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Stephanie M. Crist, Pharm.D., BCACP, BCGP Assistant Professor of Pharmacy Practice Clinical Pharmacist Specialist, Geriatrics St. Louis College of Pharmacy March 31, 2017 1. Learners will understand key aspects of pharmacokinetic and pharmacodynamic changes in the older adult. 2. Learners will apply key principles to case examples for appropriate geriatric prescribing practices. Preschool or Early Childhood: 3-6 years Young Old: 65-74 years Premature: gestation <36 weeks Infant (baby): 1-12 months Adolescence: 13-18 years Old Old: ≥85 years Middle Old: 75-84 years Middle Childhood: 6-12 Years Neonate: first postnatal month of life Toddler: 1-3 years Adult: >18 years Nutritional need and changes Pharmacokinetic changes Use of evidencebased medicine (EBM) Counseling and Education Pharmacodynamic changes Timing of Effect Lifestyle/prevention Ethical issues Severity of condition Morbidity and Mortality Patient/Care Partner involvement Pharmacokinetic (PK) Pharmacodynamic (PD) How the body affects the How the drug affects the drug body Absorption Drug concentration at the site Distribution of action Receptor-binding interaction and capacity Metabolism Elimination ↓ gastric emptying Longer time to take effect or little to no absorption ↓ parietal cell function Vitamin B12, calcium, and iron Changes in skin turgor Clinical effect may be small due to most drugs being absorbed passively in the small intestine AVOID fentanyl (Duragesic, Actiq®) patches, if possible, or stay at lowest dose possible Smaller volume of ↓ total body water ↑ total body fat ↓ muscle mass distribution higher concentrations of watersoluble drugs (e.g. ethanol, digoxin) Larger volumes of distribution of lipophilic drugs (e.g. diazepam) Increase in unbound ↓ albumin levels concentrations of certain drugs that are more proteinbound (e.g. warfarin, phenytoin) Phase 1 (oxidation, clearance, half-life) and/or Phase 2 (conjugation) affected Occurs with age and possibly with decreased cardiac output Care should be taken ↓ hepatic blood flow ↓ hepatic mass when prescribing meds with narrow therapeutic windows and pass through the liver (e.g. warfarin, theophylline, phenytoin) Liver function tests (AST and ALT) do NOT assess the effectiveness of drug metabolism in the older adult accurately Results in: ↓ renal elimination Prolonged half-life of drug Higher concentrations of drug metabolites As muscle mass decreases, the serum creatinine can remain “normal” despite significant glomerular filtration rate MUST adjust drugs that are excreted by the kidneys (e.g. digoxin, gentamycin, lithium, H2RAs, such as famotidine (Pepcid)), just to name a few Absorption: ↓ gastric emptying ↓ parietal cell function Distribution: ↓ total body water ↑ total body fat ↓ muscle mass ↓ albumin levels Metabolism: Phase 1 (oxidation, clearance, half-life) and/or Phase 2 (conjugation) affected ↓ hepatic blood flow ↓ hepatic mass Elimination: ↓ renal elimination CC: “I’m fine! I just tripped and fell.” HPI: Patient is an 82 year old male who resides in a local senior apartment complex. He is brought in to the emergency department via ambulance to be evaluated for a fall and confusion. He recently (10 days ago) completed a course of antibiotics for a urinary tract infection. PMH: Cataracts, COPD, GERD, HTN, CKD, STEMI (2 years ago), Osteoarthritis Allergies: NKDA SH: Married 55 years; widowed; has three adult children; retired high school teacher; (+) tobacco use in past (60 pack-year history), quit in 1999; (+) etoh use in past but not current; (-) illicit drug use; (-) caffeine use FH: Cancer, breast (sister, living); HTN, stroke (mother, deceased from stroke, 82); DM (father, deceased from MI, 74) Vaccinations: influenza (10/2016); PPSV23 (10/2010); tetanus (10/2009) Albuterol 0.09 mg/actuation, inhale two puffs every four hours as needed for shortness of breath Advair (fluticasone/salmeterol) diskus 250/50 mcg, inhale one puff every 12 hours Spiriva (tiotropium) Handihaler 18 mcg taken inhale two puffs once daily Aspirin 81 mg by mouth daily Cholecalciferol 2000 units by mouth daily Clopidogrel 75 mg by mouth daily Clonidine 0.1 mg by mouth three times daily Hydrochlorothiazide 25 mg by mouth daily Metoprolol tartrate 50 mg by mouth twice daily Omeprazole 20 mg by mouth twice daily Ranitidine 150 mg by mouth twice daily Senna 8.6 mg by mouth daily at bedtime as needed for constipation Tramadol 50 mg every four hours as needed for pain Acetaminophen 500 mg four times by mouth daily as needed for pain Labs: (3/23/17) Na 141 mEq/L K 3.8 mEq/L Cl 106 mEq/L CO2 22 mEq/L Gluc 112 mg/dL BUN 16 mg/dL Cr 1.1 mg/dL Ca 9.1 mg/dL WBC 7.5 K/mm3 Hgb 11.9 g/dL Hct 37.6% Plt 191 K/mm3 MCV 85 fL Alb 3.8 g/dL T. protein 6.5 TSH 0.827 mIU/L LDL 81 mg/dL TG 172 mg/dL T. chol 190 mg/dL Mg 1.6 mg/dL HgA1c 6.2% 25-hydroxyvitamin D 28.7 ng/mL HDL 42 mg/dL UA: cloudy urine, negative for nitrite and leukocyte esterase with no bacteria or WBC Vitals: (3/23/17) Ht 68 in Wt 80.5 kg BP 134/70 mmHg IBW 68.4 kg BMI 26.9 P 87 bpm 3-month BP avg 136/72 mmHg RR 18 T 97.7F P avg 75 bpm What is the clinical difference between GFR and CrCl? GFR = process by which the kidneys filter blood to remove excess fluid and waste products Calculated by using the MDRD (Modification of Diet in Renal Disease) Does NOT account for body mass Differentiates based on race Utilization = overall function of kidney; stage level of kidney disease CrCl = renal clearance of the substance creatinine Calculated by using Cockcroft-Gault equation Dependent on age, weight, and sex of the patient Affected by protein intake and muscle mass Utilization = dosing of medications 1. Adverse Drug Reactions (ADRs) 5-28% of acute hospital visits within the older adult population Suggested that ADRs are the most common type of medication-related problem in older adults living in nursing homes >95% of all ADRs are considered predictable and 50% are considered preventable 2. Adverse Drug Withdrawal Events (ADWEs) Clinically significant sets of signs or symptoms caused by the REMOVAL of a drug 3. Therapeutic Failure Inadequate or inappropriate drug therapy Not related to the natural progression of a disease Defined as the concomitant use of multiple drugs or the administration of more medications than are indicated clinically Number of minimum medications? Usually between more than 3-8 medications would qualify as polypharmacy Common/increasing problem of the older adult due to more agents available on the market and increased co-morbidities Can occur in as many as half of outpatient older adult patients Complications of: Steps to Avoid: ↑ medical expenses ↑ incidence of adverse drug events ↑ incidence of depression ↑ prescribing errors ↓ patient adherence ↓ social activity ↓ cognition Weigh benefit vs. risk Frequently review list of current medications Simplify regimen Suspect a medication for new symptoms Multiple providers and multiple pharmacies OTC, herbal products, dietary supplements Ask specifically about medications in a review-of-systems (ROS) fashion Defined as the wrong dose, duration, duplication, and/or drug- interaction Risk outweighs potential benefit Avoid the prescribing cascade… 1. Is there an indication for the drug? 2. Is the medication effective for the condition? 3. Is the dosage correct? 4. Are the directions correct? 5. Are the directions practical? 6. Are there clinically significant drug-drug, drug-disease, and/or drug-herbal interactions? 7. Is there unnecessary duplication with other drugs? 8. Is the duration of therapy acceptable? 9. Is this drug the least expensive alternative compared to others of equal utility? Hanlon et al. J Clin Epidemiology. 1992;45(10):1045 Beers Criteria Initially published by Dr. STOPP/START Criteria START criteria was first Mark Beers, a geriatrician in 1991 published in 2007 and STOPP in 2009 in Ireland Taken over by the American Recently updated in 2014 Geriatrics Society (last rev. in 2015) Must weigh the risks versus the benefits of all medications taken by the older adult (Version 2) Consider the dose, duration, and drug-drug, drug-disease, and drug-herbal interactions before making a recommendation to the patient or provider Any new symptom should be considered an ADE until proven otherwise A common occurrence, especially in older adults, is to treat an ADE symptom(s) with another medication to treat the symptom Sometimes, this new drug addition can cause a new symptom, which can again, trigger the addition of another medication; hence, the sequence of events is known as the “prescribing cascade” Examples: NSAID users are more likely to be on more antihypertensives Metoclopramide (Reglan®) used to treat N/V can have ADRs that mimic Parkinson disease carbidopa/levodopa added Donepezil (Aricept®) to treat Alzheimer disease neurogenic bladder is confused for incontinence bladder anticholinergic is added More medication increases the potential for ADEs (e.g. ADRs), drug interactions, polypharmacy, nonadherence, cost Defined as the omission of an indicated drug Example: A diabetic patient with proteinuria on three antihypertensive medications EXCEPT none of which is an ACEI/ARB which is indicated Increases: ADEs Disease progression Emergency department visits Intelligent non-adherence: Doses altered based on the patient’s perception of disease states/side effects (constipating medications and diet) Cost-related non-adherence: Doses rationed/split/shared to reduce cost Classic non-adherence: Doses forgotten, lost, or otherwise not taken (not using pill organizer) Hyper non-adherence: Taking more of the medication than originally prescribed (one is good so two must be better, right?; pain meds or other meds of abuse) Increases with perception of being overmedicated, especially during hospitalization or location of assistive prescribing Associated with preventable ADEs and hospital admissions Identify non-adherence (e.g. physical pill count, review refill history, finding missing pills) Drug / Drug Class Effects on other Conditions Acetylcholinesterase inhibitors Incontinence, diarrhea, paradoxical reactions Alpha-blockers (non-selective) Syncope Anticholinergics/Antimuscarincs Urinary retention, constipation, glaucoma, dementia (neurogenic bladder) Aspirin/NSAIDs GI bleed; CKD/HTN; ↓ effect of diuretic (+) heart failure = fluid retention; exacerbation Benzodiazepines (especially long-acting) Dementia/falls Bupropion Seizures Calcium channel blockers Swelling/edema; constipation Corticosteroids Diabetes Opioids Constipation Sedatives/Hypnotics Falls Adapted from DiPiro, eTable 11-8 Annual administration recommended in all adults throughout lifetime Fluzone High Dose® (Sanofi Pasteur) Patients ≥65 years old eligible to receive Greater risk of hospitalization and death due to the flu Respond to vaccination with lower antibody titers to influenza hemagglutinin compared to younger adults Contains 60µ of each vaccine antigen compared to the standard dose of 9µ of each vaccine antigen Inactivated, trivalent, standard 0.5 mL intramuscular injection *ANY product of the flu vaccine is better than NO vaccine annually Tdap: one lifetime dose, regardless of last Td administration Boostrix® (GlaxoSmithKline Biologicals) is only approved for older adults Adacel® (Sanofi Pasteur) is approved for adults 11-64 years of age ACIP recommends the use of Boostrix® in the older adult; however, if supply is not available or Adacel® is given instead, ACIP considers this immunogenic and provides protection so no need to also give Boostrix® Td: booster every 10 years recommended to be administered to all adults throughout lifetime PPSV23 (Pneumovax®) One lifetime dose for all adults after the age of ≥65 years old Some patients may have received 1 or 2 doses of PPSV23 prior to the age of 65 based on other health conditions (e.g. CKD, heart disease (CHF), chronic lung disease (asthma, COPD), diabetes, chronic liver disease (including chronic alcoholism), immunocompromising conditions Wait at least 5 years in between PPSV23 administrations If have received PPSV23, wait 12 months to administer PCV13 If have NOT received PCV13, administer PCV13, then wait at least 8 weeks to administer PPSV23 if immunocompromised, otherwise wait 12 months to administer PPSV23 PCV13 (Prevnar®) One lifetime dose for all adults after the age of ≥65 years old If never have received PPSV23, administer first If have received PPSV23, wait 12 months to administer If <65 years old, see CDC ACIP recommendations for list of conditions Never administer PCV13 and PPSV23 on the same day Live vaccine, subcutaneous injection All patients ≥60 years old who have had the chicken pox or chicken pox vaccine May administer if the patient has already had shingles to decrease likelihood of future flares; however, do NOT administer during an active shingles flare Know how to recognize orthostatic hypotension Change ≥20 mmHg drop in SBP or change of ≥10 mmHg drop in DBP when changing positions (lying to sitting or sitting to standing), or symptomatic upon standing (dizzy, lightheaded, off-balance, falling) 2014 ACC/AHA JNC 8 goals: Adults ≥60 years old, goal = <150/90 mmHg Caveat: if already treated with antihypertensive(s), treat BP to goal and SBP <140 mmHg and patient is tolerating well without ADRs or effect of quality of life, treatment does not need to be adjusted If 18-69 years old with CKD, goal = <140/90 mmHg Initial or add-on treatment should include an ACEI or ARB to improve kidney outcomes No recommendations for patient aged ≥75 years; however, ACEI or ARB will most likely be beneficial if BP can tolerate and use of a thiazide-like diuretic or CCB could also be used Monitor serum Cr and K+ and reduce dose as necessary (“little is better than none”) Diagnostic criteria for CKD does NOT consider age-related decline in kidney function If ≥18 years old with DM, goal = <140/90 mmHg Endorsed by the ADA and AGS Fasting blood glucose goal: <150-130 mg/dL but not <100 consistently due to increased risk of hypoglycemic events as this can lead to falls, decrease in quality of life, and associated ADRs Caution on consistently hyperglycemia due to infection rate, vision changes, confusion, and frequent urination Post-prandial blood glucose goal: <200 mg/dL Hemoglobin A1c goal: <7.5-8% for those with life expectancy >5 years with comorbid conditions and have had the DM for >10 years “Tight glycemic control” in the older adult is defined as <7.5% by AGS 8-9% for those with life expectancy <5 years (typically this is in nursing home/institutionalized patients) An A1c <6.5% linked to all-cause mortality and CV mortality, hypoglycemia, and weight gain Avoid: Glyburide (Diabeta®) due to prolonged hypoglycemia Chlorpropamide (Diabinese®) due to long half-life and potential for causing SIADH Sliding scale insulin regimen, especially when treated in the outpatient setting Per American Geriatrics Society 2013 Update on Improving Care of Older Adults with DM, NO longer recommends aspirin for primary prevention of CVD, including patients with DM (rationale = insufficient evidence) Regardless of age, recommends aspirin 81 mg with DM and known CVD for secondary prevention unless contraindicated (bleed risk, harms outweigh benefits), on anticoagulation or life expectancy is poor Per US Preventative Service Task Force (USPSTF April 2016) recommendations: 81 mg daily is recommended for primary prevention: In any ADULTS 50-59 years with a 10-year ASCVD risk ≥10% (grade B) http://cvdrisk.nhlbi.nih.gov/calculator.asp Must have a life expectancy of at least 10 years Patient is willing to take aspirin for at least 10 years In any ADULTS 60-69 years with a 10-year ASCVD risk >10% (grade C) Must have a life expectancy of at least 10 years Patient is willing to take aspirin for at least 10 years Adults over the age of 70 years, evidence is insufficient (grade I), especially for primary prevention, to assess the balance of benefits and harms for CV prevention and colorectal cancer Health Status A1c* Goal (%) Healthy (few comorbidities, intact cognition and functional status) <7.5 Complex/Intermediate (multiple comorbidities OR 2+ IADL impairments or mild to moderate cognitive impairment) <8 Very complex/poor health (lives in a longterm care facility, endstage chronic illnesses OR moderate to severe cognitive impairment or 2+ ADL dependencies) <8.5 Pre- and Postprandial Goal Glucose (mg/dL) Pre: 90-130 Bedtime Goal Glucose (mg/dL) Blood Pressure Goal (mmHg) <140/90 Yes, unless contraindicated or not tolerated Longer remaining life expectancy 100-180 <140/90 Yes, unless contraindicated or not tolerated Intermediate life expectancy, high treatment burden, hypoglycemia vulnerability, fall risk 110-200 <150/90 Consider likelihood of benefit (secondary prevention more than primary prevention) Limited remaining life expectancy makes benefit uncertain Post: <200 Pre: 100-180 Rationale 90-150 Post: <180 Pre: 90-150 Statin Use Post: <200 * “Tight glycemic control” in the older adult is defined as <7.5% by the American Geriatrics Society (AGS); an A1c <6.5% for targeted aggressive treatment in the older adult has been linked to all-cause mortality and CV mortality, hypoglycemia, and weight gain; per American Diabetes Association (ADA), an A1c goal >8.5% are not recommended as may expose patient to more frequent higher glucose values and acute risks from glycosuria, dehydration, hyperglycemic hyperosmolar syndrome, infection rate, confusion, vision changes, and poor wound healing Adapted from Table 11.1 in American Diabetes Association. Older Adults. Sec. 11. Standards of Medical Care in Diabetes-2017 Diabetes Care 2017;40(Suppl. 1):S99-S104. Focus more on the functional status of the patient than on the number of comorbidities At least 3 or presence of a single end-stage chronic illness Functional status = marker of overall health and quality of life as well as if a patient can independently take care of oneself The number of comorbidities can affect functional status; therefore multiple comorbidities increases the potential for a faster rate of decline in a patient The level of control of ANY comorbidity can affect how aggressive a patient may be treated Any change in status, reassessment of goals will be necessary Intact cognition = awareness to person, place, and time (AA&O x3); no functional changes in memory/ability to think and rationalize, make decisions for self If cognitive changes can be reversed, such as caused by medication(s) or substance-induced, this counts as intact cognition 2+ IADL (instrumental activities of daily living, more complex than ADLs) impairments* = patient CANNOT perform, on a consistent basis, at least TWO OR MORE of the following: Meal preparation (cannot Shopping (cannot perform Housework (cannot perform cook for self) basic grocery shopping (e.g. forgets list of items to get or buys inappropriate items that does not need) basic home maintenance (e.g. cleaning, changing a lightbulb) Laundry (cannot complete Able to use phone task of separating items, placing in washer and dryer then folding and putting away clean clothes properly) (answer a call or call someone, even 911) Managing/taking medications (e.g. poor or Transportation (cannot Keeping track of finances (cannot pay bills on time, drive self or manipulate public transportation system safely) complete taxes, managing funds/budget) no adherence) *NOT due access issues, such as not having money for food to cook, to shop, to pay bills, or for a car to drive; really focusing on a change from what the patient has been able to do in the past; not due to a physical impairment such as poor vision to drive a car 2+ ADL (activities of daily living, more basic, simple abilities) impairments = patient CANNOT perform, on a consistent basis, at least TWO OR MORE of the following: Bathing (cannot take a Dressing (cannot get Grooming (cannot perform shower or bath to clean oneself (safely or correctly) independently) dressed or undressed properly independently) tasks such as brushing teeth, shaving) Toileting (cannot go to the Transfer (cannot get self Walking (cannot bathroom by self safely or correctly; loses ability to know when to go to the bathroom) from one place to the next, such as out of bed to standing position independently) independently walk (does not include use of an assistive device, such as a walker) from point A to point B) Feeding (cannot eat food, drink liquid correctly, sufficiently, or at all independently) These inabilities to perform tasks is a change from the patient’s normal functioning level. Usually, a person will lose IADLs before they begin to lose ADLS; therefore that is why ADLs are listed; having the inability to perform with IADLs and ADLs is NOT considered a normal part of aging Mild to moderate to severe cognitive impairment = early to middle to end stages of dementia Click on the link to see examples from the Alzheimer’s Association: http://www.alz.org/alzheimers_disease_stages_of_alzheimers.asp End-stage chronic illnesses = examples include on hemodialysis for CKD, on hospice or palliative care measures, terminal cancer diagnosis Long-term care (LTC) facility = examples include a nursing home (NH), skilled nursing facility (SNF) (not necessarily for acute rehabilitation with the goal to go home), Does NOT include an independent living facility (apartment complex) specifically for older adults Could take place in a patient’s home where the patient receives 24/7 care from family and/or a nursing staff In general for statin use: If between 40 and 75 years, aim for high-intensity statin (lowers LDL by ≥50%) Atorvastatin 40-80 mg Rosuvastatin 20-40 mg Continue a statin if an adult is >75 years and tolerating it well (limited EBM) Make sure statin is appropriately renally dosed if CrCl <30 mL/min* If a patient has clinical ASCVD, use a moderate-intensity statin (lowers LDL by 30% to <50%) Atorvastatin 10-20 mg Rosuvastatin 5-10* mg Simvastatin 20-40* mg Pravastatin 40*-80 mg Lovastatin 40 mg (recommend max of 20 mg*) Fluvastatin 40 mg or 80 mg* (recommend max of 40 mg*) Pitavastatin 2*-4 mg If a patient does not have clinical ASCVD, risk may be overestimated and initiating a statin requires consideration of other risk factors such as comorbidities, safety (ADRs, drug interactions), prognosis, and patient preference Controversy: If we are no longer monitoring FLPs, how low can the LDL go? Prioritize by weighing the risks versus the benefits Change minimal amounts of medication at a time “Start low, go slow” Avoid “one pill for every ill” Avoid “newer” or more $$ medications that are NOT superior in efficacy to less expensive alternatives Check renal and hepatic function on EVERY patient at baseline and intermittently throughout therapy, especially if at risk or during changes of status Geriatric Dosage Handbook, Lexicomp American Society of Consultant Pharmacists (ASCP): http://www.medpass.com/geriatric-medication-handbook.html Geriatric Medication Handbook, 13th ed. ($21.95) American Geriatrics Society (AGS): http://www.americangeriatrics.org/health_care_professionals/clinical_practice/clin ical_guidelines_recommendations/ Geriatrics at your Fingertips by AGS Gerontological Society of America (GSA): https://www.geron.org/ Merck Manual of Geriatrics: http://www.merck.com/pubs/mm_geriatrics/contents.htm Please email: [email protected]