Geriatric pharmacology Flashcards
Challenges of geriatric pharmacology
Elderly most physiologically heterogenous category
-state of health varies extensively: physical strength, cardiac condition, renal and liver function for clearance of drugs
• New drugs available each year
• Changing managed-care formularies
• Advanced understanding of drug-drug interactions
• Increasing popularity of “nutriceuticals”
• Multiple co-morbid states
• Polypharmacy
• Medication compliance
• Effects of ageing physiology on drug therapy
• Medication cost
Effects of ageing on pharmacokinetic absorption
Little evidences of major absorption alteration with ageing
Rate of absorption may be delayed
Lower peak concentration
Delayed time to peak concentration
Factors affecting absorption
Route of administration What is taken with the drug -divalent cation (Ca, Mg, Fe) -food, enteral feedings -drugs that influence gastric pH -drugs that promote or delay GI motility Comorbidity > GI pH < gastric emptying Dysphagia
Distribution
Elderly have reduced
-lean body mass
-body water
-serum albumin (binds to many drugs)
-kidney weight
Elderly have increased fat as a percentage of body mass
Thus ratio of free drugs may be significantly altered
Effects of ageing on volume of distribution (VD)
< lean body mass - < VD for drugs that bind to muscle (digoxin)
< body water - < VD for hydrophylic drugs (ethanol and lithium)
< plasma protein (albumin) - > % of unbound or free drug (active)
-diazepam, warfarin, valproic acid
> fat store - > VD for lipophilic drugs (diazepam, trazadone)
> plasma protein (α1 - acid glycoprotein) - < % unbound or free drug (active)
-quinidine, propanolol, amitriptyline
Metabolism with age
Capacity of liver to metabolise drugs does not appear to decline consistently for all drugs
Most of changes occur in phase I reaction (P450)
For drugs with extensive first-pass metabolism, bioavailability
may increase because less drug is extracted by the liver
Causes of change in metabolism with age
< blood flow in liver
< liver mass
< liver’s ability to recover from injury malnutrition
Diseases affecting hepatic functions (i.e. heart failure)
Metabolism: phase I
Modification (oxidation, reduction, hydrolysis)
Converts drugs into metabolites to facilitate excretion
Hepatic clearance of drugs metabolized by phase I reactions is more
likely to be prolonged in the elderly
Metabolism: phase II
Conjugation
Adds charged species (i.e. glutathione, sulfate, glycine)
Medications undergoing Phase II hepatic metabolism are generally
preferred in the elderly due to inactive metabolites (no accumulation)
Elimination
Age related decrease of kidney function is crucial for drug elimination
Main result is marked PROLUNGATION of drugs’ HALF-LIFE and
possibility of ACCUMULATION to toxic level if dosage is not
modified.
Creatinine clearance decrease in about 2/3 of the population.
However this is not reflected in an equivalent rise in serum creatinine
as muscle mass decrease in elderly
Causes of changes in elimination
- Decreased kidney size
- Decreased renal blood flow
- Decreased number of functional nephrons
- Decreased tubular secretion
Results of changes in elimination
< glomerular filtration rate (GFR)
< drug clearance: (i.e. gabapentin, H2 blockers, digoxin)
Factors affecting drug metabolism
Glomerular filtration
-kidney clearance reduced
Cardiac index
-blood flow to all organs (i.e. kidney, liver) is reduced
-clearance is reduced
Maximal breathing capacity
-breathing affects clearance of inhaled anaesthetics
Drug absorption is normal in elderly
-slow GI tract gives plenty of time for absorption
What does the effect of ageing do to the body with benzodiazepines
> sensitivity to sedation and psychomotor impairment
What does the effect of ageing do to the body with analgesics
> level and duration of pain relief
What does the effect of ageing do to the body with beta-blockers
< heart rate response
What does the effect of ageing do to the body with anti-cholinergic agents
Increased sensitivity
Factors contributing to adverse drug reactions in elderly pts
Impaired/ altered organ function
Decreased homeostatic regulation
Altered drug concentration
Multiple disease states –> multiple drug administration –> altered compliance
Adverse drug events (ADEs)
Responsible for 5 - 28% of acute geriatric hospital admissions
>95% of ADEs in the elderly are considered predictable
and approx 50% considered preventable
Most errors occur at ordering and monitoring stages
Risk factors for ADEs
Polypharmacy
Co-morbidity
Low body weight or body mass index
Drugs involved in ADEs
Benzodiazepines, NSAIDs, Cardiovascular agents, CNS agents,
Musculoskeletal agents, Opioid analgesics, CNS agents, Anticholinergics
Drug-drug interactions causes
> or < drug’s absorption
Additive effects due to similar effects of drugs
Antagonizing effects due to opposite effects of drugs
Changes in drug metabolism (inhibition or induction)
Duplication of drug therapy
Note: Risk of drug-drug interactions increases as number of medication
taken increases
Most common drug-drug interactions
Most common are seen in association with cardiovascular and psychotropic drugs
Risk of adverse effects in CV and psychotropic drug-drug interactions
Confusion, Cognitive impairment, Hypotension, Acute renal failure
Risk from benzodiazepine + antidepressant or antipsychotic
Sedation, confusion
Risk from ACE inhibitor + potassium
Hyperkalemia
Risk from digoxin + antiarrythmic
Bradycardia, arrhythmia
CCB/ nitrate/ vasodilator/ diuretic
Hypotension
Drug-disease interaction causes
Obesity alters volume of distribution of lipophilic drugs
Ascites alters volume of distribution of hydrophilic drugs
Dementia can increase sensitivity to drugs with CNS or anticholinergic
activity (paradoxical reactions)
Renal or hepatic dysfunction may impair metabolism and excretions of
drugs
Risk from NSAIDS and CHF
Fluid retention; CHF exacerbation
Risk from alpha blockers and anticholinergic
Urinary retention
Risk from CCB; narcotics or anticholinergics + constipation
Exacerbation of conspation
Risk from NSAIDs + gastropathy
> ulcer and bleeding risk
Risk from NSAIDs + hypertension
Fluid retention; < effectiveness of diuretics
Principles of prescribing in the elderly
- Start with a low dose and titrate slowly
- Avoid starting 2 agents at the same time
- Reach therapeutic dose before switching or adding agents
- Determine therapeutic endpoints and plan for assessment
- Avoid prescribing to treat side effect of another drug
- Use 1 medication to treat 2 conditions
- Consider drug-drug and drug-disease interactions
- Use simplest regimen possible
- Adjust doses for renal and hepatic impairment
- Avoid therapeutic duplication
Non-adherence factors
Rate may be as high as 50% in elderly
Financial, cognitive, or functional status
Beliefs and understanding about disease and medications
Common errors in prescribing for elderly people
• Polypharmacy - a drug for every complaint
• Side effects are missed because they are misinterpreted as part of
ageing (i.e. senility, hearing loss)
• Elderly people often see different doctors
• Physicians often assume that the patients are ill because they are
not taking their medications when in fact they are taking them and
the amount prescribed for them too much
Compliance problems for taking medications
• Opening containers (i.e. weak/arthritis pain/tremors/spills)
• Cognitive impairment - can’t recall a few moments ago
• Fear of choking while swallowing or concerns after reading labels and
information
• Depression - sleepy - poor concept of time for doses
• Adverse drug reactions limit benefit of medications
Pharmacology in the elderly
Successful pharmacotherapy means using the correct drug at the
correct dose for the correct indication in an individual patient
• Age alters PK and PD
• ADEs are common among the elderly
• Risk of ADEs can be minimized by appropriate prescribing
