Drug-drug interactions Flashcards
Discuss environmental factors which may predispose a patient to drug interactions
Food
Herbs
Drug intake
Alcohol intake
Describe patients who may be more susceptible to DDIs
• 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
What characteristics of a drug may make it more likely to cause a DDI?
Narrow therapeutic index
Potent or high dose
Known enzyme inducers or inhibitors
Protein or drug binding
Name some vegetables that cause DDIs with warfarin
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
Name some herbs that cause DDIs with warfarin
o Ginseng o Green teas o Melilot o Tonka beans o Woodruff
Name some miscellaneous agents that cause DDIs with warfarin
o Avocado o Fish oils o Liver o Soybeans o Papain
Define drug-drug interations
- 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
What is the object drug in a DDI?
The drug whose activity is effected by such an interaction is called the “Object drug.”
What is the precipitant in a DDI?
The agent which precipitates such an interaction is referred to as the “Precipitant”.
Describe a useful DDI
o The treatment of Parkinsonism with carbidopa and levadopa
• Carbidopa is a dopa decarboxylase inhibitor and prevents the systemic side effects from levadopa
Describe some pharmacodynamic mechanisms of DDIs
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
Describe some absorption mechanisms that can cause DDIs
o Formation of insoluble complexes
o Altered PH.
o Altered bacterial flora e.g. OCP
o Altered GIT motility.
How can you avoid absorption defects in DDIs?
Wait 2-4hr before next dose
Name some drugs that are affected due to changes in bacterial flora
OCP
Digoxin
Name some classes of drugs that can delay gastric emptying
anticholinergics
tricyclic anti-depressants
opiates
Name some drugs that can increase gastric emptying
domperidone
metoclopramide
Name the two most important plasma proteins involved in drug-protein binding
o Albumin
o α1-glycoprotein
Name some drugs that inhibit cytochrome P450s
clarithromycin erythromycin cimetidine ketoconazole omeprazole Calcium channel blockers (diltiazem)
What drugs increase the metabolism of ciclosporin?
Rifampacin and St Johns wort
Give an example of direct antagonism
Beta-1 selective beta-blockers such as atenolol will block the actions of agonists e.g. bronchodilators such as salbutamol
Give an example of indirect antagonism
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
Describe some patient specific factors that increase the risk of DDIs
- Advanced ages
- Genetic polymorphisms
- Concomitant diseases
- Polypharmacy (~8 drugs almost 100% likelihood of DDI)
Describe some drug specific factors that increase the risk of DDIs
- Polypharmacy (~8 drugs 100% likelihood of DDI)
- Narrow pharmaceutical range
- Dose
- Multiple prescribing physicians
- Self prescription
- Prolonged length of stay
