Polypharmacy—the Pearls, the Perils, and the Pitfalls of Pharmaceuticals in the Aging Population<br />Barb Bancroft, RN, M...
Definitions of “age”…<br />Stratification of the older patient group into 3 groups:<br />“young old” – 65-75<br />“old”—75...
So, do you want to live to be 100?<br />“If you live to be 100, you have it made. Very few people die past that age.”<br /...
Your life expectancy as a…<br />Black Male – 2.9 years<br />Black Female – 3.0 year<br />White Male – 2.3 years<br />White...
As an FYI: Life expectancy<br />If you are 40 today: <br />WM—37.4 years<br />WF—41.6 years<br />BM—32.8<br />BF—38.1<...
Women have the age advantage at every age, except conception and over 100 for black males…<br />Why is conception the exce...
The sperm carrying the Y chromosome is the faster swimmer…<br />The early sperm gets the worm, so to speak…<br />Why?<br /...
Because…<br />The sperm carrying the Y chromosome is 23% lighter than the sperm carrying the X chromosome<br />Hence, the ...
Polypharmacy<br />Most info on pharmacokinetics and pharmacodynamics has been developed for the “young-old” (65 to 75) and...
The biggest problem… “poly”-conditions = “poly”-pharmacy<br />The average older adult has 6.5 chronic conditions, and mul...
For example…<br />72-year –old male with diabetes, hypertension, hypercholesterolemia, erectile dysfunction, benign prosta...
“alternative” and “complementary therapies…”<br />…St. John’s wort for depression<br />…cinnamon for diabetes<br />…red ye...
Soy for menopausal symptoms<br />I hate to be the bearer of bad news, but after years of study, nearly 20 clinical trials...
As an FYI…<br />Approximately one in four persons taking a prescription medication also takes a dietary supplement. Asthma...
Plus, over-the-counter drugs for aches and pain, sinus problems, allergies, colds, “indigestion”<br />Aspirin—drills a hol...
So, is there an established definition of polypharmacy?<br />Old definition? Greater than 5 drugs…hahahaha<br />New defini...
So, are there some absolute NO-NOs? <br />And if they’re not “absolute” NO-NO’s should you think twice about using certain...
And, the combination of ED drugs + certain BPH drugs can also be dangerous<br />The alpha one antagonists (no longer chose...
Another potentially deadly combination…<br />ACE inhibitors (any drug with the last name “pril”) with either of the K+ spa...
Tamoxifen, paroxetine (Paxil), fluoxetine (Prozac)<br />30% of patients on tamoxifen also take an SSRI for either depressi...
What to do?<br />Switch antidepressants or switch to an aromatase inhibitor (for example: anastrozole/Arimidex) if the pos...
Dig and clarithromycin (Biaxin)<br />A 7-year study of Ontario residents over age 66 treated with digoxin showed that thos...
Why? Dig--clarithromycin<br />Clarithromycin inhibits intestinal P-gp and dig cannot be eliminated—resulting in dig-toxcit...
Speaking of dig…fun facts for nursing students…<br />Digitalis is over 200 years old—from the foxglove plant<br />Dr. Will...
One more potentially deadly interaction—high-dose simvastatin and amiodarone<br />Amiodarone inhibits the metabolism of si...
Before the prescription pad is pulled out…<br />What is the problem being treated?  <br />What is the drug of choice for t...
Consider my Aunt Betty Jo…<br />Dx: Mild Alzheimer’s disease<br />Dx: Osteoporosis<br />Her M.D. prescribed alendronate (...
Are there nonpharmacologic alternatives?<br />Back brace for vertebral fractures<br />Cognitive behavioral therapy for mil...
NON-pharmacologic alternatives?<br />How about for the osteoporosis?Weight-bearing exercise, calcium citrate and vitamin D...
Questions…continued…<br />Is the lowest effective dose being used?<br />For most indications in the elderly, “start slow a...
Questions…<br />Does the patient have symptoms potentially attributable to the drug?   <br />Erectile dysfunction drugs an...
Digression on ED drugs and the elderly<br />The fastest rising group for STDs in U.S. is the over 60 crowd—an increase of ...
because…more sex<br />Many are swingin’ singles <br />No pregnancy risks<br />No frontal lobe…who cares what the neighbors...
More questions…<br />Is the patient capable of following directions? Amiodarone* and grapefruit juice? Alendronate and di...
Is there a more cost-effective alternative?Example: beta blockers for HF<br />Cost? Carvedilol (generic) and bisoprolol (g...
How old is the patient and how long will it take the patient to benefit from the drug?<br />It takes 8 years to see benefi...
What is the half-life of the drug?<br />If the half life is longer than the patient’s life, it’s NOT a good choice<br />Ha...
Last question…is there a drug that might “kill two birds with one stone” so to speak?<br />Losartan (Cozaar) for managing ...
And, last but not least, is this one of the medications on the Beers List? (Fick)<br />39<br />
BEERS List – USE THIS, NOT THAT<br />Medications are classified as inappropriate when the risk of adverse effects outweigh...
The proverbial caveat…<br />Prescribing medications on the Beer’s List of increases the risk of drug-related morbidity and...
Beers Criteria—the most frequently seen harmful interactions involve the following BEERS drugs:<br />1) cardiovascular dru...
Normal functions of acetylcholine<br />Mentation (CNS)<br />Pupillary constriction (PNS)<br />Decreases heart rate (PNS)<b...
Anti-cholinergic drugs—side effects<br />Confusion<br />Pupillary dilation (blurred vision, glaucoma)<br />Tachycardia (an...
Drugs for OAB (overactive bladder)—anticholinergic effects<br /><ul><li>oxybutynin (Ditropan)(Gelnique—topical gel)(Oxytro...
Toterodine (Detrol LA); fesoterodine (Toviaz)
Darifenacin (Enablex); solifenacin (Vesicare)
Trospium (Sanctura)
(Prescriber’s Letter, June 2009;16(6):36</li></ul>45<br />
Anti-cholinergic drugs—the usual suspects and some surprises…<br />Amitryptyline (Elavil)—the higher the dose, the higher ...
And then some…<br />Paroxetine (Paxil)<br />Codeine <br />Oxycodone <br />Diphenhydramine <br />Fexofenadine (Allegra)...
What is aging?<br />“Aging seems to be the only available way to live a long life.” –Daniel Auber, French composer (1782-1...
More importantly…what is senescence??<br />The rate of deterioration of the structure and function of body parts <br />Fun...
Senescence and normal aging...the 1% rule<br />Peak at 24, 6 good years, gradual decline to baseline of <br />~ 1% per yea...
But between 24 and 30…<br />We’re cookin’ on the all burners…<br />Our brain, our kidneys, our hearts, our lungs…<br />51<...
Variation on the theme: senescence accelerates with chronic disease (DM, COPD)...<br />52<br />FC%<br />Baseline function<...
Senescence and gender differences...the demise of the ovary<br />Gender differences—the ovary (51.3 +/- 2.7)<br />53<br /...
Do men’s testicles die at 51.3 +/- 2.7 years? NOOOOOOOOOOOOO<br />54<br />
The 1% rule and the kidney…<br />Glomerular filtration rate (GFR)—120-125 ml/min at age 25; decreases by ~1% per year; as ...
1% rule…renal function and aging…<br />Diminished renal blood flow<br />Increased retention of water soluble drugs such as...
The Geriatric Kidney—the scope of the problem<br />Chronic kidney disease is caused by irreversible age-related and diseas...
Assessing renal function in the elderly<br />Serum creatinine is misleading in older patient <br />Why? Serum creatinine i...
For example…<br />Radiocontrastdyes for diagnostic purposes<br />Renal staghorn calculus as demonstrated by an IVP<br />
Drugs and the kidney<br />Don’t forget to stop the metformin (Glucophage) for 48 hours after a radiocontrast dye<br />Incr...
Gross anatomy<br />
Drugs and the kidney<br />Tubular cell toxicity—especiallythe proximal tubule—extremely vulnerable to toxic effects of dr...
Various mechanisms of damage<br />Inflammation: Drugs can cause inflammatory changes in the glomerulus (glomerulonephritis...
Various mechanisms of damage<br />Inflammation with acute medullary interstitial nephritis: Usually results from an allerg...
Nephrotoxic drugs and the elderly<br />Drugs that inhibit angiotensin 2 (ACE inhibitors or the “prils” and the ARBs—angio...
The healthy kidney<br />Afferent arteriole<br /> (normally vasodilated<br /> (via prostaglandins)<br />Blood ent...
The combination of ACE inhibitors and NSAIDs can precipitate acute renal failure<br />EXPLANATION OF PREVIOUS SLIDE<br />N...
Drugs that can wreak havoc with RENAL FUNCTION in the elderly…<br />Aminoglycosideantibiotics (Amikacin/Amikin; gentamicin...
Drugs that are excreted by the kidneys and potentially retained in the elderly<br />Allopurinol<br />Aminoglycosides<br />...
Drugs that are excreted by the kidneys and potentially retained in the elderly<br />Methotrexate<br />Penicillin<br />Phen...
General changes--water loss and aging<br />Decrease in total body water stores<br />Decreased osmoreceptors and diminished...
General changes…body fat changes—distribution and amount <br />Loss of subcutaneous fat (actually you don’t LOSE the fat, ...
Body fat changes—distribution and amount<br />Somewhat variable in non-obese individuals, total body fat is 10% to 20% of ...
Benzodiazepines for example<br />Half-life (T1/2) of diazepam (Valium) is the patient’s “age, in hours”<br /> 25-ye...
Amidarone vs. dronedarone<br />Dronedarone/Multaq will shortly over take amiodarone for atrial fibrillation, if it hasn’t ...
General changes—decreased albumin levels, therefore less drug- binding sites<br />Adult/elderly levels are 3.5-5 g/dl or 3...
Hypoalbuminemia<br />Three major causes of hypoalbuminemia<br /> 1) liver disease—not making enough<br /> 2) kidney ...
Low albumin and competition for binding sites<br />As a result of hypoalbuminemia, medications that are highly albumin-bou...
Who are they?<br />Acetaminophen (yep, and how many elderly patients are on Tylenol for muscle aches and pains)?<br />Mico...
So when should the INR levels be checked in patients on warfarin?<br />Any time you add or subtract a drug from the regime...
Other examples of drugs being knocked off their binding sites<br />Digoxin– quinidine and verapamil displace dig and can i...
Drugs that are highly bound to albumin require close monitoring for adverse effects…<br />Amiodarone<br />Amlodipine<br />...
Drugs that are highly bound to albumin<br />Rifabutin<br />Sertraline<br />Sulfonylureas<br />Tamsulosin<br />Terazosin<br...
THE LIVER and DRUG METABOLISM<br />Hepatic blood flow may be reduced due to atherosclerosis<br />IS THERE ANY ARTERY THAT ...
NEUROPHARMACOLOGY OF AGING<br />85<br />
Neurology of aging…<br />5% loss of cerebral weight in females by 70<br />10% loss in men – don’t get too smug, ladies…(me...
Medial temporal lobe and the loss of hippocampal cell function<br />Loss of recent memory<br />This is the first neurologi...
Which brings us, of course, to the dementias…Alzheimer (s) disease or DAT<br />The hallmark of all dementia is memory loss...
Pathology—it takes 5 to 20+ years before the 1st symptom of memory loss<br />Beta-amyloid plaques (BAP)—sticky globs outsi...
It takes “tau” to tangle…1 to 5 years before first symptom<br />Neurofibrillary tangles—tangled microtubules inside the ce...
Cholinergic dysfunction in the AD brain<br />What do all of these plaques and tangles do? Reduce the function of acetylcho...
One of two available treatments for AD today…boost remaining acetylcholine …<br />Acetylcholinesterase inhibitors such as ...
Benefits of cholinesterase inhibitors?<br />Many clinicians doubt the practical significance of response to ChEIs; however...
Benefits of cholinesterase inhibitors?<br />Other tangible clinical outcomes: <br /> Delayed nursing home admission b...
Drug interactions with the cholinesterase inhibitors<br />Drugs with anti-cholinergic properties can potentially decrease ...
Memantine (Namenda/US;Ebixa/Canada)2nd drug used for AD<br />Namenda, {Ebixa }(memantine)—decreases excessive activation o...
On the horizon…<br />AAC-001 –vaccination against beta amyloid<br />Alzhemed (tramiprosate)—prevents neurofibrillary tangl...
Delirium in the elderly<br />1-2% of community dwelling; 10-22% of hospitalized inpatients, 58% of nursing home patients<b...
“Assume that the onset of delirium in the old person is due to infection.”—Clifton Meador, M.D.<br />It’s either a UTI or ...
If it’s a female, consider a urinary tract infection as the cause of acute delirium…<br />Check the urinary tract<br />WBC...
If it’s a male…either go with pneumonia or a UTI due to a “prostrate” the size of Texas<br />101<br />
The second major cause of delirium is polypharmacy…<br />The blood brain barrier in the elderly is more permeable to drugs...
The third major cause of delirium is electrolyte imbalance…many of the electrolyte imbalances are caused by medications<br...
Depression…	<br />More common than dementia<br />Often co-exists with dementia<br />May appear withdrawn, uncooperative or...
The usual neurovegetative signs of depression are unreliable in the elderly…(The SALSA signs)<br />Sleep disturbances, app...
Cardiovascular system and drugs in the elderly<br />106<br />
The Cardiovascular system and aging<br />Increased prevalence of cardiovascular disease with aging<br />People over 65 acc...
The aging heart and vascular system…<br />1% rule--maximal O2 consumption and cardiac output decrease by 1% per year start...
The aging heart and vascular system<br />Endothelial dysfunction—increased risk for atherosclerosis which in turn increase...
The “Statin Sisters”…	<br />Who are they?<br />lovastatin (Mevacor)<br />simvastatin (Zocor)<br />atorvastatin (Lipitor)<b...
Other manifestations of atherosclerosis in the elderly<br />Renal artery stenosis<br />Hypertension<br />Chronic kidney di...
“You’re not getting enough blood flow to your ‘private parts’”--ED<br />The little blue pill that changed the lives of mil...
Chronic Heart Failure<br />Approximately 2% of adults suffer from heart failure, but in those over the age of 65, this per...
Chronic Heart Failure-- CHF<br />Decreased contractile reserve along with multiple risk factors (atherosclerosis, hyperten...
BB’s causes of heart failure<br />The broken heart—primary cardiac muscle failure (myocarditis, alcohol and thiamine defic...
Heart failure caveats<br />The leading cause of hospitalization due to deteriorating heart failure is “excessive sodium in...
The pathophysiology of heart failure…<br />Regardless of the cause, if the heart is unable to pump adequately; the ventric...
Pathophysiology of Heart Failure<br />The sympathetic nervous system (SNS) response--the adrenal gland pumps out epinephri...
Enter the beta blockers for heart failure<br />Bisoprolol (Zebeta or generic) – QD*<br />Carvedilol (Coreg, Coreg CR or ge...
Beta blockers<br />Start with low-dose<br />Fatigue (non-selective beta blockers cross the BBB and block norepinephrine in...
The kidney compensates… “I can help!”<br />The third compensatory mechanism with heart failure—the KIDNEY “senses” low vol...
The kidney and the renin-angiotensin-aldosterone system <br />Think of HF as a “hyper-reninemic” state<br />Not enough blo...
In other words, Angie is a bad girl in heart failure<br />Angie ‘tenses’ your angios and vasoconstricts) and “al”dosterone...
To the rescue…ACE inhibitors-- “the PRILS”—block the conversion of angiotensin I to II<br />Captopril (Capoten and generic...
“PRILS”—The ACE inhibitors<br />Who is “ACE” and why do we want to inhibit him?<br />Angiotensin Converting<br /> Enzym...
A few notes on ACE inhibitors<br />Use cautiously in patients with SBP < 90 mmHg<br />Draw serum creatinine and potassium ...
Adverse effects are due to 3 mechanisms<br />inhibiting breakdown of endogenous kinins (cough—females more than males), an...
BOTTOM LINE: ACE inhibitors<br />Improve symptoms in patients with heart failure (sometimes within the first 48 hours, but...
“Sartans”--ARBs<br />Angiotensin receptor blockers (bypass ACE) and work by blocking the tissue receptors<br />Who are the...
If additional aldosterone blockade is necessary…aldosterone antagonists<br />Eplerenone (generic or Inspra) QD @ $106.20 f...
Please note:<br />RALES (1999) (Random Aldactone Evaluation Study)—adding spironolactone/Aldactonepostpones or prevents 20...
Other drugs for heart failure??<br />Digoxin, of course—especially if the myocardium needs a little extra boost<br />When ...
NSAIDs and heart failure…<br />NSAIDs and fluid retention (due to vasoconstriction of the afferent arteriole)—especially t...
Hypertension<br />Increased vascular stiffness—increased systolic BP with widened pulse pressure; increased afterload<br /...
Isolated Systolic Hypertension (ISH)<br />Two thirds of hypertensive patients over 60 have ISH<br />Systolic rises with ag...
Blood pressure—Ideal? 120/80, BUT…<br />Depending on co-morbidities it may be kept slightly higher in the frail elderly to...
So, is it worth treating patients who are over 80 for hypertension?<br />Yes, indeedy. In the HYVET, double-blind, randomi...
How many drugs? <br />Most older hypertensive patients may require at least two drugs to achieve goal BP, especially those...
When choosing…<br />Would this drug have a favorable effect on co-morbidities?<br />Angina—beta blocker, calcium channel b...
How about aspirin for one and for all? What are the risks of aspirin for cardioprotection?<br />First of all, let’s calcul...
Risk is 2%...Means 2 of 100 people with this level of risk will have a heart attack in the next 10 years<br />141<br />
Heart disease risk over 10 years? If your risk is…<br />1%--aspirin will avoid 2 to 8 heart attacks and heart-related even...
An easier way to look at it?<br />Daily aspirin use by 1000 people for 10 years is estimated to cause up to 2 hemorrhagic ...
So, who benefits?<br />Diabetics over 40, or between 30 and 40 with other risk factors such as smoking, HTN, FH, high chol...
ASA and ibuprofen (Advil, Motrin)<br />How many older patients take ASA and a NSAID??? OTC ibuprofen is a NO-NO at the sam...
Switching gears…back to the 1% rule…An exception to the 1% rule--an INCREASE in clotting factors by 1% per year<br />146<b...
Triple antithrombotic therapy<br />Scenario—72 y.o. patient who needs clopidogrel and aspirin after a coronary stent; plus...
To do…<br />Aim for the lower end of the INR target of 2.0 to 3.0<br />Try to stop clopidogrel as soon as it’s safe—often ...
Atrial fibrillation<br />Approximately 2 million; risk increases with age<br />Increased risk of TIAs/stroke<br />AF can o...
Respiratory system<br />150<br />
Respiratory <br />Fever and tachypnea in the older adult—consider an acute pulmonary syndrome—<br />Pulmonary embolism (ov...
Other anti-inflammatory measures<br />Give those flu shots! Reduces the risk of an acute coronary syndrome by 66% <br />Pn...
Geriatric changes in the GI tract<br />Decreased intestinal motility and blood flow<br />Decreased gastric acid secretion ...
Gastric pH and calcium supplements<br />Calcium carbonate supplements can be taken with or without food, but they are tole...
NSAIDs and the GI Tract<br />The older the patient, the higher the risk of a GI bleed, especially with the non-selective N...
An increased risk of constipation in the elderly…why?<br />156<br />
Constipation is one of the major complaints in the older population…drugs are a major cause<br /> Drugs—drugs with anticho...
Bibliography<br />Andersen K, et al. Do nonsteroidal anti-inflammatory drugs decrease the risk for Alzheimer’s disease? Th...
Bibliography<br />Gardiner P, Phillips R, Shaughnessy AF. Herbal and dietary supplement-drug interactions in patients with...
Bibliography<br />Linton A, Garbor M, Fagan NK, Peterson MR. Examination of multiple medication use among TRICARE benefici...
Bibliography<br />Reuben DB, et al. Geriatrics At Your Fingertips. 2008-2009. 10th ed. The American Geriatrics Society, ...
More slides…<br />The following slides contain many more blurbs for your reading and classroom pleasure.<br />162<br />
Bowel preps<br />Preps containing sodium phosphate (Fleet Phosphosoda and Fleet ACCU-PREP, have led to kidney calcificatio...
Levothyroxine (LT4) and tachycardia<br />Caution when using with elderly—in older adults who might have clinically silent ...
Interactions with LT4<br />Levothyroxine decreases digoxin’s effect; starting LT4 in a patient taking dig may reduce the t...
Historical Highlight<br />In the 1930s physicians would sometimes deliberately induce hypothyroidism in patients with seve...
Drugs and weight in the elderly<br />Drugs and weight loss (dig, metformin, chemo, cholinesterase inhibitors for dementia)...
Will pills that contain salt increase blood pressure?<br />Antacids<br />Effervescent formulations<br />Zegerid (omeprazol...
Combos<br />Beta blockers and diuretics<br />atenolol/chlorthalidone—Tenoretic (50/25, 100/25 mg)<br />bisoprolol/HCTZ—Zia...
Combos<br />ACE inhibitors and diuretics<br />benazepril/HCTZ—Lotensin HCT (5/6.25, 10/12.5, 20/12.5, 20/25 mg)<br />enala...
Combos<br />Other combinations<br />triamterene/HCTZ—Dyazide (37.5/25 mg)<br />triamterene/HCTZ—Maxide (37.5/25, 70/50 mg...
Coumadin (warfarin sodium)…	<br />Interacts with everyone and everything…<br />Usual maintenance dose is 2-10 mg/day<br />...
Stats on depression and heart disease<br />Major depressive disorder (MDD) is as serious a risk factor for CHD as HBP, ↑Ch...
3 most common drugs for ER visits for the elderly<br />Warfarin (Coumadin)(17.3%) <br />Insulin (13%)<br />Digoxin (3.2%) ...
Pathophysiology of Delirium<br />Widespread reduction in oxidative metabolism leading to neurotransmitter deficiency and/o...
Drugs/conditions and heart rate changes<br />Bradycardia—hypothyroidism, dig, beta blockers (even topical beta blocker eye...
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Polypharmacy—August 2010

Published on: Mar 4, 2016
Source: www.slideshare.net


Transcripts - Polypharmacy—August 2010

  • 1. Polypharmacy—the Pearls, the Perils, and the Pitfalls of Pharmaceuticals in the Aging Population<br />Barb Bancroft, RN, MSN<br />www.barbbancroft.com<br />August 3, 2010<br />Chicago IL <br />1<br />
  • 2. Definitions of “age”…<br />Stratification of the older patient group into 3 groups:<br />“young old” – 65-75<br />“old”—75 to 85<br />“old-old”– over 85<br />By 2020 there will be ~1,000,000 centanarians in the U.S.<br />2<br />
  • 3. So, do you want to live to be 100?<br />“If you live to be 100, you have it made. Very few people die past that age.”<br />--George Burns, who died at age 100 in 1996<br />SO, IF YOU ARE 100 TODAY…<br />3<br />
  • 4. Your life expectancy as a…<br />Black Male – 2.9 years<br />Black Female – 3.0 year<br />White Male – 2.3 years<br />White Female – 2.5 years<br />If you are 60 today—<br />WM – 20.3<br />WF – 23.6<br />BM – 17.6<br />BF – 21.6<br />4<br />
  • 5. As an FYI: Life expectancy<br />If you are 40 today: <br />WM—37.4 years<br />WF—41.6 years<br />BM—32.8<br />BF—38.1<br />If you are 50 today:<br />WM—28.5<br />WF—32.4<br />BM—21.0<br />BF—25.4<br />5<br />
  • 6. Women have the age advantage at every age, except conception and over 100 for black males…<br />Why is conception the exception?<br />6<br />
  • 7. The sperm carrying the Y chromosome is the faster swimmer…<br />The early sperm gets the worm, so to speak…<br />Why?<br />7<br />
  • 8. Because…<br />The sperm carrying the Y chromosome is 23% lighter than the sperm carrying the X chromosome<br />Hence, the Y-carrying sperm weighs less and therefore is a faster swimmer <br />And, ladies…<br />
  • 9. Polypharmacy<br />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)<br />The effectiveness of drug therapy for many disease processes in the older patient is as great as it is for the younger patient population<br />9<br />
  • 10. The biggest problem… “poly”-conditions = “poly”-pharmacy<br />The average older adult has 6.5 chronic conditions, and multidrug therapy is the rule rather than the exception to the rule (Zurakowski)<br />Usually an average of 1 to 3 drugs given per condition—YOU DO THE MATH…<br />10<br />
  • 11. For example…<br />72-year –old male with diabetes, hypertension, hypercholesterolemia, erectile dysfunction, benign prostatic hypertrophy, glaucoma, osteoarthritis, peripheral artery disease, and depression<br />Let’s do the math…how 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<br />Anywhere from 10 to 19 drugs<br />And that doesn’t include…OPRAH and Suzanne Sommers<br />11<br />
  • 12. “alternative” and “complementary therapies…”<br />…St. John’s wort for depression<br />…cinnamon for diabetes<br />…red yeast rice for high cholesterol<br />…mistletoe (Iscador) for breast cancer<br />…saw palmetto or for BPH <br />…glucosamine for osteoarthritis <br />…yohimbine for ED <br />…gingko for PAD (AHA News Release, 12/02/08)<br />…ginseng for “whatever ails ya’”<br />…soy for hot flashes<br />12<br />
  • 13. Soy for menopausal symptoms<br />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)<br />13<br />
  • 14. As an FYI…<br />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)<br />
  • 15. Plus, over-the-counter drugs for aches and pain, sinus problems, allergies, colds, “indigestion”<br />Aspirin—drills a hole in the stomach and decreases renal blood flow<br />Acetaminophen—liver and kidney damage with long-term use<br />Excedrin—aspirin + acetaminophen…a double whammy<br />Ibuprofen—can negate aspirin’s cardioprotective effect, not to mention drill another hole in the stomach and decrease renal blood flow (and damage the kidney over time)<br />Prilosec OTC can negate the effects of clopidogrel and interact with “3,456” other drugs<br />TUMS, Citracal, Oscal – calcium supplements can interfere with thyroid replacement therapy<br />Cimetidine (Tagamet), ranitidine (Zantac)<br />Antihistamines (anticholinergic and wreak havoc with the elderly)—of the two, SAY NO TO TAGAMET<br />YIKES<br />15<br />
  • 16. So, is there an established definition of polypharmacy?<br />Old definition? Greater than 5 drugs…hahahaha<br />New definition? Nine or more drugs<br />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<br />Individual patients were prescribed an average of 6.1 medications across those categories with women averaging more and also having more therapeutic categories (Linton)<br />16<br />
  • 17. So, are there some absolute NO-NOs? <br />And if they’re not “absolute” NO-NO’s should you think twice about using certain combinations?<br />Anything potentially life-threatening?<br />YES…the combination of erectile dysfunction drugs and…<br />Nitroglycerine<br />17<br />
  • 18. And, the combination of ED drugs + certain BPH drugs can also be dangerous<br />The alpha one antagonists (no longer chosen for primary BP control due to their “extreme” hypotensive effects)<br />…especially with the first dose<br />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…<br />Combo with ED drugs? Severe hypotension<br />Use tamsulosin (Flomax) or sildodosin (Rapaflo) or the “sterides”—dutasteride (Avodart) or finasteride (Proscar)<br />18<br />
  • 19. Another potentially deadly combination…<br />ACE inhibitors (any drug with the last name “pril”) with either of the K+ sparing diuretics, the aldosterone antagonists—spironolactone (Aldactone) and eplerenone (Inspra)<br />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<br />Did you know that TMP-SFX (Bactrim/Septra) can also cause hyperkalemia and is especially dangerous w/ an ACE-<br />Is thACE/Aldactone combo used all of the time? Yes…CAREFULLY in HF patients…more later…<br />19<br />
  • 20. Tamoxifen, paroxetine (Paxil), fluoxetine (Prozac)<br />30% of patients on tamoxifen also take an SSRI for either depression or hot flashes<br />Use of paroxetine (Paxil), fluoxetine (Prozac), and sertraline (Zoloft) with tamoxifen—<br />The P’s are strong inhibitors of CYP 2D6<br />Tamoxifen is converted to an active metabolite via CYP 2D6 (endoxifen—100x more potent than tamoxifen)<br />Use of either of the above antidepressants can almost double the risk of recurrence (13.9% vs. 7.5% w/placebo)<br />(Prescriber’s Letter July 2009)<br />
  • 21. What to do?<br />Switch antidepressants or switch to an aromatase inhibitor (for example: anastrozole/Arimidex) if the postmenopausal female<br />Use citalopram (Celexa)* for hot flashes if you pick an SSRI <br />*the only antidepressant that has shown some effectiveness for hot flash reduction<br />Or try gabapentin (Neurontin)<br />21<br />
  • 22. Dig and clarithromycin (Biaxin)<br />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)<br />Clarithromycin Rx is commonly chosen for community-acquired pneumonia and H. pylori infections<br />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). <br />22<br />
  • 23. Why? Dig--clarithromycin<br />Clarithromycin inhibits intestinal P-gp and dig cannot be eliminated—resulting in dig-toxcity<br />Elevated dig levels* to potentially fatal arrhythmia levels have been reported with the clarithromycin. <br />*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<br />23<br />
  • 24. Speaking of dig…fun facts for nursing students…<br />Digitalis is over 200 years old—from the foxglove plant<br />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”<br />Leeches and other forms of “blood-letting” were used by the medical establishment at the time<br />
  • 25. One more potentially deadly interaction—high-dose simvastatin and amiodarone<br />Amiodarone inhibits the metabolism of simvastatin—the higher the dose of simvastatin the greater the build up of the drug<br />Very high risk of rhabdomyolysis and subsequent acute renal failure<br />Variation on the theme…amiodarone and grapefruit juice…grapefruit juice inhibits the enzyme in the small intestine that metabolizes amiodarone—increased bioavailability and increased toxic side effects (fatal ventricular dysrhythmias)<br />25<br />
  • 26. Before the prescription pad is pulled out…<br />What is the problem being treated?  <br />What is the drug of choice for the diagnosis?<br />Is the drug necessary and is it effective for this problem?  <br /> Is the safest drug being used for this age group?<br />     <br />26<br />
  • 27. Consider my Aunt Betty Jo…<br />Dx: Mild Alzheimer’s disease<br />Dx: Osteoporosis<br />Her M.D. prescribed alendronate (Fosamax) for her osteoporosis…I said to my mother…<br />“I don’t think that was a wise move, based on her memory impairment…”<br />OK, I’ll talk to her on Saturday (it was Monday when my concern was voiced)<br />On Saturday, my Aunt Betty Jo said…”well, I don’t know why the pharmacist won’t give me any more of the pills, I ran out of them in LESS than a week…”<br />One shot of RECLAST once or twice a year would have been the better choice…<br />27<br />
  • 28. Are there nonpharmacologic alternatives?<br />Back brace for vertebral fractures<br />Cognitive behavioral therapy for mild to moderate depression<br />28<br />
  • 29. NON-pharmacologic alternatives?<br />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<br />29<br />
  • 30. Questions…continued…<br />Is the lowest effective dose being used?<br />For most indications in the elderly, “start slow and go slow” is the rule…one major exception to the rule is the group of drugs called the statins to lower the LDL cholesterol…start with a dose that reduces LDL cholesterol by 30-40%<br />      <br />30<br />
  • 31. Questions…<br />Does the patient have symptoms potentially attributable to the drug?   <br />Erectile dysfunction drugs and GERD—ED drugs induce the production of the potent vasodilator nitric oxide; nitric oxide also opens the lower esophageal sphincter and can contribute to GERD<br />Muscle aches and pains—also on a statin perhaps<br />31<br />
  • 32. Digression on ED drugs and the elderly<br />The fastest rising group for STDs in U.S. is the over 60 crowd—an increase of over 300% since sildenafil (Viagra, the Pfizer riser) hit the market in 1998 (November 1, to be exact)<br />HPV, HSV, HIV, GC, Syphilis<br />Why?<br />32<br />
  • 33. because…more sex<br />Many are swingin’ singles <br />No pregnancy risks<br />No frontal lobe…who cares what the neighbors think??<br />Sex on the beach, in swimming pools, on golf courses<br />Also an increase in UTIs<br />Increased marital bliss in some;<br />marital nightmares in others due infidelity issues and wanting sex all of the time after not having it for 30 years…<br />33<br />
  • 34. More questions…<br />Is the patient capable of following directions? Amiodarone* and grapefruit juice? Alendronate and directions…       <br />Is specific monitoring necessary (e.g., liver enzymes or drug levels)?INRs for warfarin, LFTs and TSH for amiodarone, serum creatininebeformetformin, dig levels, potassium levels for ACE inhibitors<br />34<br />
  • 35. Is there a more cost-effective alternative?Example: beta blockers for HF<br />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<br />Carvedilol/Coreg CR is $145.80 for 30 days; nebivolol/Bystolic is $55.80 for 30 days<br />35<br />
  • 36. How old is the patient and how long will it take the patient to benefit from the drug?<br />It takes 8 years to see benefits for the treatment of diabetes to reduce the microvascular complications <br />It takes 3 years to see the macrovascular benefits of treatment in diabetes<br />36<br />
  • 37. What is the half-life of the drug?<br />If the half life is longer than the patient’s life, it’s NOT a good choice<br />Half-life should be less than 24 hours with no active metabolites<br />…and that’s usually a drug like amitryptyline to NORtriptyline (choose nortryptyline to treat depression or the pain of peripheral neuropathy); meperidine to NORmeperidine (don’t choose meperidine OR NOR meperidine), don’t choose fluoxetine (Prozac) as it is metabolized to NORfluoxetine with an elimination half-life of 7 to 9 days in the elderly <br />37<br />
  • 38. Last question…is there a drug that might “kill two birds with one stone” so to speak?<br />Losartan (Cozaar) for managing chronic gout…has a modest uricosuric effect that plateaus at 50 mg/d; may be useful in patients with hypertension or heart failure or diabetes (Reuben)<br />Doxazosin (Cardura) for BPH and HTN (normally one would avoid doxazocin as a first-line therapy for HTN, however, it’s a good choice for the combination of a big ol’ “prostrate” and hypertension<br />HCTZ for hypertension in women over 60 as first-line therapy—competes with calcium excretion; the drug is excreted , the calcium is retained and bones are strong like bull.<br />38<br />
  • 39. And, last but not least, is this one of the medications on the Beers List? (Fick)<br />39<br />
  • 40. BEERS List – USE THIS, NOT THAT<br />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. <br />List updated in 2003—medications are deemed inappropriate because there are safer, equally efficacious alternative medications. <br />Whenever possible, the use of medications on the Beer’s List should be avoided. (Fick)<br />40<br />
  • 41. The proverbial caveat…<br />Prescribing medications on the Beer’s List of increases the risk of drug-related morbidity and mortality; however, not all of these medications are inappropriate in all older patients<br />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<br />Don’t JUST look at age…consider the whole patient—warts, comorbidities and all….<br />41<br />
  • 42. Beers Criteria—the most frequently seen harmful interactions involve the following BEERS drugs:<br />1) cardiovascular drugs (Digoxin, amiodarone/Cordarone)<br />2) pain medications (long-acting NSAIDS such as piroxicam/Feldene, oxaprozin/Daypro, meperidine/Demerol, propoxyphene/Darvon and it’s combination products<br />3) anti-depressants/antipsychotic drugs/anti-anxiety drugs (fluoxetine/Prozac; haloperidol/Haldol, diazepam/Valium; oxazepam/Serax; flurazepam/Dalmane; triazolam/Halcion; amitriptyline/Elavil)<br />4) OTC drugs—cimetidine/Tagamet; diphenhydramine/Benadryl)<br />Lots of drugs on the BEERS list have anticholinergic effects—amitriptyline and cimetidine, for example<br />42<br />
  • 43. Normal functions of acetylcholine<br />Mentation (CNS)<br />Pupillary constriction (PNS)<br />Decreases heart rate (PNS)<br />Increases salivation (PNS)<br />Increases peristalsis (PNS)<br />Loosens urinary sphincter (PNS)<br />43<br />
  • 44. Anti-cholinergic drugs—side effects<br />Confusion<br />Pupillary dilation (blurred vision, glaucoma)<br />Tachycardia (angina, possible MI)<br />Decreased salivation (dry mouth)<br />Decreased peristalsis in GI tract (constipation)<br />Tighten urinary sphincter (urinary retention)<br />44<br />
  • 45. Drugs for OAB (overactive bladder)—anticholinergic effects<br /><ul><li>oxybutynin (Ditropan)(Gelnique—topical gel)(Oxytrol patch)
  • 46. Toterodine (Detrol LA); fesoterodine (Toviaz)
  • 47. Darifenacin (Enablex); solifenacin (Vesicare)
  • 48. Trospium (Sanctura)
  • 49. (Prescriber’s Letter, June 2009;16(6):36</li></ul>45<br />
  • 50. Anti-cholinergic drugs—the usual suspects and some surprises…<br />Amitryptyline (Elavil)—the higher the dose, the higher the risk of anti-cholinergic effects; Rx for neuropathic pain vs. Rx for depression<br />Hyoscyamine (Anaspaz, Atropine)<br />Doxepin (Sinequan) <br />Meclizine (Antivert) <br />Captopril (Capoten), nifedipine (Procardia) <br />Prednisolone<br />dig, dipyridamole (Persantine)<br />warfarin<br />Furosemide (Lasix) <br />isosorbidedinitrate (Isordil)<br />46<br />
  • 51. And then some…<br />Paroxetine (Paxil)<br />Codeine <br />Oxycodone <br />Diphenhydramine <br />Fexofenadine (Allegra) <br />Hydroxyzine (Atarax) <br />Loratadine (Claritin) <br />dicyclomine (Bentyl)<br />Cimetidine (Tagamet), ranitidine (Zantac)<br />Haloperidol (Haldol)<br />47<br />
  • 52. What is aging?<br />“Aging seems to be the only available way to live a long life.” –Daniel Auber, French composer (1782-1871)<br />Aging is just getting older…by the time you leave here today…<br />48<br />
  • 53. More importantly…what is senescence??<br />The rate of deterioration of the structure and function of body parts <br />Functional reserve capacity of tissues is 4-10 times greater than baseline (the amount needed just to function)<br />Peak functional capacity is reached at age 24<br />6 good years<br />49<br />
  • 54. Senescence and normal aging...the 1% rule<br />Peak at 24, 6 good years, gradual decline to baseline of <br />~ 1% per year; <br />50<br />FC%<br />Baseline function<br />75 yrs<br />1yr<br />30<br />
  • 55. But between 24 and 30…<br />We’re cookin’ on the all burners…<br />Our brain, our kidneys, our hearts, our lungs…<br />51<br />
  • 56. Variation on the theme: senescence accelerates with chronic disease (DM, COPD)...<br />52<br />FC%<br />Baseline function<br />75 yrs<br />1yr<br />30<br />
  • 57. Senescence and gender differences...the demise of the ovary<br />Gender differences—the ovary (51.3 +/- 2.7)<br />53<br />FC%<br />Baseline function<br />75 yrs<br />1yr<br />30<br />
  • 58. Do men’s testicles die at 51.3 +/- 2.7 years? NOOOOOOOOOOOOO<br />54<br />
  • 59. The 1% rule and the kidney…<br />Glomerular filtration rate (GFR)—120-125 ml/min at age 25; decreases by ~1% per year; as an estimate:<br />75-year-old = 1.2 mL/min x 45 years = 53 mL/min; 120-53=67 mL/min in a HEALTHY 75-year-old (not taking into account weight, ethnicity, or gender)<br />BUT, a GFR of 60-89 mL/min=mild renal insufficiency<br />a GFR of less than 60 mL/min/1.73 m2 represents a loss of more than half of normal kidney function<br />55<br />
  • 60. 1% rule…renal function and aging…<br />Diminished renal blood flow<br />Increased retention of water soluble drugs such as dig—increased toxicity<br />Many doses of drugs need to be adjusted based on the GFR<br />
  • 61. The Geriatric Kidney—the scope of the problem<br />Chronic kidney disease is caused by irreversible age-related and disease-related damage to the kidney and affects nearly 30% of all elders<br />Among older adults, the incidence of drug-induced nephrotoxicity may be as high as 66 percent<br />Compared with 30 years ago, today’s 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<br />57<br />
  • 62. Assessing renal function in the elderly<br />Serum creatinine is misleading in older patient <br />Why? Serum creatinine is based on the breakdown of creatine from muscle mass; older patients have reduced muscle mass and therefore make LESS creatine<br />Combine that with a reduced GFR and the serum creatinine provides a false normal reading<br />Best measurement is the creatinineclearance which equates to the GFR via the Cockcroft-Gault equation (MDRD equation as it tends to overestimate kidney function in the older adult (Gill )<br />IBW (140-age)(0.85 if female)<br /> 72(stable serum creatinine<br />
  • 63. For example…<br />Radiocontrastdyes for diagnostic purposes<br />Renal staghorn calculus as demonstrated by an IVP<br />
  • 64. Drugs and the kidney<br />Don’t forget to stop the metformin (Glucophage) for 48 hours after a radiocontrast dye<br />Increased risk of lactic acidosis (albeit a low risk, but the risk is highest in the elderly)<br />Metformin competes with the contrast dye for excretion; the contrast dye wins and dives into the toilet; metformin is retained and can accumulate<br />You won’t be using Metformin anyway if the kidneys are not working well (serum creatinine should be drawn before prescribing Metformin)<br />60<br />
  • 65. Gross anatomy<br />
  • 66. Drugs and the kidney<br />Tubular cell toxicity—especiallythe proximal tubule—extremely vulnerable to toxic effects of drugs and the lack of oxygen since the proximal tubule does the lion’s share of reabsorbing the glomerular filtrate <br />(Acute Tubular Necrosis/ATN—what’s the good news? epithelial cells line the renal tubules)<br />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<br />62<br />
  • 67. Various mechanisms of damage<br />Inflammation: Drugs can cause inflammatory changes in the glomerulus (glomerulonephritis) and the medullary interstitium (interstitial nephritis)<br />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)<br />63<br />
  • 68. Various mechanisms of damage<br />Inflammation with acute medullary interstitial nephritis: Usually results from an allergic response and develops in an idiosyncratic non-dose-dependent fashion<br />Thought to bind to antigens in the kidney or act as an antigen eliciting an immune response<br />Allopurinol (Zyloprim), antibiotics (beta-lactams, quinolones, rifampin (Rifadin), sulfonamides, and vancomycin (Vancocin) <br />64<br />
  • 69. Nephrotoxic drugs and the elderly<br />Drugs that inhibit angiotensin 2 (ACE inhibitors or the “prils” and the ARBs—angiotensin receptor blockers) are especially dangerous if renal blood flow is compromised—renal artery atherosclerosis (stenosis) (Baciewicz) or with NSAIDs<br />NSAIDs and vasoconstriction of the renal artery and afferent arteriole<br />Renal blood flow relies more on prostaglandin synthesis to maintain a vasodilated state in the elderly patient<br />NSAIDs combined with ACE inhibitors or ARBs in the elderly may precipitate acute renal failure—HOW?<br />65<br />
  • 70. The healthy kidney<br />Afferent arteriole<br /> (normally vasodilated<br /> (via prostaglandins)<br />Blood entering<br />glomerulus<br />Glomerulus->filter<br />Efferent arteriole<br /> (normally vasoconstricted<br /> (via angiotensin II)<br />66<br />Prostaglandins – blocked by NSAIDs<br />filter<br />AngiotensinII—blocked by ACE --<br />Toilet<br />
  • 71. The combination of ACE inhibitors and NSAIDs can precipitate acute renal failure<br />EXPLANATION OF PREVIOUS SLIDE<br />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)<br />ACE inhibitors block ACE and the production of angiotensin II—blocking angiotensin II vasodilates the efferent arteriole of the kidney<br />Decreased blood IN and increased blood OUT = decreased filtration and acute renal failure <br />67<br />
  • 72. Drugs that can wreak havoc with RENAL FUNCTION in the elderly…<br />Aminoglycosideantibiotics (Amikacin/Amikin; gentamicin/Garamycin; tobramycin/Nebcin), diabetes, and concomitant use of ACE inhibitors increase the risk of nephrotoxicity<br />Adjust dose with GFR less than 60<br />Ears and kidneys<br />
  • 73. Drugs that are excreted by the kidneys and potentially retained in the elderly<br />Allopurinol<br />Aminoglycosides<br />Amoxicillin<br />Ampicillin<br />Atenolol<br />Captopril<br />Chlopropamide<br />Cimetidine<br />Clarithromycin<br />Colchicine<br />digoxin<br />Disopyramide<br />Enalapril<br />Famotidine<br />Fluconazole<br />Furosemide<br />Gabapentin<br />Gancyclovir<br />HCTZS<br />Levofloxacin<br />Lisinopril<br />Lithium<br />metformin<br />69<br />
  • 74. Drugs that are excreted by the kidneys and potentially retained in the elderly<br />Methotrexate<br />Penicillin<br />Phenobarbital<br />Procainamide<br />Ramipril<br />Ranitidine<br />Spironolactone<br />Sulfamethoxazole<br />Tetracycline<br />Trimethoprim<br />70<br />
  • 75. General changes--water loss and aging<br />Decrease in total body water stores<br />Decreased osmoreceptors and diminished thirst<br />Decreased volume of distribution <br />Increased drug toxicity with water-soluble drugs—examples include dig, oxycodone, atenolol (Tenormin), captopril (Capoten), venlafaxine (Effexor), cimetidine (Tagamet), ethanol, lithium <br />71<br />
  • 76. General changes…body fat changes—distribution and amount <br />Loss of subcutaneous fat (actually you don’t LOSE the fat, you just move it to the internal visceral organs) with age--difficulty maintaining internal temperatures with extremes of ambient temperature<br />Hypothermia/hyperthermia<br />“You’re not dead until you’re warm and dead.”<br />Always check the thyroid gland—myxedema coma + cold ambient temperature<br />Another implication of visceral fat? Increased insulin resistance—T2DM<br />72<br />
  • 77. Body fat changes—distribution and amount<br />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. <br />Fat-soluble drugs such as diazepam/Valium and anesthetics have much greater distribution in older and obese individuals<br />Results in retention of fat/lipid soluble drugs—can result in toxicity if dosing interval is not increased or if dose is not decreased<br />73<br />
  • 78. Benzodiazepines for example<br />Half-life (T1/2) of diazepam (Valium) is the patient’s “age, in hours”<br /> 25-year old = 25 hours<br /> 75-year old = 75 hours<br />Use of a long-acting BZ in the geriatric patient is a NO-NO (see Beers List) <br />Shorter-acting benzodiazepines should be used in the elderly (temazepam/Restoril, oxazepam/Serax, lorazepam/Ativan (Beers List)<br />74<br />
  • 79. Amidarone vs. dronedarone<br />Dronedarone/Multaq will shortly over take amiodarone for atrial fibrillation, if it hasn’t already<br />Dronedarone—elimination 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<br />
  • 80. General changes—decreased albumin levels, therefore less drug- binding sites<br />Adult/elderly levels are 3.5-5 g/dl or 35-50 g/L<br />In addition to maintaining osmotic pressure, albumin binds drugs (protein-bound (inactive) vs. “free” or active drug)<br />Drugs will be “competing” for binding sites<br />Hypoalbuminemia (less than 3.0 g/dL or 30 g/L)—what are the causes?<br />76<br />
  • 81. Hypoalbuminemia<br />Three major causes of hypoalbuminemia<br /> 1) liver disease—not making enough<br /> 2) kidney disease –excreting too much (nephrotic syndrome)<br /> 3) the very old geriatric patient due to the aging liver and malnutrition<br />
  • 82. Low albumin and competition for binding sites<br />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<br />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<br />Warfarin is a weak binder and numerous drugs knock “her” off “her” binding sites—two unexpected drugs also knock warfarin off of the albumin binding sites<br />78<br />
  • 83. Who are they?<br />Acetaminophen (yep, and how many elderly patients are on Tylenol for muscle aches and pains)?<br />Miconazole (Monistat)—yep, even topical miconazole can knock warfarin off of her binding sites<br />Sulfa-based drugs are also big bullies and can knock warfarin off albumin’s binding sites<br />Trimethoprim-sulfamethoxazole (Bactrim/Septra)<br />And, metronidazole (Flagyl), erythromycin, cipro and other FQs (floxacins)<br /> ASA competes with warfarin for binding sites<br />79<br />
  • 84. So when should the INR levels be checked in patients on warfarin?<br />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<br />Warfarin (Coumadin) is the most common drug that brings the elderly patient to the emergency room (17.3%)<br />WARF (Wisconsin Alumni Research Foundation)<br />Can anyone guess what the second most common drug that brings the elderly patient to the ER<br />80<br />
  • 85. Other examples of drugs being knocked off their binding sites<br />Digoxin– quinidine and verapamil displace dig and can increase dig levels by 50%--T O X I C I T Y…<br />Digoxin toxicity—the 3rd most common drug that brings the elderly to the ER<br />Dig is on the BEERS LIST<br />
  • 86. Drugs that are highly bound to albumin require close monitoring for adverse effects…<br />Amiodarone<br />Amlodipine<br />Antipsychotics<br />Bupropion<br />Buspirone<br />Carbamazepine<br />Cefazolin<br />Ceftotetan<br />Ceftriaxone<br />Cilostazol<br />citalopram<br />Ditiazem<br />Dipyridamole<br />Felodipine<br />Lansoprazole<br />Midazolam<br />Nifedipine<br />NSAIDs<br />Omeprazole<br />Pantoprazole<br />Phenytoin<br />Rabeprazole<br />raloxifene<br />82<br />
  • 87. Drugs that are highly bound to albumin<br />Rifabutin<br />Sertraline<br />Sulfonylureas<br />Tamsulosin<br />Terazosin<br />Valproic acid<br />Verapamil<br />warfarin<br />83<br />
  • 88. THE LIVER and DRUG METABOLISM<br />Hepatic blood flow may be reduced due to atherosclerosis<br />IS THERE ANY ARTERY THAT DOESN’T FILL WITH FAT????<br />Decreased metabolism of drugs resulting in increased bioavailability and toxicity<br />Tagamet (cimetidine) also hepatic artery vasoconstriction resulting in the decreased metabolism of drugs and a higher bioavailability<br />Can cause beta blockers to decrease the HR to dangerously low levels; morphine and derivatives may decrease respirations to dangerously low levels<br />TAGAMET—BEERS List<br />
  • 89. NEUROPHARMACOLOGY OF AGING<br />85<br />
  • 90. Neurology of aging…<br />5% loss of cerebral weight in females by 70<br />10% loss in men – don’t get too smug, ladies…(men start out with a bigger brain)<br />By 80, 17-20% loss<br />Selected areas are the frontal lobes and the medial temporal lobes<br />86<br />
  • 91. Medial temporal lobe and the loss of hippocampal cell function<br />Loss of recent memory<br />This is the first neurologic function to go with the process of senescence<br />Benign forgetfulness<br />Mild cognitive impairment<br />Full-blown dementia<br />87<br />
  • 92. Which brings us, of course, to the dementias…Alzheimer (s) disease or DAT<br />The hallmark of all dementia is memory loss<br />Alzheimer’s dementia<br />Cortical atrophy<br />Sulcal widening<br />“feathering”<br />Decreased brain weight<br />90% decline in acetylcholine, the neurotransmitter of cognition<br />88<br />
  • 93. Pathology—it takes 5 to 20+ years before the 1st symptom of memory loss<br />Beta-amyloid plaques (BAP)—sticky globs outside the cells; abnormal processing and cleaving of amyloid precursor protein—earliest indication of the development of dementia<br />Less AD in people from India and Pakistan<br />Turmeric the spice? Curcumin is the active ingredient <br />89<br />
  • 94. It takes “tau” to tangle…1 to 5 years before first symptom<br />Neurofibrillary tangles—tangled microtubules inside the cells; tau protein helps to stabilize the microtubules and thus, maintain the integrity of the neuron<br />Neuronal degeneration<br />Tau is predominant in FTD (frontal temporal dementia)<br />BAPtists vs TAUists<br />90<br />
  • 95. Cholinergic dysfunction in the AD brain<br />What do all of these plaques and tangles do? Reduce the function of acetylcholine—the transmitter of cognition<br />Cholinergic impairment has been implicated in memory and cognitive dysfunction in the elderly<br />Accentuated in patients with Alzheimer’s disease and other dementias<br />Decreased acetylcholine receptors in the forebrain and other regions as well as altered acetylcholinesterase enzyme function<br />91<br />
  • 96. One of two available treatments for AD today…boost remaining acetylcholine …<br />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<br />Others—galantamine (Razadyne, Razadyne ER), rivastigmine (Exelon)(patch is well-tolerated)<br />Reminyl was renamed Razadyne to avoid errors with the diabetes drug, Amaryl (glimepiride)…mistakes led to hospitalizations and deaths<br />Donepezil and rivastigmine have also been approved for other types of dementia—vascular/Parkinson’s, Lewy Body Dementia; galantamine w/ vascular dementia<br />92<br />
  • 97. Benefits of cholinesterase inhibitors?<br />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. <br />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. <br />93<br />
  • 98. Benefits of cholinesterase inhibitors?<br />Other tangible clinical outcomes: <br /> 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 AD—suggesting a neuroprotective effect of this particular cholinesterase inhibitor. <br />Galantamine (Razadyne) and donepezil (Aricept) have also been shown to be neuroprotective by preventing neuronal apoptosis (programmed cell suicide). <br />94<br />
  • 99. Drug interactions with the cholinesterase inhibitors<br />Drugs with anti-cholinergic properties can potentially decrease the effectiveness of the acetylcholinesterase inhibitors <br />Paroxetine (Paxil) is an excellent example—the anticholinergic effects of Paxil can negate the acetylcholine boosting effects of Aricept and friends<br />Paroxetine (Paxil) has the MOST anticholinergic effects of all SSRIs…do not use.<br />95<br />
  • 100. Memantine (Namenda/US;Ebixa/Canada)2nd drug used for AD<br />Namenda, {Ebixa }(memantine)—decreases excessive activation of NMDA receptor by glutamate; offers modest functional improvements in patients with Alzheimer’s disease<br />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<br />Mild to moderate to severe AD as an add-on or has been used alone<br />96<br />
  • 101. On the horizon…<br />AAC-001 –vaccination against beta amyloid<br />Alzhemed (tramiprosate)—prevents neurofibrillary tangles and build up of beta amyloid<br />Bapineuzumab—monoclonal antibody to beta amyloid<br />LY2042430—may inhibit beta amyloid<br />LY450139—gamma secretase inhibitor<br />PBT-2—decreased levels of beta amyloid<br />TTP488—reduces amyloid burden<br />97<br />
  • 102. Delirium in the elderly<br />1-2% of community dwelling; 10-22% of hospitalized inpatients, 58% of nursing home patients<br />15-26% of elderly with delirium die<br />Cause of death is the underlying cause of delirium<br />Treating delirium improves cognitive dysfunction<br />98<br />
  • 103. “Assume that the onset of delirium in the old person is due to infection.”—Clifton Meador, M.D.<br />It’s either a UTI or pneumonia<br />Listen to the lungs and do a urinalysis<br />99<br />
  • 104. If it’s a female, consider a urinary tract infection as the cause of acute delirium…<br />Check the urinary tract<br />WBCs in urine, WBC casts in the urine (pyelo)<br />Only 8% of the women in nursing homes today receive estrogen in one form or another<br />Estrogen and the urinary tract maintains the health of the urinary tract; lowers pH of urine, keeps it acidic<br />Topical estrogen and a reduction in urinary tract infections<br />100<br />
  • 105. If it’s a male…either go with pneumonia or a UTI due to a “prostrate” the size of Texas<br />101<br />
  • 106. The second major cause of delirium is polypharmacy…<br />The blood brain barrier in the elderly is more permeable to drugs—everything that is lipid-soluble gets in<br />Narcotics and NSAIDS<br />Benzodiazepines<br />Any drugs with “anti” as their first name…Anticholinergics, antiarrhythmics, anti-histamines, antihypertensives, antipsychoticcs, antiparkinsonism, antianxiety, antidepressants, antimicrobials<br />Cimetidine (Tagamet), digoxin, steroids, acetaminophen, diuretics, meperidine, amantidine<br />Sudden withdrawal of drugs<br />102<br />
  • 107. The third major cause of delirium is electrolyte imbalance…many of the electrolyte imbalances are caused by medications<br />Low sodium—consider 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<br />Low or high potassium—consider diuretics again for low potassium; for high potassium go straight for the ACE inhibitors especially combined with spironolactone or eplerenone<br />ACE inhibitors combined with TMP-SFX has also been shown to cause hyperkalemia<br />Hypercalcemia--#1 cause in the elderly??? Not drugs, not hyperparathyroidism, but…..<br />103<br />
  • 108. Depression… <br />More common than dementia<br />Often co-exists with dementia<br />May appear withdrawn, uncooperative or intermittently agitated<br />Functionally or cognitively impaired<br />May prolong recovery from illness due to lack of cooperation, negativism, and poor self-esteem<br />104<br />
  • 109. The usual neurovegetative signs of depression are unreliable in the elderly…(The SALSA signs)<br />Sleep disturbances, appetite changes, low, self esteem, and anhedonia (lack of interest in day-to-day activities)<br />There is NO significant illness or medical condition in late life that does NOT impinge upon sleep, appetite or energy or sense of vitality<br />Usual aging also brings changes in sleep patterns and energy expenditure…<br />If within 10 minutes…<br />Geriatric Depression Scale<br />Sertraline (Zoloft) and escitalopram (Lexapro; Cipralex) are excellent choices—few side effects, few drug interactions, short half-lives<br />105<br />
  • 110. Cardiovascular system and drugs in the elderly<br />106<br />
  • 111. The Cardiovascular system and aging<br />Increased prevalence of cardiovascular disease with aging<br />People over 65 account for 65% of all cardiovascular hospitalizations and 80% of all heart failure admissions<br />107<br />
  • 112. The aging heart and vascular system…<br />1% rule--maximal O2 consumption and cardiac output decrease by 1% per year starting at age 30; <br />Interestingly and fortunately, the heart rate does not decrease by 1% per year with age<br />However, elderly patients have a decreased heart rate reserve and maximum attainable heart rate <br />108<br />
  • 113. The aging heart and vascular system<br />Endothelial dysfunction—increased risk for atherosclerosis which in turn increases therisk of coronary artery disease, cerebrovascular disease, PAD, etc.<br />Use of the “statins”—lova, prava, simva, atorva, rosuva, pitava…<br />109<br />
  • 114. The “Statin Sisters”… <br />Who are they?<br />lovastatin (Mevacor)<br />simvastatin (Zocor)<br />atorvastatin (Lipitor)<br />fluvastatin (Lescol)<br />pravastatin (Pravachol)<br />rosuvastatin (Crestor)<br />pitavastatin (Livalo)<br />
  • 115. Other manifestations of atherosclerosis in the elderly<br />Renal artery stenosis<br />Hypertension<br />Chronic kidney disease<br />Abdominal aortic aneurysm<br />Abdominal bruit<br />111<br />
  • 116. “You’re not getting enough blood flow to your ‘private parts’”--ED<br />The little blue pill that changed the lives of millions--November of 1998<br />The “Pfizer riser” and friends<br />(sildenafil, vardenafil, tadalafil)<br />Viagra, Levitra, Cialis (the weekend warrior)<br />Boost nitric oxide and increase blood flow to the “privates”<br />Before 1998; After 1998<br />Pilots<br />Tetanus shots<br />112<br />
  • 117. Chronic Heart Failure<br />Approximately 2% of adults suffer from heart failure, but in those over the age of 65, this percent increases to 6–10%<br />6% of diabetic men develop heart failure, 10% of diabetic women<br />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%.<br />113<br />
  • 118. Chronic Heart Failure-- CHF<br />Decreased contractile reserve along with multiple risk factors (atherosclerosis, hypertension, diabetes, valvular heart disease) results in an increased risk of CHF<br />Nomenclature has changed—just a tweak…congestive to chronic; we can still keep the acronym<br />Left-sided vs. right-sided (old classification and useful for teaching purposes)<br />Current classification: Systolic vs. diastolic (is it pump failure or filling failure?)<br />An ejection fraction of less than 40% indicates systolic dysfunction; an ejection fraction of ≥ 40% indicates heart failure with preserved systolic function (diastolic dysfunction)<br />
  • 119. BB’s causes of heart failure<br />The broken heart—primary cardiac muscle failure (myocarditis, alcohol and thiamine deficiency—why don’t we just add thiamine to booze, darn-it? )—90% is dilated cardiomyopathy<br />The betrayed heart—the heart that is let down by its friends—decreased O2 with COPD, atherosclerosis, diabetes<br />The befuddled heart—the heart that beats funny<br />The defeated heart—working too hard against a resistance (HTN, stenotic or leaking valves)<br />
  • 120. Heart failure caveats<br />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)<br />The second cause of hospitalization and deteriorating heart function is respiratory infection. Archives of Internal Medicine 2001; 161 (19): 2337-42)<br />The third leading cause of deteriorating heart failure and hospitalization is not taking prescribed medications. Archives of Internal Medicine, 2001; 161 (19): 2337-42)<br />
  • 121. The pathophysiology of heart failure…<br />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<br />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<br />Synthetic BNP is nesiritide (Natrecor)—for hospitalized decompensated HF patients with dyspnea at rest<br />
  • 122. Pathophysiology of Heart Failure<br />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)<br />The epinephrine/adrenalin also causes remodeling of the heart muscle and increases the risk of ventricular dysrhythmias<br />
  • 123. Enter the beta blockers for heart failure<br />Bisoprolol (Zebeta or generic) – QD*<br />Carvedilol (Coreg, Coreg CR or generic) BID (also an vasodilator via alpha 1 blockade)<br />Metoprololsuccinate (not tartrate) Toprol XL or generic)—QD<br />Nebivolol (Bystolic)*—QD (also a vasodilator via nitric oxide production)<br />*bisoprolol and nebivolol have not been FDA approved for heart failure but they work; nebivolol is the least effective…<br />119<br />
  • 124. Beta blockers<br />Start with low-dose<br />Fatigue (non-selective beta blockers cross the BBB and block norepinephrine in the brain—makes 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<br />120<br />
  • 125. The kidney compensates… “I can help!”<br />The third compensatory mechanism with heart failure—the KIDNEY “senses” low volume and/or low pressure<br />121<br />
  • 126. The kidney and the renin-angiotensin-aldosterone system <br />Think of HF as a “hyper-reninemic” state<br />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 <br />Angiotensin II triggers the release of aldosterone<br />Too much of a good thing…<br />122<br />
  • 127. In other words, Angie is a bad girl in heart failure<br />Angie ‘tenses’ your angios and vasoconstricts) and “al”dosterone (conserves sodium and water and secretes potassium)—resulting in increased afterload and preload<br />Now the heart has to work even harder<br />Angie also remodels the myocardium and increases the risk for ventricular dysrhythmias<br />123<br />
  • 128. To the rescue…ACE inhibitors-- “the PRILS”—block the conversion of angiotensin I to II<br />Captopril (Capoten and generic)—TID (compliance problems)<br />Enalapril (Vasotec and generic)--BID<br />Lisinopril (Prinivil, Zestril and generic)--QD<br />Perindopril (Aceon)--QD<br />Trandolapril (Mavik and generic)--QD<br />Ramipril (Altace and generic)--QD<br />124<br />
  • 129. “PRILS”—The ACE inhibitors<br />Who is “ACE” and why do we want to inhibit him?<br />Angiotensin Converting<br /> Enzyme (ACE) inhibits the conversion of ATI to ATII<br />ALDOSTERONE<br />ACE--<br />125<br />
  • 130. A few notes on ACE inhibitors<br />Use cautiously in patients with SBP < 90 mmHg<br />Draw serum creatinine and potassium levels prior to starting ACE inhibitors<br />Use cautiously in patients with creatinine levels > 3 mg/dL, or potassium levels greater than 5.5 mEq/L (> 5.0 mEq/L in diabetics)<br />Do not use in patients with hx of angioedema or bilateral renal artery stenosis<br />126<br />
  • 131. Adverse effects are due to 3 mechanisms<br />inhibiting breakdown of endogenous kinins (cough—females more than males), angioedema—smokers, AA, asthmatics)<br />suppression of angiotensin II (hyperkalemia, hypotension and renal insufficiency)<br />Reduction of aldosterone production (hyperkalemia)<br />FYI: ARBs do not increase concentrations of kinins to the same degree, hence less cough and decreased risk of angioedema (8% cross-reactivity)<br />127<br />
  • 132. BOTTOM LINE: ACE inhibitors<br />Improve symptoms in patients with heart failure (sometimes within the first 48 hours, but more commonly over 4 to 12 weeks)<br />Decrease the incidence of hospitalization and myocardial infarction<br />Prolong survival<br />(Medical Letter, July 2009)<br />128<br />
  • 133. “Sartans”--ARBs<br />Angiotensin receptor blockers (bypass ACE) and work by blocking the tissue receptors<br />Who are they? The “Sartan Sisters”…<br />losartan—Cozaar<br />valsartan—Diovan<br />candesartan—Atacand<br />irbesartan—Avapro<br />telmisartan—Micardis<br />olmesartan—Benicar<br />eprosartan--Tevetan<br />
  • 134. If additional aldosterone blockade is necessary…aldosterone antagonists<br />Eplerenone (generic or Inspra) QD @ $106.20 for 30 days or Inspra for $135.30 x 30 days<br />OUCH.<br />Spironolactone (generic or Aldactone) QD @$94.00 for 30 days generic or $28.20 for 30 days for Aldactone<br />130<br />
  • 135. Please note:<br />RALES (1999) (Random Aldactone Evaluation Study)—adding spironolactone/Aldactonepostpones or prevents 200 deaths/1000 people w/CHF<br />BUT…For every 1000 new spironolactone RX in heart failure patients, there are 50 more hospitalizations for hyperkalemia<br />Dose 12.5-25 mg per day of spironolactone<br />
  • 136. Other drugs for heart failure??<br />Digoxin, of course—especially if the myocardium needs a little extra boost<br />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<br />Diuretics—HCTZ or loop diuretics depending on GFR<br />132<br />
  • 137. NSAIDs and heart failure…<br />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)<br />NSAIDs can counteract the positive effects of thiazide diuretics for blood pressure control<br />Why? Opposing actions<br />NSAIDs can exacerbate HF symptoms due to sodium and water retention (+peripheral edema) and renal dysfunction; can also increase K+ levels<br />133<br />
  • 138. Hypertension<br />Increased vascular stiffness—increased systolic BP with widened pulse pressure; increased afterload<br />One-third of the adult population in the US has HTN; somewhere in the vicinity of 65 million give or take a few<br />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<br />134<br />
  • 139. Isolated Systolic Hypertension (ISH)<br />Two thirds of hypertensive patients over 60 have ISH<br />Systolic rises with age due to arterial stiffness, diastolic tends to plateau or even decrease during 6th decade<br />Isolated systolic (ISH) is defined as (S > 140; D< 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)<br />135<br />
  • 140. Blood pressure—Ideal? 120/80, BUT…<br />Depending on co-morbidities it may be kept slightly higher in the frail elderly to avoid hypotension, falls, and a broken hip<br />But not TOO high as it is the MAJOR risk factor for strokes (besides AGE)—66% of all strokes are due to hypertension<br />Keeping the blood pressure BELOW 140/90 prevents strokes, ACS, CHF, dementia, and renal failure<br />136<br />
  • 141. So, is it worth treating patients who are over 80 for hypertension?<br />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<br />It only takes 2 years to see the benefit of antihypertensive therapy (Becket, et al. and Kostis)<br />137<br />
  • 142. How many drugs? <br />Most older hypertensive patients may require at least two drugs to achieve goal BP, especially those at high risk for CV events (Nash)<br />138<br />
  • 143. When choosing…<br />Would this drug have a favorable effect on co-morbidities?<br />Angina—beta blocker, calcium channel blocker<br />Atrial fibrillation—beta blocker, calcium channel blocker<br />Benign prostatic hypertrophy—alpha one blocker<br />Congestive Heart Failure—beta blocker, ACE inhibitor<br />Hyperthyroidism—beta blocker<br />MI—beta blocker, ACE inhibitor<br />Diabetes Mellitus—ACE inhibitors, Angiotensin receptor blockers<br />139<br />
  • 144. How about aspirin for one and for all? What are the risks of aspirin for cardioprotection?<br />First of all, let’s calculate the risks of having a heart attack or dying of heart disease<br />Go to…www.health.harvard.edu/116<br />Let’s say, just for the sake of saying it…that 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/dL…anyone in this room fit the bill?<br />140<br />
  • 145. Risk is 2%...Means 2 of 100 people with this level of risk will have a heart attack in the next 10 years<br />141<br />
  • 146. Heart disease risk over 10 years? If your risk is…<br />1%--aspirin will avoid 2 to 8 heart attacks and heart-related events, cause 0 to 2 hemorrhagic strokes, ~12 gastrointestinal bleeds—GREATER HARM THAN GOOD<br />6%--aspirin will avoid 8 to 24 heart attacks and heart-related deaths, cause 0 to 2 hemorrhagic strokes, and cause ~12 gastrointestinal bleeds—GOOD and HARM balanced<br />10%--aspirin will avoid 12 to 40 heart attacks and heart-related deaths, cause 0-2 hemorrhagic strokes, and cause ~12 GI bleeds—Greater GOOD than harm<br />(Harvard Health Letter, August 2007)<br />142<br />
  • 147. An easier way to look at it?<br />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,<br />The chances of dying from an aspirin-related complication are the same as dying in an automobile accident—about 1 per 1000 people over a 10-year period<br />Let’s compare aspirin to a class of drugs that has received a terrible “reputation” over the years due to the media…the statin drugs.<br />Aspirin is 100 x more likely to cause a fatal side effect than the statin drugs<br />143<br />
  • 148. So, who benefits?<br />Diabetics over 40, or between 30 and 40 with other risk factors such as smoking, HTN, FH, high cholesterol<br />Patients with chronic kidney disease (CKD), especially patients on dialysis<br />Patients at risk for heart disease—parent or sibling with heart attack under 55 for a man and 65 for a female, HTN, substantially overweight, no exercise<br />One or more of these plus older than 65 for female and older than 55 for male tips balance in favor of aspirin<br />144<br />
  • 149. ASA and ibuprofen (Advil, Motrin)<br />How many older patients take ASA and a NSAID??? OTC ibuprofen is a NO-NO at the same time…<br />Ibuprofen blocks aspirin’s 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<br />If that isn’t possible, hold off on the aspirin for 8 hours or so after taking ibuprofen<br />(Harvard Heart Letter, August 2007)<br />145<br />
  • 150. Switching gears…back to the 1% rule…An exception to the 1% rule--an INCREASE in clotting factors by 1% per year<br />146<br />
  • 151. Triple antithrombotic therapy<br />Scenario—72 y.o. patient who needs clopidogrel and aspirin after a coronary stent; plus warfarin for atrial fibrillation, DVT, and a mechanical heart valve<br />YIKES…what to do? What to do?<br />147<br />
  • 152. To do…<br />Aim for the lower end of the INR target of 2.0 to 3.0<br />Try to stop clopidogrel as soon as it’s safe—often after 4 weeks after a bare-metal stent or one year for a drug-eluting stent—this can vary<br />Use the low-dose 81 mg of aspirin<br />Prescribe GI prophylaxis for patients with risk factors of GI bleeding<br />PPIs (omeprazole and esomeprazole) and clopidogrel<br />(Prescriber’s Letter, September 2009)<br />148<br />
  • 153. Atrial fibrillation<br />Approximately 2 million; risk increases with age<br />Increased risk of TIAs/stroke<br />AF can occur as a part of normal aging via minor, patchy scarring that occurs in the atria that disrupt the normal circuitry<br />Lots of other causes—hyperthyroidism, hypertension, CHD, valvular heart disease, congenital abnormalities, diabetes, rheumatic heart disease, ETOH<br />Fibrillation potentiates mural thrombus formation in the left atrium and results in 2-5 fold greater risk for embolic stroke*--Middle cerebral artery<br />Warfarinis the drug of choice to reduce the risk of a mural thrombosis and stroke<br />AF reduces CO by 10-15 %<br />
  • 154. Respiratory system<br />150<br />
  • 155. Respiratory <br />Fever and tachypnea in the older adult—consider an acute pulmonary syndrome—<br />Pulmonary embolism (over 85? 700 PE/100,000)—WHY DO YOU THINK EVERYONE IS ON COUMADIN?<br />Pneumonia—confusion, tachypnea, fever and shoulder pain—referred pain due to a big “wet” lung*<br />Pneumococcus (strep pneumoniae) is the most prevalent pathogen; Strep pneumoniae and Legionella are the most serious; <br />Antibiotics are common in the geriatric population<br />151<br />
  • 156. Other anti-inflammatory measures<br />Give those flu shots! Reduces the risk of an acute coronary syndrome by 66% <br />Pneumococcal vaccine<br />
  • 157. Geriatric changes in the GI tract<br />Decreased intestinal motility and blood flow<br />Decreased gastric acid secretion (may not be a universal phenomenon with aging and may only be observed with atrophic gastritis; however, implications of decreased acid from ANY cause are important)<br />Some drugs require a gastric pH of less than 5 for absorption—the “conazoles” for example—ketoconazole (Nizoral) and itraconazole (Sporanox)<br />153<br />
  • 158. Gastric pH and calcium supplements<br />Calcium carbonate supplements can be taken with or without food, but they are tolerated better when take with food and with an acid pH <br />Calcium citrate is absorbed in low acid states and should be used in older women with osteopenia, osteoporosis or in women who are on proton pump inhibitors for GERD (the prazoles—omeprazole (Losec or Prilosec), esomeprazole (Nexium), pantoprazole (Protonix), lansoprazole (Prevacid), rabeprazole (Aciphex)<br />154<br />
  • 159. NSAIDs and the GI Tract<br />The older the patient, the higher the risk of a GI bleed, especially with the non-selective NSAIDS<br />GI complications are 3-10x more common in users of nonselective NSAIDs than in nonusers<br />Use celecoxib (selective COX-2) if possible (also decreases risk of lower GI bleeding as well as perforations, obstructions and bleeds in upper GI)<br />Use PPI with nonselective NSAIDS andcelecoxib if over age 75<br />Celecoxib does NOT affect platelets so can be used up to and following surgical procedures (Stillman MJ)<br />155<br />
  • 160. An increased risk of constipation in the elderly…why?<br />156<br />
  • 161. Constipation is one of the major complaints in the older population…drugs are a major cause<br /> Drugs—drugs with anticholinergic side effects, opiods; verapamil (Isoptin, Calan); diltiazem (Cardizem)<br />Combined with decreased fluid and fiber intake combined with laxative abuse—prune abuse combined with dementia-- “the neglect of the call to stool”, not to mention cancer of the colon, and <br /> decreased activity<br />157<br />
  • 162. Bibliography<br />Andersen K, et al. Do nonsteroidal anti-inflammatory drugs decrease the risk for Alzheimer’s disease? The Rotterdam Study. Neurology 1995;45:1441-1443.<br />Baciewicz AM, Sokos DR, Cowan RI. Ann Pharmacotherapy 2003;37<br />Beckett NS, et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med 2008;358(18):1887-97.<br />Fick DM, Cooper JW, et al. Updating the Beers criteria for potentially inappropriate medication use in older adults: results of a US consensus of a panel of experts. Arch Intern Med. 2003;163:2716-2724.<br />158<br />
  • 163. Bibliography<br />Gardiner P, Phillips R, Shaughnessy AF. Herbal and dietary supplement-drug interactions in patients with chronic illnesses. Am Fam Phys 2008 Jan 1; 77(1):73-78.<br />Gardiner P, Phillips R, Shaughnessy AF. Herbal and dietary supplement-drug interactions in patients with chronic illnesses. Am Fam Phys 2008 Jan 1; 77(1):73-78.<br />Gill J et al. Use of GFR equations to adjust drug doses in an elderly multi-ethnic group: a cautionary tale. Nephrol Dial Tranplant 2007:22:2894-99.<br />Juurlink DN, et al. Drug-drug interactions among elderly patients hospitalized for drug toxicity. JAMA 2003;289:1652-58.<br />Kostis JB. (editorial) Treating hypertension in the very old. N Engl J Med 2008;358(18):1958-59.<br />159<br />
  • 164. Bibliography<br />Linton A, Garbor M, Fagan NK, Peterson MR. Examination of multiple medication use among TRICARE beneficiaries aged 65 years and older. J Manage Care Pharm. 2007;13(2):155-162.<br />Myllykangas-Luosujarvi R, Isomaki H. Alzheimer’s disease and rheumatoid arthritis. Br J Rheumatol1994;33:501-502.<br />McGeer PL, Rogers J. Anti-inflammatory agents as a therapeutic approach to Alzheimer’s disease. Neurology 1992:42:447-449.<br />Nash DT. Systolic hypertension. Geriatrics 2006;61(12):22-28<br />160<br />
  • 165. Bibliography<br />Reuben DB, et al. Geriatrics At Your Fingertips. 2008-2009. 10th ed. The American Geriatrics Society, NY.<br />Sirtori CR et al. Risks and benefits of soy phytoestrogens in cardiovascular diseases, cancer, climacteric symptoms and osteoporosis. Drug Saf. 2001;24:665-82.<br />Stillman MJ, Stillman MT. Choosing nonselective NSAIDs and selective COX-2 inhibitors in the elderly: A clinical use pathway. Geriatrics 2007;62(2):26-34.<br />Zurakowski T. The practicalities and pitfalls of polypharmacy. The Nurse Pract2009; 34(4):36-41.<br />161<br />
  • 166. More slides…<br />The following slides contain many more blurbs for your reading and classroom pleasure.<br />162<br />
  • 167. Bowel preps<br />Preps containing sodium phosphate (Fleet Phosphosoda and Fleet ACCU-PREP, have led to kidney calcification and resulting kidney damage<br />Existing renal insufficiency can exacerbate this problem as can any drugs (NSAIDS) that reduce renal blood flow<br />Use other preps such as magnesium citrate and polyethylene glycol to avoid kidney problems<br />163<br />
  • 168. Levothyroxine (LT4) and tachycardia<br />Caution when using with elderly—in older adults who might have clinically silent cardiac disease, experts recommend an initial starting dose of 25-50mcg per day; in patients with cardiac risk factors or a hx of cardiac disease, LT4 replacement may begin at doses of 12.5-25 mcg per day<br />164<br />
  • 169. Interactions with LT4<br />Levothyroxine decreases digoxin’s effect; starting LT4 in a patient taking dig may reduce the therapeutic effect of dig; digoxin dose may need to be increased when LT4 is initiated (Med Letter 2009 (August)<br />Estrogens—increase LT4 requirements; increased thyroxine-binding globulin concentrations, leading to decreased FT4; LT4 doses may need to be adjusted when starting or stopping HT<br />165<br />
  • 170. Historical Highlight<br />In the 1930s physicians would sometimes deliberately induce hypothyroidism in patients with severe coronary artery disease to reduce the severity of angina. Unfortunately, the severely hypothyroid patient was quite debilitated by the symptoms of NO metabolism<br />166<br />
  • 171. Drugs and weight in the elderly<br />Drugs and weight loss (dig, metformin, chemo, cholinesterase inhibitors for dementia) <br />Drugs and weight gain-- insulin, sulfonylureas, SSRIs (paroxetine/Paxil; fluoxetine/Prozac), corticosteroids, atypical antipsychotics—clozapine/Clozaril and olanzepine/Zyprexa, mirtazepine/Remeron<br />167<br />
  • 172. Will pills that contain salt increase blood pressure?<br />Antacids<br />Effervescent formulations<br />Zegerid (omeprazole) has 304 mg of sodium per cap<br />Alka-Seltzer Original has over 500 mg per tab<br />Most oral meds that come as a sodium salt, such as leveothyroxine sodium or pravastatin sodium, won’t increase BP<br />168<br />
  • 173. Combos<br />Beta blockers and diuretics<br />atenolol/chlorthalidone—Tenoretic (50/25, 100/25 mg)<br />bisoprolol/HCTZ—Ziac (2.5/6.25, 5/6.25, 10/6.25 mg)<br />metoprolol/HCTZ—Lopressor HCT (50/25, 100/25, 100/50 mg)<br />nadolol/bendroflumethiazide—Corzide (40/5, 80/5)<br />propranolol/HCTZ—Inderide (40/25, 80/25 mg)<br />propranolol LA/HCTZ—Inderide LA (80/50, 120/50, 160/50 mg)<br />timolol/HCTZ—Timolide (10/25 mg)<br />169<br />
  • 174. Combos<br />ACE inhibitors and diuretics<br />benazepril/HCTZ—Lotensin HCT (5/6.25, 10/12.5, 20/12.5, 20/25 mg)<br />enalapril/HCTZ—Vaseretic (5/12.5, 10/12.5 mg)<br />lisinopril/HCTZ—Zestoretic (10/12.5, 20/12.5, 20/25 mg)<br />Angiotensin II receptor antagonist and diuretics<br /> -losartan/HCTZ—Hyzaar (50/2.5 mg)<br />170<br />
  • 175. Combos<br />Other combinations<br />triamterene/HCTZ—Dyazide (37.5/25 mg)<br />triamterene/HCTZ—Maxide (37.5/25, 70/50 mg)<br />spironolactone/HTCZ—Aldactazide (25/25, 50/50 mg)<br />amiloride/HCTZ—Moduretic (5/50 mg)<br />hydralazine/HCTZ—Apresazide (25/25, 50/50, 100/50 mg)<br />methyldopa/HCTZ—Aldoril (250/15, 250/25, 500/30, 500/50 mg)<br />reserpine/hydralazine/HCTZ—Ser-Ap-As (0.10/25/15 mg)<br />171<br />
  • 176. Coumadin (warfarin sodium)… <br />Interacts with everyone and everything…<br />Usual maintenance dose is 2-10 mg/day<br />Inhibits vitamin K-dependent activation of II, VII, IX, X which are formed in the liver<br />Has no direct effect on established thrombi and can’t reverse ischemic tissue damage<br />However, it may prevent additional clot formation, extension of formed clots, and secondary complications of thrombosis<br />
  • 177. Stats on depression and heart disease<br />Major depressive disorder (MDD) is as serious a risk factor for CHD as HBP, ↑Cholesterol, obesity, smoking, diabetes, +FH<br />Precedes a heart attack in up to 50% of cases<br />20% of patients with ACS have MDD<br />Depressed patients are 3-5x more likely to die in the first year after MI<br />Symptoms of depression are associated with impaired endothelial function; depression increases arterial plaque 2 fold<br />Treating depression significantly reduces the risk of dying from heart disease<br />(Feb 2003 Archives of General Psychiatry; July 2005 Archives of General Psychiatry)<br />
  • 178. 3 most common drugs for ER visits for the elderly<br />Warfarin (Coumadin)(17.3%) <br />Insulin (13%)<br />Digoxin (3.2%) <br />The above 3 accounted for 33.3% ER of all ER visits for Geriatric patients<br />Excessive bleeding, hypoglycemia, arrhythmias/nausea<br />(Annals of Internal Medicine, December 4, 2007)<br />174<br />
  • 179. Pathophysiology of Delirium<br />Widespread reduction in oxidative metabolism leading to neurotransmitter deficiency and/or dysfunction<br />Pharmacologic reduction of neurotransmitters involved in cognition<br />Increased levels of cytokines (acute inflammatory mediators released by the immune system—IL-1, IL-2, IL-6, TNF-alpha) caused by illness, physical stresses or both—leading to impaired neurotransmitter dysfunction<br />175<br />
  • 180. Drugs/conditions and heart rate changes<br />Bradycardia—hypothyroidism, dig, beta blockers (even topical beta blocker eyedrops {Timoptic, Betoptic, etc.) can cause bradycardia), calcium channel blockers such as verapamil and diltiazem, and cholinergic drugs for AD--galantamine (Razadyne), rivastigmine (Exelon), donepezil (Aricept)<br />176<br />
  • 181. Tachycardia<br />Tachycardia in the diabetic (loss of vagus nerve due to autonomic neuropathy) leads to silent ischemia in diabetics with atherosclerosis of the coronary arteries<br />Unexplained tachycardia (60 to 80 is the normal resting heart rate)—consider hyperthyroidism, atrial fibrillation (which can also be caused by hyperthyroidism), anticholinergic drugs<br />177<br />
  • 182. Combos of a calcium channel blocker and a “pril” in one pill…compliance!<br />Calcium channel blockers and ACE inhibitors<br />amlodipine/benazepril—Lotrel (2.5/10, 5/10, 5.20 mg)<br />diltiazem/enalapril—Teczem ((180/5 mg)<br />verapamil/trandolapril—Tarka (180/2, 240/1, 240/2, 240/4 mg)<br />felodipine/enalapril-5/5 mg<br />178<br />
  • 183. Quality of Life issues<br />CCBs “dipines” and ACE inhibitors “prils” have an overall + effect on quality of life; no class is clearly superior in quality of life issues<br />HCTZ and beta blockers increase the risk of DM (Diabetes Care 2006; 29(5):1065-70)—use of ACE inhibitors and CCBs is not associated with DM; IN FACT…<br />Prelim evidence—Combo ACE inhibitor “pril” + CCB “dipine” may lower the risk of DM (ASCOT, Lancet 2006;366(9489):895-906)<br />HTN increases risk of cognitive dysfunction— “dipine” + “pril” +/- HTCZ decreases incidence of dementia compared with placebo in patients over 60 w/ISH (Arch Int Med 2001;161(2):152-6)<br />179<br />
  • 184. Did you know?<br />Observational studies have suggested a protective effect of NSAIDs on the prevalence of Alzheimer’s Disease. (Anderson)<br />Epidemiologic studies also showed lower prevalence of AD in patients using NSAIDS regularly (Myllykangas)<br />Patients with RA have been found to die from AD 5 times less often than the general population (McGeer)<br />180<br />

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