in the early 1900 s paul ehrlich described an ideal drug as a magic bullet. magic bullet. such a...
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• In the early 1900s Paul Ehrlich described an ideal drug as a magic bullet. magic bullet. Such a drug would be aimed precisely at a disease site and would not harm healthy tissues.
What is an ideal drug?
04/21/23
Risk
• No medicinal product is entirely or absolutely safe for all people, in all places, at all times. We must always live with some measure of uncertainty.
We Must Always Ask:
• Do the potential benefits outweigh the potential risks for this individual?
ACHP
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.
:تعريف
عارضه نا خواسته WHOمطابق تعريف دارويی عبارتست از:
هرگونه پاسخ ناخواسته وزيان آور که در
مقادير مصرفمعمول دارو جهت تشخيص، پيشگيری و
. درمان بيماری ايجاد شود
History of drug safety after thalidomide eradication
1961 :
Dr William McBride (Australia)( thalidomide 4000 cases)
1964 :
UK started “yellow cards” system
1968 :
start of WHO Programme for International Drug Monitoring
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
Costs Associated with ADRs
$ 136 BILLION yearly (related to morbidity and mortality)
Greater than total costs of cardiovascular or diabetic care.
Mean length of stay, cost and mortality ADR patients are DOUBLE that for control group of patients without ADR.
ADRs cause 1 out of 5 injuries or deaths per year to hospitalized patients.
Ref: U.S. Food and Drug Administration . Center for Drug Evaluation and Research
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
So many prescriptions!
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
Who might get an ADR?
• Anyone who takes a medicine – Differential diagnosis should include the
possibility of an ADR if the patient is taking any form of medication
Who is most at risk from ADRs?
Patients who;
• are young, or old or female
• are taking multiple therapies – 50% of patients on 5 drugs or more
• have more than one medical problem
• have a history of allergy or a previous reaction to drugs
Older Adults and Medications
• Older adults make up 13% of population
• Account for:– About 30% of prescribed
medications – About 40% of over-the-counter
medications
• At least 90% take at least one prescription medication
• 12% use ten or more per weekACHP
How Knowledge About ADRs Is Created?
1-Animal experiments2- Clinical trials3- Epidemiological methods
Spontaneous reporting Cohort studies Case-control studies
Limitations of Clinical Trials
Limited size Narrow population Narrow indications Short duration
• Ref: J. Russell May. Adverse drug Reactions and interaction, In: Pharmacotherapy, A pathophysiologic Approach. 1997, Appleton &
Lange.
Drug Development
Phase IVPost-approval studies to
determine specific safety issues
Clinical development of medicines
Animal experiments for acute toxicity, organ
damage, dose dependence, metabolism, kinetics,
carcinogenicity, mutagenicity/teratogenicity
PreclinicalAnimal Experiments
Phase I Phase II
Development Post Registration
Phase III Phase IVPost-approval
SpontaneousReporting
Reg
istr
atio
n
Phase I
20 – 50 healthy volunteers to gather preliminary data
Phase II150 – 350 subjects with disease - to determine
safety and dosage recommendations
Phase III250 – 4000 more varied
patient groups – to determine short-term safety
and efficacy
How many patients one needs to treat to see with high probability the reaction?
Pre-marketing studies are carried out in limited number of patients: “The law of three”– In order to detect for sure SAE that occurs as 1 event per
2000 patients treated we need to treat • 6000 patients for 1 case• 9600 patients for 2 cases• 13000 patients for 3 cases
• The number of patients involved in pre-marketing studies has been increasing but is still limited in comparison with the exposure to the drug in post-marketing phase
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
Assessment the quality of medications
Assessment of drug safety
Detection of occurrence rate of ADR
Decreasing the risk of occurrence of adverse events
Spontaneous Reporting
Large populationAll medicinesHospital and out-patient careLong perspectivePatient analysis possibleNon-interventionalCheap
Examples of product recalls due to toxicity
• Medicine Year
• Thalidomide 1965• Practolol 1975• Clioquinol 1970• Benoxaprofen 1982• Terfenadine 1997• Rofecoxib 2004• Veralipride 2007
• Examples of serious and unexpected adverse events leading to withdrawal of medicine
• Phocomelia• Sclerosing peritonitis• Subacute nephropathy• Nephrotoxicity, cholestatic
jaundice• Torsade de pointes• Cardiovascular effects• Anxiety, depression,
movement disorders
Pharmaco - Vigilance
• Pharmaco = medicine
• Vigilare = to watch
– alert watchfulness– forbearance of sleep; wakefulness– watchfulness in respect of danger; care;
caution; circumspection– the process of paying close and continuous
attention
Detection, Assessment&
Prevention of ADRs in Human.
Ref: World Health Organization.
فارماکوويژيالنس
از • پيشگيری و ارزيابی های وروش شيوه تمام بهADRs. گويند
ارزيابی شناسايی • ناخواسته ، عوارض گزارش ،و دارويی
رافارماکوويژيالنس انسان در آنها وقوع از پيشگيری گويند.
Pharmacovigilance Major Aims
Early detection of unknown reactions and interactions
Detection of increase in frequency Identification of risk factors Quantifying risks Preventing patients from being
affected unnecessarily RATIONAL AND SAFE USE OF
DRUGS
Ref: World Health organization.
The ultimate goal of pharmacovigilance is
improving pharmacotherapy
Ref:World Health Organization
Case #11: 34 yo female with DM, Hypertension, depression and recent UTI, taking metformin, insulin,
lisinopril, paxil and ciprofloxacin. Presents with severe calf pain and difficulty with plantar flexion
What is the most likely cause?
A) Peroneal Nerve Palsy
B) Diabetic Neuropathy
C) Transient ischemia event
D) Achilles Tendon Rupture
Case #11 (cont). Which medication is the most likely cause?
A) Metformin
B) Lisinopril
C) Paxil
D) Ciprofloxacin
E) Insulin
Achilles Tendon Rupture
• Thompson Test
Misconceptions about ADR Reporting
All serious ADRs are documented by the time a drug is marketed
About patient receiving multiple medications,it is difficult
to determine if a drug is responsible for the ADR
ADRs should only be reported if absolutely certain
One reported case can’t make a different
Ref: U.S. Food and Drug Administration . Center for Drug Evaluation and Research
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.
-
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.
ADR های اطالعیه دریافت جهت
• www.fdo.mui.ac.ir
SEND A REPORT SAVE A LIFE
Dr. Goodarzian
The FDA Safety Information and Adverse Event Reporting Program:
Safety alerts Recalls WithdrawalsImportant labeling changesBiologicals, Drugs, Dietary supplements
MedWatch
www.fda.gov/medwatch/www.fda.gov/medwatch/
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