Adverse Drug Reactions Flashcards
What is meant by an adverse drug reaction
an undesirable effect causing detriment to the patient
What is the difference between a side effect of a drug and an adverse effect?
Side effects are a sub-type of ADR
They are related to the pharmacological properties of the drug
Give examples of drugs which were previously used but could cause well known adverse drug effects?
Arsenic - used for syphilis - causes jaundice
Chloroform - used as anaesthetic - causes arrythmias
Why are patients with hepatic and renal failure more at risk of adverse drug reactions?
They are unable to excrete medicines effectively from the body
=> they have higher concentrations of drug left in their body
=> More likely to suffer ADR due to toxicity
Why does polypharmacy increase the risk of an adverse drug reaction?
Patients can be on multiple different drugs (e.g. 12-13) which makes it very difficult to assess the risk of interactions between all of them
What drugs have a narrow therapeutic index?
Theophylline Warfarin Lithium Digoxin Gentamicin Vancomycin Phenytoin Cyclosporin Carbamazepine Levothyroxine
What is considered a Narrow Therapeutic Index
<2
=> it is easy to reach a toxic dose
Why are ADRs often not identified in clinical trials?
- Limited sample size
- They present later than the clinical trial runs
- ADRs often present in the elderly/frail pts who are excluded from clinical trials
When are rarer ADRs identified and why?
- During post-marketing surveillance
- Most data is available at this point
- Drugs need tested on a LARGE number of patients to identify rare ADRs
Describe the two phases of drug metabolism
Phase 1 - Cyp450 breaks drug down in liver via Oxidation/Reduction/Hydrolysis
Phase 2 - Converts drug to water soluble to allow excretion in urine and bowel
Describe the different categories of ADR
Type A - Predictable and dose dependent Type B - Bizarre and dose independent Type C - Chronic Effects Type D - Delayed Effects Type E - End of Tx Effect Type F - Failure of Tx
What predictable ADRs can be caused by a Type A reaction?
Pre-renal AKI due to hypotension/hypovolaemia
Renal AKI - AIN/Tubular Necrosis
Post-renal AKI - fibrosis, calculi
What drugs can cause a hypotension/hypovolaemia that can lead to a pre-renal AKI?
- Large diuretic dose
- Taking ACEi/ARBs during sick days of diarrhoea and vomiting
What drugs can cause a renal AKI and how?
Gentamicin in SEPSIS
- causes lysosomes to enlarge and burst
- Mitochondria swell
- Destroy apical brush border
- Induces apoptosis
What drugs can cause a post-renal AKI?
Methylsergide (for cluster headaches) causes retroperitoneal fibrosis
Chemotherapy releases purine into system => predisposes to renal/urinary stones
What are the 3 possible Type A reactions?
Drug-Drug Interactions
Drug-Disease Interactions
Drug-Food Interactions
What class of antibiotics interact with Theophylline and why?
Macrolides - they inhibit Cyp450 which breaks down Theophylline
When is it important to be aware of theophylline and macrolide antibiotics interacting?
If an asthmatic or COPD patient develops pneumonia
- macrolides are used if pt is penicillin allergic
What drug-drug interaction occurs between ACEi and sulphonylureas?
ACEi increase the ability of suplhonylureas to cause HYPOglycaemia
(especially at high dose)
With which drug class does clopidogrel experience a well known drug-drug interaction?
PPIs
What drug-disease interaction is thought to occur in Parkinson’s disease?
Increased drug induced confusion
What can be done in order to help drug induced confusion in parkinson’s disease?
Start drugs at low concentrations if they are lipid soluble as this releases less into the CNS
Why should NSAIDs, COX2 inhibitors and TZDs be avoided in heart failure?
They cause Na retention (increases preload)
Patients with what condition should NOT be given Beta-blockers?
Asthma
What drugs are known to cause a drug-disease interaction in epilepsy by lowering the seizure threshold?
Tramadol
Quinolones
Why is it important to watch K+ intake in food?
Pts can become hyperkalaemic if they are on drugs which retain K+
e.g potassium sparing diuretics
What foods are high in Vitamin K and therefore cause a drug-food interaction with warfarin?
Apples, Nuts, Chickpeas, Spinach
What foods can alter the pH of the stomach and what drugs does this affect?
Chicken, Turkey, Milk, Cheese, Yoghurt
=> makes stomach less acidic
=> antibiotics need acidic environment of stomach to act fully
What fruits are involved in inhibiting Cyp450 and therefore preventing the breakdown of drugs such as statins or antihistamines?
Grapefruit, oranges, apples, cranberries
Why are Type B drug reactions so important?
- They are completely unpredictable and ADRs cant be controlled
- Can result in death of patients
- Drug can be removed from market if reactions are so severe
Give examples of Type B drug reactions which are completely unrelated to the drug metabolism.
Drug rashes
Bone Marrow aplasia (chloramphenicol)
Hepatic necrosis (halothane - general anaesthetic)
What is a Type C chronic drug reaction?
Prolongued therapy of a drug causes a long term effect
Give examples of Type C drug reactions which can occur from steroids?
Cushing’s
Osteoporosis
What Type C reaction occurs due to use of NSAIDs?
Fluid retention
=> hypertension
Should we tell patients about chronic drug reactions when they begin a drug?
Yes
We should tell them about the common chronic side effects to make them aware
This allows us to remind them that we will follow them up
What is a Type D drug reaction?
appears many years after stopping a drug
Give an example of a Type D drug reaction?
Chemotherapy in teenage leukaemia is often teratogenic/carcinogenic
=> predisposes to secondary malignancy later in life
What is a Type E drug reaction?
Occurs when a drug is suddenly stopped in a patient
=> produces a rebound effect
What Type E drug reaction occurs when a Beta Blocker is stopped?
Rebound tachycardia
=> predisposing to angina
Steroid withdrawal can cause what Type E drug reaction?
Addisonian crisis
- high dose steroids should be tapered down to avoid adrenals giving up
How are ADRs reported?
Yellow card system
Give examples of drugs which interact with HLA genes?
Abacavir interacts with HLA-B5701
Allopurinol interacts with HLA-B5801
- produces Steven-Johnson syndrome (rash)
What genetic mutation predisposes to an abnormally fast metabolism which affects how drugs are absorbed into the body?
CYP2D6
=> larger doses are required for clinical effects in these pts
What does a black triangle in the BNF mean?
- New drug with new active ingredient
- Indicates something has been identified during clinical trials that could be a potential rare side effect
How long does a black triangle remain in the BNF?
2 years (unless a potential side effect is identified - then it may remain in longer)
