Treatment Risks vs. Treatment Opportunitiesaardvarksfly.com/files/Adverse_Drug_ReactionsREV2pdf.pdf“SJS is a serious systemic disorder with the potential for severeSJS is a serious

A D RAdverse Drug ReactionsTreatment Risks vs. Treatment Opportunities

By J. Hoyt

Adverse Drug Reactions: An Overview

Definition:“Drug or device-associated ADR that results in

death, severe organ failure, or precipitates major g jtherapeutic interventions” – Prolonged hospitalization not included

RADAR Project

ADRs: Incidence Rates

Incidence Rates:major cause of hospital admissionsmajor cause of hospital admissionsrecent data on ADRs that develop following hospital treatment is

lacking

“Adverse drug reactions are a significant cause of morbidity and mortality. “

JAMA 2004

“We estimated that in 1994 overall 2216000 (1721000-2711000)( )hospitalized patients had serious ADRs and 106000 (76000-137000) had fatal ADRs, making these reactions between the fourth and sixth leading cause of death.”

JAMA 1998


Incidence of Adverse Drug Reactions in Hospitalized Patients A Meta-analysis of Prospective Studies Jason Lazarou, MSc; Bruce H. Pomeranz, MD, PhD; Paul N. Corey, PhD JAMA.1998;279:1200-1205. Objective.— To estimate the incidence of serious and fatal adverse drug reactions (ADR) in hospital patients.reactions (ADR) in hospital patients.Data Sources.— Four electronic databases were searched from 1966 to 1996.Study Selection.— Of 153, we selected 39 prospective studies from US hospitals.Data extracted independently by 2 investigators were analyzed by a random-effects model. To obtain the overall incidence of ADRs in hospitalized patients, we combined the incidence of ADRs occurring while in the hospital plus the incidence of ADRs causing admission to hospital. We excluded errors in drug administration, noncompliance, overdose, drug abuse, therapeutic failures, and possible ADRs. Serious ADRs were defined as those that required hospitalization, were permanently disabling, or resulted in death.Data Synthesis.— We estimated that in 1994 overall 2216000 hospitalized patients had serious ADRs and 106000 had fatal ADRs, making these reactions between the fourth and sixth leading cause of death.


High Level Of Adverse Drug Reactions In Hospitals Found“I t d f th 3 000 ti t h t th“In a study of more than 3,000 patients, researchers at the University of Liverpool have found that one in seven admitted to hospital experience adverse drug reactions to medical treatment.”

S i D il (F b 12 2009)ScienceDaily (Feb. 12, 2009)

“It i ti t d th t d d ti ff t 2 illi l“It is estimated that adverse drug reactions effect 2 million people each year solely in the United States.”

New England Journal of Medicine (08/21/08)

ADRs: Solving the Problem

Center for Drug Evaluation and ResearchCenter for Drug Evaluation and Research

RADAR

Pharmocogenomics

Traditional Chinese Medicine

ADRs: FDA and CDER

Preventable Adverse Drug Reactions:Preventable Adverse Drug Reactions: A Focus on Drug Interactions

This learning module was developed based on a needs survey sent to g p yall third year medicine clerkship directors and all medicine residency program directors in the United States. This module was developed by the Center for Education and Research on Therapeutics (CERT) while at Georgetown University (CERT now located at the University of Arizona HeGeorgetown University (CERT now located at the University of Arizona Health Sciences Center) in collaboration with the Center for Drug Evaluation and Research at the Food and Drug Administration. The work was sponsored by the Agency for Healthcare Research and Quality (AHRQ).

ADRs: FDA and CDER

ADRs: FDA and CDER

ADRs: FDA and CDER

ADRs: FDA and CDER

ADRs: FDA and CDER

ADRs: RADAR

Introducing RADAR: The Research on Adverse Drug Events And Reports (RADAR) ProjectEvents And Reports (RADAR) Project

Reasons for RADAR•ADRs account for 100 000 deaths annually•ADRs account for 100,000 deaths annually •> half 45 ADRs identified >7 yrs following FDA approval •Size of many licensing clinical trials is too small to identify rare but serious ADRsrare but serious ADRs •MedWatch many limitations

Difficulties Reporting Rates/ Incidence Estimation•Reporting rates: 1-10% of ADRs reported to MedWatch

ADRs: Pharmocogenomics

Definition and Application:Individualization of drug therapies based on genetic informationOptimizing drug therapy with genetic informationOptimizing drug therapy with genetic information

“In the future, we may all carry a "gene chip assay report" thatcontains our unique genetic profile that would be consulted before q g pdrugs are prescribed. However, the application of pharmacogenomicsinformation faces significant challenges, and further basic science, clinical, and policy research is needed to determine in what areas pharmacogenomics can have the greatest impact, how it can be incorporated into practice, and what are its societal implications. “

JAMA 2000

TCM/Case Study

Sallie, 17y/o, Asian, high school student, 5’0’’, 119lbs before SJS, lives at home

Diagnosis: Stevens Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TENS)

Disease Progression: please see following slides

Surgical History: none.

Major Illness History: When 9y/o, was admitted to hospital with black splotches on entire body, hands swollen, difficulty walking, joint pain. Tests run; inconclusive but showed no kidney involvement. Skin cleared,; y ,joint pain and swelling subsided within 2 weeks. No medication given.

Medication History: Patient unsure of ibuprofen usage; says seldom used. Used amoxicillin twice previously; never used bactrim; cannot recall using anyUsed amoxicillin twice previously; never used bactrim; cannot recall using any other antibiotics

TCM/Case Study: SJS and TENS

Definition:Rare, serious disorder of the skin and mucous membranesRare, serious disorder of the skin and mucous membranesSpecific type of allergic reaction in response to medicationSJS and TENS variants of same process

t l i

M F d ti f M di l Ed ti d R h

presents severe mucosal erosionsSJS = epidermal detachment >10% of total body skintransitional SJS-TENS = epidermal detachment between Mayo Foundation for Medical Education and Research

p10%-30%

TENS = detachment greater than 30%“Often Stevens-Johnson syndrome begins with several days ofOften, Stevens Johnson syndrome begins with several days of flu-like symptoms, followed by inflammation of your mucous membranes and a painful red or purplish rash that spreads and blisters, eventually causing the top layer of your skin to die and , y g p y yshed.” Mayo Foundation for Medical Education and Research


Incidence:Cases tend to have a propensity in the early spring and winterCases tend to have a propensity in the early spring and winterMale to Female ratio is 2:1

“I th U it d St t th b t 5000 h it li ti h


“In the United States, there are about 5000 hospitalizations each year with a primary diagnosis of erythema multiform, Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis, of which 35% are specifically ascribed to drugs Annually there are more thanMayo Foundation for Medical Education and Research are specifically ascribed to drugs. Annually, there are more than 100,000 outpatient visits for these diagnoses and about two million visits for immediate hypersensitivity reactions that may be due to drugs Outpatient visits for drug eruptions and drugbe due to drugs. Outpatient visits for drug eruptions and drug allergies that include a skin component exceed 500,000 annually.”

Robert S. Stern, MD, Harvard Medical School, 2004


“SJS is a serious systemic disorder with the potential for severeSJS is a serious systemic disorder with the potential for severe morbidity and even death. Missed diagnosis is common.”

“Cutaneous eruptions are the most frequently reported adverse


Cutaneous eruptions are the most frequently reported adverse reaction to drugs, and most medications have a 1% to 3% risk of producing immunologic manifestations. Drug-induced allergic reactions occur in approximately 5% of the populationMayo Foundation for Medical Education and Research allergic reactions occur in approximately 5% of the population, and these reactions are responsible for approximately 6% to 10% of all ADRs. Of all medication classes, b-lactam antibiotics, sulfonamides, and nonsteroidal anti-inflammatory , , ydrugs (NSAIDs) are responsible for 80% of all reports of allergic and pseudoallergic reactions.”John Hopkins Medicine/Arch Dermatol 2000

TCM/Case Study: Disease Progression

Disease/Hospitalization History:

1/19 Body aches, trouble walkingAdmitted to ER for tests, sent homeDx: Urinary Tract InfectionDx: Urinary Tract InfectionTx: Bactrim for UTI; Motrin for fever

1/29 Finished medication

2/2 Afternoon: Red face; slight fever, body acheNight: same with skin lesions: flat, red, itchy burning, small like pinpricks later expandingp p p g

2/3 Morning: Admitted to ER, sent homeDx: Viral InfectionTx: Amoxicillin for VI; continued Motrin for feverTx: Amoxicillin for VI; continued Motrin for fever


2/5 Morning: Admitted to ER, transferred to Loyola University Hospital Burn UnitDx: SJS; 3rd degree burnsTx: cessation of all medication; IV for feeding/hydration only

Visual Observation by mother:Skin: swollen, red at wrists, knees, ankles, hips; blisters beginning toform filled with clear fluid; blisters worst on back, less on legs; blisters

th 85% f b dmore than 85% of bodyTongue: swollen, red, yellow, blisters beginning to form on tip

2/6 Visual Observation: Same as above with:Tongue: thick, yellow coat, beginning to turn black, blisters on tongueSkin: blistering on all observable surfacesFever: 103 to 105 degrees; heat raising off body especially by heartEvery surface I could observe was swollen almost beyond recognitionEvery surface I could observe was swollen almost beyond recognition


2/9 Visual Observation: Same as above with:Tongue: swollen, black, blisters on tongue and in back of throat;g gLips: cracked, bleeding, very painfulEyes: cloudy, white dischargePatient swallows only liquids with difficulty; small amount of cold liquidsSkin: blisters on all observable skin surfaces (hands face neck) fillingSkin: blisters on all observable skin surfaces (hands, face, neck) filling

with bloodFace: blisters seem to be crawling up face; immediate eye area and

forehead only blister free regionsPatient’s weight has gone up 10 poundsBreathing: before Reiki: shallow. Patient says has stuffy nose.

after Reiki: deep, harsh, rhythmic

2/10 Visual Observation: Same as above with:Skin: bleeding on all observable surfaceEyes: yellow, sticky dischargeF d i bl d t i f h d bl kFace: covered in blood up to eye region; forehead blackSpirit: some disorientation


2/11 Visual Observation: Tongue: pink, shaking slightly, no blistersLips: cracked not as much bleedingLips: cracked, not as much bleedingEyes: no dischargeFace: blood on skin beginning to clearPatient’s weight down 5 pounds

2/12 Visual Observation:Tongue: pink, slight white coat; blisters still at back of throatFace: most blood cleared beginning to peelFace: most blood cleared, beginning to peelSkin: lesions flat; still red; on joints no bleeding; on trunk especially clavicle area flat but bleeding; very painfulIntense lower back painU i ll /St lUrine: yellow/Stool: noneHunger/thirst: not hungry; small sips of cold liquidPhysical Therapy: can barely move legs, ankles, arms, hands

Range of motion exercise most difficult; smaller motions easierRange of motion exercise most difficult; smaller motions easierPerspiration: Back hot and moist; hands/feet coldTemperature: 100 degrees

TCM/Case Study: pictures 2/12





TCM/Case Study: Differential Diagnosis

Eight Parameters: hot, interior, excess, yangFour Channels: Blood levelAt this stage the pathogen has entered into the Blood As the HeartAt this stage, the pathogen has entered into the Blood. As the Heart controls the Blood and the Liver stores the Blood, both organs are affected.A significant symptom of this stage is bleeding. The bleeding is due to Heat in the Blood; it may occur throughout the body. The skin may bleed, the

Li

:

mouth, nose, anus, etc. This stage is considered the final stage and is usually the terminal stage of a febrile disease. At this stage, people usually die very quickly. These symptoms are excess heat symptoms.Zang Fu: Lungs Liver Heart LiveZang Fu: Lungs, Liver, HeartPathogen originated in blood supply, stored by Liver, generating Liver heat.Lungs unable to control liver; skin is affected.Heart not able to control blood results in bleeding; sweat also a fluid of theHeart not able to control blood results in bleeding; sweat, also a fluid of the Heart is generated especially in chest region.Meridians: Lung, Liver, and SpleenBesides the loss of function the paths of these organs most closelyBesides the loss of function, the paths of these organs most closely correspond with the worst blistering and bleeding on patient’s bodyTCM Pattern: Blood Heat/Liver Heat (an excess pattern)

TCM/Case Study: Differential Diagnosis

Pathological influences between an excessive Liver and other organs

HeartHeartLungsLungsLungs failing

to control Liver

Li

LungsLungs

Liver heat

to control Liver

LiveLiverLiverExcessiveExcessive

Liver heatleading toHeart failing to control blood

SpleenSpleenLiver

over-actingS lon Spleen

TCM/Case Study: TreatmentB f ki bli t i d bl di dl t i di t dBecause of skin blistering and bleeding, needles are contraindicated. These points are to be accessed through qigong, vibratory therapy (tuning forks), and/or mineral substances.

withwithSI18

Ashi point, meeting point of SI and SJalleviates pain, clears heat, reduces swelling of

face, indicated for red face, yellow eyes

SI18

Live

SP63 yin intersection

resolves dampness; harmonizes LV, calms spirit

Ren17Front Mu of PC, Hui-Mtg point of Qi, Sea of Qi

Reinforces HT function of governing blood

LU6 LV4

withwith

LiveLU6Xi-cleft of LU

clears heat, moistens the LU, stops bleeding,moderates acute conditions

withwithLV4

Jing River point and metal point of LV channelclears LV channel stagnant heat

LU1 LU11LU1Front Mu of LU, Meeting Pt of LU/SP

clears heat, indicated for heat in chest, skin pain withwithLU11

Jing well pointClears heat, indicated for extreme excess

conditions

PC6withwith

PC6Luo of PC, MC of Yin Wei Mai, chest command ptregulates HT, calms spirit, clears heat, indicated

for cracked and bleeding tongue

SJ5Luo of SJ, MC of Yang Wei Mai

clears heat, indicated for pain of 100 joints

TCM/Case Study Update

2/20Observation:Skin: Healing peeling still red in ankle areasSkin: Healing, peeling, still red in ankle areas Tongue: Pink, slightly red on sides and tipEyes: NormalPulse: Slightly weak right side, strong left sidePhysical mobility: limited, muscular sorenessUrination: frequent; weight 114lbs. Urine Color: canary yellow (B vitamins)Body temperature: no feverBody temperature: no fever,

slightly cool to touchSpirits: Great!

TCM/Case Study Update: pictures





ADRs and TCM: a Treatment Opportunity

Wh ti t i di d ith SJS/TENS ll tWhen a patient is diagnosed with SJS/TENS, all western medicine treatments stop. How can TCM fill this void?

If diagnosed early, can TCM slow the progression of SJS/TENS symptoms ie lesions fever etc ?SJS/TENS symptoms, ie lesions, fever, etc.?

If presented with SJS/TENS at a fully developed stage, can TCM lessen the risk of future SJS/TENS re-occurrence,blindness or organ failure?

Thank You especially to Sallie for sharing her story

and to Brett for the missing statistic

Treatment Risks vs. Treatment Opportunitiesaardvarksfly.com/files/Adverse_Drug_ReactionsREV2pdf.pdf“SJS is a serious systemic disorder with the potential for severeSJS is a serious

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