Lecture 16: Medicine interactions

Question 1

Define drug interactions: what does it include?

Answer 1

When effects of one drug are changed when administered with another drug, food or another substance.

Drug-drug, food, herb

Question 2

What is the relevant terminology to drug interactions?

Answer 2

Synergism
Potentiation
Additivity
Antagonism

Question 3

How are drug interactions classified?

Answer 3

Pharmacokinetic
Pharmacodynamic
Pharmacuetical

Question 4

Define pharmacokinetic drug interaction classification

Answer 4

Drug interaction due to an effect of one drug on the absorption, distribution, metabolism or elimination of another drug.

Question 5

Define pharmacodynamic drug interaction classification

Answer 5

Drug interaction due to the effects of two or more drugs on the same receptor or physiological system, without change in drug concentration

Question 6

Define pharmacuetical drug interaction classification

Answer 6

Drug interaction occurring in syringes or infusion fluids

Question 7

Describe how drug interactions can result in altered absorption:

Answer 7

• One drug may alter the RATE or DEGREE of absorption of another drug from the gastrointestinal tract.
• Decreased absorption may lead to loss of therapeutic activity
• Increased absorption may lead to exaggerated and/or prolonged activity and/or toxicity

Question 8

Whats example one drug interactions/altered absorption:

Answer 8

Metal chalate formation:
- B/w metal containing antacids or supplements, decreasing absorption of antibiotics i.e aluminium hydroxide and doxycycline or ciproflaxin

Question 9

Whats example two drug interactions/altered absorption:

Answer 9

P-glycoprotein inhibition:

- By perpertrator drug increasing the bioavailability of susceptible drug i.e ciclosporin and loperamide respectively

Question 10

Describe how induced drug metabolism functions as a drug interaction:

Answer 10

• One drug can induced an enzyme altering the metabolism of another drug
• Clinical consequences depends on metabolites
• Occurs over several days or weeks.

NB: Regulated at transcription level, involves P450 frequently

Question 11

What class of drugs are known to induce metabolising enzymes?

Answer 11

• Anticonvulsants, Antimicrobials for TB and HIV, Natural health products i.e st johns wart

Question 12

What are two specific examples of drugs that induce enzymes?

Answer 12

• Phenytoin

- Carbamazapine

Question 13

What are the susceptible drugs to induced metabolic enzymes?

Answer 13

• Ethinyloestradiol/levonorgestrel
• Warfarin
• Gefitinib (anticancer)

Question 14

Write some notes on drug interactions that inhibit drug metabolism:

Answer 14

• Inhibits other drugs metabolism:
• Frequently involves CYP450
• RAPID onset, within hours of concurrent drug administration

= Can result in exaggerated or prolonged responses or increased toxicity

Question 15

What are some drug classes that inhibit CYP450 metabolism and what are some drug classes that are susceptible because of this?

Answer 15

Perpetrators: Macrolides, azole antifungals, protease inhibitors, antidepressants, grapefruit juice

Susceptible: Anticoagulants, oral hypoglycaemics, statins

Question 16

Give two specific examples of drugs that inhibit CYP450:

Answer 16

Erythromycin inhibits simvastatin metabolism (increases toxicity)

Fluconazole inhibits warfarin metabolism (increased effects)

Question 17

Whats a specific example of a drug that inhibits aldehyde dehydrogenase metabolism:

Answer 17

Metronidazole inhibits alcohol metabolism producing dysphoria

Question 18

Write some notes on altered elimination:

Answer 18

• One drug can alter the effects of another drug by interfering with renal or biliary elimination
• These drugs may compete for renal TUBULAR secretion
• This altered elimination may slow drug clearance causing:

-> Exaggerated or prolonged activity or increased toxicity

Question 19

What is example one of specific examples of altered elimination drug interactions:

Answer 19

P-Glycoprotein

-> Inhibition of renal elimination of digoxin by erythromycin (digoxin toxicity)

Question 20

What is example two of specific examples of atlered elimination drug interactions:

Answer 20

Solute carrier transporters

-> Inhibition of renal elimination of penicillin by probenecid (increased penicillin concentration)

Question 21

Describe pharmacodynamic drug interactions:

Answer 21

• Drugs may act on same physiological system, without any change in drug concentration (effecting other drug)
• May occur from drug actions on same or different receptors
• May result in potentiation or antagonism of drug effects

Question 22

Whats an example of pharmacodynamic drug interactions of drugs acting on the same receptor:

Answer 22

Same receptor:

• > Beta-2-adrenoreceptor agonist and antagonist
• > i.e salbutamol and atenalol

Question 23

Whats an example of pharmacodynamic drug interactions of drugs acting on the same tissue:

Answer 23

Same tissue:
-> Multiple CNS depressants i.e
- Alcohol + Recreational drugs
- Polypharmacy in elderly 
I.e diazapam and notriptyline

or

• > Blood coagulation
• Warfarin and aspirin

Question 24

How do you reduce the harm from drug interactions?

Answer 24

• Know the concepts
• Know most common perpertrator drugs
• Know about drugs with low TI
• Know how to recognise high risk pts.
• Know the drugs you frequently prescribe

Question 25

What are some drugs with low TI?

Answer 25

• Anticoagulants, Anti-arrhythmitics, Anti-epileptics, Aminoglycosides, Anti-neoplastics

Question 26

What makes a patient high risk?

Answer 26

Extremes of age: Number of medicines, organ impairment