Adverse Drug Reactions and Drug Interactions

Abstract

Adverse drug reactions are unwanted effects from medicines, and these can range from mild or irritating to severe or life-threatening. They are a significant cause of mortality, morbidity and hospital admissions and a common reason why patients do not take their medicines as instructed. Identification of adverse drug reactions can be complex because symptoms are often non-specific and because reactions do not always occur immediately after a medicine is given.

Keywords

Appendices

Multiple Choice Questions

• 1. Which of the following adverse drug reactions could be characterised as a type B reaction according to the Rawlins and Thompson classification system?

  • (a) Drowsiness in a patient taking the antihistamine chlorphenamine

  • (b) Toxic epidermal necrolysis in a patient taking the antimalarial drug chloroquine

  • (c) Hypokalaemia in a patient taking the loop diuretic furosemide

  • (d) Cold extremities in a patient taking the beta-blocker atenolol

• 2. Which of the following adverse reactions does not need to be reported to the MHRA via the Yellow Card Scheme?

  • (a) A minor reaction in an adult following administration of a ‘Black Triangle’ medicine

  • (b) A minor reaction in a child following administration of an established medicine

  • (c) A minor reaction in an adult following administration of an established medicine

  • (d) A minor reaction in an adult following administration of an herbal medicine

• 3. Which of the following is not a common symptom of anaphylaxis?

  • (a) Hypertension

  • (b) Urticaria

  • (c) Rash

  • (d) Angioedema

• 4. Which of the following drugs could be safely considered for a patient who has previously experienced a severe hypersensitivity reaction with amoxicillin?

  • (a) Co-amoxiclav

  • (b) Phenoxymethylpenicillin

  • (c) Erythromycin

  • (d) Piperacillin-tazobactam

• 5. Which of the following patients with a urinary tract infection can safely receive the oral antibiotic ciprofloxacin?

  • (a) A patient who is allergic to penicillin

  • (b) A patient who is G6PD deficient

  • (c) A patient who is epileptic

  • (d) A patient taking oral calcium supplements for osteoporosis

• 6. Which of the following drugs is not known to induce cytochrome P450 enzymes?

  • (a) Rifampicin

  • (b) Carbamazepine

  • (c) Phenobarbital

  • (d) Simvastatin

• 7. Why is a patient taking warfarin at particular risk of harmful drug interactions?

  • (a) Warfarin is a substrate of cytochrome P450 enzymes and has a narrow therapeutic index

  • (b) Warfarin is an enzyme inducer

  • (c) Only a small fraction of warfarin is protein-bound

  • (d) Warfarin is renally excreted and many other medicines affect a person’s renal function

• 8. Which of the following statements about adverse drug reaction and drug interactions is incorrect?

  • (a) Age is a factor that can affect a patient’s risk of experiencing an adverse drug reaction

  • (b) Drug interactions do not occur between conventional and herbal medicines

  • (c) Adverse drug reactions sometimes arise from excipients in the medicine

  • (d) Drug interactions may not become apparent until several weeks after the combination of medicines is initiated

• 9. Which of the following is not a known drug–food interaction?

  • (a) Grapefruit and simvastatin

  • (b) Milk and ciprofloxacin

  • (c) Vodka and lorazepam

  • (d) Potatoes and amlodipine

• 10. Methadone is a long-acting opioid that is often prescribed to patients with opioid dependence. It is metabolised by the cytochrome P450 enzyme 3A4. Fluconazole is an antifungal drug that inhibits 3A4. What effects would you expect if methadone and fluconazole were administered together?

  • (a) A decrease in methadone plasma levels

  • (b) An increase in methadone plasma levels

  • (c) A decrease in fluconazole plasma levels

  • (d) An increase in fluconazole plasma levels

Answers

• 1. b

  Toxic epidermal necrolysis is a rare and severe cutaneous adverse drug reaction that cannot be predicted from the known pharmacology of chloroquine. It is a type B reaction according to the Rawlins and Thompson classification system. Drowsiness from chlorphenamine, hypokalaemia from furosemide and cold extremities from atenolol are all commonly occurring, dose-related adverse reactions that can be predicted from the pharmacology of the drug and are therefore type A reactions.

• 2. c

  Serious adverse drug reactions, reactions that occur in children and reactions following administration with herbal remedies or medicines that are intensively monitored by the MHRA (indicated by a black triangle symbol) should always be reported, even if causality is not proven. Minor reactions that occur in adults following the administration of an established medicine that no longer requires additional monitoring do not need to be reported.

• 3. a

  Anaphylaxis is a severe form of type 1 hypersensitivity characterised by immunoglobulin E (IgE) production following the administration of an allergen, such as a medicine. Anaphylaxis commonly causes rash, urticaria, angioedema and hypotension (not hypertension).

• 4. c

  The patient has previously experienced a severe hypersensitivity reaction to amoxicillin, which is a penicillin, and so should avoid further exposure to amoxicillin and all other penicillins. Co-amoxiclav, phenoxymethylpenicillin and piperacillin-tazobactam are all penicillin-containing drugs and so must be avoided. Erythromycin is a macrolide antibiotic and so can be safely considered for this patient.

• 5. a

  Ciprofloxacin belongs to the ‘quinolone’ class of antibiotics and so can safely be administered to patients who have an allergy to penicillin. Exposure to ciprofloxacin can precipitate haemolytic anaemia in patients who are G6PD deficient, and ciprofloxacin is known to reduce the seizure threshold in susceptible individuals, so it should not be administered to patients who are G6PD deficient or epileptic. Oral calcium supplements reduce the oral absorption of ciprofloxacin, which may result in inadequate treatment of the urinary tract infection.

• 6. d

  Simvastatin is a known enzyme inhibitor of cytochrome P450 enzymes, not an inducer. Rifampicin, carbamazepine and phenobarbital are all known inducers of cytochrome P450 enzymes.

• 7. a

  Warfarin is a substrate of cytochrome P450 enzymes, and therefore its metabolism can be impaired or enhanced by a multitude of drugs that induce or inhibit the enzyme system. The margin between its subtherapeutic and toxic concentration—the therapeutic index—is narrow, and therefore even a small increase or decrease in plasma level can cause the patient harm.

• 8. b

  Drug interactions can and do occur between conventional medicines and herbal medicine; an example is the interaction between St John’s wort and digoxin. St John’s wort is an enzyme inducer and can reduce the plasma levels of digoxin.

• 9. d

  Grapefruit juice contains compounds that inhibit cytochrome P450 3A4, the enzyme responsible for metabolising simvastatin. Calcium-containing products such as milk can impair the absorption of ciprofloxacin by forming insoluble complexes in the gastrointestinal tract. The combination of alcohol and a benzodiazepine such as lorazepam can cause marked sedation. There is no known interaction between potatoes and the calcium channel blocker amlodipine.

• 10. b

  Methadone is broken down by the enzyme 3A4. Fluconazole inhibits this enzyme, so if it is administered with methadone, there will be less enzyme available to metabolise the methadone which will cause a rise in the amount of methadone circulating in plasma. Patients receiving methadone together with inhibitors of 3A4, such as fluconazole, should be monitored for signs of opioid toxicity, which include drowsiness and respiratory depression.