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Polypharmacy—the Pearls, the Perils, and the Pitfalls of Pharmaceuticals in the Aging Population

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Polypharmacy the Pearls, the Perils, and the Pitfalls of Pharmaceuticals in the Aging Population Barb Bancroft, RN, MSN www.barbbancroft.com August 3, 2010 Chicago ... – PowerPoint PPT presentation

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Title: Polypharmacy—the Pearls, the Perils, and the Pitfalls of Pharmaceuticals in the Aging Population


1
Polypharmacythe Pearls, the Perils, and the
Pitfalls of Pharmaceuticals in the Aging
Population
  • Barb Bancroft, RN, MSN
  • www.barbbancroft.com
  • August 3, 2010
  • Chicago IL

2
Definitions of age
  • Stratification of the older patient group into 3
    groups
  • young old 65-75
  • old75 to 85
  • old-old over 85
  • By 2020 there will be 1,000,000 centanarians in
    the U.S.

3
So, do you want to live to be 100?
  • If you live to be 100, you have it made. Very
    few people die past that age.
  • --George Burns, who died at age 100 in 1996
  • SO, IF YOU ARE 100 TODAY

4
Your life expectancy as a
  • Black Male 2.9 years
  • Black Female 3.0 year
  • White Male 2.3 years
  • White Female 2.5 years
  • If you are 60 today
  • WM 20.3
  • WF 23.6
  • BM 17.6
  • BF 21.6

5
As an FYI Life expectancy
  • If you are 40 today
  • WM37.4 years
  • WF41.6 years
  • BM32.8
  • BF38.1
  • If you are 50 today
  • WM28.5
  • WF32.4
  • BM21.0
  • BF25.4

6
Women have the age advantage at every age, except
conception and over 100 for black males
  • Why is conception the exception?

7
The sperm carrying the Y chromosome is the faster
swimmer
  • The early sperm gets the worm, so to speak
  • Why?

8
Because
  • The sperm carrying the Y chromosome is 23
    lighter than the sperm carrying the X chromosome
  • Hence, the Y-carrying sperm weighs less and
    therefore is a faster swimmer
  • And, ladies

9
Polypharmacy
  • Most info on pharmacokinetics and
    pharmacodynamics has been developed for the
    young-old (65 to 75) and old (75 to 85)very
    little info for the old-old(older than 85)
  • The effectiveness of drug therapy for many
    disease processes in the older patient is as
    great as it is for the younger patient population

10
The biggest problem poly-conditions
poly-pharmacy
  • The average older adult has 6.5 chronic
    conditions, and multidrug therapy is the rule
    rather than the exception to the rule
    (Zurakowski)
  • Usually an average of 1 to 3 drugs given per
    conditionYOU DO THE MATH

11
For example
  • 72-year old male with diabetes, hypertension,
    hypercholesterolemia, erectile dysfunction,
    benign prostatic hypertrophy, glaucoma,
    osteoarthritis, peripheral artery disease, and
    depression
  • Lets do the mathhow many drugs for diabetes? 1
    to 4 Hypertension? 2 to 3 hypercholesterolemia?
    1 to 2 erectile dysfunction? 1 drug BPH? 1
    glaucoma? 1 to 2 osteoarthritis? 1 to 2
    peripheral artery disease? 1 to 2 depression? 1
    to 2
  • Anywhere from 10 to 19 drugs
  • And that doesnt includeOPRAH and Suzanne Sommers

12
alternative and complementary therapies
  • St. Johns wort for depression
  • cinnamon for diabetes
  • red yeast rice for high cholesterol
  • mistletoe (Iscador) for breast cancer
  • saw palmetto or for BPH
  • glucosamine for osteoarthritis
  • yohimbine for ED
  • gingko for PAD (AHA News Release, 12/02/08)
  • ginseng for whatever ails ya
  • soy for hot flashes

13
Soy for menopausal symptoms
  • I hate to be the bearer of bad news, but after
    years of study, nearly 20 clinical trials have
    failed to show a statistically significant
    improvement in menopausal symptoms (Sitiri)

14
As an FYI
  • Approximately one in four persons taking a
    prescription medication also takes a dietary
    supplement. Asthma, insomnia, depression, chronic
    GI disorders, pain, memory problems, and
    menopausal symptoms are the medical conditions
    for which supplements are most commonly used.
    Patients at high risk for interactions, such as
    those with seizure disorders, cardiac arrhythmia,
    or CHF, often report supplement use. (Gardiner)

15
Plus, over-the-counter drugs for aches and pain,
sinus problems, allergies, colds, indigestion
  • Aspirindrills a hole in the stomach and
    decreases renal blood flow
  • Acetaminophenliver and kidney damage with
    long-term use
  • Excedrinaspirin acetaminophena double whammy
  • Ibuprofencan negate aspirins cardioprotective
    effect, not to mention drill another hole in the
    stomach and decrease renal blood flow (and damage
    the kidney over time)
  • Prilosec OTC can negate the effects of
    clopidogrel and interact with 3,456 other drugs
  • TUMS, Citracal, Oscal calcium supplements can
    interfere with thyroid replacement therapy
  • Cimetidine (Tagamet), ranitidine (Zantac)
  • Antihistamines (anticholinergic and wreak havoc
    with the elderly)of the two, SAY NO TO TAGAMET
  • YIKES

16
So, is there an established definition of
polypharmacy?
  • Old definition? Greater than 5 drugshahahaha
  • New definition? Nine or more drugs
  • One study found an average of 3.8 different
    therapeutic categories per patient with CV drugs,
    CNS drugs, and hormone (thyroid, ET) as the most
    common
  • Individual patients were prescribed an average of
    6.1 medications across those categories with
    women averaging more and also having more
    therapeutic categories (Linton)

17
So, are there some absolute NO-NOs?
  • And if theyre not absolute NO-NOs should you
    think twice about using certain combinations?
  • Anything potentially life-threatening?
  • YESthe combination of erectile dysfunction drugs
    and
  • Nitroglycerine

18
And, the combination of ED drugs certain BPH
drugs can also be dangerous
  • The alpha one antagonists (no longer chosen for
    primary BP control due to their extreme
    hypotensive effects)
  • especially with the first dose
  • Prazosin (Minipress), doxazosin (Cardura), and
    terazosin (Hytrin) block the alpha-one
    receptors on the smooth muscle of the prostate,
    subsequently reducing the size however, they
    also block the same receptors on the arteriole
    smooth muscle and BP drops significantly
  • Combo with ED drugs? Severe hypotension
  • Use tamsulosin (Flomax) or sildodosin (Rapaflo)
    or the steridesdutasteride (Avodart) or
    finasteride (Proscar)

19
Another potentially deadly combination
  • ACE inhibitors (any drug with the last name
    pril) with either of the K sparing diuretics,
    the aldosterone antagonistsspironolactone
    (Aldactone) and eplerenone (Inspra)
  • Combined with the reduced GFR in the older
    population, throw in NSAIDs (which decrease blood
    flow to the kidney and cause sodium, potassium,
    and water retention) and you could have a deadly
    rise in potassium and a fatal cardiac arrhythmia
  • Did you know that TMP-SFX (Bactrim/Septra) can
    also cause hyperkalemia and is especially
    dangerous w/ an ACE-
  • Is thACE/Aldactone combo used all of the time?
    YesCAREFULLY in HF patientsmore later

20
Tamoxifen, paroxetine (Paxil), fluoxetine (Prozac)
  • 30 of patients on tamoxifen also take an SSRI
    for either depression or hot flashes
  • Use of paroxetine (Paxil), fluoxetine (Prozac),
    and sertraline (Zoloft) with tamoxifen
  • The Ps are strong inhibitors of CYP 2D6
  • Tamoxifen is converted to an active metabolite
    via CYP 2D6 (endoxifen100x more potent than
    tamoxifen)
  • Use of either of the above antidepressants can
    almost double the risk of recurrence (13.9 vs.
    7.5 w/placebo)
  • (Prescribers Letter July 2009)

21
What to do?
  • Switch antidepressants or switch to an aromatase
    inhibitor (for example anastrozole/Arimidex) if
    the postmenopausal female
  • Use citalopram (Celexa) for hot flashes if you
    pick an SSRI
  • the only antidepressant that has shown some
    effectiveness for hot flash reduction
  • Or try gabapentin (Neurontin)

22
Dig and clarithromycin (Biaxin)
  • A 7-year study of Ontario residents over age 66
    treated with digoxin showed that those admitted
    to the hospital with dig toxicity were about 12
    times more likely to have been treated with
    clarithromycin than those who have not (Juurlink)
  • Clarithromycin Rx is commonly chosen for
    community-acquired pneumonia and H. pylori
    infections
  • Digoxin with clarithromycin--elimination of
    digoxin is primarily renal however, about
    one-fourth of dig is eliminated through the
    intestinal lumen, excreted in bile, or secreted
    directly into the lumen by P-glycoprotein (P-gp).

23
Why? Dig--clarithromycin
  • Clarithromycin inhibits intestinal P-gp and dig
    cannot be eliminatedresulting in dig-toxcity
  • Elevated dig levels to potentially fatal
    arrhythmia levels have been reported with the
    clarithromycin.
  • Therapeutic dig levels are between 0.8-2.0
    ng/mL patients with AF may require higher dig
    levels patients with HF may do better at lower
    levels

24
Speaking of digfun facts for nursing students
  • Digitalis is over 200 years oldfrom the foxglove
    plant
  • Dr. William Withering gets the credit but it was
    actually a witch from the village of Shropshire
    that first discovered its clinical usefulness for
    dropsy
  • Leeches and other forms of blood-letting were
    used by the medical establishment at the time

25
One more potentially deadly interactionhigh-dose
simvastatin and amiodarone
  • Amiodarone inhibits the metabolism of
    simvastatinthe higher the dose of simvastatin
    the greater the build up of the drug
  • Very high risk of rhabdomyolysis and subsequent
    acute renal failure
  • Variation on the themeamiodarone and grapefruit
    juicegrapefruit juice inhibits the enzyme in the
    small intestine that metabolizes
    amiodaroneincreased bioavailability and
    increased toxic side effects (fatal ventricular
    dysrhythmias)

26
Before the prescription pad is pulled out
  • What is the problem being treated?  
  • What is the drug of choice for the diagnosis?
  • Is the drug necessary and is it effective for
    this problem?  
  • Is the safest drug being used for this age
    group?
  •     

27
Consider my Aunt Betty Jo
  • Dx Mild Alzheimers disease
  • Dx Osteoporosis
  • Her M.D. prescribed alendronate (Fosamax) for her
    osteoporosisI said to my mother
  • I dont think that was a wise move, based on her
    memory impairment
  • OK, Ill talk to her on Saturday (it was Monday
    when my concern was voiced)
  • On Saturday, my Aunt Betty Jo saidwell, I dont
    know why the pharmacist wont give me any more of
    the pills, I ran out of them in LESS than a
    week
  • One shot of RECLAST once or twice a year would
    have been the better choice

28
  • Are there nonpharmacologic alternatives?
  • Back brace for vertebral fractures
  • Cognitive behavioral therapy for mild to moderate
    depression

29
NON-pharmacologic alternatives?
  • How about for the osteoporosis? Weight-bearing
    exercise, calcium citrate and vitamin D however,
    neither of these do the job totally, so drugs are
    much better at building bone non-pharmacologic
    alternatives

30
Questionscontinued
  • Is the lowest effective dose being used?
  • For most indications in the elderly, start slow
    and go slow is the ruleone major exception to
    the rule is the group of drugs called the statins
    to lower the LDL cholesterolstart with a dose
    that reduces LDL cholesterol by 30-40
  •     

31
Questions
  • Does the patient have symptoms potentially
    attributable to the drug?   
  • Erectile dysfunction drugs and GERDED drugs
    induce the production of the potent vasodilator
    nitric oxide nitric oxide also opens the lower
    esophageal sphincter and can contribute to GERD
  • Muscle aches and painsalso on a statin perhaps

32
Digression on ED drugs and the elderly
  • The fastest rising group for STDs in U.S. is the
    over 60 crowdan increase of over 300 since
    sildenafil (Viagra, the Pfizer riser) hit the
    market in 1998 (November 1, to be exact)
  • HPV, HSV, HIV, GC, Syphilis
  • Why?

33
becausemore sex
  • Many are swingin singles
  • No pregnancy risks
  • No frontal lobewho cares what the neighbors
    think??
  • Sex on the beach, in swimming pools, on golf
    courses
  • Also an increase in UTIs
  • Increased marital bliss in some
  • marital nightmares in others due infidelity
    issues and wanting sex all of the time after not
    having it for 30 years

34
More questions
  • Is the patient capable of following directions?
    Amiodarone and grapefruit juice? Alendronate and
    directions       
  • Is specific monitoring necessary (e.g., liver
    enzymes or drug levels)? INRs for warfarin, LFTs
    and TSH for amiodarone, serum creatinine befor
    metformin, dig levels, potassium levels for ACE
    inhibitors

35
Is there a more cost-effective alternative?
Example beta blockers for HF
  • Cost? Carvedilol (generic) and bisoprolol
    (generic) can be purchased at WalMart, Target,
    etc. for 4.00 for a 30-day supply, 10.00 for a
    90-day supply
  • Carvedilol/Coreg CR is 145.80 for 30 days
    nebivolol/Bystolic is 55.80 for 30 days

36
How old is the patient and how long will it take
the patient to benefit from the drug?
  • It takes 8 years to see benefits for the
    treatment of diabetes to reduce the microvascular
    complications
  • It takes 3 years to see the macrovascular
    benefits of treatment in diabetes

37
What is the half-life of the drug?
  • If the half life is longer than the patients
    life, its NOT a good choice
  • Half-life should be less than 24 hours with no
    active metabolites
  • and thats usually a drug like amitryptyline to
    NORtriptyline (choose nortryptyline to treat
    depression or the pain of peripheral neuropathy)
    meperidine to NORmeperidine (dont choose
    meperidine OR NOR meperidine), dont choose
    fluoxetine (Prozac) as it is metabolized to
    NORfluoxetine with an elimination half-life of 7
    to 9 days in the elderly

38
Last questionis there a drug that might kill
two birds with one stone so to speak?
  • Losartan (Cozaar) for managing chronic gouthas a
    modest uricosuric effect that plateaus at 50
    mg/d may be useful in patients with hypertension
    or heart failure or diabetes (Reuben)
  • Doxazosin (Cardura) for BPH and HTN (normally one
    would avoid doxazocin as a first-line therapy for
    HTN, however, its a good choice for the
    combination of a big ol prostrate and
    hypertension
  • HCTZ for hypertension in women over 60 as
    first-line therapycompetes with calcium
    excretion the drug is excreted , the calcium is
    retained and bones are strong like bull.

39
And, last but not least, is this one of the
medications on the Beers List? (Fick)
40
BEERS List USE THIS, NOT THAT
  • Medications are classified as inappropriate when
    the risk of adverse effects outweighs the
    benefits. In 1991, Beers and colleagues
    published the first article to examine which
    medications are inappropriate to prescribe in the
    elderly.
  • List updated in 2003medications are deemed
    inappropriate because there are safer, equally
    efficacious alternative medications.
  • Whenever possible, the use of medications on the
    Beers List should be avoided. (Fick)

41
The proverbial caveat
  • Prescribing medications on the Beers List of
    increases the risk of drug-related morbidity and
    mortality however, not all of these medications
    are inappropriate in all older patients
  • Some healthy 80-year-olds can tolerate
    medications on this list while a 60-year-old with
    many comorbid conditions may not tolerate the
    same medication
  • Dont JUST look at ageconsider the whole
    patientwarts, comorbidities and all.

42
Beers Criteriathe most frequently seen harmful
interactions involve the following BEERS drugs
  • 1) cardiovascular drugs (Digoxin,
    amiodarone/Cordarone)
  • 2) pain medications (long-acting NSAIDS such as
    piroxicam/Feldene, oxaprozin/Daypro,
    meperidine/Demerol, propoxyphene/Darvon and its
    combination products
  • 3) anti-depressants/antipsychotic
    drugs/anti-anxiety drugs (fluoxetine/Prozac
    haloperidol/Haldol, diazepam/Valium
    oxazepam/Serax flurazepam/Dalmane
    triazolam/Halcion amitriptyline/Elavil)
  • 4) OTC drugscimetidine/Tagamet
    diphenhydramine/Benadryl)
  • Lots of drugs on the BEERS list have
    anticholinergic effectsamitriptyline and
    cimetidine, for example

43
Normal functions of acetylcholine
  • Mentation (CNS)
  • Pupillary constriction (PNS)
  • Decreases heart rate (PNS)
  • Increases salivation (PNS)
  • Increases peristalsis (PNS)
  • Loosens urinary sphincter (PNS)

44
Anti-cholinergic drugsside effects
  • Confusion
  • Pupillary dilation (blurred vision, glaucoma)
  • Tachycardia (angina, possible MI)
  • Decreased salivation (dry mouth)
  • Decreased peristalsis in GI tract (constipation)
  • Tighten urinary sphincter (urinary retention)

45
Drugs for OAB (overactive bladder)anticholinergic
effects
  • oxybutynin (Ditropan)(Gelniquetopical
    gel)(Oxytrol patch)
  • Toterodine (Detrol LA) fesoterodine (Toviaz)
  • Darifenacin (Enablex) solifenacin (Vesicare)
  • Trospium (Sanctura)
  • (Prescribers Letter, June 200916(6)36

46
Anti-cholinergic drugsthe usual suspects and
some surprises
  • Amitryptyline (Elavil)the higher the dose, the
    higher the risk of anti-cholinergic effects Rx
    for neuropathic pain vs. Rx for depression
  • Hyoscyamine (Anaspaz, Atropine)
  • Doxepin (Sinequan)
  • Meclizine (Antivert)
  • Captopril (Capoten), nifedipine (Procardia)
  • Prednisolone
  • dig, dipyridamole (Persantine)
  • warfarin
  • Furosemide (Lasix)
  • isosorbide dinitrate (Isordil)

47
And then some
  • Paroxetine (Paxil)
  • Codeine
  • Oxycodone
  • Diphenhydramine
  • Fexofenadine (Allegra)
  • Hydroxyzine (Atarax)
  • Loratadine (Claritin)
  • dicyclomine (Bentyl)
  • Cimetidine (Tagamet), ranitidine (Zantac)
  • Haloperidol (Haldol)

48
What is aging?
  • Aging seems to be the only available way to live
    a long life. Daniel Auber, French composer
    (1782-1871)
  • Aging is just getting olderby the time you leave
    here today

49
More importantlywhat is senescence??
  • The rate of deterioration of the structure and
    function of body parts
  • Functional reserve capacity of tissues is 4-10
    times greater than baseline (the amount needed
    just to function)
  • Peak functional capacity is reached at age 24
  • 6 good years

50
Senescence and normal aging... the 1 rule
  • Peak at 24, 6 good years, gradual decline to
    baseline of
  • 1 per year

FC
Baseline function
75 yrs
1yr
30
51
But between 24 and 30
  • Were cookin on the all burners
  • Our brain, our kidneys, our hearts, our lungs

52
Variation on the theme senescence accelerates
with chronic disease (DM, COPD)...
FC
Baseline function
75 yrs
1yr
30
53
Senescence and gender differences...the demise of
the ovary
  • Gender differencesthe ovary (51.3 /- 2.7)

FC
Baseline function
75 yrs
1yr
30
54
Do mens testicles die at 51.3 /- 2.7 years?
NOOOOOOOOOOOOO
55
The 1 rule and the kidney
  • Glomerular filtration rate (GFR)120-125 ml/min
    at age 25 decreases by 1 per year as an
    estimate
  • 75-year-old 1.2 mL/min x 45 years 53 mL/min
    120-5367 mL/min in a HEALTHY 75-year-old (not
    taking into account weight, ethnicity, or gender)
  • BUT, a GFR of 60-89 mL/minmild renal
    insufficiency
  • a GFR of less than 60 mL/min/1.73 m2 represents a
    loss of more than half of normal kidney function

56
1 rulerenal function and aging
  • Diminished renal blood flow
  • Increased retention of water soluble drugs such
    as digincreased toxicity
  • Many doses of drugs need to be adjusted based on
    the GFR

57
The Geriatric Kidneythe scope of the problem
  • Chronic kidney disease is caused by irreversible
    age-related and disease-related damage to the
    kidney and affects nearly 30 of all elders
  • Among older adults, the incidence of drug-induced
    nephrotoxicity may be as high as 66 percent
  • Compared with 30 years ago, todays patients are
    older, have a higher incidence of CV disease and
    diabetes, take multiple medications, and are
    exposed to more diagnostic and therapeutic tests
    with a predisposition to harm renal function

58
Assessing renal function in the elderly
  • Serum creatinine is misleading in older patient
  • Why? Serum creatinine is based on the breakdown
    of creatine from muscle mass older patients have
    reduced muscle mass and therefore make LESS
    creatine
  • Combine that with a reduced GFR and the serum
    creatinine provides a false normal reading
  • Best measurement is the creatinine clearance
    which equates to the GFR via the Cockcroft-Gault
    equation (MDRD equation as it tends to
    overestimate kidney function in the older adult
    (Gill )
  • IBW (140-age)(0.85 if female)
  • 72(stable serum creatinine

59
For example
  • Radiocontrast dyes for diagnostic purposes
  • Renal staghorn calculus as demonstrated by an IVP

60
Drugs and the kidney
  • Dont forget to stop the metformin (Glucophage)
    for 48 hours after a radiocontrast dye
  • Increased risk of lactic acidosis (albeit a low
    risk, but the risk is highest in the elderly)
  • Metformin competes with the contrast dye for
    excretion the contrast dye wins and dives into
    the toilet metformin is retained and can
    accumulate
  • You wont be using Metformin anyway if the
    kidneys are not working well (serum creatinine
    should be drawn before prescribing Metformin)

61
Gross anatomy
62
Drugs and the kidney
  • Tubular cell toxicityespecially the proximal
    tubuleextremely vulnerable to toxic effects of
    drugs and the lack of oxygen since the proximal
    tubule does the lions share of reabsorbing the
    glomerular filtrate
  • (Acute Tubular Necrosis/ATNwhats the good news?
    epithelial cells line the renal tubules)
  • What drugs? Aminoglycosides (gentamicin and
    friends), amphotericin B, cisplatin (Platinol),
    antiretrovirals (adefovir/Hepsera,
    cidofovir/Vistide, tenofovir/Viread), contrast
    dye, zoledronate (Zometa)just to name a few

63
Various mechanisms of damage
  • Inflammation Drugs can cause inflammatory
    changes in the glomerulus (glomerulonephritis)
    and the medullary interstitium (interstitial
    nephritis)
  • Drug-induced glomerulonephritis is associated
    with 3-4 proteinuria (in the nephrotic syndrome
    range)--Gold therapy, hydralazine,
    interferon-alfa (Intron A), lithium, NSAIDS, PTU,
    pamidronate (Aredia in high doses or prolonged
    courses)

64
Various mechanisms of damage
  • Inflammation with acute medullary interstitial
    nephritis Usually results from an allergic
    response and develops in an idiosyncratic
    non-dose-dependent fashion
  • Thought to bind to antigens in the kidney or act
    as an antigen eliciting an immune response
  • Allopurinol (Zyloprim), antibiotics
    (beta-lactams, quinolones, rifampin (Rifadin),
    sulfonamides, and vancomycin (Vancocin)

65
Nephrotoxic drugs and the elderly
  • Drugs that inhibit angiotensin 2 (ACE inhibitors
    or the prils and the ARBsangiotensin receptor
    blockers) are especially dangerous if renal blood
    flow is compromisedrenal artery atherosclerosis
    (stenosis) (Baciewicz) or with NSAIDs
  • NSAIDs and vasoconstriction of the renal artery
    and afferent arteriole
  • Renal blood flow relies more on prostaglandin
    synthesis to maintain a vasodilated state in the
    elderly patient
  • NSAIDs combined with ACE inhibitors or ARBs in
    the elderly may precipitate acute renal
    failureHOW?

66
The healthy kidney
  • Afferent arteriole
  • (normally vasodilated
  • (via prostaglandins)
  • Blood entering
  • glomerulus
  • Glomerulus?filter
  • Efferent arteriole
  • (normally vasoconstricted
  • (via angiotensin II)

Prostaglandins blocked by NSAIDs
filter
Angiotensin IIblocked by ACE --
Toilet
67
The combination of ACE inhibitors and NSAIDs can
precipitate acute renal failure
  • EXPLANATION OF PREVIOUS SLIDE
  • NSAIDs block prostaglandins and vasoconstrict the
    afferent arteriole decreasing blood flow to the
    glomerulus ( since prostaglandins are more
    important in the aging kidney than in the younger
    kidney the risk is much higher in an 80-year-old
    compared to a 20-year-old)
  • ACE inhibitors block ACE and the production of
    angiotensin IIblocking angiotensin II
    vasodilates the efferent arteriole of the kidney
  • Decreased blood IN and increased blood OUT
    decreased filtration and acute renal failure

68
Drugs that can wreak havoc with RENAL FUNCTION in
the elderly
  • Aminoglycoside antibiotics (Amikacin/Amikin
    gentamicin/Garamycin tobramycin/Nebcin),
    diabetes, and concomitant use of ACE inhibitors
    increase the risk of nephrotoxicity
  • Adjust dose with GFR less than 60
  • Ears and kidneys

69
Drugs that are excreted by the kidneys and
potentially retained in the elderly
  • Allopurinol
  • Aminoglycosides
  • Amoxicillin
  • Ampicillin
  • Atenolol
  • Captopril
  • Chlopropamide
  • Cimetidine
  • Clarithromycin
  • Colchicine
  • digoxin
  • Disopyramide
  • Enalapril
  • Famotidine
  • Fluconazole
  • Furosemide
  • Gabapentin
  • Gancyclovir
  • HCTZS
  • Levofloxacin
  • Lisinopril
  • Lithium
  • metformin

70
Drugs that are excreted by the kidneys and
potentially retained in the elderly
  • Methotrexate
  • Penicillin
  • Phenobarbital
  • Procainamide
  • Ramipril
  • Ranitidine
  • Spironolactone
  • Sulfamethoxazole
  • Tetracycline
  • Trimethoprim

71
General changes--water loss and aging
  • Decrease in total body water stores
  • Decreased osmoreceptors and diminished thirst
  • Decreased volume of distribution
  • Increased drug toxicity with water-soluble
    drugsexamples include dig, oxycodone, atenolol
    (Tenormin), captopril (Capoten), venlafaxine
    (Effexor), cimetidine (Tagamet), ethanol, lithium

72
General changesbody fat changesdistribution and
amount
  • Loss of subcutaneous fat (actually you dont LOSE
    the fat, you just move it to the internal
    visceral organs) with age--difficulty maintaining
    internal temperatures with extremes of ambient
    temperature
  • Hypothermia/hyperthermia
  • Youre not dead until youre warm and dead.
  • Always check the thyroid glandmyxedema coma
    cold ambient temperature
  • Another implication of visceral fat? Increased
    insulin resistanceT2DM

73
Body fat changesdistribution and amount
  • Somewhat variable in non-obese individuals, total
    body fat is 10 to 20 of total body weight in
    younger men and 20 to 30 in younger women. In
    older individuals this increases to 20 to 30
    total body fat in men and 30 to 40 total body
    fat in women.
  • Fat-soluble drugs such as diazepam/Valium and
    anesthetics have much greater distribution in
    older and obese individuals
  • Results in retention of fat/lipid soluble
    drugscan result in toxicity if dosing interval
    is not increased or if dose is not decreased

74
Benzodiazepines for example
  • Half-life (T1/2) of diazepam (Valium) is the
    patients age, in hours
  • 25-year old 25 hours
  • 75-year old 75 hours
  • Use of a long-acting BZ in the geriatric patient
    is a NO-NO (see Beers List)
  • Shorter-acting benzodiazepines should be used in
    the elderly (temazepam/Restoril, oxazepam/Serax,
    lorazepam/Ativan (Beers List)

75
Amidarone vs. dronedarone
  • Dronedarone/Multaq will shortly over take
    amiodarone for atrial fibrillation, if it hasnt
    already
  • Dronedaroneelimination half-life of less than
    24-hours versus several weeks for amiodarone
    less lipophillic much smaller volume of
    distribution, and the iodine moieties have been
    removed to reduce the toxic effects to the
    thyroid

76
General changesdecreased albumin levels,
therefore less drug- binding sites
  • Adult/elderly levels are 3.5-5 g/dl or 35-50 g/L
  • In addition to maintaining osmotic pressure,
    albumin binds drugs (protein-bound (inactive)
    vs. free or active drug)
  • Drugs will be competing for binding sites
  • Hypoalbuminemia (less than 3.0 g/dL or 30
    g/L)what are the causes?

77
Hypoalbuminemia
  • Three major causes of hypoalbuminemia
  • 1) liver diseasenot making enough
  • 2) kidney disease excreting too much
    (nephrotic syndrome)
  • 3) the very old geriatric patient due to the
    aging liver and malnutrition

78
Low albumin and competition for binding sites
  • As a result of hypoalbuminemia, medications that
    are highly albumin-bound may have elevated free
    drug concentrations, leading to a higher
    incidence of drug toxicity
  • Plus, drugs are competing for a decreased number
    of binding sites so someone is bound (no pun
    intended) to be knocked off the binding sites,
    especially if they are weak binders
  • Warfarin is a weak binder and numerous drugs
    knock her off her binding sitestwo
    unexpected drugs also knock warfarin off of the
    albumin binding sites

79
Who are they?
  • Acetaminophen (yep, and how many elderly patients
    are on Tylenol for muscle aches and pains)?
  • Miconazole (Monistat)yep, even topical
    miconazole can knock warfarin off of her binding
    sites
  • Sulfa-based drugs are also big bullies and can
    knock warfarin off albumins binding sites
  • Trimethoprim-sulfamethoxazole (Bactrim/Septra)
  • And, metronidazole (Flagyl), erythromycin, cipro
    and other FQs (floxacins)
  • ASA competes with warfarin for binding sites

80
So when should the INR levels be checked in
patients on warfarin?
  • Any time you add or subtract a drug from the
    regimen of a patient on warfarin, you should
    check the INR levels within 72 hours
  • Warfarin (Coumadin) is the most common drug that
    brings the elderly patient to the emergency room
    (17.3)
  • WARF (Wisconsin Alumni Research Foundation)
  • Can anyone guess what the second most common drug
    that brings the elderly patient to the ER

81
Other examples of drugs being knocked off their
binding sites
  • Digoxin quinidine and verapamil displace dig
    and can increase dig levels by 50--T O X I C I T
    Y
  • Digoxin toxicitythe 3rd most common drug that
    brings the elderly to the ER
  • Dig is on the BEERS LIST

82
Drugs that are highly bound to albumin require
close monitoring for adverse effects
  • Amiodarone
  • Amlodipine
  • Antipsychotics
  • Bupropion
  • Buspirone
  • Carbamazepine
  • Cefazolin
  • Ceftotetan
  • Ceftriaxone
  • Cilostazol
  • citalopram
  • Ditiazem
  • Dipyridamole
  • Felodipine
  • Lansoprazole
  • Midazolam
  • Nifedipine
  • NSAIDs
  • Omeprazole
  • Pantoprazole
  • Phenytoin
  • Rabeprazole
  • raloxifene

83
Drugs that are highly bound to albumin
  • Rifabutin
  • Sertraline
  • Sulfonylureas
  • Tamsulosin
  • Terazosin
  • Valproic acid
  • Verapamil
  • warfarin

84
THE LIVER and DRUG METABOLISM
  • Hepatic blood flow may be reduced due to
    atherosclerosis
  • IS THERE ANY ARTERY THAT DOESNT FILL WITH
    FAT????
  • Decreased metabolism of drugs resulting in
    increased bioavailability and toxicity
  • Tagamet (cimetidine) also hepatic artery
    vasoconstriction resulting in the decreased
    metabolism of drugs and a higher bioavailability
  • Can cause beta blockers to decrease the HR to
    dangerously low levels morphine and derivatives
    may decrease respirations to dangerously low
    levels
  • TAGAMETBEERS List

85
NEUROPHARMACOLOGY OF AGING
86
Neurology of aging
  • 5 loss of cerebral weight in females by 70
  • 10 loss in men dont get too smug, ladies(men
    start out with a bigger brain)
  • By 80, 17-20 loss
  • Selected areas are the frontal lobes and the
    medial temporal lobes

87
Medial temporal lobe and the loss of hippocampal
cell function
  • Loss of recent memory
  • This is the first neurologic function to go with
    the process of senescence
  • Benign forgetfulness
  • Mild cognitive impairment
  • Full-blown dementia

88
Which brings us, of course, to the
dementiasAlzheimer (s) disease or DAT
  • The hallmark of all dementia is memory loss
  • Alzheimers dementia
  • Cortical atrophy
  • Sulcal widening
  • feathering
  • Decreased brain weight
  • 90 decline in acetylcholine, the
    neurotransmitter of cognition

89
Pathologyit takes 5 to 20 years before the 1st
symptom of memory loss
  • Beta-amyloid plaques (BAP)sticky globs outside
    the cells abnormal processing and cleaving of
    amyloid precursor proteinearliest indication of
    the development of dementia
  • Less AD in people from India and Pakistan
  • Turmeric the spice? Curcumin is the active
    ingredient

90
It takes tau to tangle1 to 5 years before
first symptom
  • Neurofibrillary tanglestangled microtubules
    inside the cells tau protein helps to stabilize
    the microtubules and thus, maintain the integrity
    of the neuron
  • Neuronal degeneration
  • Tau is predominant in FTD (frontal temporal
    dementia)
  • BAPtists vs TAUists

91
Cholinergic dysfunction in the AD brain
  • What do all of these plaques and tangles do?
    Reduce the function of acetylcholinethe
    transmitter of cognition
  • Cholinergic impairment has been implicated in
    memory and cognitive dysfunction in the elderly
  • Accentuated in patients with Alzheimers disease
    and other dementias
  • Decreased acetylcholine receptors in the
    forebrain and other regions as well as altered
    acetylcholinesterase enzyme function

92
One of two available treatments for AD
todayboost remaining acetylcholine
  • Acetylcholinesterase inhibitors such as donepezil
    (Aricept)inhibit the breakdown of ACH in the
    brain helps about 50-70 percent of the patients,
    but effects are modest think back to what the
    patient was doing 7-8 months ago reprieve only
    lasts a few months
  • Othersgalantamine (Razadyne, Razadyne ER),
    rivastigmine (Exelon)(patch is well-tolerated)
  • Reminyl was renamed Razadyne to avoid errors with
    the diabetes drug, Amaryl (glimepiride)mistakes
    led to hospitalizations and deaths
  • Donepezil and rivastigmine have also been
    approved for other types of dementiavascular/Park
    insons, Lewy Body Dementia galantamine w/
    vascular dementia

93
Benefits of cholinesterase inhibitors?
  • Many clinicians doubt the practical significance
    of response to ChEIs however, other reports show
    that ChEIs have significant efficacy in the
    treatment of neuropsychiatric symptoms in AD
    patients.
  • BOTTOM LINE? the numbers needed to treat (NNT)
    for 1 additional patient to experience benefit in
    the area of cognition were 7 for stabilization or
    better, 12 for minimal improvement or better, and
    42 for marked improvement.

94
Benefits of cholinesterase inhibitors?
  • Other tangible clinical outcomes
  • Delayed nursing home admission by as much
    as 21 months with donepezil (Aricept) Donepezil
    (Aricept) also slows the progression of atrophy
    of the hippocampus in the brains of patients with
    ADsuggesting a neuroprotective effect of this
    particular cholinesterase inhibitor.
  • Galantamine (Razadyne) and donepezil (Aricept)
    have also been shown to be neuroprotective by
    preventing neuronal apoptosis (programmed cell
    suicide).

95
Drug interactions with the cholinesterase
inhibitors
  • Drugs with anti-cholinergic properties can
    potentially decrease the effectiveness of the
    acetylcholinesterase inhibitors
  • Paroxetine (Paxil) is an excellent examplethe
    anticholinergic effects of Paxil can negate the
    acetylcholine boosting effects of Aricept and
    friends
  • Paroxetine (Paxil) has the MOST anticholinergic
    effects of all SSRIsdo not use.

96
Memantine (Namenda/USEbixa/Canada) 2nd drug used
for AD
  • Namenda, Ebixa (memantine)decreases excessive
    activation of NMDA receptor by glutamate offers
    modest functional improvements in patients with
    Alzheimers disease
  • Who is glutamate? Excitatory transmitter that
    plays a major role in memory and learning
    continuous stimulation of the NMDA receptor leads
    to increased calcium influx and ultimate damage
    to the neuron Memantine allows normal glutamate
    fx blocks excessive excitation
  • Mild to moderate to severe AD as an add-on or has
    been used alone

97
On the horizon
  • AAC-001 vaccination against beta amyloid
  • Alzhemed (tramiprosate)prevents neurofibrillary
    tangles and build up of beta amyloid
  • Bapineuzumabmonoclonal antibody to beta amyloid
  • LY2042430may inhibit beta amyloid
  • LY450139gamma secretase inhibitor
  • PBT-2decreased levels of beta amyloid
  • TTP488reduces amyloid burden

98
Delirium in the elderly
  • 1-2 of community dwelling 10-22 of
    hospitalized inpatients, 58 of nursing home
    patients
  • 15-26 of elderly with delirium die
  • Cause of death is the underlying cause of
    delirium
  • Treating delirium improves cognitive dysfunction

99
Assume that the onset of delirium in the old
person is due to infection.Clifton Meador, M.D.
  • Its either a UTI or pneumonia
  • Listen to the lungs and do a urinalysis

100
If its a female, consider a urinary tract
infection as the cause of acute delirium
  • Check the urinary tract
  • WBCs in urine, WBC casts in the urine (pyelo)
  • Only 8 of the women in nursing homes today
    receive estrogen in one form or another
  • Estrogen and the urinary tract maintains the
    health of the urinary tract lowers pH of urine,
    keeps it acidic
  • Topical estrogen and a reduction in urinary tract
    infections

101
If its a maleeither go with pneumonia or a UTI
due to a prostrate the size of Texas
102
The second major cause of delirium is
polypharmacy
  • The blood brain barrier in the elderly is more
    permeable to drugseverything that is
    lipid-soluble gets in
  • Narcotics and NSAIDS
  • Benzodiazepines
  • Any drugs with anti as their first
    nameAnticholinergics, antiarrhythmics,
    anti-histamines, antihypertensives,
    antipsychoticcs, antiparkinsonism, antianxiety,
    antidepressants, antimicrobials
  • Cimetidine (Tagamet), digoxin, steroids,
    acetaminophen, diuretics, meperidine, amantidine
  • Sudden withdrawal of drugs

103
The third major cause of delirium is electrolyte
imbalancemany of the electrolyte imbalances are
caused by medications
  • Low sodiumconsider thiazide and loop diuretics,
    but a lesser known cause is the SIADH induced by
    SSRIs acetaminophen hyperglycemia lowers sodium
    (for every 100 mg/dL increase in plasma glucose,
    sodium decreases by 1.6 mEq/L
  • Low or high potassiumconsider diuretics again
    for low potassium for high potassium go straight
    for the ACE inhibitors especially combined with
    spironolactone or eplerenone
  • ACE inhibitors combined with TMP-SFX has also
    been shown to cause hyperkalemia
  • Hypercalcemia--1 cause in the elderly??? Not
    drugs, not hyperparathyroidism, but..

104
Depression
  • More common than dementia
  • Often co-exists with dementia
  • May appear withdrawn, uncooperative or
    intermittently agitated
  • Functionally or cognitively impaired
  • May prolong recovery from illness due to lack of
    cooperation, negativism, and poor self-esteem

105
The usual neurovegetative signs of depression are
unreliable in the elderly(The SALSA signs)
  • Sleep disturbances, appetite changes, low, self
    esteem, and anhedonia (lack of interest in
    day-to-day activities)
  • There is NO significant illness or medical
    condition in late life that does NOT impinge upon
    sleep, appetite or energy or sense of vitality
  • Usual aging also brings changes in sleep patterns
    and energy expenditure
  • If within 10 minutes
  • Geriatric Depression Scale
  • Sertraline (Zoloft) and escitalopram (Lexapro
    Cipralex) are excellent choicesfew side effects,
    few drug interactions, short half-lives

106
Cardiovascular system and drugs in the elderly
107
The Cardiovascular system and aging
  • Increased prevalence of cardiovascular disease
    with aging
  • People over 65 account for 65 of all
    cardiovascular hospitalizations and 80 of all
    heart failure admissions

108
The aging heart and vascular system
  • 1 rule--maximal O2 consumption and cardiac
    output decrease by 1 per year starting at age
    30
  • Interestingly and fortunately, the heart rate
    does not decrease by 1 per year with age
  • However, elderly patients have a decreased heart
    rate reserve and maximum attainable heart rate

109
The aging heart and vascular system
  • Endothelial dysfunctionincreased risk for
    atherosclerosis which in turn increases the risk
    of coronary artery disease, cerebrovascular
    disease, PAD, etc.
  • Use of the statinslova, prava, simva, atorva,
    rosuva, pitava

110
The Statin Sisters
  • Who are they?
  • lovastatin (Mevacor)
  • simvastatin (Zocor)
  • atorvastatin (Lipitor)
  • fluvastatin (Lescol)
  • pravastatin (Pravachol)
  • rosuvastatin (Crestor)
  • pitavastatin (Livalo)

111
Other manifestations of atherosclerosis in the
elderly
  • Renal artery stenosis
  • Hypertension
  • Chronic kidney disease
  • Abdominal aortic aneurysm
  • Abdominal bruit

112
Youre not getting enough blood flow to your
private parts--ED
  • The little blue pill that changed the lives of
    millions--November of 1998
  • The Pfizer riser and friends
  • (sildenafil, vardenafil, tadalafil)
  • Viagra, Levitra, Cialis (the weekend warrior)
  • Boost nitric oxide and increase blood flow to the
    privates
  • Before 1998 After 1998
  • Pilots
  • Tetanus shots

113
Chronic Heart Failure
  • Approximately 2 of adults suffer from heart
    failure, but in those over the age of 65, this
    percent increases to 610
  • 6 of diabetic men develop heart failure, 10 of
    diabetic women
  • HF costs more than 35 billion/year in the US.
    Although some patients survive many years,
    progressive disease is associated with an overall
    annual mortality rate of 10.

114
Chronic Heart Failure-- CHF
  • Decreased contractile reserve along with multiple
    risk factors (atherosclerosis, hypertension,
    diabetes, valvular heart disease) results in an
    increased risk of CHF
  • Nomenclature has changedjust a tweakcongestive
    to chronic we can still keep the acronym
  • Left-sided vs. right-sided (old classification
    and useful for teaching purposes)
  • Current classification Systolic vs. diastolic
    (is it pump failure or filling failure?)
  • An ejection fraction of less than 40 indicates
    systolic dysfunction an ejection fraction of
    40 indicates heart failure with preserved
    systolic function (diastolic dysfunction)

115
BBs causes of heart failure
  • The broken heartprimary cardiac muscle failure
    (myocarditis, alcohol and thiamine deficiencywhy
    dont we just add thiamine to booze, darn-it?
    )90 is dilated cardiomyopathy
  • The betrayed heartthe heart that is let down by
    its friendsdecreased O2 with COPD,
    atherosclerosis, diabetes
  • The befuddled heartthe heart that beats funny
  • The defeated heartworking too hard against a
    resistance (HTN, stenotic or leaking valves)

116
Heart failure caveats
  • The leading cause of hospitalization due to
    deteriorating heart failure is excessive sodium
    intake. (Archives of Internal Medicine, 2001,
    Vol. 161(19), pp. 2337-42)
  • The second cause of hospitalization and
    deteriorating heart function is respiratory
    infection. Archives of Internal Medicine 2001
    161 (19) 2337-42)
  • The third leading cause of deteriorating heart
    failure and hospitalization is not taking
    prescribed medications. Archives of Internal
    Medicine, 2001 161 (19) 2337-42)

117
The pathophysiology of heart failure
  • Regardless of the cause, if the heart is unable
    to pump adequately the ventricular myocardium,
    the kidneys, and the adrenal glands are going to
    compensate
  • A first mechanism of compensation results as a
    response to ventricular dysfunction and increased
    wall stretching the ventricular myocardium
    releases B-type natriuretic peptide (BNP). BNP
    stimulates diuresis and vasodilation as part of a
    counter-regulatory system to oppose the RAA
    system and sympathetic response
  • Synthetic BNP is nesiritide (Natrecor)for
    hospitalized decompensated HF patients with
    dyspnea at rest

118
Pathophysiology of Heart Failure
  • The sympathetic nervous system (SNS)
    response--the adrenal gland pumps out
    epinephrine/adrenalin to increase the heart rate
    and the contractile state (chronotropic and
    inotropic functions)
  • The epinephrine/adrenalin also causes remodeling
    of the heart muscle and increases the risk of
    ventricular dysrhythmias

119
Enter the beta blockers for heart failure
  • Bisoprolol (Zebeta or generic) QD
  • Carvedilol (Coreg, Coreg CR or generic) BID (also
    an vasodilator via alpha 1 blockade)
  • Metoprolol succinate (not tartrate) Toprol XL or
    generic)QD
  • Nebivolol (Bystolic)QD (also a vasodilator via
    nitric oxide production)
  • bisoprolol and nebivolol have not been FDA
    approved for heart failure but they work
    nebivolol is the least effective

120
Beta blockers
  • Start with low-dose
  • Fatigue (non-selective beta blockers cross the
    BBB and block norepinephrine in the brainmakes
    you tired and listless) hypotension, worsening
    heart failure in the first 2 to 4 weeks of
    treatment increase dose gradually full clinical
    benefits may not occur for 3 to 6 months

121
The kidney compensates I can help!
  • The third compensatory mechanism with heart
    failurethe KIDNEY senses low volume and/or low
    pressure

122
The kidney and the renin-angiotensin-aldosterone
system
  • Think of HF as a hyper-reninemic state
  • Not enough blood flowing to the kidney (low
    volume, low pressure), results in the release of
    renin, which in turn triggers the release of
    angiotensin I from the liver. Angiotensin I
    stimulates the production of Angiotensin II
  • Angiotensin II triggers the release of
    aldosterone
  • Too much of a good thing

123
In other words, Angie is a bad girl in heart
failure
  • Angie tenses your angios and vasoconstricts)
    and aldosterone (conserves sodium and water and
    secretes potassium)resulting in increased
    afterload and preload
  • Now the heart has to work even harder
  • Angie also remodels the myocardium and increases
    the risk for ventricular dysrhythmias

124
To the rescueACE inhibitors-- the PRILSblock
the conversion of angiotensin I to II
  • Captopril (Capoten and generic)TID (compliance
    problems)
  • Enalapril (Vasotec and generic)--BID
  • Lisinopril (Prinivil, Zestril and generic)--QD
  • Perindopril (Aceon)--QD
  • Trandolapril (Mavik and generic)--QD
  • Ramipril (Altace and generic)--QD

125
PRILSThe ACE inhibitors
  • Who is ACE and why do we want to inhibit him?
  • Angiotensin Converting
  • Enzyme (ACE) inhibits the conversion of ATI
    to ATII

ALDOSTERONE
ACE--
126
A few notes on ACE inhibitors
  • Use cautiously in patients with SBP lt 90 mmHg
  • Draw serum creatinine and potassium levels prior
    to starting ACE inhibitors
  • Use cautiously in patients with creatinine levels
    gt 3 mg/dL, or potassium levels greater than 5.5
    mEq/L (gt 5.0 mEq/L in diabetics)
  • Do not use in patients with hx of angioedema or
    bilateral renal artery stenosis

127
Adverse effects are due to 3 mechanisms
  • inhibiting breakdown of endogenous kinins
    (coughfemales more than males),
    angioedemasmokers, AA, asthmatics)
  • suppression of angiotensin II (hyperkalemia,
    hypotension and renal insufficiency)
  • Reduction of aldosterone production
    (hyperkalemia)
  • FYI ARBs do not increase concentrations of
    kinins to the same degree, hence less cough and
    decreased risk of angioedema (8
    cross-reactivity)

128
BOTTOM LINE ACE inhibitors
  • Improve symptoms in patients with heart failure
    (sometimes within the first 48 hours, but more
    commonly over 4 to 12 weeks)
  • Decrease the incidence of hospitalization and
    myocardial infarction
  • Prolong survival
  • (Medical Letter, July 2009)

129
Sartans--ARBs
  • Angiotensin receptor blockers (bypass ACE) and
    work by blocking the tissue receptors
  • Who are they? The Sartan Sisters
  • losartanCozaar
  • valsartanDiovan
  • candesartanAtacand
  • irbesartanAvapro
  • telmisartanMicardis
  • olmesartanBenicar
  • eprosartan--Tevetan

130
If additional aldosterone blockade is
necessaryaldosterone antagonists
  • Eplerenone (generic or Inspra) QD _at_ 106.20 for
    30 days or Inspra for 135.30 x 30 days
  • OUCH.
  • Spironolactone (generic or Aldactone) QD _at_94.00
    for 30 days generic or 28.20 for 30 days for
    Aldactone

131
Please note
  • RALES (1999) (Random Aldactone Evaluation
    Study)adding spironolactone/Aldactone postpones
    or prevents 200 deaths/1000 people w/CHF
  • BUTFor every 1000 new spironolactone RX in heart
    failure patients, there are 50 more
    hospitalizations for hyperkalemia
  • Dose 12.5-25 mg per day of spironolactone

132
Other drugs for heart failure??
  • Digoxin, of courseespecially if the myocardium
    needs a little extra boost
  • When should dig be used? Persistent symptoms,
    despite optimum therapy with ACE inhibitors,
    diuretics, and beta blockers to reduce
    hospitalization in patients with a Class IIa
    indication(Stage C with a reduced left
    ventricular ejection fraction
  • DiureticsHCTZ or loop diuretics depending on GFR

133
NSAIDs and heart failure
  • NSAIDs and fluid retention (due to
    vasoconstriction of the afferent
    arteriole)especially the long-acting
    nonselective NSAIDs -- (piroxicam/Feldane),
    meloxicam (Mobic, Mobicox), nabumetone (Relafen),
    oxaprozin (Daypro)
  • NSAIDs can counteract the positive effects of
    thiazide diuretics for blood pressure control
  • Why? Opposing actions
  • NSAIDs can exacerbate HF symptoms due to sodium
    and water retention (peripheral edema) and renal
    dysfunction can also increase K levels

134
Hypertension
  • Increased vascular stiffnessincreased systolic
    BP with widened pulse pressure increased
    afterload
  • One-third of the adult population in the US has
    HTN somewhere in the vicinity of 65 million give
    or take a few
  • Only 31 of patients on hypertensive therapy
    reached target blood pressure goals of less than
    140/90 mm Hg and control rates were lowest among
    those age 60 and older

135
Isolated Systolic Hypertension (ISH)
  • Two thirds of hypertensive patients over 60 have
    ISH
  • Systolic rises with age due to arterial
    stiffness, diastolic tends to plateau or even
    decrease during 6th decade
  • Isolated systolic (ISH) is defined as (S gt 140
    Dlt 90) pulse pressure increases in the same
    manner high S, normal or low D elevated pulse
    pressure is increasingly recognized as an
    important predictor of CAD/CVD (p.s. another
    cause of widened pulse pressure is aortic
    regurgitation)

136
Blood pressureIdeal? 120/80, BUT
  • Depending on co-morbidities it may be kept
    slightly higher in the frail elderly to avoid
    hypotension, falls, and a broken hip
  • But not TOO high as it is the MAJOR risk factor
    for strokes (besides AGE)66 of all strokes are
    due to hypertension
  • Keeping the blood pressure BELOW 140/90 prevents
    strokes, ACS, CHF, dementia, and renal failure

137
So, is it worth treating patients who are over 80
for hypertension?
  • Yes, indeedy. In the HYVET, double-blind,
    randomized, placebo-controlled trial involving
    3845 patients 80 years and older with
    hypertension the authors found that active
    treatment with indapamide to start and adding
    perindopril as needed was associated with a 21
    reduction in the relative risk of death from any
    cause, a 64 reduction in the relative risk of
    heart failure, and a 30 reduction in the
    relative risk of stroke
  • It only takes 2 years to see the benefit of
    antihypertensive therapy (Becket, et al. and
    Kostis)

138
How many drugs?
  • Most older hypertensive patients may require at
    least two drugs to achieve goal BP, especially
    those at high risk for CV events (Nash)

139
When choosing
  • Would this drug have a favorable effect on
    co-morbidities?
  • Anginabeta blocker, calcium channel blocker
  • Atrial fibrillationbeta blocker, calcium channel
    blocker
  • Benign prostatic hypertrophyalpha one blocker
  • Congestive Heart Failurebeta blocker, ACE
    inhibitor
  • Hyperthyroidismbeta blocker
  • MIbeta blocker, ACE inhibitor
  • Diabetes MellitusACE inhibitors, Angiotensin
    receptor blockers

140
How about aspirin for one and for all? What are
the risks of aspirin for cardioprotection?
  • First of all, lets calculate the risks of having
    a heart attack or dying of heart disease
  • Go towww.health.harvard.edu/116
  • Lets say, just for the sake of saying itthat
    you are a 59- year- old- nursing instructor with
    a TC of 220, HDL of 68, non-smoker with a
    systolic BP of 130 mg/dLanyone in this room fit
    the bill?

141
  • Risk is 2... Means 2 of 100 people with this
    level of risk will have a heart attack in the
    next 10 years

142
Heart disease risk over 10 years? If your risk is
  • 1--aspirin will avoid 2 to 8 heart attacks and
    heart-related events, cause 0 to 2 hemorrhagic
    strokes, 12 gastrointestinal bleedsGREATER HARM
    THAN GOOD
  • 6--aspirin will avoid 8 to 24 heart attacks and
    heart-related deaths, cause 0 to 2 hemorrhagic
    strokes, and cause 12 gastrointestinal
    bleedsGOOD and HARM balanced
  • 10--aspirin will avoid 12 to 40 heart attacks
    and heart-related deaths, cause 0-2 hemorrhagic
    strokes, and cause 12 GI bleedsGreater GOOD
    than harm
  • (Harvard Health Letter, August 2007)

143
An easier way to look at it?
  • Daily aspirin use by 1000 people for 10 years is
    estimated to cause up to 2 hemorrhagic strokes
    and 12 episodes of GI bleeding HOWEVER,
  • The chances of dying from an aspirin-related
    complication are the same as dying in an
    automobile accidentabout 1 per 1000 people over
    a 10-year period
  • Lets compare aspirin to a class of drugs that
    has received a terrible reputation over the
    years due to the mediathe statin drugs.
  • Aspirin is 100 x more likely to cause a fatal
    side effect than the statin drugs

144
So, who benefits?
  • Diabetics over 40, or between 30 and 40 with
    other risk factors such as smoking, HTN, FH, high
    cholesterol
  • Patients with chronic kidney disease (CKD),
    especially patients on dialysis
  • Patients at risk for heart diseaseparent or
    sibling with heart attack under 55 for a man and
    65 for a female, HTN, substantially overweight,
    no exercise
  • One or more of these plus older than 65 for
    female and older than 55 for male tips balance in
    favor of aspirin

145
ASA and ibuprofen (Advil, Motrin)
  • How many older patients take ASA and a NSAID???
    OTC ibuprofen is a NO-NO at the same time
  • Ibuprofen blocks aspirins entry into the COX-1
    pocket. If your patients take the two for various
    conditions, take the aspirin 1st and wait at
    least 30 minutes before taking ibuprofen
  • If that isnt possible, hold off on the aspirin
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