GERO 495 Final

changes with aging that affect pharmokinetics & pharmacodynamics

- reduction in total body water decreases volume of distribution for hydrophilic drugs

- increase in total body fat increases volume of distribution for lipophilic drugs

- drug distribution increases with age partly due to a decrease in protein binding

- decrease in total clearance

- dose adjustments in older patients required for drugs with a narrow therapeutic range

physiological changes of aging affecting medication metabolism

- decrease in liver volume and blood flow determines a reduction in metabolic reactions

- alteration in Phase 1 metabolism reduces total and free-drug clearance

- decrease in renal plasma flow

- decline in glomerular filtration rate (GFR)

- age-related prolongation in the half-life

pharmacokinetics

study of how the body interacts with administered substances for the entire duration of exposure

4 parameters examined in pharmacokinetics

- absorption

- distribution

- metabolism

- excretion

pharmacodynamics

study of a drug's molecular, biochemical, and physiologic effects or actions; interactions of drugs include receptor binding, post-receptor effects, and chemical interactions

absorption (parameters examined in pharmacokinetics)

- bioavailability; the fraction of a drug dose reaching the systemic circulation

- affects the speed and concentration at which a drug may arrive at its desired location of effect

distribution (parameters examined in pharmacokinetics)

- describes how a substance is spread throughout the body

- goal is to achieve effective drug concentration

- to be effective, a medication must reach its designated compartmental destination, described by the volume of distribution, and not be protein-bound in order to be active

- locations in the body a drug penetrates expressed as volume per weight (L/kg)

metabolism (parameters examined in pharmacokinetics)

- drug conversion to alternate compounds which may be pharmacologically active or inactive

- drugs are usually metabolized into more water-soluble substances for renal clearance

- majority of metabolism is through phase I (CYP450) and phase II (UGT) reactions in the liver

elimination/excretion (parameters examined in pharmacokinetics)

- a drug's final route(s) of exit from the body expressed in terms of half-life or clearance

- kidney plays a crucial role

factors affecting absorption

- route of administration

- food, enteral feedings

- drugs that influence gastric pH

- drugs that promote or delay GI motility

- comorbid conditions

- increased GI pH

- decreased gastric emptying

volume of distribution (Vd)

drug's propensity to either remain in the plasma or redistribute to other tissue compartments

drugs with high Vd

- has propensity to leave the plasma and enter the extravascular compartments of the body

- a higher dose of a drug is required to achieve a given plasma concentration

- high Vd --> more distribution to other tissue

drugs with low Vd

- has propensity to remain in the plasma

- a lower dose of a drug is required to achieve a given plasma concentration

- low Vd --> less distribution to other tissue

metabolic clearance of drugs by the liver may be reduced due to:

- decreased hepatic blood flow

- decreased liver size and mass

- changes in liver structure and metabolism

other factors affecting drug metabolism

- gender

- comorbid conditions

- smoking

- diet

- drug interactions

- race

effects of aging on the kidney

- decreased kidney size

- decreased renal flow

- decreased number of functional neurons

- decreased tubular secretion

- decreased drug clearance

half-life

time for serum concentration of drug to decline by 50% (expressed in hours)

clearance

- volume of serum from which the drug is removed per unit of time (mL/min or L/hr)

- reduced elimination --> drug accumulation and toxicity

consequences of overprescribing

- adverse drug events (ADEs)

- drug interactions

- duplication of drug therapy

- decreased quality of life

- unnecessary cost

- medication non-adherence

prescribing appropriately

- determine therapeutic endpoints

- consider risk vs. benefit

- avoid prescribing to treat side effect of another drug

- use 1 medication to treat 2 conditions

- consider drug-drug and drug-disease interactions

- use simplest regimen possible

- adjust doses for renal and hepatic impairment

- avoid therapeutic duplication

- use least expensive alternative

preventing polypharmacy

- review medications regularly and each time a new medication started, or dose is changed

- maintain accurate medication records (include vitamins, OTCs, and herbals)

- "brown-bag reviews"

enhancing medication adherence

- avoid newer, more expensive medications

- simplify the regiment

- utilize pill organizers or drug calendars

- educate patient on medication purpose, benefits, safety, and potential ADEs

leading cause of kidney failure in the US

diabetes and high blood pressure

risk factors for kidney disease

diabetes, high blood pressure, heart disease, family history of CKD, obesity

health consequences of CKD

anemia, increased infections, low calcium levels, high potassium levels, high phosphorous levels, loss of appetite, depression

nephron

structural and functional unit of the kidney

4 processes of the nephron

- filtration

- reabsorption

- secretion

- excretion

kidney functions

- regulation of extracellular fluid and osmolarity

- electrolyte concentrations, regulation of pH

- excretion of wastes and toxins

- filter out water-soluble waste and environmental toxins

- production of hormones (erythropoietin, renin)

- regulation of plasma calcium and glucose levels

- converts vitamin D to active form

glomerular filtration rate

- measurement of volume filtered through the glomerular capillaries and into the Bowman's capsule per unit of time

- dependent on the difference in high and low blood pressure created by the afferent (input) and efferent (output) arterioles respectively

creatinine

- breakdown product of dietary meat and creatine phosphate found in skeletal muscle

- production in the body is based on muscle mass

creatinine clearance (CrCl)

- volume of blood plasma cleared of creatinine per unit of time

- rapid and cost-effective method for measurement of renal function

aging and kidney functions

- kidney mass and size peak in the fourth decade and decline thereafter

- aging in kidney is generally characterized by a spontaneous progressive decline in renal function accompanied by histological alterations

- baseline homeostasis of fluids and electrolytes is maintained with normal aging

- impaired salt or water load or deficit

decrease in average renal blood flow

acute renal failure (ARF)

a sudden loss of kidney function caused by an illness, an injury, or a toxin that stresses the kidneys (kidney function may recover)

chronic kidney disease (CKD)

- a long and usually slow process where the kidneys lose their ability to function

- structural or functional abnormalities of the kidneys for >3 months manifested by either kidney damage or GFR < 60 ml/min/1.73 m² (with or without kidney damage)

end-stage renal disease (ESRD)

when the kidneys have completely and permanently shut down

causes of acute renal failure

1. prerenal: sudden and severe drop in blood pressure (shock) or interruption of blood flow to the kidneys from severe injury or illness

2. intrarenal: direct damage to the kidneys by inflammation, toxins, drugs, infection, or reduced blood supply

3. postrenal: sudden obstruction of urine flow due to enlarged prostate, kidney stones, bladder tumor, or injury

urinary tract infections (UTI) in older adults

- prevalence: UTI is the most common bacterial infection in older adults

- asymptomatic bacteruria: presence of bacteria in urine is often asymptomatic and regarded as colonization

- symptomatic infection: can lead to significant morbidity and, in rare cases, mortality

- management challenges: diagnostic uncertainty, concerns about excessive antimicrobial use, rising antimicrobial resistance

signs and symptoms of kidney disease

- reduced urine output

- fatigue

- nausea

- swelling in the feet

- tiredness

- poor sleep

- poor appetite

- unexplained itchiness

- puffiness of face and eyes

- shortness of breath

edema

- a sign of renal dysfunction

- puffy swelling of tissue from the accumulation of fluid

- can affect all parts of the body

- initially manifests in tissues with loose connective tissue matrix, such as the eyelids (aka periorbital edema)

prognosis of CKD

low GFR and/or high albuminuria

dementia

progressive disorder that is characterized by cognitive decline involving memory and at least 1 of the other domains:

- personality

- praxis

- abstract thinking and language

- executive functioning and complex attention

- social and visuospatial skills

*severity must be significant enough to interfere with daily functionality

Alzheimer's disease (AD)

- most common cause of dementia

- 70-80% of all cases of dementia; prevalence doubles every 5 years after 65 --> 50% of those older than 85

- main etiological components: mutation of Tau protein, abnormal production of beta amyloid

- neurodegeneration

- sporadic

- familial

vascular dementia (VD)

- accounts for 5-10% of all dementia cases

- incidence increases with age

- hypercholesteremia, diabetes mellitus, hypertension, smoking

- suspect when abrupt onset and/or stepwise decline, fluctuation course, h/o stroke, focal neurologic symptoms or signs

- often associated with executive dysfunction, gait disorder, apathy, incontinence

- usually, see bilateral infarcts

lewy body dementia (LBD)

- 5-10% of dementia

- progressive degenerative brain disorder characterized by dementia, psychosis, and features of parkinsonism

- relatively earlier occipital and basal ganglia degeneration

- similar to Parkinson disease dementia: α-synuclein and ubiquitine aggregates

- concurrent AD pathology is common

frontotemporal dementia (FTD)

- third most common cause of dementia in patients aged 65+ & second most common cause of dementia in patients less than 65 years of age

- spectrum of clinical syndromes characterized by neuronal degeneration involving the frontal and anterior temporal lobes of the brain

- strong psychiatric component

mixed dementia

- patients have more than 1 type of dementia

- AD with LBD or VD are the most common coexistent dementia

cerebrum

largest part of the brain, divided by a longitudinal fissure into 2 hemispheres

cerebral cortex

- complex association of tightly packed neurons covering the outermost portion of the brain

- it's the gray matter of the brain

- divided into 4 lobes: frontal, temporal, parietal, occipital

frontal lobe

- regulating emotions, social interactions, and personality

- critical for more difficult decisions and interactions essential for human behavior

- damage to this area may result in disinhibition and deficits in concentration, orientation, and judgement

temporal lobe

- processes sensory input into derived meanings for the appropriate retention of emotions, visual memory, and language comprehension

- primary auditory cortex

is involved in processing sound

- Wernicke's area is located in the dominant hemisphere and manages comprehension of language; a lesion affecting the superior temporal gyrus will result in receptive aphasia-- person will have trouble comprehending language but will have fluent speech that makes no sense

- medial temporal lobe consists of important neural structures, including the hippocampus

parietal lobe

- responsible for perception, sensation, and integrating sensory input with the visual system

- contains the somatosensory cortex, which received contralateral sensory information

- damage to the dominant parietal cortex leads to agraphia, acalculia, left-right disorientation

occipital lobe

- center for processing visual input in humans

- damage to a single occipital lobe can result in homonymous hemianopsia (loss of vision in half the visual field) and visual hallucinations

- bilateral damage to the primary visual cortex can cause blindness (cortical blindness)

cognitive domains

- executive function (frontal, hemispheric white matter)

- memory (frontal, hippocampus)

- attention (medial temporal lobes/hippocampus)

- language and communication (left hemisphere, usually)

- visuospatial (occipital, parietal)

mild cognitive impairment

- cognitive decline abnormal for age and education but does not interfere with function and activities

- one or more cognitive domains impaired significantly

- "at risk" state to develop a degenerative dementia

AD risk factors

- age

- mild cognitive impairment

- apolipoprotein E-e4 positivity

- family history in first-degree relative

- vascular risk (diabetes, heart disease, etc.)

- low education and physical/social activity

- female sex

AD clinical features

- earliest cognitive symptoms are poor short-term memory, anterograde amnesia, and loss of orientation

- mood disorders

- smooth, usually slow decline without dramatic short-term fluctuations

- other domains are involved with the progression of the disease

behavioral and psychiatric aspects of AD

- depression, anxiety

- irritability, hostility, apathy

- delusions, hallucinations

- sleep-wake changes

- sundowning

- agitation

FTD clinical features

- behavior and personality change (may be initially misdiagnosed as a psychiatric disorder)

- executive dysfunction

- progressive non-fluent aphasia

- may see parkinsonism or muscle weakness

treatable causes of dementia

- thyroid disease

- B12 deficiency

- untreated sleep apnea

- depression or anxiety

- alcoholism

- medicines: benzos, opioids, anticholinergics, neuroleptics, dopaminergic, and other sedatives

tests & scales to detect MCI

Montreal Cognitive Assessment (MOCA), Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB)

medications to improve cognitive functions

- cholinesterase inhibitors (donepezil, galantamine, and rivastigmine) prevent breakdown of acetylcholine

- memantine is an NMDA antagonist and decreases the activity of glutamine

treatment for behavior symptoms

antidepressants, antipsychotics, and anxiolytics

treatment of sleep symptoms

amitriptyline, lorazepam, zolpidem, temazepam, quetiapine

non-pharmacological treatments of dementia

music therapy, pet therapy, daily exercise, multicomponent cognitive behavioral therapy (CBT), etc.

homeostenosis

- reduced ability to adapt (return to homeostasis)

- caused reduced functional reserves of organs & systems + reduced efficiency of integrative systems (nervous, endocrine, and immunological)

functional reserve

- an organ or system's ability to manage increased demands beyond normal functioning, providing "extra capacity" during times of need, such as physical exertion or illness

- supports the maintenance of homeostasis despite variations and allows recovery after increased demand

- functional reserve declines with age, increasing vulnerability to health issues.

age-related changes in the cardiovascular system

- arterial wall stiffening

- increased left atrial size

- reduced left ventricular (LV) compliance

- increased myocyte size

- increased LV mass

- increased posterior wall thickness (infiltration with lipids, collagen, fat, amyloid)

age-related changes in fluid homeostasis

- reduced total body water

- blunted thirst sensation

- less drinking response

- lower renal plasma flow

- reduced ability of urine concentration

age-related changes in oral cavity

- 40% of those > 65 are edentulous, mostly because of neglect

- risk of cavities increases with age as a result of gingival recession and loss of jaw bone density

age-related changes in eyes

- presbyopia (loss of lens accommodation) due to hardening & thickening of the lens (making it opaque) and a decrease in muscle tone

- decreased visual acuity because of a narrowed pupil, fewer rods (cones spared) so poorer night vision

- need for more light to reach the retina

- problems with depth and color perception

age-related changes in respiratory system

- age-related changes resemble emphysema

- loss of elastic recoil

- early airway closure (and more dead space where you are ventilating non-perfused lung)

- decreased flow rates, FEV1, and vital capacity

- stiffer chest wall & weak muscles

- increased dead space

spirometry

procedure to measure breathing that is helpful in identifying conditions such as asthma, pulmonary fibrosis, cystic fibrosis, and COPD

age-related changes in endocrine system

- women: decreased estrogen (post-menopause) & prolactin

- men: decreased testosterone in some (andropause)

- increased insulin resistance & progressive decline in carbohydrate tolerance

- decreased aldosterone, renin, calcitonin, and GH

- slight decrease (or no change) in THs (T3, T4), PTH, and 25-hydroxy vitamin D

- cortisol alterations may be present

age-related changes in renal system

- smaller kidneys (cortical renal mass decreases ~20%)

- renal blood flow decreases

- reduction GFR (50% from age 20 to 80, little decline after 80)

age-related changes in body composition

- weight decreases, body fat increases, height decreases

- sarcopenia (up to 80% decrease in skeletal muscle mass and quality in non-active seniors)

- osteopenia (decrease in bone mass)

- total body calcium and potassium stores decrease

diagnosing geriatric patients

- illnesses present atypically and non-specifically

- illnesses cause greater morbidity and mortality

- illnesses may progress much more rapidly (delaying in diagnosis of a septic syndrome is much more likely to be fatal)

order of collecting medical history

1. general information

2. family history

3. general history, physiological functions and habits

4. past medical history

5. recent medical history

symptom

- feeling noticed by a patient, reflecting the presence of an unusual state or of a disease

- it is subjective, observed by the patient

sign

objective evidence observed by the physician during a physical examination

chief complaint

health problem for which a person goes to seek the care of a medical professional

family history

any relevant medical history from immediate family members that could contribute to the diagnosis of the current health problem

personal history

- childbirth & delivery methods (cesarian section, forceps delivery, etc.)

- breastfeeding

- menarche, period, pregnancies, menopause

- education

- marital status

- occupation/reitrement

- living arrangement

physiological functions and habits

- appetite, nutrition, alcohol intake, smoking

- amount of water/day (glasses)

- digestion

- intestinal function

- urinary function (nycturia, dysuria, etc.)

- sleep (quality, number of pillows)

vital signs

heart rate (HR), blood pressure (BP), respiratory rate (RR), oxygen saturation (SpO2), temperature (temp)

central pulse

heart and carotid; preferred pulse points used during resuscitation of adults

peripheral pulse

- upper extremities: brachial, radial

*brachial artery is often the site of evaluation during cardiopulmonary resuscitation of infants

- lower extremities: femoral, popliteal, dorsalis pedis, posterior tibialis

pulse intensity

subjectively graded on a scale of 0 to 4

- 0: nonpalpable pulse

- 1: barely detectable pulse

- 2: slightly diminished

- 3: normal pulse and should be easily palpable (full)

- 4: is "bounding" (e.g., stronger than normal)

systolic blood pressure

maximum pressure experienced in the aorta when the heart contracts and ejects blood into the aorta from the left ventricle (approx. 120 mmHg)

diastolic blood pressure

minimum pressure experienced in the aorta when the heart is relaxing before ejecting blood into the aorta from the left ventricle (approx. 80 mmHg)

measuring blood pressure using sphygmomanometer

1. when the cuff is fully inflated to this pressure, no blood flow occurs through the artery

2. as the cuff is deflated below the systolic pressure, the reduced pressure exerted on the artery allows blood to flow through it and sets up a detectable vibration in the arterial wall

3. when the cuff pressure falls below the patient's diastolic pressure, blood flows smoothly through the artery in the usual pulses, without any vibration being set up in the wall

Korotkoff sounds

pulsatile circulatory sounds heard upon auscultation of the brachial artery

phases of Korotkoff sounds

- phase I: clear tapping sounds heard for at least 2 consecutive beats (systolic blood pressure)

- phase II: the softening of the tapping sounds and the addition of a swishing sound

- phase III: the return of tapping sounds, as heard in phase I, but with an increase in sharpness and intensity

- phase IV: the abrupt muffling sounds, exhibiting of a soft and blowing quality

- phase V: the complete disappearance of all sounds (diastolic blood pressure)

2017 ACC/AHA blood pressure guidelines

- normal: less than 120/80 mm Hg

- elevated: systolic between 120-129 and diastolic less than 80

- stage 1: systolic between 130-139 or diastolic between 80-89

- stage 2: systolic at least 140 or diastolic at least 90 mm Hg

- hypertensive crisis: systolic over 180 and/or diastolic over 120

*lowered threshold for hypertension from systolic BP 140 mmHg/diastolic BP 90 mmHg and eliminate the category prehypertension

elements of physical examination

- vital signs

- heart sounds

- lung sounds

- reflexes

comprehensive geriatric assessment

- an interdisciplinary approach for the evaluation of older adults in terms of their physical and psychosocial impairments and their potential functional disabilities

- essential domains include functional status, co-morbidity, cognition, nutrition, poly-pharmacy, social support & mental status

purpose of comprehensive geriatric assessment

- prevention of decline in the independent performance of ADLs

- drives the diagnostic process and clinical decision making

- screen for preventable diseases

- screen for functional impairments that may result in physical disability and amenable to intervention

4 parts of a physical examination

1. inspection

2. palpation

3. percussion

4. auscultation

palpation

an examination technique in which the examiner's hands are used to feel the texture, size, consistency, and location of certain body parts

percussion

a diagnostic procedure designed to determine the density of a body part by the sound produced by tapping the surface with the fingers

auscultation

listening to sounds within the body