Drug Interaction:

Age, Genetics
 Can you think of three things that might
influence an individuals response to
medication?
Human Variability

 Differences in age, weight, genetics, and

gender are factors that influence the
differences in response to medication among
people.
Age

 Infants and Neonates

 Drug distribution is different in a neonate and
infant because their organ systems are not fully
developed. They do not eliminate drugs as
efficiently as adults.
Age

 Children
 Children metabolize certain drugs more rapidly
than adults.
 Metabolism rates increases between 1 year and
12 years (depends on age and drug).
 After age 12 metabolism rates decline with age to
a normal adult level.
 E.g. Azole antifungi likely requires higher dose in
children (voriconazole, posaconazole)
Age

 Adult
 Adults experience a decrease in many
physiological function after age 30.
 Decreases in affects on drug activity are gradual.
Age

 The elderly
 Elderly typically consume more drugs than any
other age group due to chronic illness and
disease.
Gender

 Women used to be excluded from drug studies. In

1993 the FDA stated that women will be included in
clinical drug trials.
 Since then many studies have been completed and
show that men and women do show differences in
absorption, distribution, metabolism, and excretion
(ADME).
 Gender based differences in drug response appear
to be related to hormonal fluctuations.
 Gender differences may also be due to differences
in body composition.
Genetics

 The field of study, pharmacogenetics,

defines the hereditary basis of individual
differences in absorption, distribution,
metabolism, and excretion (ADME)
processes.
 The largest contributing factor to variability is
metabolism.
Body Weight

 Dosage adjustments based on weight are

generally not made for adults who are slightly
overweight.

 Weight is a factor in determining drug dosage

for infants, children, or obese patients.
Psychological Factors

 Psychological factors can influence individual

responses to drugs.
 When placebo drugs are given patients
receiving them can report therapeutic and
adverse effects.
 Another factor can be patient’s willingness to
follow prescribed dosage regimens.
 Name two groups of people that need to have
adjustments in drug dosages?

 What group of people metabolises drugs the

fastest?
Adverse Drug Reactions

 Drugs generally produce a mixture of either

therapeutic (desired) or adverse (undesired)
effects.
 An adverse effect is an unintended side effect
of a medication that is negative or in some
way injures a patient’s health.
 Reactions may be rare or common, localized
or wide-spread, mild or severe depending on
the drug and the patient.
Common Adverse Reactions

 Hypersensitivity or Allergy
 Almost any drug, in any dose, can produce an
allergic or hypersensitive reaction in a patient.
 The drug will interact with antibodies, releasing
histamine and other substances that produce
reactions that can range from mild rashes to
potentially fatal anaphylactic shock.
 Allergic reactions can occur within minutes or
weeks after drug administration
Adverse Drug Reactions
 Central nervous system (CNS):
 Stimulation – agitation, confusion, disoriented
 Depression – dizziness, drowsiness, sedation
 Hepatotoxicity:
 Hepatitis
 Necrosis
 Hepatotoxic drugs include: acetaminophen, aspirin.
 Gastrointestinal effects:
 Anorexia, nausea, diarrhea
 Ulcers, colitis
Adverse Drug Reactions
 Nephrotoxicity:
 Kidney failure - Gentamicin and ibuprofen
 Idiosyncrasy:
 Unexpected reaction the first time a drug is given
 Hematological effects:
 Coagulation, bleeding, bone marrow disorders
 Drug dependence:
 Chronic use of analgesics, sedatives, hypnotics,etc
 Teratogenicity:
 Ability of a substance to cause abnormal fetal
development
 Carcinogenicity:
 Ability of a substance to cause cancer
 What is a potentially fatal hypersensitivity
reaction that produces respiratory distress
and cardiovascular collapse?

 What is an unexpected reaction the first time

a drug is given?
Drug – Drug Interactions
 Taking more than one drug at a time can
cause a drug-drug interaction.
 Drug – drug interactions can affect the
disposition (all processes of the ADME) of
any drug.
 Therapeutic effects and side effects can be
decreased or increased when more than one
drug is taken.
Drug – Drug Interactions
 Common drug-drug interactions
 Additive effects – when two drugs effects equal
to the sum of the individual effects
 Synergism – two drugs produce greater effect
than the sum of the individual effects
 Potentiation – one drug increases the activity of
another drug
 Antidote – a drug given to block or reduce toxic
effects
Drug – Drug Interactions
 Complex – decreased intestinal absorption of oral
drugs occurs when drugs complex to produce
nonabsorbable compounds
 Displacement – a drug bound to a plasma protein is
removed when another drug of greater binding
potential binds to the same protein.
 Inhibition – one drug with the elimination of a
second drug may intensify the effects of the second
drug
 Induction – a drug causes more metabolic enzymes
to be produced, increasing metabolic activity
 Urinary excretion – some drugs are altered by
raising urinary pH and decrease renal absorption
Drug – Diet Interactions
 Dietary intake may affect disposition of drugs.
 Absorption - increased or decreased when food is in
the stomach. Generally absorption is decreased.
 Distribution – a previously bound drug is displaced
and this increases the concentration of the drug in the
blood and this leads to an increased effect
 Metabolism – high protein diets are associated with
increased drug metabolism and high carbohydrate
diets are associated with decreased metabolism.
Malnourished adults have a decreased metabolism
 Excretion – high protein diet increases kidney
function.
Disease States
 The disposition (ADME process) and effect of some
drugs can be influenced by diseases other than the
one that the drug is intended for.
 Hepatic
 Cirrhosis and obstructive jaundice decrease hepatic
metabolism and will diminish drug elimination
 Viral hepatitis little change in disposition
 Circulatory
 Changes in blood flow can influence ADME and therefore
will have the potential to alter the effect of the drug
Disease States

 Renal
 Reduced renal function can effect the elimination of many
drugs and affect the plasma protein binding of drugs
 Thyroid
 Changes in thyroid function can effect many aspects of
absorption excretion and metabolism
Drug Interactions in Older Adults
Learning Objectives

At the conclusion of this talk student should be able to:

 List the 4 major types of drug interactions that can occur
in the elderly
 Discuss the epidemiology of the different types of drug
interactions in the elderly
 Implement strategies to prevent/manage drug
interactions in the elderly

Joseph T. Hanlon, PharmD, MS

 EPIDEMIOLOGY
 It is estimated that adverse drug reactions are
responsible for about 100,000 deaths yearly, and are
the 4th to 6th leading cause of death in the United
States.1,2
 Studies of geriatric outpatients have found the
percentage of potential DDIs that result in clinically
significant adverse drug reactions ranges from 6% to
25%.3, 4, 5
 It is likely that drug-gene interactions are common and
significant: CYP2D6, CYP2C9, and CYP2C19 are highly
polymorphic and are involved in approximately 40% of
CYP-mediated drug metabolism. 6
1.Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA. 1998;279(15):1200-1205.
2.Giacomini KM, Krauss RM, Roden DM, Eichelbaum M, Hayden MR, Nakamura Y. When good drugs go bad. Nature. 2007;446(7139):975-977.
3.Tulner LR, Frankfort SV, Gijsen GJ, van Campen JP, Koks CH, Beijnen JH. Drug-drug interactions in a geriatric outpatient cohort: prevalence and relevance. Drugs Aging.
2008;25(4):343-355.
4.Obreli-Neto PR, Nobili A, de Oliveira Baldoni A, et al. Adverse drug reactions caused by drug-drug interactions in elderly outpatients: a prospective cohort study. Eur J Clin Pharmacol.
2012;68(12):1667-1676.
5.Kurfees JF, Dotson RL. Drug interactions in the elderly. J Fam Pract. 1987;25(5):477-488.
6.Ingelman-Sundberg M. Pharmacogenetics of cytochrome P450 and its applications in drug therapy: the past, present and future. Trends Pharmacol Sci. 2004;25(4):193-200.
 Types of Drug Interactions
 Drug-drug interactions (DDIs) are a major cause of
adverse drug reactions. There are two other newly-
described important types of interactions: drug-gene
interactions (DGIs) and drug-drug-gene interactions
(DDGIs).
 DGI: A drug-gene interaction occurs when a patient’s
genetic metabolic type (for example, CYP2D6 poor
metabolizer) affects that patient’s ability to clear a drug.
 DDGI: In a drug-drug-gene interaction, two patient-
specific factors affect that individual’s ability to clear a
drug: 1) the patient’s genetic metabolic type, and 2)
another drug in the patient’s regimen, such as a potent
CYP2D6 inhibitor.
Paul Verbeurgt, PharmD1; Tyler Mamiya, PharmD1; Jessica Oesterheld, MD1; and Jill Marquis, PharmD1, Genelex Corporation, Seattle, WA
 How Common are Drug and Gene Interactions?
Prevalence in a Sample of 1143 Patients with Known CYP Genetics

 Potential Drug-Gene Interactions and Drug-Drug-Gene

Interactions accounted for 33.9% of all of potential
clinically significant interactions identified in this
study.
 In the study population, potential Drug-Drug-Gene
Interactions were more common than Drug-Gene
Interactions.
 When compared to potential DDIs alone, potential Drug-
Gene Interactions and Drug-Drug-Gene Interactions
increased the number of potential clinically significant
interactions by > 50%.
Paul Verbeurgt, PharmD1; Tyler Mamiya, PharmD1; Jessica Oesterheld, MD1; and Jill Marquis, PharmD1, Genelex Corporation, Seattle, WA
 Drug-Drug Interactions, Drug-Gene Interactions, and Drug-
Drug-Gene Interactions: The whole Effect Can Be Greater
than the Sum of the Parts

 Because actual DDIs are difficult to determine, the literature about DDIs in
large samples commonly researches potential DDIs, which are usually
identified by using drug interaction software. Potential drug-gene
interactions (pDGIs) and potential drug-drug-gene interactions (pDDGIs)
can also be identified by reviewing a patient’s medication list and genetic
test results, with the help of sophisticated software tools.

Paul Verbeurgt, PharmD1; Tyler Mamiya, PharmD1; Jessica Oesterheld, MD1; and Jill Marquis, PharmD1, Genelex Corporation, Seattle, WA
 In a Drug-Drug-Gene
Interaction, >1 of a Drug’s
Metabolic Pathways May be
Inhibited, Increasing Exposure
and Increasing the Patient’s Risk
of Adverse Drug Effects
 Fig.1A. Normal: Expected drug exposure for
a substrate that uses two cytochrome (CYP)
pathways for metabolism.
 Fig. 1B. Drug-drug interacttion (DDI):
Metabolism inhibit in CYPA pathway by an
inhibiting co-medication, resulting in an
increase to drug exposure.
 Fig. 1C. Drug-gene interaction (DGI):
Metabolism inhibited in CYP 8 pathway by
genetics – a “poor metabolizer” phenotype
resulting in an increase to drug exposure.
 Fig. 1D. Drug-drug-gene interaction (DDGI):
Metabolism inhibited in both CYP pathways
by an inhibiting co-medication and by
genetics – again a “poor metabolizer”
phenotype in this example, resulting in an
overdose with increased drug exposure

Paul Verbeurgt, PharmD1; Tyler Mamiya, PharmD1; Jessica Oesterheld, MD1; and Jill Marquis, PharmD1, Genelex Corporation, Seattle, WA
CYP

 Cytochrome P450 (CYP)

enzymes, particularly
CYP1A2, CYP2C9,
CYP2C19, CYP2D6 and
CYP3A4, are responsible
for the bulk of the
metabolism of known
drugs in humans (FIG. 1).
 Inhibition of these
enzymes by co-
administered drugs has
led to the removal of
several drugs from the
market during the past
years.

Wienkers&Heath, 2005
Wienkers&Heath, 2005
Huang et al 2007 Clin Pharm Ther 81(2): 298
Huang et al 2007 Clin Pharm Ther 81(2): 298
Wienkers&Heath, 2005
Wienkers&Heath, 2005
Wienkers&Heath, 2005
Software tool
 Using each individual’s medication
list and a software tool called
YouScript, the prevalence of
potential DDIs, DGIs and DDGIs
can be calculated.
 Standard CYP nomenclature was
used: poor metabolizer (PM),
intermediate metabolizer (IM),
normal metabolizer (NM), rapid
metabolizer (RM), and ultra rapid
metabolizer (UM).7, 8
 The software tool analyzes
cumulative drug-drug and drug-
gene interactions based on both
data from the literature and a
predictive algorithm. By evaluating
multiple simultaneous interactions
from both drug and gene sources,
the software provides a
cumulative estimate of
pharmacokinetic interactions. In
addition, the software alerts users
about pharmacodynamic
interactions.9
Am Fam Physician. 2008 Jun 1;77(11):1553-1560
Am Fam Physician. 2008 Jun 1;77(11):1553-1560
 Cytochrome P450 2C9 (CYP2C9)
 The CYP2C9 enzyme is involved in the metabolism of many
common drugs such as glipizide (Glucotrol), tolbutamide
(Orinase; brand not available in United States), losartan
(Cozaar), phenytoin (Dilantin), and warfarin (Coumadin).
 The phenotypes CYP2C9*2 and CYP2C9*3 are the two most
common variations and are associated with reduced
enzymatic activity.
 CYP2C9 is the principal enzyme responsible for the
metabolism of S-warfarin. Persons who are CYP2C9 poor
metabolizers have reduced S-warfarin clearance. Clinical
studies have shown that these persons require lower
dosages of warfarin and are at an increased risk of
excessive anticoagulation.10,11
Am Fam Physician. 2008 Jun 1;77(11):1553-1560
 Cytochrome P450 2C19 (CYP2C19)
 The CYP2C19 enzyme metabolizes many drugs, including proton pump
inhibitors, citalopram (Celexa), diazepam (Valium), and imipramine
(Tofranil). More than 16 variations of CYP2C19, associated with
deficient, reduced, normal, or increased activity, have been identified.
 Genotyping for CYP2C19*2 and CYP2C19*3 identifies most CYP2C19
poor metabolizers.
 The CYP2C19*17 variant is associated with ultrarapid metabolizers and
seems relatively common in Swedes (18 percent), Ethiopians (18
percent), and Chinese (4 percent).12
 The proton pump inhibitor omeprazole (Prilosec) is primarily
metabolized by CYP2C19 to its inactive metabolite, 5-hydroxyome-
prazole. Persons who are CYP2C19 poor metabolizers can have
fivefold higher blood concentrations of omeprazole and experience
superior acid suppression and higher cure rates than the rest of the
population. Conversely, blood concentrations of omeprazole are
predicted to be 40 percent lower in ultrarapid metabolizers than in the
rest of the population, thus putting persons with the CYP2C19
ultrarapid metabolizers phenotype at risk of therapeutic failure.12
Am Fam Physician. 2008 Jun 1;77(11):1553-1560
Cytochrome P450 2D6 (CYP2D6)
 The enzyme CYP2D6 is involved in the metabolism of an
estimated 25 percent of all drugs. More than 75 allelic variants
have been identified, with enzyme activities ranging from
deficient to ultrarapid.
 The most common variants associated with poor metabolizer
phenotype are CYP2D6*3, CYP2D6*4, CYP2D6*5, and CYP2D6*6
in whites and CYP2D6*17 in blacks.
 Codeine is metabolized by CYP2D6 to its active metabolite,
morphine. Clinical studies have shown that CYP2D6 poor
metabolizers have poor analgesic response as a result of the
reduced conversion of codeine to morphine. Conversely,
CYP2D6 ultrarapid metabolizers quickly convert codeine to
morphine and have enhanced analgesic response.13
The activity of drug-metabolizing enzymes may be induced or
inhibited by many other intrinsic and extrinsic factors,
including comorbid conditions, use of other medications,
smoking, alcohol intake, and dietary factors.
Am Fam Physician. 2008 Jun 1;77(11):1553-1560
 Medication Counts
 Patients who had no
potential Major or Substantial
interactions (56%) had a
mean medication count of
6.5, lower than that of the
study population (8.4).
 Patients with potential Major
or Substantial interactions
had a mean medication
count of 11.0, higher than the
mean for the study.
Genetic

 Absorption, distribution, metabolism, excretion

 Body weight

 Genetic conditions

 Genetic polymorphism of drug-metabolizing enzymes

 Height

 Race

 Receptor sensitivity

 Sex/gender

Although still in its infancy, the field of pharmacogenetics and

pharmacogenomics already provides useful clinical information to
enhance patient care and offers a growing potential to individualize
drug therapy and improve clinical outcomes..
RECEPTOR GENES
 Ethnic differences in allele frequencies for
selected enzymes, transporters, and
pharmacologic targets

doi: 10.1038/clpt.2008.141 CliniCal pharmaCology & TherapeuTiCs | VOLUME 84 NUMBER 3 | SEPTEMBER 2008
doi: 10.1038/clpt.2008.141 CliniCal pharmaCology & TherapeuTiCs | VOLUME 84 NUMBER 3 | SEPTEMBER 2008
doi: 10.1038/clpt.2008.141 CliniCal pharmaCology & TherapeuTiCs | VOLUME 84 NUMBER 3 | SEPTEMBER 2008
doi: 10.1038/clpt.2008.141 CliniCal pharmaCology & TherapeuTiCs | VOLUME 84 NUMBER 3 | SEPTEMBER 2008
 Survey of ethnicity data in labeling
of new molecular entities approved
2004–2007

doi: 10.1038/clpt.2008.141 CliniCal pharmaCology & TherapeuTiCs | VOLUME 84 NUMBER 3 | SEPTEMBER 2008
Types of Drug Interactions

1. Drug-Drug Pharmacokinetic
2. Drug-Drug Pharmacodynamic
3. Drug-Food/Nutrient
4. Drug-Disease
Drug-Drug Interactions Affecting
Absorption and Distribution
Precipitant Drug(s) Object Drug(s) Outcome
Antacids, Iron Tetracycline, Ciprofloxacin  abs.
Chloral hydrate Warfarin  PPB

 Generally absorption and distribution drug-drug-

interactions are not clinically important.

Drugs & Aging 1998;12:485-94

Hepatic Metabolism

Phase I (CYP 450) Phase II

 Oxidation  Conjugation
hydroxylation glucuronidation
dealkylation sulfation
sulfoxidation glycine
 Reduction acetylation
 Hydrolysis
Cytochrome P450 Phase I Isoenzymes,
%Total and Substrate Examples
Isoenzymes % Substrate
CYP1A2 17 Olanzapine, Theophylline
CYP2C9/19 26 Phenytoin, Warfarin
CYP2D6 2-4 Codeine, Desipramine, Tramadol
CYP2E1 9-10 Chlorzoxazone, Ethanol
CYP3A4 35-45 Diazepam, Triazolam, Quinidine,
Methadone, Carbamazepine

www.drug-interactions.com
Inhibitors of Hepatic Cytochrome P450

1A2 2C9/19 2D6 3A4

Fluvoxamine Amiodarone Fluoxetine Erythromycin
Cimetidine Fluconazole Paroxetine Azole antifungal
Ciprofloxacin Fluvastatin Quinidine Nefazodone
Fluoxetine Ritonavir Clarithromycin
Isoniazid Bupropion Ritonavir
Sertraline Cimetidine Cimetidine
Omeprazole
Cimetidine

www.drug-interactions.com
Effect of Age on Theophylline Hepatic
Metabolism Inhibition

J Pharmacol Exp Ther 1997;280:627-37.

Drugs That Interact with Theophylline

Inhibitors Inducers
 Cimetidine  Barbiturates
 Propafenone  Phenytoin
 Mexiletine  Smoking
 Propranolol  Rifampin
 Erythromycin  Carbamazepine
 Ciprofloxacin
 Fluvoxamine

Drugs Aging. 2003;20:71-84 JAPHA 2004;44:142-51

Drug-Drug Interactions With Warfarin
Interacting Drug Mechanism Anticoagulant Effect
Aspirin PD 
Barbiturate PK 
Cimetidine PK 
Dipyridamole PD 
Fibrates PD 
Fluvoxamine PK 
Macrolides PK 
Phenytoin PK 
Quinolones PK 
Rifampin PK 
Sulfinpyrazone PK/PD 
Thyroid hormones PD 
Ticlopidine PD 

N Engl J Med. 2003; 14;349:675-83; JAPHA 2004;44:142-51

Clinically Significant
Drug-Drug Interactions with AEDs
Object Drug Interacting Drug Outcome
Carbamazepine Danazol  CBZ level
Carbamazepine Diltiazem  CBZ level
Carbamazepine Macrolides  CBZ level
Carbamazepine Propoxyphene  CBZ level
Carbamazepine Verapamil  CBZ level
Phenytoin Amiodarone  DPH level
Phenytoin Cimetidine  DPH level
Phenytoin Fluoxetine  DPH level
Phenytoin INH  DPH level
Phenytoin Omeprazole  DPH level

Neuropharmacology 2002;5:280-9
Inducers of Hepatic Cytochrome P450

1A2 2C9/19 2D6 3A4

Smoking Rifampin None Carbamazepine
Omeprazole Phenobarbital Phenytoin
Phenytoin Phenytoin Phenobarbital
Rifampin
St. John’s wort

www.drug-interactions.com
Effect of Age on Theophylline Hepatic
Metabolism Induction by DPH

Crowley J. J Phamacol Exp Ther 1988;245:513-

Selected Phenytoin
Induction Interactions
Object Drug Interacting Drug CYP Isoenzyme
Induced
Methadone Phenytoin 3A4
Quinidine Phenytoin 3A4
Theophylline Phenytoin 1A2
Warfarin Phenytoin 2C9

Neuropharmacology 2002;5:280-9.
Selected Drugs Secreted
by Renal Tubules
Basic (cationic) Agents Acidic (Anionic) Agents
 Amiodarone  Cephalosporins

 Cimetidine  Indomethacin

 Digoxin  Methotrexate

 Procainamide  Penicillins

 Quinidine  Probenecid

 Ranitidine  Salicylates

 Trimethoprim  Thiazides

 Verapamil
Drug-Drug Interactions With Digoxin

Interacting Drug Effect on Levels

Amiodarone 
Clarithromycin 
Propafenone 
Quinidine 
Verapamil 

Drug Saf. 2000;23:509-32; JAPHA 2004;44:142-51

Drugs that Interact with Lithium

 Diuretics
 ACE-I
 NSAIDs
Pharmacokinetics Pharmacodynamics

Plasma
Dosage Concen Site of
Regimen Effects
tration Action
Drug-Drug PD Interactions

Object Drug Interacting Drug (s)

ACE-I K+ & K+ sparing diuretics
Beta blockers Verapamil
Digoxin Diuretics
MAOI SSRI, Dextromethorphan,
Pseudoephedrine, Anorexiants
Meperidine MAOI
Hydroxyine Thioridazine
Drug- TCA PD Interactions

 Concurrent use with any other drugs with

antimuscarinic properties
 Concurrent MAOI
 Type I antiarrhythmics
 Clonidine
 Guanadrel
 Guanethidine
Drug-NSAID PD Interactions

Object Drug Interacting Drug Outcome

Antihypertensives NSAIDs  BP
Corticosteroids NSAIDs  risk of PUD
Diuretics NSAIDs  diuretic effect
Triamterene Indomethacin  K+
Warfarin NSAIDs  anticoagulant
effect
CNS Polypharmacy and Falls in
Elderly Persons

4
Adjusted odds ratio

3
2.37
2
1.54
1 1

0
0 1 >2
CNS - active medications (n)

Weiner D, et al. Gerontol 1998;44:217-21

Drug-Food/Nutrient Interactions

Drug Effect

Phenytoin ↓ Folate
Isoniazid ↓ Vit B6

Phenytoin ↓ Absorption with NG feedings

Levodopa High protein meals effect blood-

brain transport
Captopril Altered taste sensation
Clinically Significant Drug –St. John Wort
Interactions

Object Drug Outcome

Antidepressants serotonergic syndrome
Cyclosporine  levels, transplant rejection
Digoxin  digoxin levels
Estrogen breakthrough bleeding
Indinavir  indinavir levels
Methadone withdrawal sx’s
Tacrolimus  levels
Theophylline  theophylline levels
Warfarin  INR

CPT 2004;75:1-12

Joseph T. Hanlon, PharmD, MS

Other Clinically Significant Herb- Drug Interactions

Object Drug Interacting Drug Outcome

Anticonvulsants Wormwood  seizure threshold
Anticonvulsants Gingko biloba  seizure threshold
Digoxin Hawthorne  digoxin activity
Saquinavir Garlic  saquinavir levels
Warfarin Feverfew  risk of bleeding
Warfarin Garlic  risk of bleeding
Warfarin Ginger  risk of bleeding
Warfarin Ginkgo  risk of bleeding
Warfarin Ginseng 
anticoagulant

Lancet 2000;355:134-8.
Clinically Important Drug-Disease Interactions
Determined by Expert Panel Consensus
Drug Disease
 Anticholinergics BPH, constipation, dementia
 Antiarrhythmics (Type 1A) CHF (systolic dysfunction)
 Amphetamines HTN, insomnia
 Aspirin PUD
 Atypical antipsychotics DM
 Barbiturates Depression
 Benzodiazepines COPD,dementia, falls
 Beta-blockers COPD, DM, syncope
 CCB 1st generation CHF (systolic dysfunction)
 Chlorpromazine Postural hypotension, seizures
 Clozapine Seizures
 Corticosteroids DM, PUD
 Decongestants Insomnia
 Digoxin Heart block

Lindblad C, Hanlon J et al. (abstract) J Am Geriatr Soc 2004;52:S135

Clinically Important Drug-Disease Interactions
Determined by Expert Panel Consensus

Drug Disease
 Metoclopramide Parkinson’s disease
 Nitrofurantoin Chronic renal failure
 Non-aspirin NSAIDs CRF, CHF, HTN
 Non-aspirin, non-COX II NSAIDs PUD
 Opioid analgesics BPH, constipation, dementia
 Sedative/hypnotics Falls
 Skeletal muscle relaxants BPH
 SSRIs Falls
 Theophylline Insomnia
 Thioridazine Postural hypotension,
seizures
 Thorazine Seizures
 Tricyclic antidepressants Arrhythmias, BPH,
constipation dementia, falls, heart block
postural hypotension
 Typical antipsychotics Falls
Learning Objectives

At the conclusion of this talk student should be able to:

 List the 4 major types of drug interactions that can occur
in the elderly
 Discuss the epidemiology of the different types of drug
interactions in the elderly
 Implement strategies to prevent/manage drug
interactions in the elderly
Epidemiology of Drug-Drug or Drug-Disease
Interactions
 Incidence of potential drug-drug interactions ranges from 2-
17% of all Rx's and up to 6-42% of elderly patients.
 Incidence of potentially clinically significant drug interactions
is low in the elderly (usually must involve narrow therapeutic
range drug and inhibitor/inducer of drug metabolism or renal
excretion)
 There is evidence suggesting that adverse health outcomes
associated with drug-drug interactions is infrequent.
 Drug-disease interactions occur in 6.2-40% of elderly
patients
 Drug disease interactions may result in higher risk of
adverse outcomes (e.g., decline in functional status and
increased health services use) due to alterations in
homeostatic mechanisms and diminished functional
reserve.
 Drug Interactions Are Avoidable

Previous
adverse Contraindicated Drug
reactions drugs interactions Totals
Avoidable 7 57 67 131

Probably ---- ---- 37 37

avoidable
Uncertain ---- 3 29 32

Total 7 60 133 200

Gosney et al. Lancet 1984;2:564

Strategies to Prevent/Manage
Drug Interactions
1. Encourage patients to report all prescription, over-
the- counter and complementary and alternative
drugs at every health care encounter.
2. Support the implementation of electronic prescribing
and/or the use by patients of one pharmacy with
updated drug interaction software.
3. Work with pharmacists and be familiar with drug
interaction information sources
4. Consider whether drug therapy is necessary
5. When adding a new drug to regimen, screen for
potential drug-drug interactions.
Strategies to Prevent/Manage
Drug Interactions

6. When adding a new drug to regimen in a patient, screen

for potential drug-disease interaction.
7. If drug interaction can not be avoided, adjust doses and
or/dosage intervals for affected medication and monitor
the patient closely.
8. Carefully monitor other drug therapy when withdrawing
a drug that can inhibit or induce hepatic metabolism.
9. Regularly review the need for chronic medications-
reduce polypharmacy
Learning Objectives

At the conclusion of this talk student should be able to:

 List the 4 major types of drug interactions that can occur
in the elderly
 Discuss the epidemiology of the different types of drug
interactions in the elderly
 Implement strategies to prevent/manage drug
interactions in the elderly