Drug-drug interactions

Question 1

Discuss environmental factors which may predispose a patient to drug interactions

Answer 1

Food
Herbs
Drug intake
Alcohol intake

Question 2

Describe patients who may be more susceptible to DDIs

Answer 2

• Polypharmacy (~8 drugs 100% chance of DDI)
• The elderly
• The young
• The critically ill
• Patients undergoing complicated surgery
• Those patients who have chronic conditions e.g.
o Liver disease
o Renal impairment
o Diabetes mellitus
o Epilepsy
o Asthma

Question 3

What characteristics of a drug may make it more likely to cause a DDI?

Answer 3

Narrow therapeutic index
Potent or high dose
Known enzyme inducers or inhibitors
Protein or drug binding

Question 4

Name some vegetables that cause DDIs with warfarin

Answer 4

o	Alfalfa
o	 Asparagus
o	 Broccoli
o	 Brussel sprouts
o	 Cabbage
o	 Cauliflower
o	 Kale
o	 Lettuce
o	 Onions
o	 Spinach
o	 Turnip greens
o	 Watercress

Question 5

Name some herbs that cause DDIs with warfarin

Answer 5

o	Ginseng
o	 Green teas
o	 Melilot
o	 Tonka beans
o	 Woodruff

Question 6

Name some miscellaneous agents that cause DDIs with warfarin

Answer 6

o	Avocado
o	Fish oils
o	Liver
o	Soybeans
o	Papain

Question 7

Define drug-drug interations

Answer 7

• A drug interaction is defined as the modification of a drugs effect by prior or concomitant administration of another Drug, Herb, Foodstuff, Drink
• A drug interaction has occurred when the pharmacological effect of two or more drugs given together is not just a direct function of their individual effects

Question 8

What is the object drug in a DDI?

Answer 8

The drug whose activity is effected by such an interaction is called the “Object drug.”

Question 9

What is the precipitant in a DDI?

Answer 9

The agent which precipitates such an interaction is referred to as the “Precipitant”.

Question 10

Describe a useful DDI

Answer 10

o The treatment of Parkinsonism with carbidopa and levadopa

• Carbidopa is a dopa decarboxylase inhibitor and prevents the systemic side effects from levadopa

Question 11

Describe some pharmacodynamic mechanisms of DDIs

Answer 11

o Agonist or antagonistic Interactions
o Additive or synergistic interactions
o Interactions due to changes in drug transport
o Interactions due to fluid and electrolyte disturbances
o Indirect pharmacodynamic interactions

Question 12

Describe some absorption mechanisms that can cause DDIs

Answer 12

o Formation of insoluble complexes
o Altered PH.
o Altered bacterial flora e.g. OCP
o Altered GIT motility.

Question 13

How can you avoid absorption defects in DDIs?

Answer 13

Wait 2-4hr before next dose

Question 14

Name some drugs that are affected due to changes in bacterial flora

Answer 14

OCP

Digoxin

Question 15

Name some classes of drugs that can delay gastric emptying

Answer 15

anticholinergics
tricyclic anti-depressants
opiates

Question 16

Name some drugs that can increase gastric emptying

Answer 16

domperidone

metoclopramide

Question 17

Name the two most important plasma proteins involved in drug-protein binding

Answer 17

o Albumin

o α1-glycoprotein

Question 18

Name some drugs that inhibit cytochrome P450s

Answer 18

clarithromycin
erythromycin
cimetidine
ketoconazole
omeprazole
Calcium channel blockers (diltiazem)

Question 19

What drugs increase the metabolism of ciclosporin?

Answer 19

Rifampacin and St Johns wort

Question 20

Give an example of direct antagonism

Answer 20

Beta-1 selective beta-blockers such as atenolol will block the actions of agonists e.g. bronchodilators such as salbutamol

Question 21

Give an example of indirect antagonism

Answer 21

o NSAIDs and antihypertensive medication – both have different effects on BP, leads to uncontrollable BP and potentially RF
o NSAIDs and treatment for heart failure

Question 22

Describe some patient specific factors that increase the risk of DDIs

Answer 22

• Advanced ages
• Genetic polymorphisms
• Concomitant diseases
• Polypharmacy (~8 drugs almost 100% likelihood of DDI)

Question 23

Describe some drug specific factors that increase the risk of DDIs

Answer 23

• Polypharmacy (~8 drugs 100% likelihood of DDI)
• Narrow pharmaceutical range
• Dose
• Multiple prescribing physicians
• Self prescription
• Prolonged length of stay