idiopathic PH were 10 times more likely to report meth

use than patients who had PH d/t a known risk factor

• Cocaine*


• Cocaine

STIMULANTS – PULMONARY

• Crack Cocaine

• Pigment Deposition

• Barotrauma → pneumothorax, pneumomediastinum

• Bronchospasm

• Bronchiolitis Obliterans

• Hypersensitivity pneumonitis and interstitial fibrosis (AKA Crack Lung)

Pulmonary Complications from Cocaine and Cocaine-based Substances: Imaging Manifestations Carlos S. Restrepo, Jorge A. Carrillo, Santiago Martínez, Paulina Ojeda, Aura L. Rivera, and Ami Hatta RadioGraphics 2007 27:4, 941-956

https://pubs.rsna.org/doi/abs/10.1148/rg.274065144

Pulmonary Complications from Cocaine and Cocaine-based Substances: Imaging Manifestations Carlos S. Restrepo, Jorge A. Carrillo, Santiago Martínez, Paulina Ojeda, Aura L. Rivera, and Ami Hatta RadioGraphics 2007 27:4, 941-956

pneumothorax,

pneumomediastinum

By Bo-Qia Xie, Wei Wang, Wen-Qian Zhang, Xin-Hua Guo, Min-Fu Yang, Li Wang, Zuo-Xiang He, Yue-Qin Tian -

http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0098381, CC BY 4.0,

https://commons.wikimedia.org/w/index.php?curid=51386580

Bronchiolitis Obliterans

https://pubs.rsna.org/doi/abs/10.1148/rg.274065144

• Combustion of crack cocaine results carbon pigments which are inhaled and deposit in alveoli (due to their

small size) which in turn leads to accumulation of extracellular pigment (dark sputum on BAL) and the

accumulation of macrophages with large amounts of pigment15

• overload macrophages, intracellular, extracellular

• Barotrauma → pneumothorax, pneumomediastinum15

• Cough + Intentional Valsalva used in some crack cocaine users to

• Bronchospasm

• Smoked cocaine causes bronchospasm and wheezing in 32% of users15

• Bronchiolitis Obliterans in crack cocaine users

• Characterized by fibroblastic plugs in terminal bronchioles and alveoli15

• Cocaine causes Interstitial fibrosis in bronchiole epithelium and thick bronchiolar smooth muscle

hypertrophy15

• hypersensitivity pneumonitis vs. fibrosis (aka crack lung) found in 38% of autopsies of patients who had

positive cocaine test15

• This can progress to respiratory failure (thickening of alveolar septum)

• BAL shows elevated eosinophils

• CXR shows perihilar interstitial ground glass opacities

• Syndrome includes fever, hypoxemia, hemoptysis, resp failure,

• Crack Cocaine


• Cocaine

• Lung histopathology from 52 autopsies of patients who tested positive

for cocaine

• 58% had acute hemorrhage

• 40% had chronic hemorrhage

• 38% had pneumonitis vs. fibrosis

• 77% had intra-alveolar edema (some cite as high as 85%)

Both IV and smoked cocaine → pulm edema

1. Rupture of submucosal blood vessels or injury to alveolar capillary network15

2. Can range from asymptomatic (discovered incidentally on autopsy) to hemoptysis to life threatening

hemorrhage15

5. No significant differences based on mode of use

6. Most common cause od death was cocaine OD, followed by “natural causes,” and homicides

a. Natural deaths = MI, ruptured aortic aneurysms, hemorrhagic stroke, fulminant hepatitis, asthma

STIMULANTS - CARDIOVASCULAR

Havakuk O, Rezkalla SH, Kloner RA. The Cardiovascular Effects of Cocaine. J Am Coll Cardiol. 2017;70(1):101-113. doi:10.1016/j.jacc.2017.05.014

STIMULANTS - CARDIOVASCULAR• Acute HTN

• Arrythmia

• Sinus tachycardia

• SVT

• Ventricular dysrhythmias

Christopher G. Kevil. Arteriosclerosis, Thrombosis, and Vascular Biology. Methamphetamine Use and Cardiovascular Disease, Volume: 39, Issue: 9, Pages: 1739-1746, DOI: (10.1161/ATVBAHA.119.312461)

© 2019 American Heart Association, Inc.


• Arrythmia - Cocaine

• Vasoconstriction

• Ion Channel blockade:

1. Na+ blockade (class 1C)

2. K+ blockade

3. Ca++ channel - variable

Patient specific Long QT syndrome type 3 cardiomyocytes can be used for clinical drug safety assessments Masterproef ingediend met het oog op het behalen van de graad van Master in de Geneeskunde - Scientific Figure on

ResearchGate. Available from: https://www.researchgate.net/figure/Cardiac-action-potential-and-the-sequence-of-well-concerted-ion-channel-activities-are_fig1_330351147 [accessed 13 Jun, 2021]


• Arrythmia

• Myocardial Infarction

• Ionotropic, chronotropic

• Increased SVR

• Impaired perfusion


• Dissection of coronary arteries

1. Risk of MI increases 24 fold in first hour after cocaine use

1. That said, on 2 retrospective studies of cocaine using patients presenting w/ chest pain; 6% had MI (most had

extra-cardiac cause)

2. CAN HAPPEN IN ABSCENSE OF CAD – chronic Cocaine may increase CAD – smoking is a confounder

3. Coronary vasoconstriction

4. Pulmonary effects (decreased oxygen)

5. If cocaine user has chest pain

1. ECG – look for ST elevation/depression

1. Cath lab (worry about stent thrombosis from either continued cocaine use or difficulty adhering to antiplatelet

therapy)

2. Fibrinolytic use is difficult given risk of AD

2. Cardiac troponins

3. Unstable vitals

4. If low risk follow w/ ECG for 12 hrs and d/c

6. Medical mgmt.

1. IV benzos if hyperexcitable

2. NO, phentolamine, verapamil may reverse coronary vasospasm, but may also further increase HR (including verapamil)

3. Non-selective beta blockers (labetalol)

4. Antiplatelet/anticoag31

MI Risk in Cocaine


• Arrythmia

• Myocardial Infarction

• Takotsubo cardiomyopathy and reverse takotsubo cardiomyopathy

Eglė Kazakauskaitė, Antanas Jankauskas, Tomas Lapinskas, Rasa Ordienė, Eglė Ereminienė,

Takotsubo cardiomyopathy: The challenging diagnosis in clinical routine, Medicina, Volume 50,

Issue 1, 2014, Pages 1-7, ISSN 1010-660X, https://doi.org/10.1016/j.medici.2014.05.009.

Patankar, G.R., Choi, J.W. & Schussler, J.M. Reverse takotsubo cardiomyopathy: two case reports and

review of the literature. J Med Case Reports 7, 84 (2013). https://doi.org/10.1186/1752-1947-7-84


• Arrythmia

• Myocardial infarction


• Aortic dissection

Graphic 100115 Version 4.0

© 2021 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

a. aortic dissection

a. Methamphetamine is second only to idiopathic HTN in USA32

b. Cocaine users are extremely high risk

a. In 1 single-center study from 2002, 37% of cases of

acute AD also had cocaine use

This makes sense as in addition to an increase in BP, there is vascular

smooth muscle apoptosis and cystic medial necrosis that leads to

weakness or the arterial wall (also what leads to coronary and carotid artery

dissections)


• Arrythmia




• Intracardiac thrombi• Has been found in up to 33% of MA users

CASE 2020 4170-174DOI: (10.1016/j.case.2020.01.007) Copyright © 2020 American Society of Echocardiography Terms and Conditions

http://www.elsevier.com/termsandconditions


• Arrythmia




• Intracardiac thrombi

• Cardiomyopathy


• Cardiomyopathy

Catecholamine excess

Vasospasm and ischemia

Uncoupling of oxidative phosphorylation and

oxygen wastingReactive oxygen species

Myocardial remodeling w/ perivascular and interstitial fibrosis

myocyte destruction, [proliferation of fibromyocytes, cellular vacuolization, patchy cellular infiltration, eosinophilic

degeneration, edema.

Contraction band necrosis prominent


• Cardiomyopathy

• Meth> cocaine

• Typically dilated cardiomyopathy with reduced EF

Schwarzbach V, Lenk K, Laufs U. Methamphetamine-related cardiovascular diseases. ESC Hear Fail. 2020;7(2):407-414. doi:10.1002/ehf2.12572

Meth Estimated risk is ~10% (based on a retrospective

study that looked for elevated BNP)When people who use stimulants are admitted for acute heart failure, they are at

higher risk for complications including cardiogenic shock, v-tach, PE, AKI

Not all dilated cardiomyopathy

Study of almost 900 autopsies of MA associated deaths

CAD 19%

LV dilation 26.3%

LV hypertrophy 19%

Myocardial fibrosis 19.8

STIMULANTS - CARDIOVASCULAR• Cardiomyopathy

• Mild and moderate cases may be reversible with abstinence

• In one study, over half had NYHA class improvement within 8 weeks

Sliman, S. et al. “Methamphetamine-Associated Congestive Heart Failure: Increasing Prevalence and Relationship of Clinical Outcomes to Continued Use or Abstinence.” Cardiovascular Toxicology 16 (2015): 381-389.

LVEF P = 0.06NYHC Class

STIMULANTS - CARDIOVASCULAR• Cardiomyopathy

• Diagnostics

• BNP may help with early detection

• Cardiac MR w/ late gadolinium may identify areas where damage is

reversible and degree of fibrosis

• If clinically suspicious consider echo, left heart cath, right heart cath

STIMULANTS - NEUROLOGICAL• Seizure

Cocaine metabolites lower seizure threshold, benzoylecgonine can has half life of

7.5 hours so can induce seizures hours/days after last use


• Stroke

• In young meth users 80% of strokes are hemorrhagic

• Ischemic strokes are due to


• Thromboembolism

• Vasculitis

Topcu A, Yagci I, Gedik-Topcu B, Tasdelen Y. Methamphetamine induced

intracerebral hemorrhage: a case report. Psychiatry and Behavioral

Sciences 2018;8(3):126-9.

https://doi.org/10.5455/PBS.20180528091317

Ng CF, Chong CY. Methamphetamine-

induced internal carotid artery vasospasm:

A rapidly fatal stroke. Neurol India [serial

online] 2018 [cited 2021 Jun 13];66:826-

7. Available from:

https://www.neurologyindia.com/text.asp

?2018/66/3/826/232337


• Stroke

• Motor impairments

• Myoclonus

• Bruxism

• Transient chorea

• Tic


• Stroke

• Motor impairments

• Chronic use associated with cognitive impairment

• Executive function

• Episodic Memory

• Information processing

STIMULANTS – METABOLIC/RENAL• Lactic Acidosis

• Rhabdomyolysis

• Ischemia

• Hyperactivity, seizure

• Trauma

CK reaches peak 48 -72 hours after intoxication → decreases by 50% every 48 hours28


• Rhabdomyolysis

• Acute Kidney Injury (AKI)

• Most commonly from Rhabdomyolysis

• Can be from intra-renal vasoconstriction


• Rhabdomyolysis

• Acute Kidney Injury (AKI)

• Malignant Hyperthermia

• Hypermetabolic state

• Poor heat dissipation

https://pmgbiology.files.wordpress.com/2014/05/vaso.jpg

STIMULANTS – COCAINE AND…

• Levamisole

https://igsrv.org/vets-trace-unexpected-source-of-banned-substance-aminorex


• Meth

• Cocaine*• Levamisole is metabolized to Aminorex

• Aminorex Associated w/

• Pulm HTN

• Agranulocytosis

• Vasculitis

Barker, S.. “The formation of aminorex in racehorses following levamisole administration. A quantitative and chiral analysis following synthetic aminorex or levamisole

administration vs. aminorex-positive samples from the field: a preliminary report.” Journal of veterinary pharmacology and therapeutics 32 2 (2009): 160-6 .

STIMULANTS – COCAINE AND…

• Levamisole

• ANCA positive vasculitis

• Local or systemic

Arora, N. P., Jain, T., Bhanot, R., & Natesan, S. K. (2012). Levamisole-induced leukocytoclastic vasculitis and

neutropenia in a patient with cocaine use: An extensive case with necrosis of skin, soft tissue, and cartilage.

Addiction Science and Clinical Practice, 7(1). https://doi.org/10.1186/1940-0640-7-19Sebastian, SM; Otero, R; Valdez, E; Fonseca, AA; Okanlawon, A; Kwang, H. READING BETWEEN THE LINES: LEVAMISOLE INDUCED

NECROSIS SYNDROME SECONDARY TO COCAINE USE. Abstract published at Hospital Medicine 2020, Virtual Competition. Abstract 1028

Journal of Hospital Medicine. https://shmabstracts.org/abstract/reading-between-the-lines-levamisole-induced-necrosis-syndrome-

secondary-to-cocaine-use/. June 13th 2021.

https://shmabstracts.org/abstract/reading-between-the-lines-levamisole-induced-necrosis-syndrome-secondary-to-cocaine-use/

STIMULANTS – COCAINE AND…• Levamisole

• Alcohol

• Cocaethylene

• More euphoric

• Longer half-life

• More cardiotoxic and hepatotoxic

Jones, Alan. (2019). Forensic Drug Profile: Cocaethylene. Journal of analytical toxicology. 43. 10.1093/jat/bkz007.

Cocaine half life is 1

hour → cocaethylene is

2 hours

Cardiotoxic (especially

the Na+ and K+ channel

effects

QUESTION!!!Which of the following is false regarding dental disease among people

who use methamphetamine?

A. Oral health behaviors (brushing) are the most important determinant

of dental health

B. Smoking methamphetamine is more damaging to the teeth than

snorting or injecting

C. People who use methamphetamine drink more sugary beverages

than the general population

D. Bruxism, xerostomia, and poor access to dental healthcare all

contribute to dental disease

STIMULANTS – METH AND DENTAL HEALTH• Study: rates of moderate and severe periodontitis were 54.8% and 22.9%

• Compared 5% of age matched group from the 1999 – 2004 NHANES

• More frequent meth use did not increase risk for severe periodontitis

• No difference seen in route of administration (Smoking vs. snorting vs. IV)

These studies 80% men, 42% AA, 31% Hispanic, mean age was 44, 25% HIV positive,

70% were smokers, 34% took xerogenic medications; 64% used MA > 15 days per

month; 53% smoked exclusively36

STIMULANTS – METH AND DENTAL HEALTH• Likely contributing factors

• Age

• Likely more than years of use


• Age

• Bruxism

• Xerostomia

• Saliva inhibits strep mutans colony and biofilm formation

• Saliva acts as a pH buffer

a. Severity of xerostomia did not correlate w/ having more carries, but did correlate with severities of carries36

b. Neither mode nor frequency of meth use influenced severity of xerostomia36


• Age

• Bruxism

• Xerostomia

• Sugary beverage intake

• Study: 3.5 sugary drinks per day (2.7 when adjusted for outliers)

• Other Studies have estimated 35.3 sodas per month

• NHANES cohort drank 0.3 sugary drinks per day


• Age

• Bruxism

• Xerostomia

• Sugary beverage intake

• Dental Healthcare

• Teeth Brushing

• Study: Frequent tooth brushing was the highest impact variable

Lee HH, Sudhakara P, Desai S, Miranda K, Martinez LR. 2021. Understanding the basis of METH mouth using a rodent model of methamphetamine injection, sugar consumption, and Streptococcus mutans infection. mBio 12:e03534-20.

https://doi.org/ 10.1128/mBio.03534-20.

https://doi.org/

QUESTION!!!Which of the following is false regarding dental disease among people

who use methamphetamine?

A. Oral health behaviors (brushing) are the most important determinant

of dental health

B. Smoking methamphetamine is more damaging to the teeth than

snorting or injecting

C. People who use methamphetamine drink more sugary beverages

than the general population

D. Bruxism, xerostomia, and poor access to dental healthcare all

contribute to dental disease

CNS DEPRESSANTS• Aspiration pneumonia

• Opioids

• Benzos

• Alcohol

• Immobilization

• Compressive neuropathy

• Compressive rhabdomyolysis

• Compartment Syndrome

Arora, N. P., Jain, T., Bhanot, R., & Natesan, S. K. (2012). Levamisole-induced leukocytoclastic vasculitis and neutropenia in a patient with cocaine use: An extensive case with necrosis of skin, soft tissue, and cartilage. Addiction Science

and Clinical Practice, 7(1). https://doi.org/10.1186/1940-0640-7-19

Radial Nerve Palsy

ALCOHOL – LIVER DISEASE• Injury

http://themedicalbiochemistrypage.org/ethanol-alcohol-metabolism-acute-and-chronic-toxicities/

↑ fatty Acid Synthesis

Binds to DNA, proteins, and glutathione


• Direct injury from ETOH and metabolites

• Induced CYP 2E1 → free radicals →↑ oxidative stress

Leiber, 2004

i. CYPP2E1 is expressed in mitochondria and ER, has high NADPH oxidase activity → free radicals

→ damage to mitochondria dna and other macromolecules 48

ii. 10 fold increase in people who recently drank6



• Induced CYP 2E1 → free radicals →↑ oxidative stress

• Changes to carbohydrate/lipid metabolism

→ steatosis

→ ↑ increased inflammation



• Induced CYP 2EI → free radicals →↑ oxidative stress

• Changes to carbohydrate/lipid metabolism

• ETOH impairs intestinal barrier

→ bacterial particles travel to the liver

→ Bind to TLRs on hepatic Kupffer cells

→ inflammatory cascade

ETOH disrupts the gut microbiome (dysbiosis)

Endotoxins (LPS & other particles from bacteria are known as PAMPs)

Lackner, 2018

ALCOHOL – LIVER DISEASE• Centrilobular injury

• Fibrosis progresses and becomes Cirrhosis

• Dx

• Liver biopsy

• Transient elastography

• Serum tests - Enhanced Liver Fibrosis Test and Fibrotest

• Staging

• Child-Pugh

• MELD

FIB4 and APRI don’t work well in ETOH

ALCOHOL – LIVER DISEASE• Loss of hepatocyte function

• Coagulopathy

• Thrombocytopenia

• Hypoalbuminemia

• Ammonia accumulates in circulation → Hepatic Encephalopathy

• Impaired conjugation and decreased bilirubin excretion → Jaundice

• Decreased hepatic clearance of vasoactive compounds leads to

splanchnic and systemic arterial vasodilation → Decreased SVR

ALCOHOL – LIVER DISEASE• Loss of hepatocyte function (cont.)

• Accumulation of vasodilators

• Cirrhotic Cardiomyopathy

• Hepatorenal Syndrome

• Hepatopulmonary Syndrome

ALCOHOL – LIVER DISEASE• Loss of hepatocyte function

• Impaired blood flow through liver → ↑ portal system pressure

• Ascites

• Esophageal varices

• Splenomegaly

Premkumar, Madhumita & Rangegowda, Devaraja & Sahney, Amrish & Vyas, Tanmay. (2015). Cardiac Cirrhosis

May Present Ten Years after Pericardiectomy for Chronic Constrictive Pericarditis. Journal of Gastrointestinal &

Digestive System. s13. 10.4172/2161-069X.S13-002.

Esophageal Varices; Causes, Symptoms, Diagnosis & Treatment

https://my.clevelandclinic.org/health/diseases/15429-esophageal-varices Accessed: 2021-06-13

https://my.clevelandclinic.org/health/diseases/15429-esophageal-varices

ALCOHOL -- NEUROLOGICAL• Wernicke-Korsakoff Syndrome

• Thiamine deficiency

• Thiamine homeostasis

• Absorbed in GI tract

• Food

• Colonic bacteria make TPP

• Reabsorbed in the kidney

• Stored in liver and brain


• Thiamine deficiency results in

• Cell death

• Increased BBB permeability

• Areas of high metabolic activity

• Mammillary bodies

• Thalamus

• Periaqueductal grey

• Tectum

• Cerebellum

• Cranial nerve nuclei


• Thiamine deficiency

• Classical findings

• Ophthalmoplegia

• Mental status changes

• Ataxia

Harper CG, Giles M, Finlay-Jones R. Clinical signs in the Wernicke-Korsakoff complex: A retrospective analysis of 131

cases diagnosed at necropsy. J Neurol Neurosurg Psychiatry. 1986;49(4):341-345. doi:10.1136/jnnp.49.4.341


• MRI is highly specific, poor sensitivity

Sullivan, E. V., & Pfefferbaum, A. (2009). Neuroimaging of the Wernicke-Korsakoff syndrome. Alcohol and Alcoholism, 44(2), 155–165. https://doi.org/10.1093/alcalc/agn103


• MRI is highly specific, poorly sensitive

• Caine Criteria (drink >80g ETOH for most of their adult life)

• Positive = 2 out of 4

• Eye Signs

• Cerebellar signs

• Mild memory impairment or confusion

• Signs of malnutrition


• Suspicion = treat

• 200mg – 500mg IM or IV thiamine TID

• Even with thiamine, 56 – 84% will go on to KS

ALCOHOL -- CARDIOVASCULAR• HTN

• Holiday heart

• Alcoholic Cardiomyopathy

• Non-Ischemic Dilated cardiomyopathy

Cardiomyopathy - Symptoms and causes - Mayo Clinic https://www.mayoclinic.org/diseases-conditions/cardiomyopathy/symptoms-causes/syc-20370709 Accessed: 2021-06-13

https://www.mayoclinic.org/diseases-conditions/cardiomyopathy/symptoms-causes/syc-20370709

• HTN

•Increased sympathetic tone

•Increased corticotropin releasing hormone → increased cortisol

•Increased activation of the RAAS System

•Increased endothelial intracellular Ca++ concentrations → increased sensitivity to vasoconstrictors

• Holiday heart

• Typically a supraventricular arrhythmias

• Associated w/ binge alcohol intake

• Can occur w/o evidence of cardiac disease

• Symptoms resolve and do not recur if ETOH abstinence is achieved

• Can range from asymptomatic to palpitations, chest pain, dyspnea, or syncope

• (a. fib being the most common, may also present as a. flutter, A tach, PVCs)

• ETOH Cardiomyopathy

• Ethanol and acetaldehyde affect mitochondrial function, intra-myocyte calcium homeostasis,

increased oxidative stress, impaired protein synthesis, decreased contractile proteins, increased

apoptosis, inflammation

• Non-Ischemic Dilated cardiomyopathy

• Hypertrophy w/ interstitial fibrosis

• Thin ventricular wall w/ decreased contractility

ALCOHOL -- PANCREATITIS• Increases viscosity of pancreatic secretions → small ducts are occluded by

plugs → caliculi → tissue injury

Introduction to Pancreatic Disease: Acute Pancreatitis | Pancreapedia, https://www.pancreapedia.org/reviews/introduction-to-pancreatic-disease-acute-pancreatitis Accessed: 2021-06-13

https://www.pancreapedia.org/reviews/introduction-to-pancreatic-disease-acute-pancreatitis

ALCOHOL -- CANCER• Causal agent in (with dose dependent effect – amount and time)

• Oral cavity

• Pharynx

• Larynx

• Esophagus (squamous cell)

• Liver (HCC)

• Colorectum

• Breast

• High suspicion for

• Pancreatic

• Gastric

ALCOHOL – TOXIC ALCOHOLS

Kraut JA, Mullins ME. Toxic Alcohols. Campion EW, ed. N Engl J Med. 2018;378(3):270-280. doi:10.1056/NEJMra1615295



• Ethylene Glycol (Antifreeze, hydraulic brake fluid, coolant)

• Seizure, abdominal pain, n/v, HA; hematuria

• Ca++ and oxalic acid → calcium oxalate

• Renal injury

• Hypocalcemia

• Sometimes co-formulated with fluoresceine



• Methanol (cleaning agents, automotive fluids)

• Abdominal pain, HA, n/v, vision changes (blindness), parkinsonism

• Formic acid → inhibition of cytochrome oxidase

• Retina and basal ganglia (also Caudate, putamen, optic nerve)



• Isopropyl alcohol

• n/v, abdominal pain, hemorrhagic gastritis

• May cause ketosis without metabolic acidosis or anion gap

• Acetone in serum can interfere w/ creatine assay → false

positive for renal injury/failure



Fomepizole

QUESTION

A 22 y/o Air Force cadet w/ progressive stocking glove sensory deficits

(characterized by impaired proprioception and vibratory sense) and ataxic

gait was referred to neurology after an MRI spine was read as c/f Multiple

Sclerosis.

A robust laboratory evaluation was obtained and includes the values below:

CBC: WNL

B12 Level: WNL

Homocysteine Level: Elevated

Methylmalonic Acid level: Elevated

Urine Drug Screen: Negative

PEth: WNL

QUESTIONCBC: WNL

B12 Level: WNL


Methylmalonic Acid level: Markedly elevated


PEth: WNL

The best course of treatment for this patient will likely include:

A. IM Cobalamin

B. IV thiamine followed by oral thiamine

C. Penicillin G Benzathine

D. IV Vancomycin

INHALANTS• LOC

• Anoxic brain injury

• Cardiac Arrest (Aka: Sudden Sniffing Death)

• Falling injury

• Chronic use leads to CNS injury

Put A Plastic Bag Over Your Head To Make You Pass Out So Work Feels Shorter | Funny tips, Funny

wallpaper, Life hacks https://www.pinterest.com/pin/422281196350678/ Accessed: 2021-06-13

https://www.pinterest.com/pin/422281196350678/

INHALANTS – NITROUS OXIDE (NOS)• Subacute combined degeneration of the spinal cord

• N2O Causes oxidation of cobalt ions in vitamin B12 → inactivation

• ↓ methylation of myelin sheath phospholipids → demyelination

Al-Sadawi M, Archie C, Claris H, Jayarangaiah A, I. McFarlane S. Inhaled Nitrous Oxide ‘Whip-Its!’ Causing Subacute Combined Degeneration. Am J Med Case Reports. 2019;6(12):237-240. doi:10.12691/ajmcr-6-12-3

INHALANTS -- NOS• Subacute combined degeneration of the spinal cord

• Starts with dorsal column lesions, may → lateral corticospinal tract

Jiang J, Shang X. Clinical-radiological dissociation in a patient with nitrous oxide-induced subacute combined degeneration: A case report. BMC Neurol. 2020;20(1):99. doi:10.1186/s12883-020-01685-5

INHALANTS -- NOS• Subacute Combined Degeneration of the spinal cord

• Most frequently presenting symptoms

• Sensory disturbances (First in LE, may advance to UE) +/- ataxia

• Labs

• Hgb: normal or low

• MCV: normal or high

• Vitamin B12: Normal or low

• Methylmalonic Acid (MMA): Elevated

• Homocysteine: elevated

Al-Sadawi M, Archie C, Claris H, Jayarangaiah A, I. McFarlane S. Inhaled Nitrous Oxide ‘Whip-Its!’ Causing Subacute Combined Degeneration. Am J Med Case Reports. 2019;6(12):237-240. doi:10.12691/ajmcr-6-12-3

INHALANTS -- NOS• Subacute combined degeneration of the spinal cord

• Treatment consists of Vit B12 supplementation

• IM hydroxycobalamin 1mg QOD until neuro exam stops improving

• Then 1mg Q60days

• IM B12 1.5mg Qday + PO folic acid 15mg per day

• PO Methylcobalamin 500 mcg TID + PO Vitamin B1 TID for 1 month

QUESTIONCBC: WNL

B12 Level: WNL


Methylmalonic Acid level: Markedly elevated


PEth: WNL

The best course of treatment for this patient will likely include:

A. IM Cobalamin

B. IV thiamine followed by oral thiamine

C. Penicillin G Benzathine

D. IV Vancomycin

OPIOIDS• Respiratory suppression and overdose

• Hypogonadism

• 9-29% of chronic opioid users

• Direct suppression of hypothalamic-pituitary-gonadal/adrenal axes

• Decreased sexual function

• Irregular menses or amenorrhea

• Osteopenia/osteoporosis

ANABOLIC STEROIDS• Cardiovascular/heme/metabolic

• MI and stroke

• Accelerate atherosclerosis

• Increase LDL, decrease HDL

• Promote platelet aggregation, prothrombotic

• Polycythemia

• Glucose intolerance

• Skin

• Acne

• MSK

• Tendon rupture

ANABOLIC STEROIDS

• Male

• Testicular atrophy

• Oligo-azospermia

• Hair loss

• Gynecomastia

• Prostate hypertrophy and cancer

• Renal Carcinoma

• Female

• Hirsutism

• Menstrual irregularities,

amenorrhea

• Clitoral hypertrophy

• Uterine atrophy

• Stigma plays a significant role in exacerbating health issues faced by PWUD

• Route of administration can be a key determinant of what health effects PWUD experience

• For stimulants, most health effects are due to catecholamine surge, endovascular effects, an prothrombosis

• Alcohol and its metabolites are directly toxic and lead to large increases in oxidative stress. Alcohol decreases the absorption of micronutrients while increasing the absorption of bacterial particles

• Chronic inhalant use can damage the nervous system either due to its lipophilic nature or by direct inactivation of micronutrients

SUMMARY/TAKEAWAYS

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ROUTES OF ADMINISTRATION - INHALATION• Nicotinic stomatitis

• Inflammation → Keratosis of palatal epithelium and minor salivary glands

• papules w/ punctate red centers

• Mostly Pipe smokers, cigar, Reverse smoking

http://www.exodontia.info/Nicotinic_Stomatitis.htmlhttp://www.exodontia.info/NicotinicStomatitis.html

Harini G, Krishnam Raju K V, Raju DK, Chakravarthy K K, Kavya S N. Psychosocial

factors associated with reverse smoking: A qualitative research. J Int Soc Prevent

Communit Dent [serial online] 2016 [cited 2021 Jun 12];6:529-34. Available from:

https://www.jispcd.org/text.asp?2016/6/6/529/195521

Cardiovascular Effects

of Meth

Fuster, 2018

Schematic of

effects of

Alcohol

Tanwar, 2020

Centrilobular location of

injury from Alcohol use -

This area is more

metabolically active

ALCOHOL – LIVER DISEASE• Centrilobular Injury leads to

• Lipid accumulation within hepatocytes

• Inflammation and fibrosis

• Alcoholic Hepatitis

• Maddrey’s discriminant function of >32 = Severe AH

• 30 – 50% mortality at 30 days

• Five year survival after hospitalization

• Abstinent from ETOH: 75.3%

• Return to use: 26.8%

• Continued use 21.0%

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