Transcript Medical Errors: Definition, Causes, and Prevention

‫&‬
‫‪Iran ADR Center‬‬
‫دكترپارسائي‬
‫گروه فارماكولوژي دانشكده پزشكي‬
ADR
(Adverse Drug Reaction)
WHO definition:
Any response to a drug which is Noxious
and Unintended
and which occurs at doses used in man for prophylaxis, diagnosis
or treatment.
‫هرگونه پاسخ داروئي مضرو نامطلوبي كه با دوز معمولي دارو‬
‫ تشخيص و يا درمان ايجاد شده‬،‫درانسان جهت پيشگيري‬
‫باشد‬
‫اصطالحات رايج‪:‬‬
‫عوارض كم اهميت و مختصر‬
‫‪*Side Effects‬‬
‫عوارض مهم و كامال نا خوشايند ‪Reaction‬‬
‫اثرات سمي مستقيم دارو (غالبا دوز باال (‬
‫آثارثانوي غيرمستقيم‬
‫‪Effects‬‬
‫‪* Adverse‬‬
‫‪* Toxicity‬‬
‫‪* Secondary‬‬
‫عدم تحمل بدليل آستانه پايين پاسخ دهي ‪* Intolerance‬‬
‫پاسخ غيرنرمال بدليل اختالل ژنتيكي ‪* Idiosyncrasy‬‬
Why Should We Learn about
Adverse Drug Reactions (ADR)?
 Over 2 MILLION serious ADRs yearly
 100,000 DEATHS yearly
 6.7% of hospitalized patients have an ADR
with a fatality of 0.32
Ref: U.S. Food and Drug Administration . Center for Drug Evaluation and Research
Annual death rates in USA
AIDS
 Breast cancer


Highway accidents
 ADR
16,516
42,297
43,458
100,000
percentage of hospital admissions
due to ADR:
USA
UK
France
Norway
28%
15.6%
12.6%
11.5%
Costs Associated with ADRs
 $ 136 BILLION yearly (related to morbidity and mortality)
 Greater than total costs of cardiovascular or diabetic care.
The total cost of drug-related morbidity and
mortality exceeds the cost of the medications
themselves.
Ref: U.S. Food and Drug Administration . Center for Drug Evaluation and Research
The cost of adverse drug events: estimated lost patient
activity days per year in hospitalised patients
Country
US
Germany
UK
Australia
Sweden
Serious ADRs
700,000
206,000
148,000
48,000
22,000
Lost Activity Days
1,218,000
358,440
257,520
83,520
38,280
ADR has financial and social effects:
1- Unreliability on manufacturer
2- Unreliability on health system
(Physician, Pharmacist & Nurse)
3- Unreliability on governments in
saving the social safety
4- Causing mortality & morbidity
 Tow-thirds of patients visits result in a prescription
 2.8 BILLION outpatients prescriptions were filled in the
year 2000 (about 10 prescriptions per person in the U.S.)
 ADRs increase exponentially with 4 or more medications
Ref: U.S. Food and Drug Administration . Center for Drug Evaluation and Research
So many prescriptions!
Even more, dramatic situation with drug
safety is in developing countries (IRAN)
• They often have older, cheaper drugs which may be
more toxic.
• Health professional have less opportunity for postgraduate education on clinical pharmacology.
• Useful,easily available, balanced information on
adverse effects and their management is absent or not
enough.
•
Ref:World Health Organization
‫طبقه بندي عوارض جانبي )‪(A-E‬‬
‫انواع اصلي‪:‬‬
‫•‬
‫نوع ‪)Augmented) A‬‬
‫• نوع ‪B‬‬
‫)‪)Bizarre‬‬
‫انواع فرعي‪:‬‬
‫• نوع ‪)Continuos) C‬‬
‫• نوع ‪) Delayed) D‬‬
‫• نوع ‪) Ending of use) E‬‬
‫مقايسه عوارض جانبي نوع ‪ A‬و ‪B‬‬
‫‪A‬‬
‫•‬
‫•‬
‫•‬
‫•‬
‫•‬
‫قابل پيش بيني ‪+‬‬
‫وابستگي به دوز ‪+‬‬
‫ميزان شيوع‬
‫كم‬
‫مرگ و مير‬
‫درمان‬
‫‪B‬‬
‫‬‫‬‫كم‬
‫زياد‬
‫زياد‬
‫تنظيم دوز‬
‫قطع مصرف‬
Some drugs cause serious ADRs at
very low frequencies
 bromfenac hepatotoxicity
1 in 20,000 patients,
removed from the market in 1998,
less than 1 year after it was
introduced).
•
Ref: U.S. Food and Drug Administration . Center for Drug Evaluation and Research
‫چگونه يك عارضه جانبي به‬
‫دارو نسبت داده ميشود؟‬
‫شرايط ارزيابي ارتباط عارضه جانبي با دارو‬
‫‪ -1‬ارتباط منطقي بروزعارضه با زمان مصرف دارو‬
‫‪ -2‬ارتباط عارضه با خصوصيات شناخته شده دارو‬
‫‪ -3‬رفع عارضه با قطع مصرف دارو‬
‫‪ -4‬عود عارضه با شروع مصرف مجدد دارو‬
‫‪ -5‬توجيه منطقي ارتباط عارضه با بيماري مريض يا ‪...‬‬
‫بررس ي ارتباط عارضه جانبي با دارو‬
‫ارزيابي ارتباط‬
‫‪1‬‬
‫‪2‬‬
‫‪3‬‬
‫‪4‬‬
‫‪5‬‬
‫‪Definit‬‬
‫‪+‬‬
‫‪+‬‬
‫‪+‬‬
‫‪+‬‬
‫‪0‬‬
‫احتمالي‬
‫‪Probable‬‬
‫‪+‬‬
‫‪+‬‬
‫‪+‬‬
‫‪0‬‬
‫_‬
‫ممكن‬
‫‪Possible‬‬
‫‪+‬‬
‫‪+‬‬
‫‪0‬‬
‫‪0‬‬
‫‪+‬‬
‫مشروط‬
‫‪Conditional‬‬
‫‪+‬‬
‫_‬
‫‪0‬‬
‫‪0‬‬
‫_‬
‫‪0‬‬
‫‪0‬‬
‫‪0‬‬
‫‪0‬‬
‫‪0‬‬
‫_‬
‫‪0‬‬
‫‪0‬‬
‫‪0‬‬
‫‪+‬‬
‫قطعي‬
‫غير قابل بررس ي‬
‫غير محتمل‬
‫‪Unassessable‬‬
‫‪Unlikely‬‬
Detection,
Assessment,
Prevention
of ADRs in Human.
Ref: World Health Organization.
‫اهداف اصلي فارماكوويژيالنس‬
‫•‬
‫•‬
‫•‬
‫•‬
‫•‬
‫•‬
‫شناسائي زودهنگام واكنشهاي ناشناخته داروئي‬
‫تعيين ميزان افزايش در بروز عوارض‬
‫شناسائي فاكتورهاي خطر‬
‫ارزيابي كيفي مخاطرات‬
‫پيشگيري از بروز مخاطره غير ضروري در بيمار‬
‫مصرف منطقي و سالم داروها‬
The ultimate goal of pharmacovigilance is
improving pharmacotherapy
Ref:World Health Organization
‫تاريخچه فارماکوويژيالنس‬
‫• حدود ‪ 160‬سال قبل (‪:)1848‬‬
‫فوت جوان ‪ 15‬ساله در بيهوش ي با کلروفرم بعلت فيبريالسيون بطني‬
‫بيانيه‪” :‬فراورده هاي داروئي بايد خالص و عاري از هرگونه آلودگي باشند“‬
‫(جراحي ناخن پا)‬
‫• سال ‪:1936‬‬
‫‪ 107‬مورد مرگ ناش ي ازدي اتيلن گليکول بعنوان حالل سولفوناميد‬
‫• سال ‪: 1961‬‬
‫گزارش ‪ 4000‬مورد نقص عضو ناش ي ازتاليدوميد ازاستراليا‬
‫• سال ‪:1964‬‬
‫شروع استفاده ازسيستم کارت زرد درانگليس‬
‫• سال ‪:1968‬‬
‫شروع برنامه ‪ Drug Monitoring‬توسط سازمان ملل‬
Drug Classes Responsible for ADRs
Drug Class
Frequency
Antibiotics
Antitumor agents
Anticoagulants
Cardiovascular agents
Anticonvulsant agents
Antihypertensives
Analgesics
Antiasthmatics
Sedative/hypnotics
Antidepressants
Antipsychotics
Peptic ulcer therapy
Most frequent
Least frequent
Ref: J. Russell May. Adverse Drug Reactions and Interactions, In: Pharmacotherapy, A pathophysiologic Approach. 1997,
Types of Drug-Related Effects by Frequency
Type of adverse event
Frequency
Marrow suppression
Bleeding
Central nervous system
Allergic/cutaneous
Metabolic
Cardiac
Gastrointestinal
Renal
Respiratory
Most frequent
Least frequent
Ref: J. Russell May. Adverse Drug Reactions and Interactions, In: Pharmacotherapy,
A pathophysiologic Approach. 1997, Appleton & Lange.
• Patient’s specification
• Patient’s drug history
• Pharmacology of prescribed drugs
• Prescription of minimum effective
dosage
Preventing ADR
Over 75% of all ADR are
dose-dependent
Dosage of many drugs widely
different to individual needs.
Ref:World Health Organization
Essential factors causing
ADRs:
Factors related to drug:




Route of administration
Dosage
Duration of treatment
Problems with drug:
1-Formulation
2-Problems with preparing of drug
Essential factors causing ADRs:
Factors related to patient:
 Sex
 Age (weight)
 Genetic (PHARMACOGENOMICS)
 Drug allergy
 Lack of knowledge in patients
Concomitant drugs
Factors related to patient (Cont):
Non-compliance - underestimated
Route of Administration - bioavailability
Food - protein malnutrition
Pollutants -
smoking/herbicide residues
Timing - chronopharmacology
‫فوايد وجود برنامه ‪ ADR‬در بيمارستان‬
‫‪ -1‬افزايش كيفيت درمان‬
‫‪ -2‬جلوگيري ازشكايات حقوقي‬
‫‪ -3‬ارزيابي مشكالت دارويي‬
‫‪ -4‬ارزيابي مشاهدات پزشكان و ديگرحرف پزشكي‬
‫‪ -5‬ارتقاء دانش دارويي دست اندركاران درمان‬
‫داليلي كه باعث كاهش گزارشات‪ ADR‬ميگردد‪:‬‬
‫‪ -1‬عدم اطالع ازمكانيزم موجود براي ارسال گزارش‬
‫‪ -2‬عدم دسترس ي به فرم مربوطه‬
‫‪ -3‬عدم اهميت عارضه ازنظرگزارشگر‬
‫‪ -4‬نداشتن وقت‬
‫‪ -5‬دررابطه با تكميل فرم مربوطه‬
‫‪ -6‬اجتناب ازدرگيري دركارهاي اداري‬
‫‪ -7‬ترس ازشكايات حقوقي‪ ,‬كيفري‬
‫‪ -8‬عدم اطمينان ازبوجود آمدن ‪ ADR‬توسط دارو‬
Drugs cause hospitalization
Digoxin
Aspirin
Prednisone
Warfarin
Guanethidine
41
24
15
9
5
Aspirin
Digoxin
Warfarin
Prednisone
25
24
12
8
The numbers of reports, registered in
ADR center of Iran
•From the year 1377 to Mordad 83 ,
5861 cases of Adverse Drug
Reaction have been sent to Iranian
ADR Center
en
tis
t
U
th
er
s
nk
no
w
n
O
ph
ar
m
ac
is
t
D
nt
s
ur
se
Pa
tie
N
Sp
ec
ia
lis
t
io
ne
r
al
pr
ac
tit
lin
ic
al
en
er
C
G
Ph
ar
m
ac
is
t
Reporters
Diclofenac Na
Above 100 Cases of Foot drop
Withdrawal from Iranian Pharmacopoeia
Streptokinase
Tramadol?
• From 04.81 to 05.83, 289 cases of adverse
effects of Tramadol have reported to ADR
center
• Among them :
81 cases have been in Male
&
208 cases have been in Female
Adverse Reaction of Tramadol from 04.81 to 03.83
6 Major Adverse Effects of Tramadol:
•Nausea
125
•Vomiting
116
•Vertigo
109
•Asthenia
57
•Dyspnea
42
•Hypotension 41
Rout of administration
(In patients with Tramadol adverse effects)
.
%
.
.
%
IM
PO
IV
ID
Unknown
%
.
%
.
%
Bupivacaine
4 Cases of Para-plegia
following IT injection
2 of them led to Death
Sildenafil
•Sildenafil has cardiac related side effect.
•Some cases of myocardial infarction
were reported to ADR center due to this
drug.
‫معاونت غذا و دارو‬
‫‪www.fdo.ir‬‬
‫دبيرخانه تحقيقات كاربردی‬
‫مركز ثبت و بررسی عوارض ناخواسته دارويی‬
‫‪Iranian Adverse Drug Reaction Monitoring Center‬‬
‫مركز ثبت و بررس ي عوارض ناخواسته داروها‬
‫دفتر تحقيق و توسعه‪-‬معاونت غذا و دارو‬
‫وزارت بهداشت درمان و آموزش پزشكي‬
‫تلفن‪6405569:‬‬
‫نمابر‪6417252:‬‬
‫‪E-mail: [email protected]‬‬
Report of Iranian ADR
monitoring center
WHO Drug Monitoring Programme
Participating countries 1999
58 countries have joined the programme
Official member countries
Associate member countries
International Vigilance
Every healthcare professional in the
world should be constantly
alert
for
adverse effects or potentional new
hazards and reporting them to their
National Centers.
Countries with the best reporting rates generate:
• Over 200 reports per 1,000,000 inhibitants per year.
• Over 150 reports per 1000 physicians per year.
N
S
A
ge
Mordad 83
A
nt
s
nt
ib
C
io
ar
tic
B
di
lo
o
va s
od
sc
&
ul
C
ar
oa
gu
la
tio
M
is
n
al
le
no
us
H
or
m
El
on
ec
e
G
t
ro
Va
IA s
ly
cc
ge
te
in
&
nt
e
M
s
&
et
im
A
a
bo
nt
m
in
un
e o lic
ol
pl
og
as
ic
m
al
s
pr
od
uc
Sk
ts
in
A
Sm
EE
ge
oo
nt
N
th
s
T
m
A
ge
us
cl
nt
e
s
re
la
xa
nt
Vi
ta
m
in
s
C
Adverse Drug Reaction vs Drug classes
From:
1377
To
Site of Reaction (CNS agents )
From:
CNS
77
GI
Body as a whole
To
Skin & apprndages
Application site
Cardiovascular
Psychiatric
Respiratory
Autonomic
Musculoskeletal
Urinary
Vision
Heart rate & rhythm
Mordad 83
C
B
a
C
r&
S
ep
ro
du
ct
iv
e
Sy
s
Vi
si
on
bi
lia
ry
oa
gu
la
tin
g
R
N
w
ho
le
I
es
pi
ra
to
ry
Li
ve
R
as
G
Ap
pe
nd
ag
es
od
y
&
77
Sk
in
From:
Site of Reaction (Antibiotics)
To
Mordad 83
Age groups
(Reaction of Tramadol):
 0-10
 11-20
 21-30
 31-40
 41-50
 51-60
 61-70
 71-80
 >80
 Unknown
3
7
86
61
51
29
18
11
3
20
Adverse effects of Tramadol from 04.81 to 03.83
Reaction
Number
Reaction
Number
Sweating
24
Myalgia
7
Headache
21
Pale
7
Agitation
20
Ataxia
6
Somnolence
17
Vision disorders
6
Pruritus
16
Paraesthesia
6
Rigors
15
Injection site reaction
6
Flushing
11
Delusion
6
Urticaria
11
Tachycardia
6
Bronchospasm
10
Respiratory depression
6
Hallucination
9
Palpitation
5
Convulsion
9
Rash
4
Hypertension
8
Cold extremity
4
Confusion
8
Apnoea
3
Abdominal pain
8
Anxiety
3
Dry mouth
7
Stupor
3
Adverse effects of Tramadol from 04.81 to 03.83
Reaction
Number
Reaction
Number
Cardiac arrest
3
Back pain
1
Anorexia
3
Arrhythmia
1
Shock
3
Bradycardia
1
Allergic reaction
2
Lacrimation abnormal
1
Cyanosis
2
Myocardial Ischemia
1
Constipation
2
Diarrhea
1
GI disorders
2
Depression
1
Leg pain
2
Erythem
1
Dysphagia
2
Coma
1
Speech disorders
2
Edema
1
Urinary retention
2
Hearing decrease
1
Chest pain
2
Facial pain
1
Fever
2
Withdrawal syndrome
1
Syncope
2
Foot drop
1
Insomnia
2
Tremor
1
The following tips must be reminded
when using Sildenafil:
• Cardiovascular adverse effects such as atrial fibrillation, cardiomyopathy,
flushing, hypotension, myocardial infarction, thrombosis, ventricular
tachycardia have been reported with Sildenafil.
• Concomitant use of Sildenafi with following drugs are forbidden:


Organic nitrates (eg. Nitroglycerin)
Nitrates & Nitric donors (eg. Nitroproside)
Lamotrigine
 Common adverse effects:
Skin reaction: rash ,Steven's Johnson
syndrome, TEN
Women more than men
 Onset
 Caution
 Adverse events causing hospitalization
 Weight limitation
Age Limitation
• Not effective & safe in children under 16 years old
• Person younger than 16 years old:
• Risk factor for severe skin reactions
Lindane
•*This drug has entered to the world drug
market since 1901.
•*Since the year 1990 Lindane has been
introduced as a second line treatment.
Suggestion:
Single dose of use
Second line of treatment
Labeling
Contraindication
Precaution
FDA alert (2003)
•Systemic adverse effects of Lindane
•70% of adverse effects have been the CNS
adverse events,including:
•Seizure,Vertigo,Headache,Parasthesia
•17 cases of death have been reported to FDA,
•IN 3 cases an established relationship between
the events and using of drug were found
Celecoxib
Labelling Changes
• Celecoxib Long-term Arthritis Safety Study
(Class) did not show a safety advantage of
upper GI events for celecoxib compared with
diclofenac or ibuprofen.
Hypiran
Drug Interaction with:
• Indinavir
• OCPs
• Antidepressants
• Digoxin, Warfarin, Theophylline, Cyclosporin
Risperidone
Extrapyramidal Reactions:
Rabbit Syndrome

1 Case in the USA
 2 Cases in the English- Language Literature
 4 Cases reported to IADRMC
IV IG
.
2 Cases of Death
following Administration of Vials with Unusual Color
Benzyl benzoate
.
5 Cases of Sever Systemic Side Effects
following Topical Administration
3 of them led to Death
MedWatch
The FDA Safety Information and Adverse
Event Reporting Program:
www.fda.gov/medwatch/
Safety alerts
Recalls
Withdrawals
Important labeling changes
Biologicals, Drugs, Dietary supplements