Adverse drug reactions Flashcards
Define an ‘adverse drug reaction’
Any response to a drug which is noxious, unintended and occurs at doses used in man for prophylaxis (prevention), diagnosis or treatment
UK statistics about ADRs
5% of hospital admissions are due to ADRs
Types of ADRS (classification)
6 types Types:- A- augmented B- bizarre C- chronic D- delayed E- end of treatment F- failure of treatment
Type A ADR
augmented ie increases in size
- these pharmacologic effects are dose related and predictable.
- Due to excess pharmacological action ie drug to slow the heart causing excessive slowing of the heart bradycardia and beta- blockers
- easily reversible on reducing the dose or stopping the drug
- not usually life threatening
Classification of severity of reaction
Mild
moderate
severe
severe reaction
disabling or life-threatening ie results in hospitalisation and death
ie kidney failure
moderate reaction
requires change in therapy
additional treatment
hospitalisation
i.e amphotericin (an antifungal drug) induced hypokalemia (low K+ levels in blood)
Mild reaction
bothersome but requires no change in therapy
metallic taste with metronidazole (treats bacterial infections)
Type B ADR
Bizarre effects
are rare, unpredictable, aggressive and cause serious illness or death.
can be unidentified for months or years.
usually long term or delayed
- It’s unrelated to the dose, and not readily reversed.
They are idiosyncratic (an abnormal physical reaction by an individual).
There is a delay between exposure to drug and ADR.
Manifests as rash asthma, serum sickness
Type C ADR
chronic/ long term effects
related to the duration of treatment as well as the dose, and does not occur with a single dose
it is semi-predictable
common with things like steroid use- obvious when patients have been on steroids for a long time- can cause osteoporosis (fragile) and stretch marks etc
Type D ADR
delayed- occur a long time after treatment. Secondary cancers in those treated with alkylating agents.
children whose mothers took medication during pregnancy (about 50% of women do)
All drugs should be avoided during pregnancy unless they are safe or the benefit outweighs potential risk
Type E
Adverse reactions which occur when a drug treatment is stopped, especially suddenly following long-term use.
E.g unstable angina and beta blockers, rheumatoid arthritis- steroids need to be weened off slowly
if anti-epileptics are stopped suddenly it could cause withdrawl seizures
Type F
failure of therapy.
Common (esp in children) and dose related
frequently caused by drug interactions e.g failure of the OCP (oral contraceptive pill) when administered with hepatic enzyme inducers/antibiotics
detecting and reporting ADRs
detection: differential diagnosis, medication history (past and present), assess time of onset and dose relationship
- lab investigations (plasma concentration measurement and allergy tests)
reporting of ADRs
all significant or unusual drug reactions, as well as unanticipated or novel events that are suspected to be drug related, are meant to be reported using yellow card scheme however only about 10% are and this is why severe ADRs take so long to be known about
what is an adverse drug event?
it occurs during treatment, not necessarily caused/linked by/to the drug itself and cannot be proven to be linked to the drug either. A harmful side effect of the drug.
different to reaction as reaction is usually linked to the drug
what is an adverse drug reaction?
proven to be caused by the drug
What are some of the reasons for having a Type A ADR?
too high a dose
pharmaceutical variation
often caused by disease (ie renal or liver) :-
- pharmacokinetic variaton (how moves through the body ie path it takes etc)
- pharmacodynamic variation (effects of the drug)
what is pharmacokinetic variation?
the effect of absorption, distribution, metabolism and elimination on the drug
e.g abs- can be different depending on the dose, formation, GI motility and first pass metabolism
if problems occur with absorption then drugs lose their effect ie there is therapeutic failure
pharmacogenetic
acetylation- under genetic control
this process is key for how a number of drugs metabolise
don’t test for links between genetics and drugs so just have to start with a low dose of a drug and increase it.
How does cardiac failure reduce drug absorption in the liver?
fluid overflow due to cardiac failure as oedema forms (maybe in the gut, legs, lung etc)- this can reduce the drug absorption from the gut
decreased blood flow to the liver accounts for some of the change in absorption/ clearance of a drug
When are Type B ADRs more common?
- with macromolecules (big)- proteins, vaccines, polypeptides
- patients with a history of asthma or excema
HLA status- presence of particular human leukocyte antigen is a risk of a type B reaction
teratogenesis
abnormal cogenital malformations in the fetus
due to mother using medication in 1st trimester of pregnancy
How can we diagnose ADRs?
be suspicious
really important to get a thorough medical history of the patient to detect past, current medications, conditions, allergies etc
assess time of onset and dose relationship
lab investigations- allergy tests etc
who is most at risk of ADRs?
children- can’t communicate
elderly- comorbidities ie may be on a number of medications for different health conditions
people with prior history of ADRs
genetic predisposition
what are antineoplastics commonly involved with treating?
anti cancer drug
what percentage of ADRs and ADEs are preventable?
60%
although some effects cannot be avoided e.g nausea in chemo
list the non-dose related ADRs
Type B,
list the dose related ADRs
Type A, C, F
Type B delayed effects
include tardive dyskinesia (disorder that results in involuntary, repetitive body movements) carcinogenesis
surveillance of ADRs
a comprehensive adverse drug reaction (ADR) surveillance program is necessary to detect, evaluate, and develop mechanisms to prevent ADRs and their associated morbidity, mortality, and increased costs.
