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
