ADRs And DDIs Flashcards
(118 cards)
1
Q
what may ADRs be caused by?
A
any drug working in human body,
by toxicity/ normal mechanism of drug
2
Q
treatment of ADRs? (3)
A
- Meds treatments for long/short term
- Vaccination
- Treatments for diagnostic patients
3
Q
role of pharmacist in this topic?
A
Prevent visceral reactions of patients by choosing which drug to/ not to prescribe.
De-prescribing
Body systems change throughout life e.g. kidneys: change to how patient react to drugs- important to know
Susceptibility factors may make patients prone to ADRs
4
Q
Downsides of ADRs:
A
- Harm to patients: morbidity, disability..
- Big burden on NHS and patients
also may:
reduce compliance and effects of drugs
5
Q
WHO ADR definition:
A
any response to a drug that is noxious and unintended and that occurs at doses used in man for prophylaxis, diagnosis (X rays)/ therapy (antibiotics)
6
Q
EU definition, what do ADRs arise from?
A
”” This includes adverse reactions which arise from:
• the use of a medicinal product within the terms of the marketing authorisation;
- the use outside the terms of the marketing authorisation, including overdose, off-label use, misuse, abuse and medication errors;
- occupational exposure.
7
Q
2 main classification systems of ADRs?
A
The Rawlins Thompson Classification system
The DOTS classification system.
8
Q
T/F any ADR that occurs after use of drug is linked to it?
A
false: may/ may not be linked to use of drug.
Temporal relationship: timing, overlaps…
9
Q
What is an adverse drug event?
A
An adverse outcome in a patient which occurs after the use of a drug, but which may or may not be linked to use of the drug
10
Q
classifying ADRs on serious/ not serious.
when may reaction be “serious”?
A
any reaction which results in or prolongs hospitalisation (42%)
11
Q
Apart from resulting in/ prolonging hospitalisation, what else are serious reactions? (5)
A
those that are: • fatal (5%) • life-threatening (20%) • disabling/incapacitating (10%) • cause congenital abnormalities (1%) • medically significant (22% - e.g. hyperkalaemia having no symptoms but still risk factor for cardiac arrhythmias)
12
Q
What is an example of occupational exposure mentioned in the EU definition of ADRs?
A
e.g. pharmacist has anaphylactic reaction to antibiotic while making it
13
Q
drug classes resulting in ADRs and their % (most common-> least)
A
NSAIDs diurietics warfarin ACEi antidepressants Beta blockers opiated digoxin prednisolone
14
Q
What is the difference between an adverse drug reaction and adverse drug event?
A
- adverse drug events are not necessarily caused by the drug
- therefore all ADRs are ADEs, but not all ADEs are ADRs
15
Q
What are the 2 main ADR groups of the Rawlins-Thompson classification system?
A
type A ADRs:pharmacology planning to expect action in person
type B ADRs: not directly related to pharmacology of drug
16
Q
RT classification system:
Are type A ADRs dose-related or not?
A
type A are dose-related, meaning the higher the dose the stronger the ADR
17
Q
RT classification system:
Are type B ADRs dose-related or not?
A
type B are NOT dose-related, meaning the reaction is the same independent of the dose
18
Q
What is a type A ADR? (dose related? common? predictable? related to pharmacology? morbidity? mortality?)
A
- Dose related
- Common
- predictable as they’re related to the pharmacology
- high morbidity
- Low mortality
19
Q
What are 3 examples of type A ADRs
(of digoxin, betablocker, hypnotic)?
A
digoxin = toxicity betablocker = bradycardia hypnotic = sedation (fall and break hip)
20
Q
What is a type B ADR?
dose related? common? predictable? related to pharmacology? morbidity? mortality?
A
- Not dose related/dependant
- Uncommon
- unpredictable due to not being related to pharmacology
- low morbidity
- High mortality
21
Q
What are 3 examples of type B ADRs
(of penicillin, anaesthetics, statins)?
A
- penicillin = hypersensitivty (anaphylaxis)
- anaesthetics = malignant hyperthermia
- statins = hepatitis
none of these reactions are related to the pharmacologically desired effect
22
Q
What type B reaction can occur with carbamazepine?
A
Stevens Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN)
23
Q
What allele significantly increases the risk of Stevens Johnson syndrome with carbamazepine use?
A
HLA-B*1502 allele, almost exclusively in patients with ancestry across Asia
24
Q
What type B reaction can occur with ace-inhibitors?
A
angioedema:
• Life threatening
• Rare
• Unlikely to be picked up in clinical trials
• Biggest cause of angioedema presenting to A&E
• 0.2% incidence
25
Explain Type C AD reaction
- dose related and time related
- uncommon
- related to cumulative dose
- repeated and chronic use of a drug leads to an ADR
- don't use high dose steiroids- can cause this
26
how can type C ADR be dexcribed and give examples
chronic
. Cushing’s syndrome: oversupply of endrogenous corticosteroids e.g. prednisolone
27
Explain Type D ADR
- time related
- uncommon
- usually dose related
- occurs soon or some time after the use of the drug
28
examples of Type D ADR
Carcinogens
Renal cancer with Aristolochia, skin cancers, lymphomas
Another classification type: DoTS
Outlines how reac happens, important factors of ADR and patient
29
Explain type E ADR
- withdrawal reactions
- uncommon
- occur soon after withdrawal
30
example of type E ADR
myocardial infarction after beta-blocker withdrawal and there's no regulation of receptors
31
Explain type F ADR
- common
- dose related
- cause by DDI
32
example type F ADR
St Johns Wort and oral contraceptives (failure in presence of enzyme inducer)
33
what do rawlins-thompson types of reactions A-F stand for?
```
Actions expect
Bizarre
Chronic
Delayed
End of use
Failure
```
34
what does DoTS system stand for?
3 factors in which ADR can occur- Dose, Time, Susceptibility
35
DoTS system:
| explain dose relatedness (3 sections)
Dose (response) The ADR can occur
- at doses below therapeutic doses (hypersusceptibilty)
- in the therapeutic dose range (collateral effects)
- at high doses (toxic effects)
36
DoTS system:
| explain time relatedness (2 sections)
Time independant/ dependant reacts
Time ( Course) can be characteristic
- with the first dose
- early or after a time, or with long-term treatment
- on stopping treatment
- delayed
37
DoTS system:
explain susceptibility- when may it increase
and example
Susceptibility can be defined
- Genetics
- Age
- Sex
- Physiological state
- Disease
- Exogenous drugs or food
e.g. congenital defects: men not at risk
38
give examples of DoTS class: ADRs occuring during
a) low doses
b) in therap range
c) high doses
a) toxicity: anaphylaxis with penicillin
b) collateral: nausea with morphine
c) hypersusceptibilty: liver failure with paracetamol form overwhelming the pathways
39
how do dose related effects look like on dose response curve?
(therap response/ dose)
sigmoidal shape:
hypersuscep... collateral (increasing).... toxic effects
40
example of when time course characteristic • Early/ after time/ with long term treatment:
- nitrate induced headache first few days, body may start to tolerate after.
- 10 days- 10 weeks: toxic epidermal necrolysis.
- Several weeks: drug induced Cushings syndrome
On stopping treatment (withdrawal): paroxetine withdrawal syndrome
Delayed: clear cell cancer with stilbestrol
41
```
DoTS: susceptibility
give examples of each of the following:
-Genetics
-age
-sex
-Physiological state
-Exogenous drugs/foods
-Disease
```
* Genetics: haemolysis with chloroquine in G6PD deficiency
* Age: parkonism with prochlorperazine in elderly
* Sex: ACE inhibitor cough in women
* Physiological state: phenytoin in pregnancy, sodium valproate
* Exogenous drugs/foods: warfarin increased by cranberry juice: and increased INR
* Disease: Gentamicin and deafness in renal failure
42
Using DoTS system: type C example
```
1. Osteoporosis due to corticosteroids: typically Type C
• Dose: collateral
• Timing: late
• Susceptibility: age older, sex female
Helps see factors to change to avoid ADR
```
43
Using DoTS system: type D example
2. Anaphylaxis due to penicllin: typically Type B
• Dose: hypersusceptibility
• Timing: first dose
• Susceptibility: unclear, requires previous sensitisation
44
aims of Causality assessment?
* Decide on nature of further enquiries. Set up cohort study/ case control
* Satisfy regulatory requirements
* Decide whether drug caused an ADR. Normally based on probability- if accessible, enough data
* Aid signal identification. finding new signal of ADR harm in drug prev.
* Classify reports: i.e. likely/unlikely/probable
* Provide basis for label change: ADR list in summary of product
45
why is a clinical causallity assessment done?
assess Does drug -----> ADR for sure?
Making regulatory decisions to keep drug on market/ restrict use
46
9 Important factors to consider in causality assessment
```
Temporal relationship: time
Clinical characteristics of event
Pharmacological plausibility
..Existing info about drug and ADRs
Concomitant meds
Underlying/concurrent diseases
Dechallenge/rechallenge
Patient characteristics
Potential for drug interactions
```
47
whys Temporal relationship: time
| an important factors to consider in causality assessment
- Can strengthen causal association- case of anaphylaxis occurring immediately after parenteral med admin.
- Timing of ADR may be misleading e.g. cholestatic jaundice caused by flucloxacillin may manifest days-weeks after therapy completion. Week relationship
- With long term reactions: think reaction systemic- ADRs to steroids usually.
- Can be complex, look at DoTS system for info
48
whys Clinical characteristics of event
| an important factors to consider in causality assessment
- Some clinical events e.g., acute dystinias, blood dyscranias, skin reacs typically med related
- Other ADRs may have diff causes: hepatitis: infection/ other disease/alcohol/med/med interaction
49
whys Pharmacological plausibility
an important factors to consider in causality assessment
- where can it be checked?
* Is event likely to be result of known pharmacology of drug?
* Can check clinical plaus from BNF/ manufac data sheet
* Even if event unreported, other factors may be sufficient to support causality suspicion
* Not the be all end all for new events arising
50
whys ..Existing info about drug and ADRs
an important factors to consider in causality assessment
where to check?
* Is ADR in literature? Has it been noted by others?
* Listed in BNF? In section 4.8 of Summary of product characteristics?
* Even if event unreported, other factors may be sufficient to support causality suspicion
51
whys Concomitant meds
an important factors to consider in causality assessment
what to check?
* What other meds being taken? Their ADRs
* Taken full med history?
* Could be other drugs causing ADRs
* Check whether causually related to the ADR seen
52
whys Underlying/concurrent diseases
an important factors to consider in causality assessment
whats needed to confirm cause?
* Illness/newly manifest disease may cause SYMPTOMS/ alter nature of drug
* May not spec cause ADR
* Lab investigations may be req to confirm cause
* Disease issue not drug issue. People with heart disease e.g. may have stronger symptoms with certain drugs
53
whys Dechallenge/rechallenge
| an important factors to consider in causality assessment
* Recovery after med withdrawal important pointer in causal relationship
* Recurrence on rechallenge strongly suggestive med responsible but must have valid reason and be prepared for any eventuality
* Deliberate rechallenge often unethical
54
whys Patient characteristics
an important factors to consider in causality assessment
what to check
```
check..
• Previous history of allergies?
• Hepatic/renal impairment?
• History of atopy?
• Low body weight, sex, renal/ hepatic function
```
55
whys Potential for drug interactions
| an important factors to consider in causality assessment
Are interactions with other drugs potentially causing ADR?
56
whys Potential for drug interactions
| an important factors to consider in causality assessment
Are interactions with other drugs potentially causing ADR?
57
what does Dose relationship in ADRs relate to?
| and affect on ADRs?
drug pharmacokinetics
* Many ADRs: idiosyncratic, argued some not dose related (Type B in Rawlins Thompson classification)
* Adverse events which appear/worsen with dose increase and abate with dose reaction (rechallenge/dechallenge effect)
58
purpose of/ what is implied by Spontaneous reports (Yellow cards)?
* Report ADR to regulator
* Causal relationship implied unless reporter explicitly states its been excluded
* Don’t need to prove causation, if any suspicion drug causes ADR, can report
59
purpose of Bradford Hill criteria?
| difference compared to causality assessment
Association/causation
Used to see if drug associated with ADR.
Similar to factors in causality assessment, but may need to make decisions based on multiple evidence- working at population level for example. Looking at multiple patients, studies like cohort/case control/ clinical trial etc.
Used for population level
60
9 sections in bradford hill criteria?
```
Strength
Consistency
Specificity
Temporality
Biological gradient
Plausibility
Coherence
Experimental
Analogy
```
61
whats assessed in 'strength' section of bradford hill criteria - checking if drug associated w ADR
Is association strong?
Weak association: more likely caused by biases
E.g. relative risk of lung cancer from smoking: 10-30 relative risk: strong association
In most epidemiology: RR of <2 considered weak
Because drugs with high RR for harms would have failed clinical trials
Other methods used in drug safety: proportional reporting rates
62
whats assessed in 'Consistency' section of bradford hill criteria - checking if drug associated w ADR
Does association occur in repeated studies in different population?
RR weak but consistent across studies = strong causal effect
Consistent finding in many studies?
Additional support for causal association but doesn’t mean for sure.
More important in pharmacovig as RR becomes more low 1.5-2 e.g.
Consistency in pharmacovig suggests causal effect
63
whats assessed in 'Specificity' section of bradford hill criteria - checking if drug associated w ADR
How specific is effect?
A cause-> single effect not multiple ones
Drugs cause ADRs by spec mechanisms, even if not known at time
True associations more likely specific e.g. HRT and breast cancer
False association? Vit K injections cause cancer in children but specific studies found no link
Important to follow up on details of cases to get specific diagnosis
64
whats assessed in 'Temporality' section of bradford hill criteria - checking if drug associated w ADR
Cause must precede effect in time
Many ADRs occur in particular time patterns (see DoTS)
Consistent temporal patterns suggest causality: not just random results
Should take interactions and concomitant diseases
65
whats assessed in 'Biological gradient' section of bradford hill criteria - checking if drug associated w ADR
what does dose repsonse suggest?
Is effect dose-related? (DoTS)
The more you smoke = more chance of lung cancer
Dose response suggests causation, as does cumulative doses over time. ADRs, build up of drug over time
Dose response between DVT and oral contracept was found based on ADR reports to yellow card, supporting causation
Sometimes can be complex (Alcohols J shaped curve)
66
whats assessed in 'Plausibility' section of bradford hill criteria - checking if drug associated w ADR
what can this be affected by?
Is there a mechanism for effect?
NSAIDS and gastrointestinal bleeding: easy= mechanism, can work out biology. Plausible
Practolol and oculomucutaneous syndrome: harder as no known mechanism..
Can be affected by our current knowledge
67
whats assessed in 'Coherence' section of bradford hill criteria - checking if drug associated w ADR
If effect coherent, with known facts of biology?
Shouldn’t conflict with known facts of natural history and biology of a disease
Vit K injections in children did notalign with known mechanisms of how cancer occurs: wasn’t coherent argument
Can only judge on basis of current state of scientific knowledge
68
whats assessed in 'Experimental' section of bradford hill criteria - checking if drug associated w ADR
Is experimental evidence demonstrating effect?
Biological models you could use? Human experiments/ animal studies?
e.g. if drug interaction, can be repoicated in lab/ pharmacokinetic studies?
69
whats assessed in 'Analogy' section of bradford hill criteria - checking if drug associated w ADR
Can analogy be made with another known association?
Some circumstances: fair to judge by analogy?
e.g. after thalidomide caused birth defect, should we be expected to accept same level of evidence for another drug? Probably not
Be careful with analogies as can go wrong…
ACE inhibs cause cough in 20% patients. ARBs mechanism different so analogy may not hold
70
3 main categories of Methods of causality assessment?
Subjective methods of assessing patients...
1. Unrestricted clinical evaluation/ global introspection (subjective)
2. Algorithms with/without scoring (rule based methods)
3. Bayesian probilistic methods: assign prior probability and look and modify in light of new info. Problem: mostly don’t have prior probability so cant work out new
71
3 points about subjective methods of caus assesment?
Subjective methods
• Global introspection
• Striking case methos
• Unstructured clinical judgement
72
Who-UMC causality categories
Certain -> Possible -> Unassessible not enough info to make decision
Balances different elements of the report
Positive and negative elements contribute to decision
73
what do all Rule based methods
AKA generalised rule based/ standardised decision aids
contain? (3)
```
Involve rating adverse event using questionnaire/algorithm
All contain:
• Set of structured responses
• Weighting algorithm
• Scaling algorithm
```
74
Benefits/limitation of algorithms
| Methods of causality assessment
* Reduce intra and inter-rater variability (in well controlled studies)
* Variability may arise in less than perfect conditions, difficult to compare
* Subjective questions = variations in scores
* Different systems highly divergent
* Little attention given to design and validation
75
example of algorithm for assessing causality
Naranjo scale: popular scoring system
9- def ADR
5-8- probable
1-4 possible
0- doubtful
Tend to get possible and probable scores often
76
When to assess causality?
* Clinical trials: investigator
* Spontaneous reports: reporter
* On initial receipt of report – regulatory agency
* When all/most clinical info available
* Signal identification and evaluation
* Periodic review - aggregate data
77
what to consider when using algorhtms to assess causality?
hard to make the decisions if drug caused, is linked to ADR
| Yellow cards may have missing data too, not same as when patient in front of you with their full medical minds
78
why are pharmacovigilance systems to detect new adverse drug reactions essential?
as few adverse reactions are identified during pre-marketing studies
79
common method of pharmacovigilance and what do they depend on?
Spontaneous reporting scheme
depend primarily on health professionals, but patients are encouraged to report suspected adverse reactions themselves in many countries.
80
ADR fact
• Adverse drug reactions are a significant cause of morbidity and mortality, are responsible for approximately 1 in 20 hospital admissions and are a considerable financial burden on health systems.
81
Predisposing factors for adverse drug reactions include ...
age, sex, ethnicity, genetic factors, comorbidities and concomitant medication.
82
Many adverse drug reactions may be preventable through (2)
rational prescribing and careful monitoring of drug therapy.
83
What is the definition of DDI?
When effects of one drug taken by a patient are changed by another drug, food or drink also taken by the patient
84
outcomes of DDIs?
they can be beneficial e.g. treating hypertension
they can be clinically insignificant
they can be harmful- worsen the outcomes
85
How do warfarin and clarithromycin interact?
clarithromycin - increases warfarin levels -> increase in INR( prothrombin time) -> bleed in the brain
86
Patient risk factors for a DDI?
- age
- neonates and children
- gender
- co-morbidities
- diet
- smoking
- illicit drugs
87
how may drugs interact?
Interact via working on body: diff routes and mechanisms/ interact with each other
Many herbs also interfere with how drug works. Not prescribed so herb epidemiology may be unknown. St John’s wort etc
88
How often do DDIs happen? Epidemiology
1 in 20 admissions associated with ADRs
•1 in 5 of those associated with interactions
•1 in 6 inpatients have an ADR
•59% of those linked to drug-drug interactions
89
How is age a risk factor for DDI?
- if older there is more drug use
- with age there is more change in body composition so more fat and less muscle
- co-morbidities- more at risk
- Neoneates and children different ‘more watery’
- <28 days- hepatic function reduced
- older children have a rapid improvement in drug elimination
90
How is sex a risk factor for DDI?
women - eliminate drugs more rapidly and are more subject to some ADRs
91
what is polymorphic enzyme expression? what does it mean for metabolism?
Diff enz= diff expressions. E.g. some people are slow metabolites some fast
when a single base pair changes in the DNA sequence
have drug metabolising enzymes
- rapid metabolisers
- the wild type is the most common
92
how is comorbidites a risk factor? and what is an example relating to liver failure?
- increases DDI risk
- As less reserve/headroom to deal with consequences on increased conc of drug
- liver failure/malnutrition reduces albumin levels leading to changes in availability of protein bound drugs
- liver/renal dysfunction -> accumulation leading to potentially severe toxicity
Due to kidney elinm of water soluble drugs
93
How does illicit drugs act as a risk factor for DDI?
- acute effects: warfarin and metronidazole
- cannabis can enhance drug clearance and tachycardia
- respiratory depression with heroin - accentuated by opiates
94
how is Diet a risk factor for DDI?
. E.g. lots of green veg can change how Warfarin works due to Vit K
95
What is the percentage of pharmacodynamic and pharmacokinetic of DDI's?
92% is pharmacodynamics ; receptor level interactions and tissue/organ impact
5% pharmacokinetic; biotransformational changes -> enzyme induction/enzyme inhibition
- distribution changes and protein binding
96
What are the pharmacokinetic interactions of an DDI?
- when one drug impacts on the biotransformation or distribution of a drug
97
What does the pharmacokinetic interactions graph look like?
conc. vs time
steep increase with onset time being first and then reaches peak where Cmax and tmax are reached.
then steadily decreases until it plateaus eventually.
The graphs peak time is the duration of action and the MTC and MEC difference is the therapeutic range
98
describe Pharmacodynamic interactions
Receptors: 2 drugs act on same receptor/ same organ via different mechanisms = additive effect
* Amplification or negation of each other’s effects: can occur in:
* Receptor, tissue, organ level
* Time/persistence linked to half-life
* Drug concentrations may be in therapeutic window, anti/ additive? pharmacological effect
* “Off target” effects possible
99
describe Pharmacodynamic interactions: affect on same receptor
Same receptor – antagonist/agonist
• Competitive or non-competitive (irreversible)
• Drugs can act at more than 1 receptor – H1 antagonists are also
• anti-cholinergic
100
describe Pharmacodynamic interactions: affect on different receptors
examples
* Beta-blockers and vasodilators (angina) decrease BP, may induce falls
* Hypertension (beta-blockers & diuretics)
* Combination cytotoxic chemotherapy
101
describe Pharmacokinetic interactions DDI
Distribution and elimination of drugs
To water soluble drgs
If enzyme inhibition = drugs accumulate, off target, toxicity effects
Prodrug: efficacy wil decrease as enzyme converting from inactive to active state
Metabolise faster = loss of drug efficacy
When one drug (or herb/food) impacts on the
biotransformation or distribution of a drug.
102
Explain the induction of biotransformation. What does it lead to and how long does it last?
- drug entry constant
- increased biotransformation -> premature loss of drug -> reduce/abolish clinical effect
time frame- day and weeks to get clinical effect you want
Enzyme induction of biotransformation will happen over days and weeks and lead to clinical effect failure
103
example of induction (enzyme) of biotransformation- warfarin
• Drug no longer inhibited = drug accumulation = target effects and toxicity.
E.g. drug that interefered with CYP450 enzyme = warfarin no longer metabolised, accumulate = toxicity usually from increased INR, bleeding. Hours and days.
103
example of induction (enzyme) of biotransformation- warfarin
• Drug no longer inhibited = drug accumulation = target effects and toxicity.
E.g. drug that interefered with CYP450 enzyme = warfarin no longer metabolised, accumulate = toxicity usually from increased INR, bleeding. Hours and days.
104
explain the inhibition of biotransformation. What does it lead to and how long does it last?
- drug entry constant
- removal of drug inhibited -> drug accumulation -> off-target effects and toxicity
time frame- hours and days
105
how do enzyme induction and inhibition of biotransformation compare?
Inhibition of biotransformation would = toxicity, happens quicker than loss of efficacy = more dangerous istuation
106
Explain the P-glycoprotein - efflux pump . Give an example of what it does
- major efflux system
- uses ATP to transport many absorbed drugs to gut
- e.g. transports digoxin back into gut
107
What are influx pumps and how do they work? What do they contain
contain Organic Anion Transporting Polypeptides (OATPs)- liver cell membranes and gut
these pumps are solute carriers for nutrients- diverse range of water soluble drugs are carried by OATPS; fexofenadine absorption prevented by grapefruit juice
108
what drugs can inhibit OATPs?
o Rifampicin inhibits OATP – atorvastatin does not enter liver cells
o 7-fold increase in plasma concentration
o Fexofenadine absorption prevented by grapefruit juice
109
how do influx pumps work in terms of first pass metab?
| How are some organs involved in first pass metabolism?
absorption form gut via HPV -> liver -> distributed to body via vena cava
110
How does the cytochrome P450 system work?
* Major focus of biotransformation
* Evolved, widespread in nature
* Can manipulate virtually any chemical
* Can change the shape and physiochemical properties of a molecule
* Used to build and destroy
* Drugs/toxins caught up in destruction process
* Poorly water-soluble to water-soluble to be elim from body
111
main drugs that inetrfere with the CYPs and what effect?
```
CYP3A4
CYP3A5
CYP2D6
CYP2C9.CYP2C8
CYP2C19
CYP1A2
CYP2E1
```
* CYP3A4 – half of metabolic capability
* CYP3A5 – similar, increased prevalence in Afro-Caribbean
* CYP2D6 - antidepressants, SSRIs, opiates, beta-blockers
* CYP2C9/CYP2C8 – warfarin, anticonvulsants
* CYP2C19 – PPIs, clopidogrel
* CYP1A2 – clozapine/SSRis/Warfarin
* CYP2E1 – paracetamol and in ethanol
112
What occurs when CYP induction by drug happens? How long does it last for?
* Happens within hours – full effect 2-3 weeks
* Drug conc will fall outside of therapeutic window – increase dose? having increased metabolism / stop induced drug. Depends on nature of interactions and what drugs
* 2-3 weeks stable – will need higher dose
* Stop inducer – inductive effect lost in days
* Breaks in drug therapy put patients at risk of overdose = danger
113
CYP inducer example
Rifampicin – induces most important P450s
114
explain CYP inhibition compared by induction, by a drug
More common
drug accumulates -> + Pharmacological effects -> toxicity (unless there is an alternative metabolic pathway- explain in vitro pathways may not cause big problem- alternative pathway
* Reversible or irreversible (erythromycin)
* Focus on potential toxicity of inhibited drug
115
what to consider about me too drugs and ADRs? (Naranjo scale)
may have similar side effects or one drug specific side effects different to that class.
116
what to consider during polypharmacy and ADR?
If patient had bradycardia, would remove the drugs beta blockers and let pulse increase normally
Other drugs can induce/ reduce the HR. explore indications and side effects of all the drugs.
Dose increases, ADR related to this.
117
what are the WHO-UMC causality categories?
```
certain
probable/likely
possible
unlikely
conditional/unclassified
unaccessable/unclassifiable
```
