Pharmacology Considerations

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					Pharmacology Considerations in
         the Elderly
Common Concerns with the use
       of Medications

       Roger Hefflinger, Pharm.D.
            Associate Professor
          Idaho State University
           College of Pharmacy
   Family Medicine Residency of Idaho
                 Disclosure
• I have no fiscal connections to disclose with
  any of the manufactures of medications
  discussed during this presentation
                  Objectives:
• Upon completion of this presentation the
  audience member shall be expected to:
  – Recognize changes in the elderly that may
    contribute to medication adverse events
  – Identify classes of medications that are more likely
    to have adverse events in the elderly
  – Organize therapy plans for appropriate
    management of various disease states in the
    elderly
  – Modify existing therapy plans for more effective
    and potentially safer disease state management
                 The “Life-Span”
• Fetal Development      • Puberty
    – First Trimester    • Adult
    – Second Trimester      – Organ System Failure
    – Third Trimester          • Renal
•   Gestational Issues         • Liver

•   Perinatal Issues     • Geriatrics
•   Infant               • End of Life
                            – Hospice Care
•   Toddler
•   Adolescent
                            Epidemiology
• 40 million adults aged 65 and older in
  the US today.
• By 2030 expected to rise to 72 million.
• Direct medical costs of medication
  related issues in the U.S. is 104.2 billion
• 28% of hospitalizations among elderly
  are due to adverse drug events.
• Elderly 65-69 take on average 14
  prescriptions a year.
• Elderly 80 and older take on average 18
  prescriptions a year.
• ADEs are the 5th leading cause of death
  in the US.
      What Factors Most Affected
• Pharmacokinetics of Medications:
• Dissolution
   – Stomach acid, motility, affect product delivery
• Absorption
   – Stomach acid inc/dec effect, concurrent medications
• First Pass Metabolism
   – Genetic inc/dec, enzyme inducers, enzyme inhibitors
• Distribution
   – Protein binding, albumin stores, fat stores
• Elimination
   – Gut, liver, renal function
      What are realistic goals of
      medication administration
• Stop the disease process
  – Cancer chemotherapy, Antibiotics
• Slow the progression of the disease
  – High blood pressure, Diabetes, Depression
• Minimize the symptoms of the disease
  – COPD, Pain,
• Minimum amount of side effects
• In the most cost effective manner
       Pharmacy Related Issues
• Drug names:
  – Every medication has a Generic and Trade Name
  – Example:
     • Acetaminophen = Tylenol®
     • Fluoxetine = Prozac®
     • Alprazolam = Xanax®
• Barriers to Elderly Access:
  – Cost (Medicare Part D)
  – Side Effects
         What is “Acceptable Risk”
• Food and Drug              •   Side Effects:
  Administration             •   Pick an organ system
                             •   Central Nervous System
•   Phase 1 drug trials      •   Cardiovascular System
•   Phase 2 drug trials          – Heart, Blood vessels
•   Phase 3 drug trials      •   Respiratory System
•   Drug approval            •   Hepatic (Liver)
•   Drug release             •   Renal (Kidney)
•   Post marketing adverse   •   Gastrointestinal
    event reporting          •   Skin
                             •   Bone Marrow
           Central Nervous System
•   Drowsiness        • Elderly:
•   Dizziness            – Altered sleep patterns
•   Ringing in ears      – More easily sedated
                         – More likely to get
•   Confusion              dizziness
•   Depression              • Underlying vertigo
•   Psychosis            – Changes in brain wire
                           chemistry as age
                         – Decrease in brain mass
                           as age
                            • Cerebral atrophy
                 CNS Depression
           Meta Analysis prevalence >50
• Dimensional Depression:                                            • Also concurrent
    – 19.47%                                                           depression:
• Lifetime Major Dep:                                                       – Worsens outcomes
                                                                                   • Heart Attack
    – 16.52%
                                                                                   • Heart Failure
• Lifetime Alcohol:                                                                • Orthopedic hospital
    – 11.17%                                                                               – Longer length stay
                                                                                           – Higher pain scores
                                                                                   • Pain syndromes
  Volkert, J., Schulz, H., H¨arter, M., Wlodarczyk, O., Andreas,
  S., The prevalence of mental disorders in older people in Western countries - a metaanalysis,
  Ageing Research Reviews (2010),
        Depression Treatment Options:
• Selective Serotonin
  Uptake Inhibitors SSRI
   –   Fluoxetine Prozac
   –   Sertraline Zoloft
   –   Citalopram Celexa
   –   Escitalopram Lexapro
   –   Paroxetine Paxil
• Serotonin
  Norepinephrine RI
   – Venlafaxime Effexor
   – Duloxetine Cymbalta
   – Desvenlafaxime Pristiq
Central Nervous System Sleep
              • One of most common
                complaints of elderly
              • Sleep Hygiene
              • Difficulty Falling Asleep:
                 –   Hypnotic medications
                 –   Zolopidem Ambien®
                 –   Eszopiclone Lunesta®
                 –   Zaliplon Sonata®
              • Staying Asleep:
                 – Trazodone Desyre®l
                 – TCA’s- Many
         Elderly Cognitive Disorders
• Dementia:              • Delirium:
• Chronic age associated • Acute confusional state
  cognitive decline      • 10-30% hospitalized elderly
   – 5%- 70-80           • Usually secondary to
   – 37% - >90
                              –   Urinary tract infection
• RX-                         –   Stroke
• Cholinesterase Inhibitors   –   Myocardial infarction
   – Donepezil Aricept®       –   Renal Failure
   – Rivastigmine Exelon®     –   Electrolyte abnormality
• NMDA Antagonists      • Worsens outcomes
   – Memantine Namenda® • Lengthens Hosp Stay
              Elderly Psychosis
• Symptoms:            • Treatment: Dopamine
                         Blocking Medications
                       • Old:
                         – Haloperidol Haldol®
                       • Newer:
                         –   Olanzapine Zyprexa®
                         –   Risperedone Risperdal®
                         –   Quetiapine Seroquel®
                         –   Aripirazole Abilify®
                         –   And many others
           Parkinson’s Disease
• Disease that is a functional decline in the
  balance between 2 nervous system
  transmitters- Dopamine and Acetylcholine
               Presenting Symptoms:
• Initial:                         • Bradykinesia:
   – Aches, pains, parasthesias,      – Slowing of movements
     numbness coldness                – Hypokinesia
• Classic:                               • decreased ability to move
                                      – Masked Facies
• Temor:
                                      – Emotionless
   – Pill rolling, thumb finger,
     feet                             – Walking difficulties
   – At rest                       • Ridgidity:
   – Stress makes worse               – Cog wheeling
   – Usually initial presenting       – Coordination difficulties
     symptoms                         – Walking difficulties
    Options of Medication Management:
•   1. Replace the deficient chemical
•   2. Normalize relative imbalance of chemicals
•   3. Stimulate the receptor
•   4. Stop the normal breakdown of the chemical
•   5. Stimulate the release remaining chemicals
•   6. Increase the numbers or sensitivity of
    remaining receptors
         Therapy for Parkinson’s
• Anticholiniergics:         • Increase Dopamine
   – Diphenhydramine           – Carbidopa/Levodopa
     Benadryl®                    • Sinemet®
   – Trihexylphenadyl          – Stimulate DA receptor
     Artane®                      • Amantadine
   – Benztropine Cogentin®        • Pramipaxole Mirapex®
                                  • Ropinerole Requip®
                               – Stop the breakdown
                                  •   Selegiline Eldepryl®
                                  •   Rasagaline Azilect®
                                  •   Tolcalpone Tasmar®
                                  •   Entacapone Comtan®
                               – Combinations of above
           Cardiovascular System
•   Heart block           • Elderly more likely to:
•   Arrhythmias              – Have more medications
                               that can become
•   High blood pressure        additive in CV SE
•   Low blood pressure       – Heart becomes more
•   Angina                     sensitive to ischemia
•   Heart Failure            – Beta receptors decrease
                               in elderly
•   Edema                       • Altered sympathetic
                                  nervous system tone
High Blood Pressure = Hypertension
• Elderly more likely to have hardening of
  vascular walls = Hypertension
• All Lifestyle modifications and medications
  attempt to lower blood pressures =
  – Decrease risk of heart failure
  – Decrease risk of stroke
  – Decrease risk of renal failure


• Medications slow the progression of the
  disease process
     Endothelial Smooth Muscle
• Sight for Pathology
            Based on the Above:
           Pharmacologic Targets
• Relax the vasculature   • Prevent “white clot”
• Prevent and reverse       formation
  fatty plaque            • Control inflammatory
                            overlay
     “The Brain Quests to Classify and
          Organize Information”
• Adrenergics:                  • RAAS:
   – Beta Blockers                  –   ACE
   – Alpha/Beta Blocker             –   ARB
   – Alpha1 Antagonists             –   Renin Antagonist
   – Alpha 2 Agonists               –   Aldosterone antagonists
• Calcium Channel Modulators:   • Vasodilators:
   – Dihydropyridine                –   Hydralazine-
   – Non- Dihydropyridine           –   Minoxidil
• Diuretics:                        –   Nitrates
   – Thiazide                       –   Combo
   – Thiazide Like                  –   Miscellaneous
   – Loops
   – Potassium Sparing
                                 “What are the factors that influence
   – Aldosterone antagonists
                                 your selection of one drug within a
                                 class over another drug within a class-
                                 ?”- rgh
             Respiratory System
• Shortness of breath     • Elderly more likely to:
• Pulmonary scaring          – Have either long
   – Pulmonary fibrosis        standing asthma or if
                               smoking history COPD
                             – May also have anemia
                                • Decrease in red blood
                                  cells = carry oxygen
                                  around the body
                                • More sensitive to
                                  decrease in oxygen drops
   Sorry: Smoking always decreases FEV1




Fletcher et al. Br Med J 1977;1:1645-1648
Prevalence:
• Remember P-Col
• “Quick Relief
  Medications:
  – Beta-agonists
  – Anticholinergics
• “Long Term Control”
  –   Steroids
  –   Long acting B-agonists
  –   Theophylline
  –   Leukotriene agents
  Elderly Respiratory Pneumonias
• Bacterial:                • Viral:
   – Streptococcus          • Influenza Virus:
   – H. Influenza           • PREVENTION:
   – Atypical pathogen         – Fluvirin®, HP®
• Elderly patients more
  likely to have
  respiratory decline
• More symptoms
• More Hospitalizations     • Treatment:
• Lots antibiotic options   • Worse outcomes in
                              elderly
   Altered Organ System Function
• Liver dysfunction           • Renal dysfunction
   – Much more to follow      • It is a normal part of
                                aging to have a gradual
• Long standing alcohol         decline in the kidneys
  may affect livers ability     ability to filter and
  to metabolize and clear       excrete
  medications                 • Many drugs are
                                eliminated in the urine
                              • Many drugs affect the
                                ability to urinate
          Gastrointestinal System
•   Nausea                 • Elderly more likely to:
•   Vomiting                  – Have less protective
                                mucus in stomach
•   Diarrhea                     • More sensitivity to
•   Constipation                   medications

•   Abdominal Cramping        – Less nerve innervation of
                                the intestinal tract
•   Peptic ulcer disease         • = more diarrhea or more
                                   common more
                                   constipation
                              – More SE if on
                                medications and get viral
                                infections
              Adult Medicine
• All medications are formulated for effective
  dosing in the “Normal” adult population
• Very general rule- Lower tablet strengths
  availability is/are generally acceptable starting
  dose for desired action
  – Citalopram: 10,20, 40 mg- 10 mg HS good start
  – HCTZ: 12.5, 25, 50 mg- 12.5 mg q d good start
        At what individual risk?
• Every patient has the right to refuse a
  medication if they feel the risk is too great

• Back to goals of therapy
  – If you are going to refuse all medications that are
    offered – why are you here?- rgh
Example Package Insert
                      Adult Medicine
• Drugs with a “Narrow Therapeutic Window”
  deserve to be monitored.
  – Digoxin Lanoxin
  – Levothyroxine Synthroid, Levoxyl
  – Warfarin Coumadin
  – Sodium channel blocker for seizure disorder
     • Enzyme inducers and inhibitors- look for interactions!
        – Birth Control lose of efficacy
     • Monitor for established drug levels
     • For Bipolar?, Migraine?, Depression?, Psychosis?
Adult Medicine Drug Interactions
Substrates- metabolized this route
Adult Medicine Drug Interactions
 Inhibitors- Stop the metabolism
   Adult Medicine Hepatic Impairment
• You need to destroy 95% of your hepatocyte
  function before you start to lose medication
  clearing ability
• Transaminitis:
  – AST/ALT elevations- Most drugs with transiently
    elevate
• Liver Function-
  – INR- synthetic marker of clotting factor production
     • Auto anticoagulated- other drugs contribute bleed risk?
  – Albumin- synthetic
     • Alter distribution of protein bound medications
   Potentially Clinically Significant
• Benzodiazepines for etoh withdrawal
                                    Short Acting:
                                    Lorazepam
                                              Ativan
                                    Oxazepam
                                              Serax
                                    Alprazolam
                                              Xanax
 Adult Medicine Renal Impairment

• Cockcroft and Gault
• “Normal” GFR                 Metformin
                               Contraindication:
  – 100-130                    SrCr > 1.5 men
                               SrCr> 1.4 Women
• “Obligated to look GFR”      CrCl <60

  – 60
• “Most drugs need GFR dosing adjustment”
  – 30
• “Most All drugs need renal dosing”
  – 15
        Adult Medicine Significant
               Interactions
• Lithium                         • MAO-Inhibitors
   – Very effective under         • Parkinsons
     used                            – Selegiline Eldepryl®
   – Short yet significant list      – Transdermal Emsam®
• NSAIDs                             – Rasagiline Azilect®
• Diuretics                       • REFRACTORY Depression
• ACEs, ARBs,                        – Parnate®
                                     – Nardil®
• Lithium toxicity may be            – Marplan®
  fatal                           • Anti- MRSA antibiotic
                                     – Linezolid Zyvox®
                 Elderly Medicine
• Lean mass declines            • Gastrointestinal PH
   – Sarcopenia, decrease         changes
     strength, mass                –   B-12 deficiency
   – Andropause?                   –   Folate deficiency
      • Androgen replacement
        therapy males?             –   Iron deficiency
                                   –   Drug induced?
• Fat deposits increase
                                        • PPI
   – Alterations of fat
     deposited medications      • Albumin decreases
      • Lipophilicity              – Less protein binding
      • Altered loading doses      – More free drug = toxicity
                                • Less balance
                                   – Falls- drug induced dizzy
     Elderly Medicine Beers List
• http://www.fmda.org/beers.pdf
• Comprehensive list of every medication that
  may cause ADR in elderly patients
“Collective Overconsumption”- rgh
• 2 Distinct different phenomenon
• #1- “Tipping over the edge”
  – Poly-pharmacy and the latest dosage change of
    medication addition causes the patient adverse
    events
  – Make small dosing changes and only 1 drug
    change at a time
• #2- “Oh my goodness- Loved one is on TOO
  MANY medications”
  – When you break it down individually- they are not
                Elderly Medicine
• Fixed income concerns:
• If you get a sample from your provider- it is
  not inexpensive
  – Co-pay waivers
  – Actual costs health plan
• What disease can you not manage
  generically?
• Price matching education
  – Every chain will price match if the PATIENT asks
  – Does not work if they have insurance
     • Less than co-pay?
   Elderly Medicine: Bone Health
• Bisphosphonates                    • Women are 4 times
  – Alendronate                        more likely to develop
     • Fosamax PO                      osteoporosis than men
  – Abandronate                          – 77% of women who are
     • Boniva PO                           osteoporotic are
  – Risedronate                            undiagnosed
     • Actonel PO                    • 1 in 3 women will
  – Zoledronic Acid                    develop a fracture
     • Reclast IV
                                     • 1 in 8 men will develop
                                       a fracture
                Don’t forget the Calcium 1500 mg a day
                And the Vitamin D- 400-800 units a day!
  Elderly Medicine Arthritis = Pain
• Osteoarthritis           • Rheumatoid Arthritis
   – Wear and tear         • Inflammatory disorder
   – Knees, Hips, Feet       characterized by the body
• Decrease in the            attacking itself and eating
  “softness of the           up the meniscus, cartilage,
  meniscus” resulting in     and eventually bone
  thinning, tearing of     • Treatment:
  tissue                      – Analgesics
• Treatment:                  – Disease Modifying Agents
   – Analgesics               – Immune modulating agents
  How do we measure efficacy?




• Drug A “Better” than Drug B
• TOPAR
   – “Total Pain Reduction” 4 hours, 8 hours, 12 hours
 How do we measure functionality
• Range of motion          • Specific disease state
  – With or without pain     assessments
                              –   RA
                              –   Osteoarthritis
                              –   Back Pain
                              –   Neuropathic
                           • Quality of Life
            First Line Therapy:
• Acetaminophen        •   Hepatic Toxin
• = Tylenol®           •   NMT 4 grams total/day
• Scheduled improves   •   Blood Pressure?
  pain                 •   Drinker > 3 a day
• Does not relieve         – NMT 2 grams a day
  swelling
                       • Overdose
• Propionic Acid       •   Indene acetic acid
                                                         • Fenamates:
                            – Sulindac
   – Ibuprofen                                              – Mefanamic Acid
                                 • Clinoril
      • Motrin et al                                           • Ponstel
                       •   Indole acetic acid
   – Fenprofen                                              – Meclofenamate
                            – Indomethacin
      • Nalfon                                                 • Meclomen
                                 • Indocin
   – Ketoprofen                                          • Oxicams:
                       •   Pyrole acetic acid
      • Orudis                                              – Piroxicam
                            – Tolmentin
      • Oruvail
                                 • Tolectin                    • Feldane
   – Naproxen HCL                                           – Meloxicam Mobic
      • Naprosyn       •   Phenylacetic acids
                            – Diclofenac Sodium          • Pyranocarboxylics
      • EC Naprosyn
                                 • Voltaren, Arthrotec      – Etodolac
   – Naproxen Sodium
                            – Diclofenac Potassium             • Lodine
      • Anaprox RR
                                 • Cataflam                    • Etodolac XR
      • Naprelen SR
                       •   Miscellaneous
                                                         • Napthylakanones:
   – Flurbiprofen           – Ketorolac Toradol
      • Ansaid                                              – Nabumetone
   – Oxaprosin Daypro                                          • Relafen
         COX-2 Inhibitors Pain
• Rofecoxib: Vioxx®          • Meloxicam: Mobic®
   – Osteoarthritis:            – Osteoarthritis:
      • 12.5-25 mg q day            • 7.5-15 mg q day
   – Acute Pain:                – Is it selective?
      • 25-50 mg q day
      • > Celecoxib
      • = to Ibuprofen
                             • Valdicoxib Bextra®
                                – 10 mg
• Celecoxib:   Celebrex®
                                – 20 mg
   – Osteoarthritis:
      • 100-200 mg q day
   – Rheumatoid Arthritis:
      • 100-200 BID
      • (400 BID)
     Additional Options of Analgesia
• Acetaminophen = Tylenol    • Tramadol
• NSAIDS:                      – Tramadol plus APAP
   – Cox-1 vs Cox-2          • Muscle Relaxants:
• Steroids:                  • Topical agents
• Opioids                      – Caine anesthetics
   – C-II law                  – Capsacian
• Opioids plus APAP            – Menthol Camphor
   – Dozens                  • Adjunctive
   – Increase Usage            medications
• Opioids plus NSAIDS          – Anti-depressants
                               – Membrane Stabilizers
   – Empirin®, Vicoprofen®
Opioids
in Elderly:
Opioid Side
Effects
All not just
Elderly
            End of Life Issues
• Can the elderly make decisions for
  themselves?
• Power of attorney

• TALK about it BEFORE elderly is very sick
• Get ALL family members on the same page
            Hospice Concerns
• Die with dignity
• Treat pain appropriately
• Morphine High dose
  – Morphine 3 Glucuronide is INACTIVE
     • 95% of MSO4 metabolite
  – Morphine 6 Glucuronide is ACTIVE
  – M3G ANTAGONIZES M6G and MSO4
• May be worth you while to switch to another
  phenanthrene opioid
             Hospice Concerns
• “The death rattles”
  – Air hunger
  – Inhaled morphine effective
  – Injectable and oral opioids effective
• Constipation
  – Softeners at minimum, senna, stimulates, Mirilax®
• Hypersecretions:
  – Glycopyralate Robinul®
     • 1-2 mg PO TID-QID, IM or IV 0.1 mg Q 3-4 hours
         Summary The “Life-Span”
• Fetal Development      • Puberty
    – First Trimester    • Adult
    – Second Trimester      – Organ System Failure
    – Third Trimester          • Renal
•   Gestational Issues         • Liver

•   Perinatal Issues     • Geriatrics
•   Infant               • End of Life
                            – Hospice Care
•   Toddler
•   Adolescent
Questions?
roger@otc.isu.edu

				
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