Drug Interactions

Question 1

Definition

Answer 1

• An interaction is said to occur when the effects of one drug are changed by the presence of another drug, herbal medicine, food, drink or by some environment chemical agent

Question 2

Outcomes

Answer 2

• Harmful by increased toxicity of a drug
• Harmful by decreased efficacy of a drug
• Beneficial
• No clinical difference

Question 3

Types of drug interactions

Answer 3

• Pharmacodynamic
  
  • effects of one drug are changed by the presence of another drug as it’s a site of action
• Pharmacokinetic
  
  • Effects of a drug on the process of ADME of another drug

Question 4

Pharmacodynamic

Additive or synergistic

Answer 4

• Additive or Synergistic
  
  • E.g. sedative drugs have additive CNS depressant effects with alcohol
  • SSRI AND SJW
  • ACEI and K⁺- sparing diuretic
  • Insulin and sulphonylurea
  • ACEI and thiazide

Question 5

Pharmcodynamic

Antagonistic or opposing

Answer 5

• NSAIDs and Loop diuretics
• Hypoglycaemic and glucocorticoids
• Levodopa and typical antipsychotics
• Beta-agonists (Salbutamol) and beta-antagonists (propranolol)

Question 6

PK- Absorption

Answer 6

• Change in GI pH
• Adsorption, chelation and other complexing mechanisms
• Change in Gastric motility
• Induction or inhibition of drug transport proteins
• Malabsorption caused by drugs

Question 7

PK- distribution

Answer 7

• Protein binding- usually only result in transient increase in free drug
• Induction or inhibition of drug transport proteins

Question 8

PK- metabolism

Answer 8

• Changes in first pass metabolism- grapefruit juice and calcium channel blockers
• Enzyme induction- phenytoin, rifampicin, smoking
• Enzyme inhibition- erythromycin, acute alcohol

Question 9

PK- Elimination

Answer 9

• Change in urinary pH- MTX and sodium bicarbonate
• Change in active renal tubular transport- MTX and NSAIDs
• Change in renal blood flow- NSAID and Li

Question 10

Factors affecting susceptibility

Answer 10

• Age
  
  • Elderly- decreased renal and hepatic function
  • Elderly- Polypharmacy
• Genetic
• Clinical status

Question 11

Time course of interactions

Answer 11

• Starting
• Stopping
• Change of dose
• Route of administration
• Half life of drugs
• Mechanism of interaction e.g. enzyme inducers vs enzyme inhibitors

Question 12

Managing drug interactions

Answer 12

• Avoid the combination
• adjust doses
• Monitor
• If not clinically significant, do nothing

Question 13

Where to find information

Answer 13

• BNF
• Stockleys
• SPC
• MI centre