Pharmacotherapy of Geriatrics

by

Ibtisam Haider
FA19-PHM-065/ATD
Maryan Yousaf
FA19-PHM-066/ATD
Muhammad Asghar Khanzada
FA19-PHM-067/ATD
Muhammad SAAD Kahlid
FA19-PHM-068/ATD
Muhammad Usman Khan
FA19-PHM-069/ATD
Pharm-D (Doctor of Pharmacy)
Thesis
in
Clinical Pharmacy
COMSATS University Islamabad
Abbottabad Campus - Pakistan
Department of Pharmacy
Spring, 2024
2
COMSATS University Islamabad - Abbottabad
Campus

Pharmacotherapy of Geriatrics

A Thesis Presented to

COMSATS University Islamabad,

Abbottabad Campus

in partial fulfilment of the requirement for the degree of

Pharm-D (Doctor of Pharmacy)

by
Ibtisam Haider
FA19-PHM-065/ATD
Maryam Yousaf
FA19-PHM-066/ATD
Muhammad Asghar Khanzada
FA19-PHM-067/ATD
Muhammad Saad Kahlid
FA19-PHM-068/ATD
Muhammad Usman Khan
FA19-PHM-069/ATD
Spring, 2024
2

Pharmacotherapy of Geriatrics
An undergraduate thesis submitted to the Department of Pharmacy as partial
fulfilment of the requirement for the award of Degree of Pharm-D (Doctor of
Pharmacy)

Student Name Student Registration Number

Ibtisam Haider FA19-PHM-040/ATD

Maryam Yousaf FA19-PHM-074/ATD

Muhammad Asghar
FA19-PHM-081/ATD
Khanzada

Saad Kahlid FA19-PHM-082/ATD

Muhammad Usman Khan FA19-PHM-085/ATD

Dr. Ashfaq Muhammad

Assistant Professor

Department of Pharmacy
COMSATS University Islamabad (CUI)
Abbottabad Campus
April 2024
2

Final Approval

This project titled

Pharmacotherapy of Geriatrics
by

Ibtisam Haider
FA19-PHM-065/ATD
Maryam Yousaf
FA19-PHM-066/ATD
Muhammad Asghar Khanzada
FA19-PHM-067/ATD
Saad Kahlid
 FA19-PHM-068/ATD
Muhammad Usman Khan
FA19-PHM-069/ATD

has been approved

for the COMSATS University Islamabad, Abbottabad Campus,

Department of Pharmacy

External Examiner: ___________________________________________________

Supervisor: __________________________________________________________
Dr. Ashfaq Muhammad
Assistant Professor
Department of Pharmacy, CUI, Abbottabad Campus

HoD: ______________________________________________________________
Prof. Dr. Abdul Mannan
Department of Pharmacy, CUI, Abbottabad Campus

Declaration

We, Laiba Iftikhar (FA18-PHM-040/ATD), Zara Shoaib (FA18-PHM-074/ATD),

Muhammad Waqar (FA18-PHM-081/ATD), Waqas Khan (FA18-PHM-082/ATD),
and Ammarah Ijaz (FA18-PHM-085/ATD), hereby declare that we have produced the
work presented in this project, during the scheduled period of study. We also declare
that I have not taken any material from any source and have attached the plagiarism
report
Date: _________________ Signature of the student:

___________________________
Ibtisam Haider
FA19-PHM-040/ATD
Signature of the student:

___________________________
Maryam Yousaf
FA19-PHM-074/ATD
Signature of the student:

____________________________
Muhammad Asghar Khanzada
FA19-PHM-081/ATD
Signature of the student:

____________________________
Saad Kahlid
FA19-PHM-082/ATD
Signature of the student:

____________________________
Muhammad Usman Khan
 FA19-PHM-085/ATD
Signature of the student:

Certificate

It is certified that Ibtisam Haider (FA19-PHM-065/ATD), Maryam Yousaf (FA19-

PHM-066ATD), Muhammad Asghar Khanzada (FA19-PHM-067/ATD), Saad Kahlid
(FA19-PHM-068/ATD) and Muhammad Usman Khan (FA19-PHM-069ATD) have
carried out all the work related to this project under my supervision at the Department
of Pharmacy, COMSATS University Islamabad, Abbottabad and the work fulfils the
requirement for award of Pharm-D degree.

Date: _________________

Supervisor

__________________________
_
Dr. Ashfaq Muhammad

Head of Department

_____________________________
Prof. Dr. Abdul Mannan
Department of Pharmacy
ACKNOWLEDGEMENTS
 Ibtisam Haider, FA19-PHM-065/ATD
Maryam Yousaf, FA19-PHM-
066/ATD
Muhammad Asghar Khanzada, FA19-PHM-
067/ATD
Saad Kahlid, FA19-PHM-
068/ATD
Muhammad Usman Khan, FA19-PHM-
069/ATD

ABSTRACT
Pharmacotherapy of Geriatrics
 TABLE OF CONTENTS

1. Introduction
2. Physiological Changes that occur with Aging
a. Changes in Central Nervous System
b. Changes in Muscular System
c. Changes in Urinary and Excretory System
d. Changes In Reproductive System
e. Changes in Respiratory System
f. Changes in Integumentary System
g. Changes in Cardiovascular System
h. Changes in Lymphatic System
i. Changes in Endocrine System

LIST OF FIGURES

Fig 1.1 Structure of Eye……………………………………………………………….

LIST OF TABLES
Table 1.1 DNA Markers for Gene Mapping…………………………………….......
2

LIST OF ABBREVIATIONS

Alpha

Beta

g Microgram

l Microliter

m Micrometer

Chapter No
1.Introduction

Why Geriatrics?
As our lives lengthen and we enjoy better health, it's crucial to consider how we age,
foster innovations for sustained well-being, and shape a healthcare system ready for the
future. This emphasizes the pivotal role of geriatrics as a profession for all of us as we
journey through the aging process.
A Complex Challenge:
The increasing lifespan within our communities offers promising opportunities but
failing to address the specific healthcare needs of aging individuals’ risks undermining
this progress. This is where geriatrics, a healthcare specialty focusing on innovative
elder care, comes into play.
Geriatrics encompasses a diverse range of healthcare professionals, including doctors,
nurses, physician assistants, pharmacists, and social workers, all extensively trained in
addressing the unique health challenges of older adults. They understand the
complexities of aging and are skilled in collaborative care, essential given that many
seniors manage multiple chronic conditions and make care decisions alongside family
members or other stakeholders.
A Growing Field:
The field of geriatrics is expanding rapidly. Take, for instance, the career prospects for
geriatricians, physicians specializing in the care of older adults. The demand for
approximately 20,000 geriatricians currently outstrips the supply, with fewer than 7,300
certified geriatricians practicing nationwide. Looking ahead to 2030, projections
indicate a need for as many as 30,000 geriatricians. Meeting this demand requires
innovative strategies to expand the workforce, not only among physicians but also
among nurses, physician assistants, pharmacists, social workers, and others.
The field of geriatrics presents a wealth of opportunities for the future of healthcare. As
demand for expertise in this area continues to grow, the field remains dynamic,
fulfilling, and ripe with opportunities for those willing to seize them.

Physiological Changes that occur with Aging:

1. Changes in Central Nervous System:
▪ Brain Atrophy: One of the most noticeable changes is a decrease in brain volume.
This is primarily due to a reduction in the number of neurons, as well as a decline in
the size of remaining neurons. The frontal cortex and hippocampus, areas important
for memory and executive functions, are particularly affected.
▪ Changes in Neurotransmitters: Levels of certain neurotransmitters, such as
dopamine and acetylcholine, may decrease with age. These neurotransmitters play
crucial roles in cognitive functions, mood regulation, and motor control.
▪ Cerebral Blood Flow Reduction: Blood flow to the brain tends to decrease with
age. Reduced blood flow can affect the delivery of oxygen and nutrients to brain
cells, impacting cognitive function.
▪ White Matter Changes: White matter, composed of myelinated nerve fibers, may
experience structural changes with aging. This can affect the speed and efficiency
of communication between different regions of the brain.
▪ Formation of Beta-Amyloid Plaques: In some individuals, the accumulation of
beta-amyloid plaques can occur. These plaques are associated with Alzheimer's
disease and can interfere with normal brain function.
▪ Decrease in Synaptic Plasticity: Synaptic plasticity, the ability of synapses
(connections between neurons) to change and adapt, may decline with age. This can
affect learning and memory processes.
▪ Inflammation: Chronic low-grade inflammation, often referred to as
neuroinflammation, is associated with aging and may contribute to the progression
of neurodegenerative disorders.

2. Changes in Muscular System:

▪ Sarcopenia: refers to the age-related loss of muscle mass and strength. It typically
begins in the third or fourth decade of life and accelerates after the age of 75.
Reduction in the number and size of muscle fibers contributes to a decrease in
muscle mass.
▪ Decreased Muscle Strength: Reduction in the force-generating capacity of muscles,
especially in the lower extremities. Loss of strength contributes to difficulties in
activities such as standing from a seated position or climbing stairs.
▪ Impaired Muscle Endurance: Aging is associated with a decline in the ability of
muscles to sustain force or contract over prolonged periods. Reduced muscle
endurance can impact daily activities and contribute to fatigue.
▪ Changes in Muscle Tone: Alterations in muscle tone, including increased stiffness
and decreased flexibility. Loss of elasticity in tendons and ligaments, affecting joint
flexibility.
▪ Decline in Motor Neuron Function: Age-related changes in the nervous system can
lead to a decline in motor neuron function, affecting the communication between
nerves and muscles. Slower motor response times and reduced precision in
movements.
▪ Reduction in Muscle Blood Flow: Decline in the efficiency of the circulatory
system, leading to reduced blood flow to muscles. Impaired nutrient and oxygen
delivery to muscle tissues, affecting their overall function.
3. Changes in Urinary and Excretory System:
The kidneys filter the blood and help remove wastes and extra fluid from the body. The
kidneys also help control the body's chemical balance. The kidneys are part of the
urinary system, which also includes the ureters, bladder, and urethra. Muscle changes
and changes in the reproductive system can affect bladder control.
AGING CHANGES AND THEIR EFFECTS ON THE KIDNEYS AND
BLADDER
As you age, your kidneys and bladder change. This can affect their function.
Changes in the kidneys that occur with age:

• Thickening of basement membrane in Bowman’s capsule and impaired permeability

• Degenerative changes in tubules.
• Amount of kidney tissue decreases and kidney function diminishes.
• Number of filtering units (nephrons) decreases. Nephrons filter waste material from
the blood. The number of nephrons is halved in an average lifespan.

• Blood vessels supplying the kidneys can become hardened. This causes the kidneys
to filter blood more slowly. Renal blood flow is halved by 75 years.
Changes in the bladder:

• The bladder wall changes. The elastic tissue becomes stiffer and the bladder becomes
less stretchy. The bladder cannot hold as much urine as before.

• The bladder muscles weaken.

• The urethra can become partially or totally blocked. In women, this can be due to
weakened muscles that cause the bladder or vagina to fall out of position (prolapse).
In men, the urethra can become blocked by an enlarged prostate gland.

• In a healthy aging person, kidney function declines very slowly. Illness, medicines,
and other conditions can significantly degrade kidney function.
COMMON PROBLEMS
Aging increases the risk of kidney and bladder problems such as:

• Bladder control issues, such as leakage or urinary incontinence (not being able to
hold your urine), or urinary retention (not being able to completely empty your
bladder)

• Bladder and other urinary tract infections (UTIs)

• Chronic kidney disease
• Enlargement of prostate gland
• Constipation
Contact your health care provider right away if you have any of the following:

• Signs of a urinary tract infection, including fever or chills, burning when urinating,
nausea and vomiting, extreme tiredness, or flank pain

• Very dark urine or fresh blood in the urine

• Trouble urinating
• Urinating more often than usual (polyuria)
• Sudden need to urinate (urinary urgency)

4. Changes In Reproductive System:

● Male Reproductive System:
In male mammals, various changes occur throughout the hypothalamic-pituitary-
testicular axis as individuals age. These changes encompass alterations in the GnRH
pulse generator, gonadotropin secretion, and testicular steroidogenesis, alongside
adjustments in feed-forward and feed-back relationships. These factors collectively
contribute to the decline in circulating testosterone concentrations associated with
aging. The rate at which testosterone levels decline with age can be influenced by
several factors such as chronic illness, body fat, medications, timing of sample
collection, and the methods used for testosterone measurement.
Epidemiological studies indicate a correlation between low testosterone levels and
changes in sexual function, body composition, physical function, mobility, and an
increased risk of various health issues including diabetes, late-life persistent depressive
disorder (dysthymia), unexplained anemia of aging, osteoporosis, and bone fractures.
It's crucial to differentiate age-related testosterone decline from classical hypogonadism
caused by known diseases affecting the hypothalamus, pituitary gland, or testes.
In young hypogonadal men with diagnosed conditions affecting the hypothalamus,
pituitary gland, or testes, testosterone therapy is generally beneficial and has a low rate
of adverse effects. However, the long-term benefits and risks of testosterone therapy in
older men with age-related testosterone decline are not well understood. Well-designed
randomized trials have shown that testosterone replacement therapy in older men with
clearly low testosterone levels can improve sexual desire, erectile function, overall
sexual activity, lean body mass, muscle strength, certain aspects of physical function
and mobility, bone density and strength, depressive symptoms, and correct anemia of
aging. Testosterone treatment does not worsen lower urinary tract symptoms, but its
effects on the long-term risk of prostate cancer and major adverse cardiovascular events
remain uncertain.
While testicular morphology, semen production, and fertility can be maintained in men
until very old age, there is evidence of decreased fertility and an increased risk of
genetic disorders related to paternal age among the offspring of older men. This
highlights the emerging significance of reproductive aging in men as a public health
concern with broader societal implications beyond the individual quality-of-life issues
associated with low testosterone levels.
The aging of male mammals is a recent evolutionary development primarily observed
in humans and captive animals. In the wild, most animal species, except for a few like
short-finned pilot whales, killer whales, and some fish, do not survive beyond their
reproductive years. This contrasts with humans, where only the past three generations
have experienced life expectancies exceeding fifty years. Today, due to increased life
expectancies globally, a significant portion of human populations spend a considerable
part of their lives beyond their reproductive years.
This historical shift towards aging populations has had a profound impact on the health,
well-being, and economies of human societies. At an individual level, conditions
related to reproductive aging such as sexual dysfunction, infertility, sex-steroid
deficiency-related issues, and reproductive organ cancers drive middle-aged and older
individuals to seek medical attention. Societally, reproductive aging raises concerns
about declining birth rates, especially evident in the United States since 1971, with
factors like delayed childbearing and changes in career and lifestyle contributing to this
trend.
Various societal factors, including contraceptive availability, women's increasing
participation in the workforce, and delayed childbearing, have influenced these
demographic shifts. However, postponing childbearing increases the risk of infertility
due to age-related declines in fertility, increased health risks associated with older
parents, and changes in reproductive behaviors. These trends highlight the complex
interplay between reproductive aging, societal norms, and individual health choices.
Since 1970, significant demographic shifts have occurred in the United States
concerning birth rates, the mean age of mothers at first childbirth, and the proportion of
infants born to women over 35 years old:

• Birth Rate: The birth rate per 1000 population has decreased from 18.4 in 1970
to 11.8 in 2017.
• Mean Age of Mothers at First Childbirth: The mean age of mothers at first
childbirth has risen from 21.4 years in 1970 to 26.6 years in 2016.
• Proportion of Infants Born to Women over 35: The proportion of all infants born
 to mothers over 35 years old has increased from 4.6% in 1970 to 14.9% in 2012.

These trends highlight a demographic shift towards delayed childbearing and a higher
proportion of births occurring to older mothers in the United States over the past few
decades. These data are sourced from a study published in the Journal of Clinical
Endocrinology and Metabolism and based on information from the Centers for Disease
Control and Prevention's National Vital Statistics System.

• Female Reproductive System:

Research on health issues related to reproductive aging in women has been extensive
for nearly 50 years and is covered in other sections of this textbook. However, this
chapter focuses solely on the reproductive aging of men, which has recently gained
attention with the opening of numerous men's health clinics and an increase in sales of
testosterone and erectile dysfunction products.

Aging in men involves functional changes across the reproductive axis, impacting both
steroidogenic and gametogenic aspects. While it's widely accepted that serum
testosterone levels decline with age, this decline is further affected by the presence of
comorbidities. However, the long-term effects of testosterone supplementation on
health outcomes in older men, including its impact on prostate cancer risk and major
cardiovascular events, remain understudied.

Recent placebo-controlled trials of testosterone in middle-aged and older men have

improved our understanding of its effects on sexual function, mobility, lower urinary
tract symptoms, and atherogenesis progression. Yet, there is a lack of long-term,
adequately-powered randomized trials assessing testosterone's impact on critical health
outcomes such as fractures, falls, physical disability, diabetes progression, remission of
depressive disorders, wellbeing, and dementia risk.

The first section of this chapter reviews the pathophysiology and health consequences
of age-related testosterone decline, proposing a patient-centric approach to treatment
decisions. The second section discusses age-related changes in the testes' gametogenic
compartment.

Female fertility peaks in a woman's twenties and gradually declines until around age
35, after which it decreases more rapidly until menopause, which marks the end of
fertility. Menopause is characterized by the cessation of menstruation due to the
depletion of ovarian follicles and their hormone production. A woman is deemed
postmenopausal after not menstruating for a full year, typically occurring between ages
50 and 52 but varying individually.

As menopause approaches, declining ovarian follicles affect hormonal regulation.

Inhibin levels decrease, leading to increased follicle-stimulating hormone (FSH) levels,
prompting more follicles to grow and secrete estrogen. However, most follicles undergo
atresia, depleting ovarian reserves and causing a dramatic decline in estrogen
production, resulting in menopausal symptoms.

Perimenopause precedes menopause, marked by irregular menstrual cycles but ongoing

estrogen levels. Decreased progesterone production during this phase can lead to
endometrial hyperplasia, increasing endometrial cancer risk. Harmless conditions like
uterine fibroids and irregular bleeding may also occur. Menopausal symptoms include
hot flashes, night sweats, sleep disturbances, vaginal dryness, mood swings, cognitive
difficulties, and changes in hair growth patterns.

Symptom severity varies among individuals, ranging from absent to severe. Factors like
smoking and poor health can influence the timing of menopause and fertility decline.
Postmenopause, lower estrogen levels can lead to various changes. Cardiovascular
disease becomes as prevalent in women as in men, possibly due to estrogen's
cholesterol-lowering effects. Without estrogen, many women experience high
cholesterol and related cardiovascular issues. Osteoporosis is another concern as bone
density decreases rapidly after menopause, increasing the risk of fractures.

Hormone therapy (HT), using synthetic estrogens and progestins, can alleviate
menopausal symptoms. A study by the Women’s Health Initiative in 2002 observed HT
outcomes over 8.5 years but was halted at 5.2 years due to a higher breast cancer risk
with estrogen-only HT. However, other studies over 50 years, including a 2012 study
with 1,000 menopausal women for 10 years, showed cardiovascular benefits with
estrogen and no increased cancer risk. Some researchers suggest the age group in the
2002 trial might have skewed results. The ongoing debate focuses on HT benefits and
risks. Current guidelines endorse HT for reducing hot flashes, ideally starting at
menopausal symptom onset, using the lowest effective dose for the shortest duration (5
years or less), and regular pelvic and breast exams for women on HT.

5. Changes in Respiratory System:

Understanding Age-Related Changes in Lung Function
Variation in Effects of Aging
Aging affects lung function differently among individuals, with notable variations in
chest wall compliance and air trapping.
Physiological Changes
FEV1 Decline:
The decline in forced expiratory volume in one second (FEV1) with age typically
follows a nonlinear pattern, with an accelerated rate of decline occurring after the age
of 70.
Airspace Enlargement:
Aging leads to an increase in airspace size due to the loss of supporting tissue within
the lungs.
Respiratory Muscle Strength:
There is a decrease in respiratory muscle strength with age, particularly prominent in
men compared to women.
Respiratory System Resilience
Maintenance of Oxygenation and Ventilation:
Despite age-related changes, the respiratory system can maintain adequate oxygenation
and ventilation throughout life.
Limited Reserve: However, the respiratory system's reserve diminishes with age,
making it more vulnerable to ventilatory failure during periods of high demand, such as
in heart failure or pneumonia.
Clinical Implications
• Ventilatory Response: Diminished ventilatory response to hypoxia and hypercapnia
increases the risk of ventilatory failure and poor outcomes during high-demand
situations.
• Delayed Medical Attention: Reduced perception of bronchial constriction in older
adults may lead to delayed medical attention for respiratory symptoms.
• Inflammation and Susceptibility: Sustained inflammation in the lower respiratory
tract predisposes older adults to increased susceptibility to environmental toxins and
accelerated lung function decline.
Clinical Implications of Aging, Future studies must address the clinical implications
of "normal" age-related changes in the respiratory system. Understanding these changes
is essential for optimizing respiratory health in older adults.
6. Changes in Integumentary System:
Effects of Aging on Skin
• Changes in Epidermis: Thinning of the outer skin layer (epidermis) occurs, while
the number of cell layers remains constant. Decrease in pigment-containing cells
(melanocytes), leading to thinner, paler, and translucent skin. Appearance of
pigmented spots, known as lentigos, particularly in sun-exposed areas.
• Connective Tissue Changes: Reduction in strength and elasticity of the skin due to
changes in connective tissue, known as elastosis. Solar elastosis produces a
leathery, weather-beaten appearance in individuals exposed to sunlight.
• Blood Vessel Fragility: Fragility of dermal blood vessels leads to bruising, bleeding
under the skin (senile purpura), and cherry angiomas.
• Changes in Oil Production: Decreased oil production by sebaceous glands,
resulting in dryness and itchiness of the skin, especially in older women after
menopause.
• Thinning of Subcutaneous Fat Layer: Thinning of the subcutaneous fat layer
reduces insulation and padding, increasing the risk of skin injury and impacting
body temperature regulation.
• Sweat Gland Function: Reduction in sweat production makes it harder to regulate
body temperature and increases the risk of overheating or heat stroke.
• Common Growths and Blemishes: Skin tags, warts, seborrheic keratoses, and
actinic keratosis become more common with age, increasing the risk of skin cancer
development.
Effects of Skin Changes:
• Increased Risk of Skin Injury: Thinner, fragile skin and loss of protective fat layer
increase susceptibility to skin tears and bruising. Fragile blood vessels can easily
break, leading to bruises, purpura, and hematomas even with minor injuries.
• Risk of Pressure Ulcers: Skin changes, loss of fat layer, reduced activity, and poor
nutrition contribute to pressure ulcers, most commonly observed on forearms and
other body areas.
• Delayed Wound Healing: Aging skin repairs itself more slowly, contributing to
delayed wound healing, pressure ulcers, and infections.
• Common Skin Disorders: Skin disorders are prevalent among older adults, making
it challenging to distinguish normal changes from disorders, with over 90%
experiencing some type of skin disorder.

7. Changes in Cardiovascular System:

The cardiovascular system undergoes various physiological changes with aging, which
can impact its structure and function.
1. Structural Changes:
• Arterial Stiffness: Aging leads to increased arterial stiffness due to
changes in arterial wall composition, resulting in decreased compliance
and elevated blood pressure.
• Atherosclerosis: Accumulation of atherosclerotic plaques in arteries
narrows vessel lumens, reducing blood flow and raising the risk of
cardiovascular diseases.
• Cardiac Hypertrophy: The aging heart may experience hypertrophic
changes, thickening the myocardium and potentially leading to diastolic
dysfunction and heart failure.
2. Functional Changes:
• Decreased Cardiac Output: Aging is associated with a decline in
maximal cardiac output due to reduced heart rate reserve and impaired
contractility, limiting the heart's ability to respond to increased demands.
• Impaired Diastolic Function: Aging results in impaired ventricular
relaxation during diastole, leading to decreased compliance and
increased filling pressures, predisposing individuals to diastolic heart
failure.
• Autonomic Dysfunction: Age-related changes affect autonomic
regulation, contributing to decreased baroreflex sensitivity and heart rate
variability, potentially leading to orthostatic hypotension and
arrhythmias.
3. Electrophysiological Changes:
• Prolonged Action Potential Duration: Aging prolongs cardiac myocyte
action potential duration, increasing susceptibility to arrhythmias like
atrial fibrillation and ventricular tachycardia.
• Altered Pacemaker Activity: Age-related changes in nodal function can
lead to disturbances in pacemaker activity and conduction, resulting in
bradyarrhythmias and conduction abnormalities.
4. Vascular Changes:
• Endothelial Dysfunction: Aging is associated with endothelial
dysfunction, impairing vasodilation and promoting a prothrombotic
state.
• Increased Peripheral Resistance: Changes in vascular tone and structure
elevate peripheral resistance, contributing to isolated systolic
hypertension.
5. Changes in Blood Pressure Regulation:
• Baroreceptor Sensitivity:Aging reduces baroreceptor sensitivity,
impairing blood pressure regulation and increasing the risk of orthostatic
hypotension.
• Renin-Angiotensin-Aldosterone System (RAAS): Aging leads to
increased RAAS activity, contributing to sodium and water retention,
 vascular remodeling, and hypertension.
6. Changes in Cardiac Conduction:
• Conduction Velocity: Aging decreases cardiac conduction velocity,
potentially resulting in conduction abnormalities observed on
electrocardiogram.
• Sinus Node Dysfunction: Aging may lead to sinus node dysfunction,
increasing the risk of symptomatic bradyarrhythmias.
7. Hormonal Changes:
• Agingalters hormonal regulation, affecting blood pressure, electrolyte
balance, fluid homeostasis, and vascular tone

8. Changes in Lymphatic System:

The lymphatic system plays a crucial role in immune function, fluid balance, and lipid
absorption. Similar to other organ systems, the lymphatic system undergoes
physiological changes with aging.
1. Structural Changes:
• Agingleads to increased fibrosis, reduced vessel density, and alterations in
vessel morphology, impairing lymphatic drainage and immune
surveillance.
2. Lymph Node Morphology and Function:
• Agingresults in smaller, less numerous lymph nodes with altered
architecture, affecting immune cell trafficking and response to antigens.
3. Immune Cell Composition and Function:
• Changes in immune cell composition and function, including decreased T
cell diversity and impaired antigen presentation, contribute to
immunosenescence and increased susceptibility to infections and cancer.
4. Lymphatic Fluid Dynamics:
• Alteredlymphatic contractility and flow dynamics with aging lead to
decreased clearance, tissue edema, and inflammation, exacerbating age-
related pathologies.
5. Lymphatic Drainage and Immune Surveillance:
• Declining lymphatic drainage capacity compromises immune surveillance,
tissue repair, and contributes to chronic inflammation and diseases such
as cardiovascular and neurodegenerative disorders.
6. Lymphatic Pump Function:
• Aging-related
declines in muscle strength and mobility can impair
lymphatic pump function, increasing the risk of lymphedema and fluid
retention.
7. Impact of Chronic Diseases and Medications:
• Comorbidities like chronic kidney disease and heart failure exacerbate
lymphatic dysfunction, while certain medications and therapies can
directly affect lymphatic function.
8. Role of Physical Activity and Exercise:
• Regularphysical activity improves lymphatic circulation, muscle
contraction, and immune surveillance, reducing the risk of lymphatic
dysfunction.
9. Psychosocial Factors:
a. Psychosocial factors such as stress and social isolation influence
lymphatic function and immune health, emphasizing the importance of
holistic approaches to wellness in the elderly population

9. Changes in Endocrine System

In older individuals, endocrine changes lead to a

decline in both tissue responsiveness and hormone
secretion from peripheral glands. Additionally, there
are alterations in the central mechanisms controlling
the timing of hormone release, resulting in
dampened circadian rhythms. The ageing process
affects all endocrine glands, with interconnected
functions, so reduced function in one gland can
impact others. Ageing is also associated with
changes in body composition, such as decreased
muscle mass, increased fat mass, and reduced
strength, compared to younger individuals. These
changes involve various endocrine systems,
including oestrogen (menopause), testosterone
(andropause), growth hormone/insulin-like growth
factor-I axis (somatopause), hypothalamic–pituitary–
thyroid axis, hypothalamic–pituitary–cortisol axis,
and dehydroepiandrosterone and its sulphate
(adrenopause).

This article aims to explore the relationship between

the regulation of endocrine function and ageing,
focusing on age-related changes in hormone
metabolism and production and their clinical
implications. It is crucial to differentiate between the
genuine effects of ageing on endocrine mechanisms
and any influences from age-related illnesses that
may confound the analysis.

Menopause
By around the mid-sixth decade, women universally
undergo menopause, marked by a reduction in
ovulation frequency and eventual cessation of
reproductive ovarian function within approximately
15 years. During this transition, ovarian follicles
function less efficiently, leading to lower oestradiol
levels and higher follicle-stimulating hormone (FSH)
concentrations, while luteinizing hormone (LH)
remains unchanged. Although oestrogen
concentrations decrease, small amounts of the
weaker oestrogen, oestrone, are still produced.
These hormonal changes are associated with
increased cardiovascular risk, rapid bone loss,
vasomotor symptoms, psychological effects, and
atrophy of oestrogen-responsive tissues.

Postmenopausal women experience an increased

risk of cardiovascular disease due to changes in lipid
profiles, such as elevated low-density lipoprotein and
total cholesterol levels, along with decreased high-
density lipoprotein. This lipid profile shift contributes
to conditions like coronary heart disease, myocardial
infarction, and stroke. While hormone replacement
therapy (HRT) improves biochemical markers, it
does not improve cardiovascular outcomes.

Bone loss accelerates postmenopause due to

oestrogen withdrawal, leading to increased fracture
risk. HRT or medications like bisphosphonates and
raloxifene help maintain bone mass and reduce
fracture risk in postmenopausal women.

Vasomotor symptoms like hot flushes originate from

hypothalamic changes, while cognitive disturbances
and vaginal atrophy are also common. HRT can
alleviate some symptoms but does not eliminate
them entirely.

The risk-benefit ratio of HRT has been extensively

debated, especially following the Women's Health
Initiative (WHI) study, which revealed increased risks
of breast cancer, coronary events, and cognitive
impairment associated with HRT. Given these risks,
HRT should only be considered for severe
menopausal symptoms and for the shortest duration
possible after informed discussion of potential
hazards.

Reference: Crawford F, Langhorne P. Time to review

all the evidence for hormone replacement therapy. Br
Med J 2005; 330(7487): 345.
https://pathsocjournals.onlinelibrary.wiley.com/doi/full
/10.1002/path.2110#:~:text=All%20endocrine%20gla
nds%20are%20subject,a%20decline%20in%20functi
onal%20status.

Andropause
As men age, there is a gradual decline in
testosterone levels, known as andropause. This
decline is more significant for free testosterone due
to increased sex hormone-binding globulin levels.
The age-related reduction in testosterone is mainly
due to decreased production rates, affecting the
hypothalamic–pituitary–testicular axis.

Clinical features of reduced testosterone in older

men include increased fat mass, muscle and bone
loss, fatigue, depression, anaemia, decreased libido,
erectile dysfunction, insulin resistance, and higher
cardiovascular risk. These symptoms are similar to
testosterone deficiency in younger men, leading to
the proposal of androgen deficiency of the ageing
male (ADAM) syndrome. However, not all older men
with these symptoms have low androgen levels, so
the syndrome is not universally accepted.

There's a notion that supplementing testosterone in

older men with low levels might prevent or reverse
ageing effects. Yet, clinical studies examining this
are inconclusive, with no consensus on the benefits
of androgen treatment for men over 50 due to the
short duration of many trials.

Reference: Hak AE, Witteman JC, de Jong FH,

Geerlings MI, Hofman A, Pols HA. Low levels of
endogenous androgens increase the risk of
atherosclerosis in elderly men: the Rotterdam study.
J Clin Endocrinol Metab 2002; 87(8): 3632–3639.
https://pathsocjournals.onlinelibrary.wiley.com/doi/full
/10.1002/path.2110#:~:text=All%20endocrine%20gla
nds%20are%20subject,a%20decline%20in%20functi
onal%20status.

1. Pathophysiology Related to Aging: -

Aging is a complex process that involves a multitude of physiological changes at the
molecular, cellular, tissue, and organ levels. While aging is a natural and inevitable part
of life, it is also associated with an increased risk of various diseases and functional
decline. Some key pathophysiological changes associated with aging include:

• Cellular senescence: Cells undergo senescence, a state of irreversible growth

arrest, as a response to various stressors such as DNA damage, oxidative stress,
and telomere shortening. Senescent cells accumulate with age and contribute to
tissue dysfunction by secreting pro-inflammatory cytokines, growth factors, and
matrix metalloproteinases, leading to chronic low-grade inflammation, known
as inflammaging.

• Genomic instability: DNA damage accumulates over time due to endogenous

factors (e.g., reactive oxygen species) and exogenous factors (e.g., radiation,
chemicals). Decreased efficiency of DNA repair mechanisms with age leads to
genomic instability, which can result in mutations, chromosomal abnormalities,
and cellular dysfunction.

• Telomere shortening: Telomeres, protective caps at the ends of chromosomes,

shorten with each cell division. Telomere shortening is accelerated by oxidative
stress and inflammation. Critically short telomeres trigger cellular senescence or
apoptosis, contributing to aging-related phenotypes and diseases.

• Mitochondrial dysfunction: Mitochondria, the cellular powerhouses

responsible for energy production, accumulate damage over time due to
oxidative stress and impaired quality control mechanisms. Mitochondrial
dysfunction leads to decreased energy production, increased production of
 reactive oxygen species (ROS), and impaired cellular function.

• Altered protein homeostasis: Proteostasis, the balance between protein

synthesis, folding, and degradation, is disrupted with age. This results in the
accumulation of misfolded and damaged proteins, leading to cellular
dysfunction and increased susceptibility to proteotoxic stress.

• Dysregulated immune function: Aging is associated with immunosenescence,

characterized by alterations in the immune system, including decreased function
of T cells, B cells, and natural killer cells, and chronic low-grade inflammation.
This dysregulated immune function contributes to increased susceptibility to
infections, autoimmune diseases, and age-related chronic diseases.

• Altered intercellular communication: Aging disrupts cell-cell communication

pathways, including hormonal signaling, growth factor signaling, and cell
adhesion molecules. Dysregulated intercellular communication contributes to
tissue dysfunction, impaired tissue repair, and increased susceptibility to age-
related diseases.

• Epigenetic alterations: Changes in DNA methylation, histone modifications,

and non-coding RNA expression patterns occur with age, leading to alterations
in gene expression and cellular function. Epigenetic alterations contribute to
age-related changes in tissue function, cellular senescence, and disease
susceptibility.

• Altered sleep pattern: Physiological changes as we get older are also reflected
by changes to our sleep patterns. Sleep is a continuous, dynamic
neurophysiological process involving the complex interaction of many different
networks within the brain.
These pathophysiological changes interact with each other and with environmental
factors to drive the aging process and increase the risk of age-related diseases, such as
cardiovascular disease, neurodegenerative diseases, cancer, and metabolic disorders.

Morbidity and aging:

As the prevalence of degenerative issues associated with older age increases, a
significant portion of healthcare services is focused on managing chronic conditions. In
many instances, these conditions prove challenging to cure once they become apparent.
Differentiating between age-related disease accumulation (morbidity) and the natural
aging process presents a complex task.

Frequently, conditions that develop gradually are underestimated by individuals, their

families, or healthcare providers. For instance, changes such as alterations in voice,
facial appearance, cold sensitivity, lethargy, and slowed movements may be erroneously
attributed solely to aging, potentially leading to overlooking underlying conditions like
myxoedema (hypothyroidism).

Similarly, postural changes, stiffness, and reduced mobility, commonly associated with
aging, can mask symptoms indicative of Parkinson's disease, such as rigidity and
bradykinesia. Consequently, these symptoms may go unnoticed or undiagnosed.
Changes in body composition:
The human body comprises fat, lean tissue (muscles and organs), bones, and water.
Beyond the age of 40, there is a discernible shift in body composition, characterized by
a decline in lean tissue. Vital organs such as the liver, kidneys, and others also
experience cellular loss during this phase. This reduction in muscle mass is closely
linked with increased vulnerability to weakness, disability, and morbidity.
Height diminution is a consequence of age-related alterations in bone, muscle, and joint
structure. On average, individuals tend to lose approximately 1 cm in height every
decade after reaching 40 years of age, with the rate of loss accelerating notably after 70.
Adopting a nutritious diet, maintaining physical activity, and proactively addressing
bone density loss are effective strategies for mitigating these changes.

Shifts in total body weight exhibit gender-specific patterns, with men typically
experiencing weight gain until around the age of 55, followed by a gradual decline later
in life. This phenomenon may be attributed to a decline in testosterone levels, the
primary male sex hormone. Conversely, women typically observe weight gain until
approximately 67–69 years of age before entering a phase of weight loss. Research also
indicates that older individuals may harbor nearly one-third more fat compared to their
younger selves, with adipose tissue preferentially accumulating around the body's core
and internal organs.

Altered response to illness:

Illnesses often present differently in old age than in youth.

Regulation of body temperature is unstable or less responsive, so pyrexia may not be as

marked as would be expected even in severe infections such as pneumonia, appendicitis
or pyelonephritis.
A lack of awareness of cold, or of the capacity to react normally to it, may lead to
hypothermia.

Pain:
Pain is common in older people. However, as people age, they complain less of pain.
The reason may be a decrease in the body's sensitivity to pain or a more stoical attitude
toward pain. Pain is often not correctly recognized and treated in people with dementia,
and use of a scale such as the Abbey pain scale may help to recognize when a person is
in pain.

2. Multiple Pathology and Polypharmacy:-

The aging process encompasses a spectrum of transformations across biological,
functional, psychological, and social domains, which are influenced by genetic
predispositions, age-related susceptibilities, and variations in organ function and
reserves.
Typically, aging coincides with the onset of numerous chronic ailments, comorbidities,
functional limitations, frailty, and instances of social seclusion. Rarely do elderly
individuals present with a solitary disease affecting only one organ or system.

Multimorbidity is prevalent among the elderly population, necessitating thorough

evaluation that considers genetic predispositions, biological markers, lifestyle choices,
socioeconomic factors, and the intricate interplay among these variables in shaping the
landscape of multimorbid conditions.

Polypharmacy: The prescription and use of multiple drugs to deal with concomitant
multiple diseases is known as polypharmacy.
Polypharmacy and Adverse Drug Events:

The high prevalence of polypharmacy in aging populations heightens the likelihood of

various risks, including inappropriate medication utilization, inadequate use of
beneficial treatments, medication errors, suboptimal adherence, as well as interactions
between drugs and diseases. Particularly significant among these risks are adverse drug
reactions, which frequently stem from the frailty and heightened sensitivity to
pharmacotherapy commonly observed in elderly individuals. Such heightened
sensitivity often arises from alterations in pharmacokinetic and pharmacodynamic
parameters, compounded by impairments in multiple organ functions.

Polypharmacy is an important risk factor for inappropriate medication prescribing,

which is very frequent among elderly people. Certain drugs are considered
inappropriate or potentially inappropriate in older patients not only because of the
higher risk of intolerance related to adverse pharmacokinetics or pharmacodynamics or
drug–disease interactions but also because they are prescribed at too high dosages or for
too long.
Moreover, polypharmacy is often an adverse consequence of the so-called ‘prescribing
cascade’, which involves the clinician’s failure to recognize a new medical event as an
adverse drug reaction. In this case, another drug is unnecessarily prescribed to treat the
adverse event instead of withdrawing the drug responsible, creating a vicious circle and
adding further risks.
Polypharmacy can also negatively influence medication adherence. Among elderly
people, non-compliance has a prevalence of 25–75%, and the likelihood rises in
proportion to the number of drugs and daily doses prescribed. Poor adherence often
becomes more marked with age, in relation to problems such as the complexity of the
therapeutic regimen, visual or hearing impairment, functional and cognitive
deterioration, depression, disease burden, and social isolation. Non-adherence or poor
adherence may result in progression of the disease, hospital admissions, and a higher
healthcare cost.
The table refer to medications which should be avoided in elderly patients regardless of
disease.
Balancing risk and benefit:

Given the practical difficulties of studying older and frail people in randomised clinical
trials, alternate mechanisms for determining risk to benefit ratios need to be considered.
Cost effectiveness models have been used to balance clinical trial efficacy data with
adverse effect data from observational and case control studies.

3. Prescribing for Older Patients:-

The decision to prescribe a drug is often based on a disease-oriented approach that
stems from guideline recommendations for each single symptom, disease, or clinical
problem. This paradigm of care focused on a specific disease and closely related
comorbidities can be implemented easily in younger adults, but has many limitations in
older patients, because it fails to take into account age-related changes in
pharmacokinetics and pharmacodynamics, coexistence of other acute or chronic
diseases, use of multiple drugs, risk of drug–drug or drug–disease interactions,
cognitive status, and disability

DOSE To Prescribe: Traditionally, it has been proposed that the dosage of many drugs
should be reduced in older people to compensate for the age related changes in
pharmacokinetics.

Clinical implications of dosage changes:

The critical concern revolves around whether adjusting medication dosage affects
clinical outcomes, encompassing both safety and efficacy. Presently, there exists a
dearth of clinical trial evidence supporting the reduction of medication doses for elderly
patients. Nonetheless, many healthcare practitioners opt for lower dosages to mitigate
the risk of adverse drug reactions that are dose-dependent. For instance, it is common
practice to prescribe reduced doses of digoxin to older individuals to minimize
concentration-dependent adverse effects.

While dose reduction may mitigate adverse drug reactions, its impact on efficacy in
elderly patients remains uncertain. Indeed, there is a debate regarding the potential
necessity for higher medication doses in certain contexts; for instance, age-related
immunosuppression may warrant higher doses of broad-spectrum antibiotics in some
cases.
Reviewing appropriateness of prescription:

Geriatricians and pharmacists have developed two primary sets of criteria for
medication management: explicit and implicit criteria. Explicit criteria typically focus
on either drugs or specific diseases and are formulated through expert consensus to
compile lists of medications that are either contraindicated or should be approached
with caution in elderly patients or those with particular medical conditions. On the
other hand, implicit criteria rely predominantly on clinical judgment to evaluate each
prescribed medication in a tailored manner, considering factors such as indication,
efficacy, dosage, adverse effects, and cost.

Both sets of criteria offer unique advantages and face distinct limitations, reflective of
their intended purposes, applicability across different countries or elderly populations,
frequency of updates, metrics used to gauge appropriateness, provision or absence of
information regarding failure to prescribe drugs indicated for treating or preventing
specific diseases, and inclusion or exclusion of the most vulnerable elderly individuals
with multiple chronic conditions.

Pharmacokinetic Variations in Geriatric Patients:

Introduction: While older adults make up only 12-20% of the population in most
Western countries, they receive a disproportionate share, around 30-40%, of prescribed
medications. This group is also particularly vulnerable to experiencing adverse drug
reactions, especially those that are predictable based on pharmacology and dosage (type
A reactions). Various factors contribute to this phenomenon, some of which are
discussed in this supplement. One crucial factor is the alteration in pharmacokinetics.

General Principles: Pharmacokinetics refers to how a drug behaves within the body,
including its absorption through the gut, initial metabolism in the gut and liver, binding
to proteins, distribution throughout the body, and elimination via kidneys, liver, or other
pathways. Aging brings about several changes that could potentially impact these
variables (see Table 1).
Drug Absorption: Although age-related changes such as reduced gastric acid, altered
gastric emptying rates, and shifts in liver and gut blood flow could theoretically affect
absorption, the actual impact on drug absorption across the gut is minor and often
clinically insignificant. While some studies suggest a slower rate of drug absorption in
the elderly, overall, age does not significantly alter the bioavailability of drugs that do
not undergo substantial first-pass elimination.
First-Pass Elimination: After absorption, drugs enter the portal circulation and
undergo first-pass metabolism in the liver before entering systemic circulation. Water-
soluble drugs, which are generally not extensively metabolized by the liver, are less
affected by first-pass metabolism. However, for lipophilic drugs, a substantial portion
of the dose may undergo extraction in the liver during first pass, greatly affecting
bioavailability. Even slight changes in hepatic function can significantly alter
bioavailability, as seen with certain widely used drugs like nitrates, beta-blockers, and
calcium channel blockers.
Protein Binding and Distribution: Age-related changes in body composition, such as
decreased plasma albumin, can impact protein binding of drugs. This alteration means
that the free fraction of drugs bound to albumin increases with age, leading to greater
pharmacological activity upon acute administration. However, the raised free fraction
also results in increased clearance, maintaining a new steady-state. While total plasma
drug concentrations may decrease, free drug plasma concentrations remain constant due
to hepatic or renal clearance of free drugs.
Changes in drug distribution also occur with age. For instance, a decrease in body water
affects the distribution of water-soluble drugs, resulting in relatively higher plasma
concentrations per unit dose in older individuals. Conversely, lipid-soluble drugs
exhibit more extensive distribution, leading to lower plasma concentrations. The
increased distribution volume primarily impacts the drug's half-life and duration of
action, which can be crucial, especially with drugs like hypnotics that may cause a
lingering 'hangover' effect in the elderly.
Renal Clearance: It has been long understood that renal clearance of drugs typically
decreases with age, leading to the common practice of reducing doses for renally
excreted medications like digoxin in elderly patients. Parameters such as glomerular
filtration rate, renal plasma flow, and various measures of tubular function have been
observed to decline with age. However, recent studies have highlighted significant
variability in the age-related decline in renal function among individuals. While many
older patients experience a notable decrease in glomerular filtration rate, some maintain
relatively normal renal function. This inter-individual variability underscores the
importance of individualized drug therapy rather than rigid adherence to standard
guidelines.
Hepatic Clearance: Numerous studies have demonstrated impaired clearance of drugs
eliminated by the liver in elderly populations, increasing the risk of type A adverse
events. Hepatic clearance (CLH) of a drug is influenced by factors such as hepatic
blood flow, extraction ratio, and liver size. Age-related changes in these factors have
been reported, including a decrease in liver blood flow and size. While early studies
suggested a decline in critical drug-metabolizing enzymes with age, recent data indicate
minimal changes in humans and non-human primates. However, in frail or hospitalized
elderly individuals, certain enzyme activities may be significantly reduced, leading to a
higher risk of adverse drug reactions.
Ageing and Drug Metabolism: There has been debate regarding the impact of ageing
on drug metabolizing enzymes' activities. While some studies suggested impaired
enzyme induction in response to stimuli in the elderly, recent research has challenged
this notion. Studies using an isolated peripheral blood monocyte model failed to
demonstrate impaired enzyme induction or decreased sensitivity to inducing stimuli
with age. Further research is needed to fully understand the relationship between ageing
and drug metabolism induction.
Ageing, Injury, and Drug Reactions: Elderly patients undergoing surgery or trauma
are particularly susceptible to adverse drug reactions, possibly due to reduced enzyme
activity. Studies have shown a marked decrease in plasma aspirin esterase activity
following hip fracture or hip replacement surgery. This decline in enzyme activity could
have significant clinical implications by affecting drug metabolism pathways.
Pharmacodynamic Variations in Geriatric Patients:
Pharmacodynamic variations in geriatrics refer to how elderly patients respond to drugs
due to age-related physiological changes, crucial for safe pharmacotherapy. Firstly,
aging alters receptor sensitivity, affecting drug-receptor interactions. For example, beta-
adrenergic receptor density in the heart and opioid receptor sensitivity in the CNS
change with age. Secondly, elderly patients may show altered responses to medications,
experiencing increased sensitivity to certain drugs like benzodiazepines and opioids,
heightening the risk of adverse reactions such as sedation and falls. Thirdly, age-related
organ dysfunction, like decreased renal and hepatic clearance, impacts drug metabolism
and elimination, necessitating dosage adjustments to prevent toxicity, especially for
renally excreted drugs like digoxin and lithium. Moreover, aging can disrupt
homeostatic mechanisms, increasing susceptibility to orthostatic hypotension and
electrolyte imbalances, affecting drug responses, notably with antihypertensives and
diuretics. Additionally, polypharmacy in older adults raises the risk of drug interactions,
which can result in additive, synergistic, or antagonistic effects, particularly concerning
medications with narrow therapeutic indices like warfarin and digoxin. Lastly,
neurological changes in aging, such as alterations in neurotransmitter levels and
neuronal function, affect drug responses in the CNS, influencing the efficacy and
tolerability of psychiatric and neurological medications. Understanding these variations
is critical for optimizing pharmacotherapy in older adults.
ADRs in geriatrics
Medications arguably stand out as the foremost technological advancement in
healthcare, particularly in safeguarding the geriatric population against illness,
disability, and premature death. With advancing age, alterations in drug metabolism and
pharmacological responses carry substantial clinical ramifications, accentuating the
likelihood of medication-related complications amidst heightened medication usage.
The correlation between escalating medication utilization, notably prescription drugs,
and the elderly demographic is firmly established. Predominantly, adverse drug
reactions (ADRs) leading to hospital admission or occurring during hospitalization
manifest as type A reactions, comprising approximately 80% of cases. Although less
prevalent among the elderly, type B ADRs can provoke severe toxicity in certain
instances. Research has underscored the intrinsic link between advancing age and
heightened ADR incidence, attributable to the intertwined influence of age and
polypharmacy compounded by age-induced changes in pharmacodynamics and
pharmacokinetics across specific medical conditions.
Implications and Strategies
In some scenarios, the combined administration of drugs may precipitate synergistic
toxicity, surpassing the cumulative risk of toxicity associated with each agent used
independently. Regrettably, prevailing international policy responses, particularly in
regions like India grappling with burgeoning elderly populations and chronic ailments,
have not accorded due emphasis to strategies aimed at enhancing ADR detection and
management. There exists a pressing need for comprehensive epidemiological
investigations encompassing substantial cohorts of elderly medication users to furnish
insights into the frequency and economic impact of ADRs. Such insights are pivotal in
fostering judicious therapeutic decision-making among individual clinicians and
formulating more efficacious social policies geared towards optimizing healthcare
outcomes.
How to minimize the ADRS in geriatrics
Strategies to Mitigate Adverse Drug Reactions (ADRs) in Older Adults
Role of Prescribers
1. Comprehensive Patient Examination:
Conduct thorough assessments, considering both symptoms and underlying conditions,
to discern adverse drug reactions from disease progression.
2. Complete Medication Record
Maintain comprehensive records of all medications, including non-pharmacological
agents, to mitigate drug interactions and polypharmacy risks.
3. Benefit-Risk Assessment:
Evaluate medication prescriptions based on individual patient benefits and risks to
minimize unnecessary medication use and associated adverse events.
4. Dose Adjustment:
Adjust drug dosages for renal impairment in elderly patients to mitigate adverse
reactions, considering age-related declines in renal function.
5. Avoidance of Inappropriate Medications:
Utilize tools like the Beers criteria and STOPP criteria to prevent unnecessary
medication use and reduce adverse drug reactions, while also addressing underuse of
essential medications.
6. Initiate Treatment with Low Doses:
Begin drug therapy at lower doses and gradually titrate based on patient response to
minimize adverse effects, particularly in the context of altered pharmacodynamic
responses in the elderly.
7. Optimized Drug Frequency and Timing:
Consider chronotherapy and optimal dosing schedules to align drug administration with
biological rhythms and reduce the incidence of adverse drug reactions.
8. Management of Drug Interactions:
Vigilantly assess for potential drug-drug, drug-disease, and drug-food interactions,
selecting alternative medications to minimize adverse outcomes associated with
polypharmacy.
9. Economic Considerations:
Recommend cost-effective medication options to enhance treatment adherence and
reduce the economic burden on elderly patients.
10. Patient Education:
Educate patients and caregivers about medication effects, potential adverse reactions,
adherence strategies, and the importance of timely communication with healthcare
providers.

Role of Patients/Caregivers
1. Understanding Medications:
Ensure comprehension of medication effects, administration timing, and dietary
restrictions to facilitate proactive communication with healthcare providers.
2. Improving Adherence:
Employ strategies such as pill organizers, alarms, and reminders to enhance medication
adherence and reduce errors in administration.
3. Monitoring Over-the-Counter (OTC) Medications:
Maintain awareness of all medications, including OTC, herbal, and supplemental
remedies, to prevent potential interactions and adverse effects.
4. Regular Medication Record Updates:
Regularly update medication lists and provide them during healthcare visits to
streamline treatment and eliminate unnecessary medications.

Polypharmacy
Understanding the Impact of Polypharmacy in Aging Populations

Global Aging Trends and Polypharmacy: The demographic shift towards an aging
population poses significant healthcare challenges globally. With increasing age,
individuals are more prone to chronic diseases, necessitating the use of multiple
medications, a phenomenon known as polypharmacy. This trend is particularly
pronounced in low- and middle-income countries, where rapid rates of aging are
observed.
Risks Associated with Polypharmacy: Polypharmacy amplifies the risk of adverse
drug reactions (ADRs) in older adults due to age-related metabolic changes and
reduced drug clearance. Additionally, the likelihood of drug-drug interactions escalates
with the use of multiple medications, contributing to further complications such as hip
fractures and prescribing cascades.

Recognizing Symptoms and Challenges: Symptoms of polypharmacy often mimic

typical signs of aging, making it challenging to differentiate between medication-
related effects and natural aging processes. Common symptoms include fatigue,
constipation, confusion, falls, and depression, among others.
Impact on Oral Health: Polypharmacy can also adversely affect oral health,
commonly resulting in dry mouth syndrome (xerostomia). Medications associated with
dry mouth include cardiovascular drugs, antidepressants, sedatives, and antacids,
among others.
Evaluating and Addressing Polypharmacy: Effective management of polypharmacy
necessitates comprehensive medication reviews and risk assessments conducted by
interdisciplinary teams. Various tools, such as Assess Review Minimize Optimize
Reassess and Screening Tools for Inappropriate Prescriptions, aid in identifying and
minimizing polypharmacy-related risks.
Strategies to Mitigate Polypharmacy: Regular monthly evaluations of medication
regimes, prescribing single agents instead of multiple drugs whenever feasible,
initiating medications at lower dosages, and discontinuing unnecessary medications are
essential strategies to mitigate polypharmacy risks. Additionally, substituting safer
drugs for high-risk medications and eliminating redundant prescriptions from different
healthcare providers can optimize treatment outcomes and improve quality of life for
elderly patients.
Conclusion: Vigilant evaluation and management of polypharmacy are crucial for
enhancing healthcare outcomes and quality of life in aging populations. Regular
medication reviews and adherence to evidence-based prescribing practices are essential
to mitigate the adverse effects associated with polypharmacy and promote optimal
aging.
Appropriate prescribing in geriatrics
Strategies to Reduce Inappropriate Prescribing in Older Adults
Good Prescribing Practices
• Conduct regular medication reviews and involve patients in decision-making
regarding medication changes.
• Cease any medications that lack clear indications and prescribe new drugs
judiciously.
• Avoid medications known to have deleterious effects in older adults, such as
benzodiazepines, and adjust dosages appropriately.
• Opt for simple drug regimens and consider once-daily or once-weekly formulations
when feasible.
• Utilize non-pharmacological treatments when suitable and limit the number of
prescribers for each patient.
Medication Review
• Implement regular medication reviews, especially for patients on four or more
medications, to ensure appropriateness and detect new conditions.
• Refer older adults with complex medication needs for specialist review by a
geriatrician.

Pharmacist Involvement
• Explore pharmacist-led interventions, although evidence is limited, to potentially
enhance concordance and reduce adverse outcomes.
• Engage community pharmacists in spotting adverse drug reactions, interactions, and
concordance issues.
Minimizing Prescribers
• Encourage communication between primary and secondary care to minimize
unintentional discrepancies in medication.
• Reduce the number of prescribers involved in a patient's care to mitigate the
incidence of adverse drug reactions.
Education
• Utilize educational outreach visits to modify prescribing behavior among healthcare
professionals.
• Consider the impact of practice size on the effectiveness of educational
interventions.
Electronic Prescribing
• Implement electronic prescribing systems to reduce errors and enhance
communication between healthcare providers.
• Provide necessary support to patients to facilitate the adoption of electronic
 prescribing.
Audit and Feedback
• Develop prescribing quality indicators tailored to older patients to provide immediate
feedback and facilitate continuous improvement.
• Utilize quantitative, qualitative, and evidence-based indicators to assess prescribing
quality and identify areas for improvement.
sebaceous glands, resulting in dryness and itchiness of the skin, especially in older
women after menopause.
Criteria used in Geriatric Pharmacotherapy:
Beer’s Criteria:
The Beers Criteria for Potentially Inappropriate Medications (PIMs) used in older
adults serves as a reference list for healthcare providers when prescribing medications
for individuals aged 65 and above. It is a tool used to ensure safe medication practices,
aligning with the principle of "do no harm." Updated by the American Geriatrics
Society every three years. [1]
The Beers Criteria, also known as the Beers list, was initially conceived in 1991 by the
late Dr. Mark Beers, a renowned geriatrician. It identifies medications that may cause
adverse drug events in older adults due to their pharmacological properties and the
physiological changes associated with aging. In 2011, the AGS started an update of the
criteria, comprising a team of experts and funding the development of the AGS 2012
Beers Criteria using an enhanced, evidence-based methodology.
Objectives: The aim of the AGS Beers Criteria is threefold: (1) to minimize older
adults' exposure to potentially inappropriate medications (PIMs) by enhancing
medication selection; (2) to provide education for both clinicians and patients; and (3)
to function as a tool for assessing the quality of care, cost-effectiveness, and medication
utilization trends in the older adult population.[2]
Major Divisions: The Beers Criteria comprises five sections delineating:
1. Medications unsuitable for individuals over 65 years old and not in hospice or
palliative care.
2. Medications to be avoided for individuals with specific health conditions.
3. Medications to be avoided due to potential drug interactions with other
medications.
4. Medications to avoid because their adverse effects outweigh the benefits.
5. Medications to be cautiously administered at reduced doses or avoided
altogether due to their impact on kidney function (renal impairment).

Methodology:
Study Design:
A cross-sectional observational study was conducted during September 2023 to March
2024 on 256 elderly patients with 65 years of age and above. Data was collected from
various hospitals of Haripur, Abbottabad and Mansehra region which were as under:
▪ District head quarter hospital (DHQ) Haripur, K.P.K Pakistan.
▪ Abbottabad medical complex (AMC) and Ayub teaching hospital Abbottabad,
K.P.K Pakistan.
▪ King Abdullah Teaching Hospital Mansehra K.P.K Pakistan.
Inclusion criteria
1. Patients who are 65 years of age or older are enrolled in this study.
2. Patients who were hospitalized between September 2023 to March 2024 are
included in this report.
Exclusion criteria
1. Patients who died during collection of data.
Sample size and data collection:
Data was collected by reviewing the case profile of 256 elderly patients who were
hospitalized or discharged during the study period. Data obtained from the patient
medical records consisted mainly of the following information.
▪ Personal information
▪ Patient's identification & demographics information
▪ Presenting main complaints
 ▪ Past medical history
▪ Family history
▪ Personal history
▪ Medication history
▪ Laboratory data
▪ Diagnosis/impression
▪ Medication before admission
▪ Medication in hospital
▪ Assessment of Drug/drug interactions
▪ Assessment of drug/food interaction
▪ Drug related problems and recommendation.
Identification of PIMs
All the medications for PIMs were assessed by all the project group students using the
Beer's Criteria 2023.
The medications in the record listed in the Beer's Criteria were PIMs according to the
major divisions of the criteria, which include the following:
Category A: Potentially inappropriate medications used in older adults.
Category B: Potentially inappropriate medications used in older adults due to drug
disease or drug-syndrome interactions that may exacerbate the disease or syndrome.
Category C: Potentially inappropriate medications; Drugs to be used with caution in
older adults.
Category D: Potentially inappropriate medications; Clinically important drug-drug
interactions that should be avoided in older adults.
Category E: Potentially inappropriate medications, that should be avoided or have their
dosage reduced with varying levels of kidney function in older adults.
3.6 Statistical analysis
The data collected were entered in Microsoft Office Excel 365 and analyzed using
Statistical Package for the Social Sciences (SPSS) statistical software (version 20, IBM,
SPSS). The methods used to analyze the data include an analysis of descriptive
statistical variables such as frequency and percentages whereas chi-squire test was used
for statistical analysis of categorical variables.