Drug Safety - ADRs and Drug Interactions Flashcards
What is the difference between ADRs & Side Effects?
Side effects can be adverse or beneficial, ADRs are only adverse
What proportion of hospital admissions are ADR related?
5%
What are the most common causes of hospital admissions for ADRs?
NSAIDs
Diuretics
Warfarin
Define Type A ADRs
Adverse
Normal pharmacological response is undesirable
Dose-related & predictable
Managed by dose adjustment
Describe several common antimuscarinic side effects
Dry Mouth
Blurred Vision
Constipation
Urinary Retention
Describe several common beta blocker side effects
Cold Extremities
Bradycardia
Nightmares
Bronchospasm
Describe the main side effect of cimetidine/spironolactione
Gynaecomastia
Describe the main side effect of opioids/antimuscarinics
Constipation
Describe the most common side effect of antibiotics
Diarrhoea
Describe the side effects of NSAIDs/Beta Blockers in Asthma sufferers
NSAIDs - Wheezing
B-blocker - Fatal Bronchospasm
Describe several common side effects of Digoxin
Nausea
Vomiting
Visual Disturbances
Describe the main side effect of cytotoxics
Myelosuppression
Describe the most common side effect of NSAIDs
Gastric Damage
Changes in what two pharmacokinetic factors most commonly lead to ADRs?
Absorption
Elimination (R+H)
What value can be used to estimate renal function?
GFR/eGFR
Why do neonates/elderly conjugate drugs at a slower rate?
Microsomal enzyme activity decreases at extremes of age
How can LFTs be used to predict liver metabolic function?
They cannot - poorly predict metabolic activity
Define Type B ADRs
Bizarre (Idiosyncratic) Unpredictable Rare Often severe Related to genetics/immunology
What is the pathophysiology underlying a penicillin allergy?
Penicillins couple to proteins, form immunogens
Type 1 Hypersensitivity reaction
How should penicillin allergies be treated?
H1-antagonist
What are the two most common haematological ADRs?
Agranulocytosis
Thrombocytopenia
Describe Agranulocytosis
Absence of neutrophils (mouth ulcers, severe sore throat, infections) Caused by: -Clozapine -Carbimzole -Carbamazepine
Describe Thrombocytopenia
Low platelet count (bruising/bleeding)
What patients are particularly at risk for gastric damage when treated with NSAIDs?
Over 65
History of ulcers
What treatment is available to reduce the risk of gastric damage when treating with NSAIDs?
Prophylaxis w/ PPIs
Misoprostol
In what group is treatment w/ Misoprostol contraindicated?
Pregnant women (all women of child bearing age not proven non-pregnant)
What ADRs may NSAIDs cause in patients suffering from CVD?
Fluid retention
Exacerbated hypertension/CHF
How do NSAIDs cause renal damage?
Inhibit renal PGs
Reduced renal blood flow
Reduced GFR
Why are beta-blockers contraindicated in asthma?
Block bronchial B2 adrenoceptors
Cause bronchospasm
What ADR are statins associated with most commonly?
Muscle damage/myopathy
Progresses to Rhabdomyolysis
What are the most common skin ADRs?
Urticaria
Erythematous Eruptions - reddening, maculopapular
Toxic Epidermal Necrolysis - blistering, peeling skin
Stevens-Johnson Syndrome - fever, rash, blisters
Define Drug Interactions
An interaction occurs when the effects of one drug are changed by the presence of another drug, food, drink or an environmental chemical agent
Alterations in which pharmacokinetic mechanisms may lead to drug interactions?
Absorption - 2 drugs may interact, alter rate of uptake
pH - passive absorption of drugs best in uncharged form (rises in pH influence absorption)
Binding - ie. colestyramine
GI Motility - changes in motility/gastric emptying affect absorption (Metoclopramde acc. absorption)
What are the two CYP-mediated mechanisms of drug interaction?
Inhibition
Induction
Describe CYP Inhibition
Inhibition of CYP enzymes resulting in decreased metabolism
Occurs immediately
Reverses quickly
ie. Erythromycin
Describe CYP Induction
Induction of CYP enzymes resulting in increased metabolism
May take a week or 2
Persist on stopping
ie. Rifampicin, Carbamazepine
What drugs are contraindicated with Simvastatin?
Macrolides (complete contraindication)
Amlodipine, Verapamil, Diltiazem (lower statin dose)
Describe the interaction between NSAIDs and Methotrexate
Compete for elimination
Leads to myelosuppression
What effect does pH have on renal elimination?
Increased pH = Increased Excretion of Weak Acids
Describe the interaction between Diuretics and ACEi
Diuretics lead to volume depletion
w/ ACEi risk of severe first dose hypotension
Describe the interaction between loop and thiazide diuretics
Cause hypokalaemia (increase digoxin toxicity)
In what situation might K-sparing diuretics cause hyperkalaemia?
Concordant treatment w/ K supplements or ACEis
Define Pharmacological Interactions
When the actions of one drug opposes/augments the effect of another
Describe the interaction between Beta Blockers and RL Ca Channel Blockers
Risk of potentially fatal bradycardia/asystole
AVOID
Describe the interaction between Warfarin and NSAIDs
Increased bleeding
Monitor w/ INR
What is St. John’s Wort?
A herbal medicine that is a potent inducer
What drugs should St. John’s Wort not be taken with?
Oral contraceptives Antiepileptics HIV drugs Ciclosporin Warfarin Simvastatin MAOIs/SSRIs (Serotonergic syndrome)
Which drugs have significant interactions with Alcohol?
Labels 2/4
CNS depressant
Few antibiotics (Metronidazole = nausea)
Gastric effects
What are the most clinically important drug interactions?
Warfarin w/ NSAIDs (bleeding)
Warfarin w/ Erythromycin/Ciprofloxacin (bleeding)
NSAIDs w/ Methotrexate (methotrexate toxicity)
ACEis w/ K+ sparing diuretics (hyperkalaemia)
Verapamil w/ B-Blockers (asystole)
Digoxin w/ Amiodarone (digoxin toxicity)
Digoxin w/ Verapamil (digoxin toxicity)
Oral Contraceptives w/Inducers (failure of OC)
