adr. ebm. 3. cvičenie. each pharmacotherapy means risk akceptation, each drug can have potential...
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ADR. EBM.ADR. EBM.
3. cvičenie3. cvičenie
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• Each pharmacotherapy means
risk akceptation,
each drug can have potential
risk for patient
• Risk of pharmacotherapy
should never exceed risks
of not treating particular
disease!!!
risk
benefit
pharmacotherapy
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PharmacovigilancePharmacovigilance
Includes all aspects of postmarketing development:
- monitoring of clinical safety
- identification of new threats
- estimation of risk and contribution
- action and communication
Goal: to prove product safetyto prove product safety
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PharmacovigilancePharmacovigilance• We take into consideration during drug selection:
– EFFICACY– SAFETY– PRICE– SUITABILITY
• in 60th after talidomid scandal, WHO established monitoring focused to earlyearly dete detection of ADRction of ADR
• WHO created system of spontanneous ADR monitoring with center in Uppsala (Sweden)
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TALIDOMIDTALIDOMID
• 1959-1961: sedative, hypnotic drug for pregnant women (marketed in Germany, England, Canada..., never in USA)
• Born were > 12 000 children with phocomelia
• Now: new indications – imunomodulatory, antiangiogenic and antiinflammatory properties:– skin lupus erythematodes– skin form of lepra– Kaposi´s sarcoma at AIDS ...
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ADVANTAGES of ADVANTAGES of pharmacovigilancepharmacovigilance
at at worldwideworldwide cooperation cooperation
• Large number of treated patients
• Detection of possible race variations
• Detection of rare ADR
• Possibility of soon warning of particular
drug risk all over the world
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SIDE EFFECT Each unintend drug effect, occuring at normal
doses used for patients, which is in relation to pharmacologic properties of drug.
(antihypertensive effect of minoxidil + hypertrichosis)
ADVERSE EVENT Each noxious health event, which can occur during therapy, but doesn´t have to have relation with this therapy.
(patient takes ATB and breaks his leg)
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ADVERSE DRUG REACTION = ADR
• Reaction to drug which is noxious and unintended and occurs at doses of drugs normally used for prophylaxis, diagnosis or treatment of disease or to modify physiologic functions
• Detection of ADR at targeted monitoring 10-30%.
• At spontanneous monitoring < than 1%.
• Intoxications and mistakes in therapy don´t belong here
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UNEXPECTED ADVERSE REACTION
Adverse reaction whose character or intensity isn´t in concordance with domestic informations about drug or isn´t expected according to drug characteristic.
SIGNAL
Reported information about possible causal relationship between adverse event and, this relationship was yet unknown or incompletely documented. Usually more than 1 report is required for signal.
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Risk factors of ADRRisk factors of ADRDrugDrug
• nonselective and nonspecific
• with narrow therapeutics range
• lipophilic
Prescription• Wrong selection of drug, drug
combination, dose, route of administration, therapy length
PacientPacient• polymorbidity
• diseases of organs of elimination
• age, women
• pharmacokinetic variability (etnic group, genetic polymorphism)
• compliance
Number of drugs 0-5 6-10 11-15 > 16
ADR 4% 10% 28% 54%
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I. ADR according to I. ADR according to mechanism of mechanism of originorigin
1. Typ1. Typee A („augmented“) A („augmented“)• these ADR are expected • they can be predicted on the base of
pharmacodynamic properties of drug• they depend on drug dose, they appear at higher
doses • frequency is high > than 1% • mortality is low• therapy consists in dose adjustment• e.g.: cough after ACEI, bleeding from GIT after NSA, aspirin, corticoids ...
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rash
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2. 2. TypTypee B („bizard“) B („bizard“)
• idiosyncratic reactions
• these ADR are not expected
• they can be hardly predicted
• doesn´t depend on dose
• frequency is low < than 0,1%
• mortality is high
• treatment consists in stopping drug administration
• e.g.: haemolytic anaemia after metyldopa,
hepatitis induced by isoniazid,
allergic reaction after PNC ...
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TYPTYPEE A A TYPTYPEE BBPredictability + –
Dosage dependence
+ –
Occurrence high low
Mortality
low high
Treatment dose adjustment
stopping administration
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1 drug – different types of ADR1 drug – different types of ADR
DRUGDRUG Type A reactionType A reaction Type B reactionType B reaction
Ampicillin Pseudomembr. colitis
Intersticial nephritis, allergy
Chlorpropamid Sedation Hepatotoxicity
Naproxen GIT haemorrhage Agranulocytosis
Warfarin Bleeding Breast necrosis
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3. 3. TypTypee C („continous“) C („continous“)• this type of ADR increases number of
“spontanneous“ diseases • they occur usually after long-lasting
administration• they are often serious and persistant • mechanism of genesis is unclear• they are unexpected, not predictable • they can´t be verified experimentally• e.g.: oral contraceptives and increased
occurrence of thromboembolia, analgetic nephropaty
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4. 4. TypTypee D („delayed“) D („delayed“)
• late ADR (years resp. generations)• teratogenity• carcinogenity• mutagenity• e.g.: ca. of vagina at daughters of mothers treated
with dietylstilbestrol
5. 5. T Typypee E („End of use“) E („End of use“) • after therapy ending (syndrom from omitting) • rebound phenomenon• e.g.: beta blockers, opioids, corticosteroids, nitrates ...
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II. ADR according to II. ADR according to intensityintensity
• mild –mild – don´t require to stop or to change treatment
• moderate –moderate – require to change therapy, but don´t
threat life of the patient
• serious – serious – death, hospitalization, invalidization,
teratogenity
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III. ADR according to III. ADR according to frequencyfrequency
Frequency
• frequent >1,0 % (sedative effect after
promethazin)
• seldom >0,1% (rhabdomyolysis after statins)
• rare > 0,01% (agranulocytosis after
metamizol)
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Determination of causalityDetermination of causality
Basic categories:
A. High probability of causality
B. No sufficient proof of causality
0. Isn´t possible to evaluate causality
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AACTIONS AT PROOF OF CTIONS AT PROOF OF CAUSALITYCAUSALITY
• warning
• methodic direction
• limitation of indication
• change of dose
• deregistration of the drug
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Deregistered drugsDeregistered drugs
• troglitazon
• benaxoprofen
• terfenadin
• mibefradil
• cerivastatin – 2001-2002
• rofekoxib, vadekoxib – 2004-2005
• group with the highest risk NSA
(> 30% of deregistrations)
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• % of ADR reported at active monitoring :
10-30% (mostly done by pharmaceutical companies
during clinical trials)
at pasive monitoring < 1%• Type A ADR: - 80% • Treatment of ADR represents 13-15% of therapy
costs• ADR occurs mostly between 1-10 day from
beginning of therapy
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EBM EBM ((Evidence based medicine )• EBM brings proofs about efficacy and safety
from large clinical studies
• Applied are relevant statistic methods, metaanalysis
• These results are used for creating recommandations for therapy (guidelines)
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PREDP
ÍŠTE
RECEPT
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