ADR Flashcards
What is an ADR
- ‘A response to a medicinal product which is noxious and unintended’
- EMA: This may arise form use of the product within or outside the terms of MA or from occupational exposure
Who can get ADR
-Anyone who takes drugs
Are they important
- Major cause of hospital admission- 6.5%
- Affect quality of life
- Cost to NHS in £hundreds of millions
- Many are preventable
- Several hundred deaths per year
Issues faced
- Not enough information from clinical trials
- Increased polypharmacy and co-morbidities
- Number of patients admitted to hospital with ADR increasing
Type of classification
- Rawlins and Thompson
- DoTS
Rawlins and Thompson- TYPE A
- Dose related
- Common, predictable
- Related to the pharmacology
- Low mortality
e. g. digoxin toxicity, constipation from morphine or sedation from hypnotic
Rawlins and thompson- TYPE B
- Not dose related
- Uncommon, unpredictable
- Not related to pharmacology
- High mortality
e. g. penicillin hypersensitivity, malignant hyperthermia, hepatitis
ACEI induced angioedema
- Life threatening
- Rare
- Unlikely to be picked up on clinical trials
- Biggest cause of angioedema presenting to A&E
- 0.2% incidence
Rawlins and thomspons- TYPE C,D,E and F
Classification became complicated -Type C- long term -Type D- Delayed -Type E- end of use (withdrawal) -Type F- Failure of treatment NEW and simplified classification DoTS
DoTS-DOse, Time, Sususceptibility:
DOSE (response)
The ADR can occur -At doses below therapeutic doses \+Anaphylaxis with penicillin -In the therapeutic dose range \+Nausea with morphine -At high doses \+Liver failure with paracetamol
DoTS-DOse, Time, Sususceptibility:
TIME (course) can be characteristic
- With the first dose
- Early, or after a time or with long-term treatment
- On stopping treatment (withdrawal)
- Delayed
TIME (course)
- Easily observed in the patient
- Relevant to monitoring and prevention in a patient
- Relevant to pharmacovigilance and drug development
Time- Independent
-Time-independent
-e.g. increased risk of haemorrhage with change in effective dose fo warfarin
-NSAID- induced GI bleeding
SO
-Close monitoring throughout treatment
Time- immediate
-Immediate, due to rapid administration
e.g.
-Red man syndrome from vancomycin
-Or cardiac arrest in rapid infusion of K+
SO
-Infuse slowly
Time- first dose
-After first dose
e.g.
-Hypotension from ACEI
-Anaphylaxis (type I hypersenstiivity)
so
-Take special precautions for first dose
Time- Early
- Early risk falls with time
e. g. Nitrate induced headache - MONITOR
Time- intermediate
Intermediate- risk maximal after a few weeks or days
- e.g. ampicillin rash, delayed hypersensitivity
- Quinine and thrombocytopenia (Type II)
- Penicillin and interstitial nephritis (Type III)
- Cutaneous reactions to anti-histamine (type IV)
Time-Late
- Late (risk increase with time)
- e.g.
- Osteoporosis with corticosteroids use
- Withdrawal reactions
- SO prevent; monitor those on long term treatments
Time- delayed
Delayed
-e.g. carcinogenesis (ciclosporin
-Teratogenesis with thalidomide
So avoid
Time- After withdrawal
After withdrawal e.g. -Withdrawal syndromes (opiates, benzodiazepines) -MI from Beta blockers So withdraw slowly
Types of time reactions
- Independent
- Immediate
- First dose
- Early
- Intermediate
- Late
- Delayed
- After withdrawal
DoTS-DOse, Time, Sususceptibility:
SUSCEPTIBILITY
Increased risk of ADR can be due to
1)Genetic variation (Porphyria- cant produce enough Haem; Malignant hyperthermia- severe reaction to meds in anesthesia (fever, tachycardia)
2)Age (aspirin in U16- Reyes; Neonates- chloramphenicol Greys syndrome))
3)Sex (Osteoporosis in menopausal women; mefloquine and psychiatric effects in females)
4)Physiological variation
5)Exogenous factors (interacitons with food e.g. grapefruit juice and simvastatin or warfarin)
6)Disease (CKD effects clearance with Li)
NB- more than one factor can be present at any one time
Examples of DoTS
Steroids
Oseteoporisis due to corticosteroids
DOSE- collateral effect (unintentional effects)
TIME- Late
SUSCEPTIBILITY- older people; women
Examples of DoTS
Isoniazid
Hepatoxicity
Dose- collateral effect
Time- intermediate
Susceptilibility- Genetics (drug metabolism), Age, Exogenous (Alcohol) disease (malnutrition)
Spontaneous reporting systems
- Main system for national and international pharmacovigilance
- Reports are analysed to detect signals
- Significant under reporting
Why report ADRs
-Important for patient safety
-Allow continuous monitoring of old and new drugs
-Provide data on ADRs to new drugs
-Provide data on special patient groups
+Young and old
+Pregnant
+with Co-morbidities or polypharmacy
Yellow card scheme
-MRHA-run ADR reporting scheme 1964 response to thalidomide disaster
-Secure, spontaneous, suspicions
-Provide early warning of possible ADR
-Provide ‘real world data’
-The scheme collects reports of suspected problems or incidents involving
+side effects (ADR)
+Medical device adverse incidents
+Defective medicines (those that are not of an acceptable quality)
+Counterfeit or fake medicines or medicinal device
How to complete yellow card
- https://yellowcard.mhra.gov.uk
- On back of BNF
- APP
What to report
- Serious reactions to established drugs
- Even if well recognised
- Report suspicion, not proven causality
What is a serious reaction
-Any reaction which results in hospitalisation (42%)
Serious reaction also include those that are
+Fatal (5%)
+Life-threatening (20%)
+Disabling (10%)
+Cause congenital abnormalities (1%)
+Medically significant (22%)
Medical significance
1) Mild- No antidote or treatment is required
2) Moderate- A change in treatment, but not necessarily discontinuation of the drug, is required; Hospitalisation may be prolonged or specific treatment may be required
3) Severe- An ADR is potentially life threatening and requires discontinuation of drug and specific treatment of the ADR
4) Lethal- ADR directly or indirectly contributes to a patient death
Black triangle drugs
- Means intensive monitoring
- Contains new active substance
- Is a biological medicine
- New indications
- Has conditionsal approval
- Company been asked for more data
Who may report
-1964- doctors, dentists, coroners
-1997- Hospital pharmacists
-1999- Community pharmacists
-2002- Nurses, midwives and health visitors (2005 pilot patient scheme)
2008- Patients
Pharmaceutical companies MUST report
Areas of Instrest
MRHA particularly keen on reports in \+Children \+Over 65s \+Biological medicines and vaccines \+Delayed ADRs and interactions \+Complimentary and herbal medicines
Future of pharmacovigilance
- Studies are being conducted on social media sites and blogs
- Smart technology
- Genomic technology to understand the genetic basis of variable drug responses
- Spontaneous reports along side new initiatives
