8. Adverse Drug Reactions Flashcards
(50 cards)
1
Q
Why do dentists need to understand these?
A
- need to fully understand potential for interactions of drugs
- under-reported often as inability to recognise them or not seen
2
Q
Define ‘adverse drug reaction’
A
- harmful or seriously unpleasant event
- occurring at a dose intended for therapeutic effect
- calls for reduction of dose or withdrawal of drug
3
Q
Historical events and dates of major issues
A
- 1937 - sulphanilamide
- 1961 - thalidomide
- 1971 - diethylstilbestrol (uterine cancer in offspring)
- 2006 - TGN1412 (excess cytokine release)
4
Q
How does the iceberg theory link to clinical trial?
A
- tip of the iceberg is what we know at the end of the clinical trial
- below the sea is what happens when drug is in normal practice
5
Q
Are any drugs fully harmless?
A
- no
- any drug which is pharmacologically effective carries some hazard
6
Q
Drug safety is a relative concept and takes into account …
A
- severity of adverse drug reaction
- disease
- therapeutic alternatives
- individual perception and acceptance of risk
7
Q
What suggests a cause and effect relationship between drug administration and adverse drug reaction?
A
- time sequence between taking drug and adverse reaction
- reaction corresponds to known pharmacology of drug
- reaction stops on cessation of drug
- reaction returns on restarting drug
8
Q
After what is a causal relationship highly probable?
A
- event has reasonable temporal association with drug
- de-challenge from drug
- observed event abated upon de-challenge
- re-challenge
- reaction reappeared upon re-challenge
9
Q
What’s the yellow card?
A
- from Medicines and Healthcare products Regulatory Agency (MHRA)
- filled in after reactions and filed
10
Q
Define ‘side effect’
A
- unavoidable consequence of drug administration
- arising as unwanted action is just as integral as therapeutic effect to pharmacology of drug
- can be of clinical benefit sometimes
11
Q
Define ‘secondary adverse effect’
A
- indirect causation
- secondary to the drug
- e.g opportunistic infections due to glucocorticoid therapy
12
Q
How is age a risk factor for ADR?
A
- 3 fold increase in ADR over 60 compared to under 30
- can be due to increased medications or pharmacokinetic factors
- neonates and children susceptible due to difference in pharmacokinetic factors
13
Q
How is sex a risk factor for ADR?
A
- females more likley
- pharmacokinetics and hormone influence
14
Q
How is medical history a risk factor for ADR?
A
- if ADR to one drug, more likely to experience it with another
15
Q
How is disease a risk factor for ADR?
A
- pharmacokinetics
16
Q
How is current medication a risk for ADR?
A
- drug interactions
17
Q
How is ethnicity a risk factor for ADR?
A
- intrinsic ones (pharmacokinetics and pharmacodynamics)
- pharmacokinetics - metabolism 90% japanese are fast acetylators, 50% of caucasians
- pharmacodynamics - Ashkenazi Jews susceptible to agranulocytosis after clozapine (20% to 1% in normal pop), response to beta blockers (more in chinese than caucasian than african)
- extrinsic is alcohol, diet, smoking
18
Q
Classifications of ADRs
A
- A to E
- augmented pharmacological effect, bizzare effect, chronic effect, delayed effect, end of treatment effect
19
Q
Define ‘augmented pharmocological effect’
A
- adverse effect known to occur from primary pharmacology of drug
- usually dose dependent
20
Q
Define ‘bizarre effects’
A
- adverse effects that are unpredictable from pharmacology of drug
21
Q
Define ‘chronic effects’
A
- due to chronic treatment with drug
22
Q
Define ‘delayed effects’
A
- occur remote from treatment
- either in children of treated patients or in patient themselves
23
Q
Define ‘end of treatment effects’
A
- adverse effects occur as a result of stopping treatment
- withdrawal effects
24
Q
Examples of Type A ADR
A
- bradycardia from treatment with beta blocker - primary pharmacology is to decrease hard rate but is dose is too high, will be bradycardic
- hypoglycaemia from insulin injection
- tachycardia from muscarinic antagonist ipratropium
- common/low mortality
25
Parasympathetic activation normally
- pupils constrict
- lens of eye readjust for closer vision
- airways in lungs constrict
- heart rate decreases
- blood vessels to limb muscles constrict
- blood vessels to visceral organs more dilated
- salivary secretions normalise
26
Effect of a muscarinic antagonist on parasympathetic activation
- pupils dilate (relaxation of constrictor pupillary muscle/blurred vision)
- increased focal length of lens (relaxed ciliary muscle)
- bronchodilation
- increased cardiac output (rate and force)
- decreased GI motility
- decreased exocrine grand secretion (dry mouth, decreased sweating)
27
Muscarinic antagonists are known as ...
parasympatholytic
28
Pupil dilation can be an ADR to ... and a therapeutic effect to ...
- atropine
- tropicamide
29
Bronchodilation can be an ADR to ... and a therapeutic effect to ...
- nothing
- ipratropium
30
Increased heart rate can be an ADR to ... and a therapeutic effect to ...
- ipratropium
- nothing
31
Decreased gut motility can be an ADR to ... and a therapeutic effect to ...
- nothing
- hyoscine
32
Decreased exocrine secretions/dry mouth can be an ADR to ... and a therapeutic effect to ...
- iprapropium
- atropine
33
Examples of bizarre type B reactions
- anaphylaxis due to penicillin
- bone marrow suppression due to chloramphenicol
- uncommon so often have high mortality
34
Explain the TGN1412 Clinical trial
- phase 1 clinical trial - autoimmune/leukaemia treatment
- ADRs included decreased blood pressure, nausea, pain, soft tissue damage and multi-organ failure
- caused excess cytokine release (cytokine storm) and indiscriminate immune response
35
Example of type 3 chronic ADR
- iatrogenic Cushing syndrome from chronic glucocorticoid therapy
36
Explain hypercortisolaemia
- Cushing's syndrome
- caused by adrenal/pituitary tumour (Cushing's disease)
- side effect of chronic glucocorticoid therapy
37
Examples of delayed type D ADRs
- diethylstilbestrol given to pregnant mother (causes high incidence of avginal cancer in offspring in 20s)
- isotretinoin (accutane) causes birth defects
- second cancers in response to Hodgkin's disease treatment
38
Example of type E end of treatment ADR
- adrenal insufficiency after glucocorticoid therapy
39
Regulation of metabolism by corticosteroids
- hypothalamic nuclei
- with CRH goes to anterior pituitary
- with ACTH and negative feedback goes to adrenal cortex
- produces cortisol
40
Explain adrenal atrophy in response to glucocorticoid treatment
- exogenous glucocorticoids used for anti-inflammatory or immunosuppressive therapy
- act of HPA axis negative feedback system and over time adrenal atrophy
- on termination of treatment, atrophied adrenals cannot produce enough cortisol so results in adrenal insuffiency
41
Symptoms of adrenal insufficiency
- general weakness
- weight loss
- nausea
- Addinson's disease
42
When one drug modifies the action of another, the modification can be ... or ...
- potentiation
- attenuation
43
What are the pharmacodynamic interactions of drugs?
- similar of opposing pharmacological effects
- ethanol increasing sedative effect of antihistamine drugs or some antidepressants
44
What are the pharmacokinetic interactions of drugs?
- one drug interferes with disposition (e.g metabolism or excretion) of other
- monoamine oxidase inhibitors blocking metabolism of dietary amine
- many drugs inhibit CYP450 (like fluvoxamine) so can interfere with metabolism of other drugs
45
CBZ is what?
carbamazepine
46
Stages of carbamazepine metabolism?
- CBZ is the parent drug (active)
- with CYP3A3/4 becomes CBZ-Epoxide (an epoxide metabolite which is also active)
- with epoxide hydrolase, becomes CBZ-diol (a diol metabolite - inactive)
47
What increases metabolism of CBZ?
- carbamazepine
- phenobarb
- phenytoin
- primidone
48
Things that decrease CBZ metabolism
- cimetidine
- danazol
- fluozetine
- verapamil
- diltazem
- antiretrovirals
49
Things that increase CBZ-E to CBZ-diol stage
- SAME AS CBZ TO CBZ-E
- carbamazepine
- phenobarb
- phenytoin
- primidone
50
Things that decrease CBZ-E to CBZ-diol
- lamotrigine
- valproate
