Adverse Drug Reactions Flashcards
What can too much vitamin C give you
Kidney stones
What is important to remember about clinical pharmacology
All substances are poisons: there is none that
is not a poison. The right dose differentiates
a poison from a remedy.
What is meant by an adverse drug event
preventable or unpredicted medication event—with harm to patient
could be due to an adverse drug reaction or due to a medication error ( wrong drug or wrong dose prescribed)
Describe the importance of adverse drug reactions
They are costly and cause a lot of morbidity and mortality in patients.
Describe the epidemiology of ADRs
substantial morbidity and mortality
estimates of incidence vary with study methods, population, and ADR definition
4th to 6th leading cause of death among hospitalized patients*
6.7% incidence of serious ADRs*
0.3% to 7% of all hospital admissions
annual costs in the billions (?$120 billion in US)
30% to 60% are preventable
Generally, how can we classify ADRs
Onset
Severity
Type
Summarise the classification of ADRs based on onset
Acute - most commonly anaphylactic immune reactions
Within 1 hour
Sub-acute
1 to 24 hours
Latent
> 2 days
Summarise the classification of ADRs based on the severity of the reaction
Mild
requires no change in therapy
Moderate
requires change in therapy, additional treatment, hospitalisation
Severe
disabling or life-threatening
Outline the consequences of a severe ADR
Results in death
Life-threatening
Requires or prolongs hospitalisation (LIVER DAMAGE)
Causes disability
Causes congenital anomalies
Requires intervention to prevent permanent injury (ANTIDOTES, AVOID THE DRUG ALTOGETHER)
Describe type A ADRs
extension of pharmacologic effect
usually predictable and dose dependent
responsible for at least two-thirds of ADRs
e.g., atenolol and heart block, anticholinergics and dry mouth (also visual problems and constipation), NSAIDS and peptic ulcer
Augmented and often predictable effect of the pharmacology of the drug- but sometimes we don’t understand why the side effects are produced.
How can we reverse type A ADRs
In many instances, this type of unwanted effect is reversible, and the problem can often be dealt with by adjusting the dose to obtain a more favourable balance between efficacy and safety.
This may be problematic in patients who have developed tolerance for opiods.
Compare the relationship between the incidence of ADRs (y-axis) and dose (x-axis) for digoxin and paracetemol
§ Paracetamol has a threshold below which it has minimal side effects (and then exceeding this, side effects rapidly increase). Digoxin just has a dose-dependent line with constant increasing SEs. (linear relationship with digoxin)
Summarise type B ADRs
Examples of such ADRs, which are often immunological in nature, include drug-induced hepatic or renal damage, bone marrow suppression, carcinogenesis and disordered fetal development. Uncommon but severe unpredictable adverse effects that have been mentioned in earlier chapters include aplastic anaemia from chloramphenicol and anaphylaxis in response to penicillin. They are usually severe – otherwise they would go unrecognised – and their existence is important in establishing the safety of medicines. The unpredictable nature of such reactions means that adjustment of the recommended therapeutic regimen (e.g. using a lower dose) may not prevent them.
Outline the classification for type B ADRs
idiosyncratic or immunologic reactions includes allergy and “pseudoallergy” rare (even very rare) and unpredictable e.g., chloramphenicol and aplastic anemia, ACE inhibitors and angioedema
Many serious ADRs are totally unexpected eg Herceptin
and cardiac toxicity
What is meant by aplastic anaemia
Total bone marrow failure
Describe angioedema
Similar to anaphylaxis:
Swelling of lips and tongue, heart failure, breathlesness to bronchoconstriction.
Nowadays, what are all anti-cancer drugs tested for
cardiac toxicity
Outline type C ADRs
associated with long-term use
involves dose accumulation
e.g., methotrexate and liver fibrosis, antimalarials and ocular toxicity
What is the key factor in type C ADRs
how much of the drug has accumulated over time
What is methotextrate used to treat
Immunosupressant
anti-cancer drug
Give an example of some antimalarial drugs
Chloroquinolone and hydrochloroquinolone
Outline the type D classification of ADRs
delayed effects (sometimes dose independent) carcinogenicity (e.g. immunosuppressants) teratogenicity (e.g. thalidomide)
Outline the type E ADRs
End of treatment side effects. BDP = benzodiazepines.
§ Withdrawal reactions – patient cannot make endogenous supply – opiates (cold turkey reaction), corticosteroids, BDPs.
§ Rebound reactions – disease gets worse when drugs stopped – clonidine, b-blockers, corticosteroids.
§ “Adaptive” reactions – adapted body reactions to drugs – neuroleptics (tranquilisers). and anti-psychotics for schizophrenia.
Why is it important not to stop prescribing corticosteroids immediately to a patient who has been on them for a long period of time
The patient will have lost the ability to make steroids
Therefore their CVS may collapse after sudden withdrawal.
Describe and explain the clonidine rebound
Clonidine is an alpha-2 agonist so it suppresses the release of noradrenaline
Long-term use of clonidine leads to an upregulation in adrenergic receptors on the post-synaptic membrane
If the dose of clonidine is missed once or twice, it will cause an increase in noradrenaline release, which then acts on an increased number of receptors so has a greater effect
This causes a large increase in blood pressure
