Geriatric pharmacology
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This document summarizes geriatric pharmacology and aging-related changes. It discusses theories of aging, how aging affects drug absorption, distribution, metabolism, and excretion. It also covers age-related changes in drug sensitivity and interactions, principles of prescribing for older adults, and common diseases in the elderly. Potential anti-aging therapies like calorie restriction, DHEA, and estrogen/progesterone are also mentioned.
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Geriatric pharmacology
- 1. Geriatric Pharmacology Dr Shahid Saache Dept. of Pharmacology BJ GMC, Pune Guide: Dr S.A. Divhare
- 4. Programmed Aging Theory Hayflick Phenomenon/limit Telomere shortening
- 5. • Somatic Mutation Theory/Error Theory • Wear & Tear Theory • Cross-linking Theory
- 6. Free Radical Theory/Accumulation Theory
- 7. How “old” is older?
- 8. How “old” is older? 60-69 70-79 80+ Old Old - Old Oldest- Old 60-74 75- 84 85+ Young Old Middle old Old-Old
- 9. Peculiarities of the old • Healthy old: Age related changes are minimal • Increased drug intake: Multiple diseases, nutritional problems, etc. • Changed lifestyle: ↓ financial resources • Pharmacological responses: May be altered with age • Adverse drug reactions: More common • Variability: Organ functions and responses are more variable
- 10. 1980 1990 2000 2010 2020 World 381.2 484.7 608.7 754.2 1011.6 Developed 173.3 203.6 234.6 232.4 308.2 Developing 207.9 281.8 374.1 491.8 703.4 Asia (excl. Japan) 160 218.2 290 377.7 539.9 China 78.6 101.2 131.7 167.9 238.9 India 44.6 60.2 81.4 107 149.7
- 11. 0 2 4 6 8 10 12 14 16 2000 2005 2010 2015 2020 2025 9.9 10.2 11 12.2 13.4 14.9 Percentage aged 60 or over (%)
- 14. Drug Consumption amongst the elderly • Elderly: consume 31% of prescribed drugs. • Average of 4.5 medications at any one time. • Average of 13 to 15 prescriptions per year
- 23. Pharmacokinetic changes related to aging
- 24. Effects of Aging on Absorption • Gastrointestinal tract changes seem to be of minor • Altered rate of absorption – altered nutritional habits, greater consumption of non-prescription drugs (antacids, laxatives), changes in gastric emptying (often slow)
- 25. Pharmacokinetic variable affected Age related physiological changes Pathological conditions Therapeutic & Environmental factors Absorption ed gastric pH ↓ed absorptive surface ed splanchnic blood flow ed GI motility Achlorhydria, Diarrhoea, post- gastrectomy malabsorption syndrome, Pancreatitis Drug interactions (eg. Antacids, anticholinergics, cholestyramine) Food/meals
- 26. Effects of Aging on Distribution
- 27. Distribution: Important Age-Related Changes: • Lean Body Mass and Total Body Water - Higher concentrations of water-soluble drugs •↑in fat as % of body weight - Increase in volume of distribution for lipophilic drugs, such as sedatives that penetrate CNS. • albumin, ↑ acid glycoprotein
- 28. Pharmacokinetic variable affected Age related physiological changes Pathological conditions Therapeutic & Environmental factors Distribution ed cardiac output ed total body water ed lean body mass ed S alb conc. ed 1-acid glycoprot ed proportion of body fat CCF, Dehydration Oedema or ascitis, Hepatic failure, Malnutrition, Renal failure
- 29. Metabolism Liver Decline in overall metabolism metabolic capacity • Due to liver mass and hepatic blood flow. • Animal studies – both basal & inducibility of microsomal enzymes es • Non microsomal enzyme pathway less affected • ability of liver to recover from injury – Alcohol, hepatitis etc (h/o recent liver disease important)
- 30. • Malnutrition and diseases affecting liver are more common in elderly (CCF) • Concurrent drug use • Metabolic capacity is highly variable; no good estimation algorithm existsPhase I (oxidation, reduction, hydrolysis) is more likely to ↓ with advancing age. • Phase II (conjugation) usually unchanged
- 32. Age related ↓in hepatic clearance found in Alprazolam Flurazepam Barbiturates Meperidine Carbenoxolone Nortryptaline Chlordiazepoxide Phenylbutazone Chlormethiazole Propranolol Clobazam Quinidine Desmethyldiazepam Quinine Diazepam Theophylline Imipramine Tolbutamide
- 33. Pharmacokinetic variable affected Age related physiological changes Pathological conditions Therapeutic & Environmental factors Metabolism ed hepatic mass ed hepatic bld flow CCF, Fever, Hepatic insufficiency, Malignancy, Thyroid disease, Viral infection or immunization Dietary composition. Drug interactions, Insecticides Tobacco (smoking)
- 34. Excretion • renal blood flow, GFR, tubular secretion, and renal mass. (Preserved in 1/3) • lean body mass leads to creatinine production; Serum creatinine may appear normal even when significant renal impairment exists. • Prolongation of t1/2 & possible accumulation to toxic levels ( if dose amount or frequency not adjusted ) • A good estimation formula (Crokcroft-Gault Formula ) for age over 40.
- 35. Creatinine clearance = (140-age) x (BW in Kg ) S. creatinine x 72 multiply by 0.85 for females • Nutritional changes – severe dehydration (stroke etc) Renal clearance decreases • Lungs – decreased lung capacity, increased pul diseases (volatile drugs)
- 38. Pharmacokinetic variable affected Age related physiological changes Pathological conditions Therapeutic & Environmental factors Excretion ed renal bld flow edTubular secretion Hypovolemia, Renal failure Drug interactions
- 39. Pharmacodynamics • Generally, lower drug doses are required to achieve the same effect with advancing age. • Clinical studies prove increased sensitivity to sedatives, hypnotics & analgesics. • Receptor numbers, affinity, or post-receptor cellular effects may change. • Changes in homeostatic mechanisms can increase or decrease drug sensitivity. • Aged patients exhibits ↓ tolerance to adverse effects
- 40. Homeostasis • Impaired ability to compensate for physiologic challenges. • Progressive decline of reserve organ function that occurs with aging • Some clinically important aging-related changes may interact with medication responses: • Blood pressure regulation Tendency to orthostatic hypotension. Homeostenosis
- 41. Homeostenosis
- 42. • Narrowed BP range for adequate CNS perfusion. May not increase heart rate when needed. • Thermoregulation - diminished Impaired reserve against both heat and cold. • Volume Regulation ↓ reserves of body water ↓thirst ↓maximum urinary concentration • ↓ ability to excrete free water load. • Glucose metabolism 2 hrs PP bld sugar level by 1 g/dl for each yr above 50.
- 43. Adverse drug reactions Overall incidence is double • Linearly related to the number of medications, which in turn reflects the number of acute and chronic illnesses. • Associated with ↑ risk for hospital admissions, cognitive impairment, injurious falls, and other adverse outcomes. • Errors in prescribing drugs – -Age related pharmacokinetic changes not taken into account -Unawareness of incompatible combinations.
- 44. • Errors in drug use by patients – Non compliance Use of non prescription drugs • Common drug reactions – confusion, ataxia, falls, postural hypotension, urinary retention &constipation. • Careful drug h/o esp over the counter drugs.
- 47. Drug interactions • Congestive Heart Failure: Decreased clearance of many medications • Benign Prostatic Hypertrophy: Obstructive symptoms with anticholinergic drugs • Chronic Renal Insufficiency: NSAIDS, aminoglycosides, contrast dye • Postural Hypotension: May be worsened with diuretics, antihypertensives, tricyclic antidepressants, L-dopa, vasodilators, others • Dementia: Superimposed delirium can result with anticholinergics, opiates, and psychotropic agents
- 48. Selected interactions of Drugs, Food, and Nutrition: • Drug therapy can contribute to anorexia: digoxin, narcotics, NSAIDS, others • Dry mouth can contribute to poor intake: clonidine, B-blockers, TCAs, antihistamines • Frequent laxative use: fat soluble vitamin deficiencies • Food can impair absorption of: Some medications, such as bisphosphonates
- 49. Selected Drug-Drug Interaction Examples: • Absorption; impaired by resins and fiber products • Metabolism: • cimetidine inhibits oxidative metabolism of several other medications • induction of enzymes by alcohol or phenytoin: increases metabolism of other agents cleared by the same enzymes
- 50. Renal excretion: • Competition for renal tubular secretion: (e.g. Digoxin renal excretion reduced by several other antiarrhymics) • NSAIDS reduce renal prostaglandins and decrease renal blood flow, and thus may reduce effects of some diuretics • Protein Binding changes are important for highly protein bound agents with narrow therapeutic index: • Particularly when drug is displaced and metabolism is inhibited: • Example: warfarin with sulfonamides, which both displace drug (increased free concentration) and inhibit hepatic metabolism
- 51. Principles of prescribing drugs in elderly • Is drug therapy required? • Treatment VS no treatment • If required, what should be the aim? • If required, which is the appropriate one? • The ones with good therapeutic margin and less abuse liability. • Is the pt taking drug tolerable? • Smallest no of drugs that should always be used. • Medication errors and noncompliance should also be accounted for. ?
- 52. Contributors to Non-Adherence with Medication Regimen • Complex or frequently changing schedule • Large number of medications (>8) • Adverse reactions • Difficult-to-open containers • Expensive medications • Rectal, vaginal etc. modes of administration • Confusion about brand name/trade name and duplicates
- 53. Prevalence of Medication Non-adherence in Older Adults: • Rates estimated at 25-50% • Intentional about 75% of the time but usually not spontaneously reported • Changes in regimen made by patients to increase convenience, ↓ adverse effects or ↓refill expense • Simplification of regimen, pre-filled medication boxes, and legible instructions reduce the extent of non- adherence
- 54. The future… You can expect more: • Quality monitoring of physician prescribing habits with "profiling" of use of poorly tolerated drugs in aged patients. • More computer-based checks for drug interactions. • Regulatory pressure to include more aged subjects in trials of new agents; hopefully an improved evidence base in future.
- 55. • Case management as a tool for coordinating complex care from multiple providers, avoiding polypharmacy & for enhanced patient education. • Continued time pressure that makes it difficult to fully address medication regimen and adherence in brief office visits.
- 56. General Principles of Medication Management for Older Adults: • Review all medications; ask patient to bring all medications in. • Avoid prescribing for nonspecific symptoms or without clear diagnosis. • Update and discontinue medications where able. • Remember...medication lists accumulate if untended! • Consider drug adverse effects if you observe decline in physical or cognitive functions or self-care abilities. • Medication boxes setup in advance may be helpful.
- 57. Prescribing Principles when a new medication is needed: • Start Low, Go Slow. • Treat adequately to achieve goals of therapy. • Provide patient education, using written instructions to reinforce proper drug use at home. • Avoid complex dosing schedules if possible.
- 58. Medication Reduction Targeting Medication Reduction Strategies • Patients on multiple medications (>8) • People taking a drug to counteract side effects of another drug • Selected drugs have been identified as generally inappropriate for older adults, due to poor tolerability. These include: • long-active sedative hypnotics • amitriptyline • indomethacin and phenylbutazone • chlorpropamide • propoxyphene • muscle relaxants
- 59. Principles of prescribing drugs in elderly- BEER’S list
- 60. Some common diseases and illnesses in elder
- 62. Disease state Aggravating drug Potential adverse effect Diabetes Corticosteroids (eg, prednisone) Drug-induced hyperglycemia Osteoporosis Corticosteroids (eg, prednisone) Increased fracture risk Constipation Anticholinergics/antihistam ines/narcotics All slow gastrointestinal tract motility Parkinson Antipsychotics Aggravate movement disorder Hypertension Nonsteroidal anti- inflammatory drugs Fluid retention increases blood pressure Benign prostatic hypertrophy Anticholinergics/antihistam ines Urinary problems
- 63. • Cardiovascular diseases • Constipation • Delirium • Dementia and cognitive impairment • Insomnia • Parkinson’s disease • Osteoarthritis • Osteoporosis • Psychiatric illnesses • Ophthalmological disorders
- 65. Aminoguanide • Effective in halting glycosylation, • In aging process, glycosylation is considered to play a major role alongside oxidation in the development of degenerative diseases of arterial system, the eye and the brain. • 300mg/day, is recommended as part of an effective anti-aging program Anacervix • A "smart drug" medication - combines the vasoregulatory action of Vincamine , with the cerebral metabolic activation of Piracetam • It wakes up the brain and focuses thinking and concentration
- 66. Arginine • An important amino acid - best known as a human growth hormone releaser. • of growth hormone in the human body - a major reason why muscle mass & body fat with age. • GH not effective orally, injections are expensive. • GH releasers - arginine or ornithine.
- 67. Calorie restriction • Shown to extend maximum life span (up to 40%) • Slow the aging process, (rodents, water fleas, rotifers, spiders and fish). • Theories : 1. Energy-using system or levels of circulating glucose causes destruction of life-preserving body systems (CR reduces circulating glucose levels and slows metabolic rate) 2. Lack of melatonin an important aging factor (CR inhibits the usual decline in circulating melatonin levels) 3. Decline in immunological efficiency (CR strengthens the immune system)
- 68. Cardiovascular rejuvenation therapy • Proper exercise and a dietary regime geared toward the reduction of LDL cholesterol (using monounsaturated fats) • Maintenance of youthful antioxidant levels (including folic acid) • Special supplements - niacin, DHEA, folic acid, and the vitamins B-6 vitamin B-12 and E.
- 69. Chromium picolinate • Trace mineral known to lower blood sugar • Anti-aging effect,( antiglycosylation process) • Human studies – Decrease body fat Enhance lean body mass Lowering blood cholesterol levels
- 70. D-Deprenyl • The "anti-aging aphrodisiac" • Developed as an advanced treatment for Parkinson's disease • Found to have profound life-extension effects as well. • Clinical trials - protect brain neurons from toxins, improve the condition of Alzheimers disease Elevate levels of antioxidant enzymes, Extend the lifespan of laboratory animals.
- 71. Estrogen & progestrone • Help to maintain bone density, strength, and sexual function • Contribute to mental function (including protection from Alzheimer's disease) in men and women • Estrogen and Progesterone are now available in drug and plant-derived formulations.
- 72. DHEA • Declines with advancing age in both men and women. • Studies - oral DHEA improves brain function, immune function, stress disorders, and protects against cardiovascular disease • Increases lean body mass and muscle strength (as well as perceived physical and psychological well-being). • "The Anti-Aging Hormone"
- 73. Herbal therapies • Ginseng has long been considered a "longevity" herb • Ginko bilboa - antioxidant and therapeutic properties for the brain • Green tea polyphenols are powerful antioxidants • Stress-reducing herbs such as kava, St. John's Wort, and chamomile lead to life-extension.
- 75. Clinical Trials In Geriatrics • Under-representation of the geriatric population • Geriatric Minimum Data Set (GMDS) for clinical trials • Guidelines for Clinical trials in the elderly • PK/PD studies • Drug-drug interaction studies • Ethical Principles
- 76. Take home message • Medication misuse in the elderly is a common and serious problem. • Recognizing age-related changes in pharmacodynamics and pharmacokinetics will contribute to better prescribing practices for geriatric patients. • Final aim should be tailor make regimens as per the individual. • Promoting clinical research in the elderly to better extrapolate the findings.
- 77. M minimize number of meds A alternatives to be considered S start low and go slow T titrate therapy E educate patient R review and monitor regularly
- 78. Thank you…
Notas do Editor
- Gerontology- the scientific study of old age, the process of ageing, and the particular problems of old people- broad term Geriatrics (Clinical gerontology) -the branch of medicine or social science dealing with the health and care of old people.
- human cell is limited in the number of times it can divide. 50-times Eventually (after 50-odd times of division) there is simply not enough DNA information available to complete any sort of division? We also know that calorie restriction in animals significantly increases their life-span. Telomeres act to maintain the integrity of our chromosomes. Every time our cells divide telomeres are shortened, leading to cellular damage and cellular death associated with aging.
- -Each time a cell divides, there is a chance that some of the genes will be copied incorrectly, this is called a mutation. Additionally, exposures to toxins, radiation or ultraviolet light can causes mutations in your body's genes. The body can correct or destroy most of the mutations, but not all of them. Eventually the mutated cells accumulate, copy themselves and cause problems in the body's functioning related to aging. -He believed that the body and its cells were damaged by overuse and abuse. -The Cross-Linking Theory of Aging is also referred to as the Glycosylation Theory of Aging. In this theory it is the binding of glucose (simple sugars) to protein, (a process that occurs under the presence of oxygen) that causes various problems. Once this binding has occurred the protein becomes impaired and is unable to perform as efficiently. Living a longer life is going to lead to the increased possibility of oxygen meeting glucose and protein and known cross-linking disorders include senile cataract and the appearance of tough, leathery and yellow skin.
- Free radical concept of aging discusses the biochemical phenomenon of aging. Free radical is an extra electron that creates a negative charge. The free radical has the ability to pair with other molecules in its attempt to find stability. Successful pairing of free radicals generates more free radicals which has the potential of damaging the cells in the body. Even though the effects of free radical have a negative effect, the body benefits from nerve conductions, energy production and immune responses.
- According to WHO ,most developed countries have accepted the chronological age of 65 years and above as a definition of 'elderly' or older persons.
- According to WHO ,most developed countries have accepted the chronological age of 65 years and above as a definition of 'elderly' or older persons. The medical study of the ageing process is called gerontology. The study of diseases that afflict the elderly is geriatrics.
- Epidemiology
- More in women
- Pacemaker cells in SA node decreases (More than 75% by 75 yrs) Myocyte activity is decreses LV wall thickness increases – stiff myocardium Arteries become rigid with lipid deposition ( increased risk of ischemia)
- decreased vital capacity (slight decrease in PO2 – ventilation perfusion mismatch) Decreased hepatic function , decreased hepatic blood flow decreased vitamin D absorption
- Reduction renal blood flow & filtration Reduced bladder capacity Prostrate size increases – urinary retention Vaginal mucosal atrophy (low estrogen) –Vaginitis Reduction: nerve cells, cerebral blood flow, & metabolism
- decreased bone density – fractures body water body fat Sleep: Poor quality of sleep & insomnia Immunological functions: Poor T cell function Babies are wet and older people are dry
- Absorption is affected by site of administration and formulation of medication. (Bioavailability is influenced by absorption and by the extent of first-pass metabolism.) Ph= potential of hydrogen
- Acidic drugs: Barbitrates, NSAIDs- aspirin, Methotrexate, Penicillins, Sulfonamides. Basic drugs- Morphine, atropine, amphetamines, quinine, hyoscine
- . Phenazine (antipyrine) – used as an index of hepatic function. (Prolonged T1/2, & decreased metabolic clearance in elderly)
- Warfarin and ciprofloxacin (inducer)
- Because of ↓hepatic blood flow
- Coexisting diseases: dehydration, CCF, hypotension, urinary retention, DM nephropathy may further alleviate declining renal fn.
- Coexisting diseases: dehydration, CCF, hypotension, urinary retention, DM nephropathy may further alleviate declining renal fn. T1/2=0.693 Vd /CrCL
- Men (younger than age 40): 107-139 milliliters per minute (mL/min) or 1.8-2.3 milliliters per second (mL/sec) Women (younger than age 40): 87-107 mL/min or 1.5-1.8 mL/sec
- more ‘sensitive’ to drug action Animal studies have shown decreased responsiveness to beta adrenoreceptor stimulation & to beta blockers with age. Concomitantly, the a. Constipation, urinary retention Dry mouth, dry eyes, dry skin Memory impairment Delirium
- Homeostenosis: As people get older or develop chronic diseases like dementia, there's a narrowing (or stenosis) of reserve capacity;. This phenomenon has been called homeostenosis, which is a decreased ability to maintain homeostasis (balance) under stress. it is defined as a fall in systolic blood pressure of at least 20 mm Hg or diastolic blood pressure of at least 10 mm Hg when a person assumes a standing position. Consuming alcohol may also lead to orthostatic hypotension due to its dehydrating effects.
- decreased ability to maintain homeostasis (balance) under stress.
- Homeostenosis: As people get older or develop chronic diseases like dementia, there's a narrowing (or stenosis) of reserve capacity;. This phenomenon has been called homeostenosis, which is a decreased ability to maintain homeostasis (balance) under stress. Thermoregulation: Ambient temperature: immediate surroundings
- High protein bind drugs: Barbiturates, BZDs, penicillins, sulfonamides, warfarin
- Profiling means assessing anylysng
- Diabetes complications
- Constipating Medications. Opiod analgesics Anticholinergics Tricyclic antidepressants Antipsychotics Antacids – Aluminium, Calcium Calcium supplements Iron supplements
- Human growth hormone
- Vinpocetine-
- a food, drink, or other thing that stimulates sexual desire. psychological reinforcement
- Dehydroepiandrosterone
- Gene therapy Melatonin- free radical scavenger, antioxidant Cell replacement
- “A third of the original research papers in major medical journals excluded elderly people without justification.” GMDS- To overcome the weak evidence base coming from often poor and insufficient clinical research in older people, a minimum data set to achieve harmonisation is highly advisable. This will lead to uniform nomenclature and to the standardisation of the assessment tools.
- ‘ You don't heal old age; you protect it; you promote it; you extend it …’
- ‘ You don't heal old age; you protect it; you promote it; you extend it …’