Drug Safety - ADRs and Drug Interactions

Question 1

What is the difference between ADRs & Side Effects?

Answer 1

Side effects can be adverse or beneficial, ADRs are only adverse

Question 2

What proportion of hospital admissions are ADR related?

Answer 2

5%

Question 3

What are the most common causes of hospital admissions for ADRs?

Answer 3

NSAIDs
Diuretics
Warfarin

Question 4

Define Type A ADRs

Answer 4

Adverse
Normal pharmacological response is undesirable
Dose-related & predictable
Managed by dose adjustment

Question 5

Describe several common antimuscarinic side effects

Answer 5

Dry Mouth
Blurred Vision
Constipation
Urinary Retention

Question 6

Describe several common beta blocker side effects

Answer 6

Cold Extremities
Bradycardia
Nightmares
Bronchospasm

Question 7

Describe the main side effect of cimetidine/spironolactione

Answer 7

Gynaecomastia

Question 8

Describe the main side effect of opioids/antimuscarinics

Answer 8

Constipation

Question 9

Describe the most common side effect of antibiotics

Answer 9

Diarrhoea

Question 10

Describe the side effects of NSAIDs/Beta Blockers in Asthma sufferers

Answer 10

NSAIDs - Wheezing

B-blocker - Fatal Bronchospasm

Question 11

Describe several common side effects of Digoxin

Answer 11

Nausea
Vomiting
Visual Disturbances

Question 12

Describe the main side effect of cytotoxics

Answer 12

Myelosuppression

Question 13

Describe the most common side effect of NSAIDs

Answer 13

Gastric Damage

Question 14

Changes in what two pharmacokinetic factors most commonly lead to ADRs?

Answer 14

Absorption

Elimination (R+H)

Question 15

What value can be used to estimate renal function?

Answer 15

GFR/eGFR

Question 16

Why do neonates/elderly conjugate drugs at a slower rate?

Answer 16

Microsomal enzyme activity decreases at extremes of age

Question 17

How can LFTs be used to predict liver metabolic function?

Answer 17

They cannot - poorly predict metabolic activity

Question 18

Define Type B ADRs

Answer 18

Bizarre (Idiosyncratic)
Unpredictable
Rare
Often severe
Related to genetics/immunology

Question 19

What is the pathophysiology underlying a penicillin allergy?

Answer 19

Penicillins couple to proteins, form immunogens

Type 1 Hypersensitivity reaction

Question 20

How should penicillin allergies be treated?

Answer 20

H1-antagonist

Question 21

What are the two most common haematological ADRs?

Answer 21

Agranulocytosis

Thrombocytopenia

Question 22

Describe Agranulocytosis

Answer 22

Absence of neutrophils (mouth ulcers, severe sore throat, infections)
Caused by:
-Clozapine
-Carbimzole
-Carbamazepine

Question 23

Describe Thrombocytopenia

Answer 23

Low platelet count (bruising/bleeding)

Question 24

What patients are particularly at risk for gastric damage when treated with NSAIDs?

Answer 24

Over 65

History of ulcers

Question 25

What treatment is available to reduce the risk of gastric damage when treating with NSAIDs?

Answer 25

Prophylaxis w/ PPIs | Misoprostol

Question 26

In what group is treatment w/ Misoprostol contraindicated?

Answer 26

Pregnant women (all women of child bearing age not proven non-pregnant)

Question 27

What ADRs may NSAIDs cause in patients suffering from CVD?

Answer 27

Fluid retention | Exacerbated hypertension/CHF

Question 28

How do NSAIDs cause renal damage?

Answer 28

Inhibit renal PGs Reduced renal blood flow Reduced GFR

Question 29

Why are beta-blockers contraindicated in asthma?

Answer 29

Block bronchial B2 adrenoceptors | Cause bronchospasm

Question 30

What ADR are statins associated with most commonly?

Answer 30

Muscle damage/myopathy | Progresses to Rhabdomyolysis

Question 31

What are the most common skin ADRs?

Answer 31

Urticaria Erythematous Eruptions - reddening, maculopapular Toxic Epidermal Necrolysis - blistering, peeling skin Stevens-Johnson Syndrome - fever, rash, blisters

Question 32

Define Drug Interactions

Answer 32

An interaction occurs when the effects of one drug are changed by the presence of another drug, food, drink or an environmental chemical agent

Question 33

Alterations in which pharmacokinetic mechanisms may lead to drug interactions?

Answer 33

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)

Question 34

What are the two CYP-mediated mechanisms of drug interaction?

Answer 34

Inhibition | Induction

Question 35

Describe CYP Inhibition

Answer 35

Inhibition of CYP enzymes resulting in decreased metabolism Occurs immediately Reverses quickly ie. Erythromycin

Question 36

Describe CYP Induction

Answer 36

Induction of CYP enzymes resulting in increased metabolism May take a week or 2 Persist on stopping ie. Rifampicin, Carbamazepine

Question 37

What drugs are contraindicated with Simvastatin?

Answer 37

Macrolides (complete contraindication) | Amlodipine, Verapamil, Diltiazem (lower statin dose)

Question 38

Describe the interaction between NSAIDs and Methotrexate

Answer 38

Compete for elimination | Leads to myelosuppression

Question 39

What effect does pH have on renal elimination?

Answer 39

Increased pH = Increased Excretion of Weak Acids

Question 40

Describe the interaction between Diuretics and ACEi

Answer 40

Diuretics lead to volume depletion | w/ ACEi risk of severe first dose hypotension

Question 41

Describe the interaction between loop and thiazide diuretics

Answer 41

Cause hypokalaemia (increase digoxin toxicity)

Question 42

In what situation might K-sparing diuretics cause hyperkalaemia?

Answer 42

Concordant treatment w/ K supplements or ACEis

Question 43

Define Pharmacological Interactions

Answer 43

When the actions of one drug opposes/augments the effect of another

Question 44

Describe the interaction between Beta Blockers and RL Ca Channel Blockers

Answer 44

Risk of potentially fatal bradycardia/asystole | AVOID

Question 45

Describe the interaction between Warfarin and NSAIDs

Answer 45

Increased bleeding | Monitor w/ INR

Question 46

What is St. John's Wort?

Answer 46

A herbal medicine that is a potent inducer

Question 47

What drugs should St. John's Wort not be taken with?

Answer 47

``` Oral contraceptives Antiepileptics HIV drugs Ciclosporin Warfarin Simvastatin MAOIs/SSRIs (Serotonergic syndrome) ```

Question 48

Which drugs have significant interactions with Alcohol?

Answer 48

Labels 2/4 CNS depressant Few antibiotics (Metronidazole = nausea) Gastric effects

Question 49

What are the most clinically important drug interactions?

Answer 49

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)