Reducing Polypharmacy in the Elderly; Clinically Significant Drug Interactions

Question 1

Discuss the difference between polypharmacy and polytherapeutics

Answer 1

• Polypharmacy – the use of medications with duplicative indications, drug-drug interactions, and/or inadequate attention to pharmacokinetic and pharmacodynamic principles
• Polytherapeutics – the art of using medications for the treatment of co-morbid conditions

Question 2

Indicators of Polypharmacy

Answer 2

• Prescribing medications with no apparent indications
• Use of medications in same drug category
• Concurrent use of interacting medications
• Prescribing drugs contraindicated in the elderly
• Ordering inappropriate dosages
• Using a drug to treat an ADR
• Clinical improvement following discontinuation of medications

Question 3

Describe strategies to reduce polypharmacy

Answer 3

• Avoid therapeutic class duplication
• Single prescriber to coordinate all prescribed medications
• Single pharmacy to maintain patient data base (Rx plus OTC)
• Patient education about role of drug therapy in health and wellness
• Health care provider education
• Alternatives to medications should be sought
• Review medication regimen regularly
• Home review by family or health care provider

Question 4

Describe mechanisms of drug interactions

Answer 4

• Enhancement or reduction of action of one drug by another
• Enhanced or toxic response is by far more clinically significant in terms of morbidity or mortality
• Reduced response is more common but less significant (70%)
• Inhibition of metabolism
• Induction of metabolism
• Protein binding interactions
• Pharmacodynamic interactions

Question 5

Inhibition of Metabolism

Answer 5

• Cytochrome P450 isozymes - at least 6 pathways are known to be inhibited by drugs
• CYP1A2 - r-warfarin, clozapine
• CYP2C9 - s-warfarin, phenytoin, amitriptyline
• CYP2C19 - diazepam
• CYP2E1 - alcohol, acetaminophen
• CYP2D6 - codeine, haloperidol, imipramine, paroxetine, venlafaxine
• CYP3A4 - erythromycin, terfendadine, carbamazepine, quinidine
• Some drugs inhibit more than one CYP isoenzyme - cimetidine, erythromycin
• Inhibition of metabolism occurs quickly

Question 6

Induction of Metabolism

Answer 6

• Rifampin, carbamazapine, phenytoin, phenobarbital increase the activity of several CYP isoenzymes
• Full effect of induction take several day (7 to 10) and thus may be difficult to recognize
• Resolution of induction is likewise delayed

Question 7

Protein Binding Interactions

Answer 7

May be less important than originally thought and may coincide with inhibition of metabolism (ex. Sulfonamides and warfarin mechanism of interaction is more likely due to inhibition of metabolism than displacement from protein binding sites)

Question 8

Pharmacodynamic Interactions

Answer 8

• Additive or synergistic effects of drugs in older people with reduced homeostatic mechanisms
• Postural hypotensive effects
• Additive risk of GI bleeding from NSAIDS plus corticosteroids
• Additive CNS effects (sedation, confusion, etc) (ex. opioids and benzodiazepines)
• Additive anticholinergic effects (antidepressants plus antihistamines)

Question 9

List strategies to avoid drug interactions

Answer 9

• Minimize number of drugs used
• Alternatives to drug therapy should be sought
• Single prescriber
• Single pharmacy
• Review regularly
• Monitor for benefit of prescribed regimen regularly
• Monitor for toxicity of prescribed regimen regularly
• Educate patients to notify prescriber or pharmacist about unusual effects after new agents are initiated
• Audit drug interactions
• Report drug interactions
• Establish good database and information sources
• Develop appropriate education programs