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PHARMACOLOGY – Simplified, not Mystified. “ The arrival of a good clown exercises a more beneficial influence on the health of a town than 20 asses laden with drugs.” Dr. Thomas Sydenham (1624-1689). The Numbers…. 30 years ago there were 900 drugs to choose from in the PDR

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pharmacology simplified not mystified
PHARMACOLOGY – Simplified, not Mystified
  • “The arrival of a good clown exercises a more beneficial influence on the health of a town than 20 asses laden with drugs.”
  • Dr. Thomas Sydenham (1624-1689)
the numbers
The Numbers…
  • 30 years ago there were 900 drugs to choose from in the PDR
  • Today there are over 11,000…
  • Plus….
the numbers3
The numbers….
  • Over 600 herbals products —many of which interact with prescribed drugs including cardiac drugs and antidepressants
  • St. John’s Wort is the number one herbal product that interacts with over 60 percent of all prescription drugs. The interaction is to make the drugs LESS effective: Cyclosporine, tamoxifen, HAART (highly active anti-retroviral therapy) for AIDS patients, and Combined Oral Contraceptives
  • Side effect?
vitamins and herbal supplements
Vitamins and herbal supplements….
  • Vitamin supplements—A (liver toxicity), B6 (peripheral neuropathy), C (doesn’t work to prevent colds but is an excellent way to help absorb iron when iron supplements are necessary), D for bones, balance, boosting immune system, E (no extra benefit on hearts, and in the very old may actually exacerbate heart failure)…but vitamin E reduces fat in the liver in patients with fatty liver disease (800 IU)
  • Calcium supplements, iron supplements, soy supplements interfere with levothyroxine (Synthroid)
speaking of levothyroxine
Speaking of levothyroxine…
  • Nighttime dosing may be more efficacious than daytime dosing
  • Most important—take at the same time of day
  • Adjust doses as the patient ages—why?
  • Levothyroxine RX can also cause atrial fib if the dose is too high; levothyroxine doses DECREASE with aging; some patients only need 0.5 mcg/kg/day vs. younger adults with 1.7 mcg/kg/day (Prescriber’s Letter July 2011)
the gs and platelet aggregation
The Gs and platelet aggregation
  • How about the “Gs”??
  • Garlic vs. garlic supplements (interfere with all sorts of drugs)
  • Gingko—not beneficial for dementia, but is beneficial for PAD
  • grapeseed extract—EAT GRAPES
  • ginseng –whatever ails ya’; side effects?
  • Glucosamine--??
  • green tea** (a potentially harmful interaction is with green tea and simvastatin—the higher the dose of simvastatin the greater the risk of rhabdomyolysis with green tea)
  • Over 10,000 over-the-counter (OTC) drugs that can wreak havoc—examples:

1) cimetidine (Tagamet)—for heartburn

2) acetaminophen (Tylenol) is in over 300 over-the-counter products (Tylenol)—inadvertent overdoses (narrow therapeutic index—toxic dose is not much higher than therapeutic dose)

….as well as numerous prescription analgesics… Fioricet, Lorcet, Percocet, Propacet, Roxicet, Ultracet (limit “cets” to 325/mg per tab to reduce toxicity)

acetaminophen tylenol
  • “itchy, sneezy, wheezy, snotty, achy, breaky” products
  • Vicodin for pain, Excedrin for headache, Theraflu for cold or flu, Sinutab for allergies, Robitussin for cough, Allerest for sleep…
  • 3,000 mg day is recommended total dose (McNeil Consumer Healthcare, bulletin on July 28, 2011 to reduce risk of acetaminophen liver toxicity)—even less for people who have more than 3 adult beverages per day
what s in a name
What’s in a name???
  • When you hear “Bayer” what do you think?
  • Bayer Aspirin is aspirin; but Bayer Select Maximum Strength Headache is acetaminophen and caffeine
  • Aspirin’s principal use today is in low doses as a platelet inhibitor
  • Bayer Select Pain Relief is ibuprofen
non selective nsaids
Non-selective NSAIDs
  • “profens”

Ibuprofen (Advil, Motrin, etc) PO—200 mg = to 650 of ASA; 400 mg superior w/ longer duration of ASA; 400 mg comparable to acetaminophen/codeine combination without the constipation w/ codeine; interferes with ASA cardiovascular prophylaxis; take 2 hours after aspirin

IV ibuprofen is Caldolor (400-800 mg q 6h)

Flubiprofen (Ansaid)—osteoarthritis, RA


  • Diclofenac (Cataflam, Voltaren, Arthrotec (combined with misoprostol to decrease GI toxicity); Flector as a topical patch for minor trauma; gel (Voltaren 1%) for osteoarthritis of knees and hands)
  • Ketorolac IM, IV, PO—5 –day use only due to GI toxicity; comparable to moderate doses of morphine
more on nsaids
More on NSAIDS
  • Naproxen (Naprosyn, others)
  • Naproxen sodium (Anaprox)—prescription; 550 mg is superior to 650 of ASA with longer duration of action
  • Naproxen sodium OTC (Aleve)—440 mg comparable to 400 mg of ibuprofen with longer duration
  • Celecoxib (Celebrex)—less effective than full doses of naproxen or ibuprofen; less GI toxicity; no platelet effects
  • All NSAIDS can decrease renal blood flow—may cause hypertension; don’t use in CHF patients; liver toxicity especially with diclofenac

Medical Letter, April 2010 (volume 8, issue 92)

don t panic
Don’t PANIC….
  • Know the 30 or 40 drugs you use daily in your clinical practice as well as the most common drugs most likely used by your patients…(age and gender specific)
  • Helpful hints…
generics vs brand names
Generics vs. Brand names

As a general rule, classes of drugs have the same generic “last” name

  • “Prils”—ACE inhibitors (BP + more)
  • “Sartans”—ARBs (angiotensin receptor blockers)—BP + more
  • “Triptans”—treatment of acute migraine headache
  • “Statins”—Lower LDL-cholesterol
  • “Dipines”—calcium channel blockers (BP+)
  • “Tidines”—H2 blockers reduce nighttime acid
  • “Prazoles”—Proton Pump Inhibitors, GERD
  • “Azoles”—antifungal
first line therapy for reducing blood pressure the prils
First line therapy for reducing blood pressure—the “prils”
  • Captopril (Capoten)(1981)
  • Enalapril (Vasotec)(1983)
  • Fosinopril (Monopril)
  • Lisinopril (Prinivil, Zestril)
  • Perindopril (Aceon)
  • Moexipril (Univasc)
  • Benazepril (Lotensin)
  • Quinapril (Accupril)
  • Trandolapril (Mavik)
  • Ramipril (Altace)
a little refresher on the kidney
A little refresher on the kidney…
  • At any given moment, the kidney is “sensing” the pressure and volume of blood flow
  • Low volume or low BP, the kidney will release renin from a small area (the JGA) just inside the afferent arteriole
  • Renin (the messenger)→(liver) angiotensin I →angiotensin II→ via Angiotensin Converting

Enzyme (ACE) (primarily in the pulmonary circulation)

  • Angiotensin II triggers the release of “AL” (aldosterone) from the adrenal cortex
what does angie ii do
She “tenses” your “angios”—vasoconstricts your arteries

She triggers release of “AL”—aldosterone (from the adrenal cortex to save sodium & H2O in the kidney)

She increases inflammation in the arteries

She’s prothrombotic

She increases tissue resistance to insulin

She’s a potent growth factor and “remodels tissues”…

What does “angie II” do?
So if you were an ACE inhibitor, what would you do? Inhibit ACE? Inhibit the formation AT angiotensin II
  • Anti-hypertensive agent via vasodilation (due to inhibiting angiotensin 2) and inhibition of aldosterone (excrete SODIUM and H20 BUT you save POTASSIUM)—

(as many as 70% of hypertensive patients in U.S. may have elevated RAA systems (renin-angiotensin-aldosterone)

  • Treatment of heart failure by inhibiting renin-angiotensin-aldosterone—CHF is a HYPER-RENINEMIC state
  • Anti-inflammatory
  • Anti-thrombotic
  • Hypoglycemic (be careful when starting ACE inhibitors in diabetics)
  • Decrease growth of tissues or “remodeling”

Is “remodeling” a good word? Hmmmmm….

remodeling and angiotensin
Remodeling and angiotensin…
  • Remodels myocardium and disrupts the conduction system…Increases the risk of ventricular dysrrhythmias
  • Remodeling increases vascular fibrosis—hypertension
  • Remodeling increases intraglomerular blood pressure resulting in intraglomerular hypertension leading to CKD
angie and the healthy kidney
“Angie” and the healthy kidney…
  • Afferent arteriole

(vasodilated via


  • Blood entering


  • Glomerulus→filter
  • Efferent arteriole

(vasoconstricted via

(angiotensin II)

  • Blood exiting






angie the prils and the diabetic hypertensive kidney hyperglycemia htn
“Angie, the “prils” and the Diabetic/hypertensive Kidney…hyperglycemia/HTN
  • Afferent arteriole

( ↑ vasodilation by

( ↑ prostaglandins)

  • Blood entering


  • Glomerulus→filter
  • Efferent arteriole

( ↑ vasoconstriction via

( ↑ angiotensin II)

  • Blood exiting


PRILS inhibit ATII/vasodilate the efferent arteriole


to summarize ace inhibitors are used for
To summarize…ACE inhibitors are used for:
  • Hypertension (*night time dosing of anti-hypertensive drugs—dippers (10% decline @ night) vs. non-dippers)

(American Journal of Kidney Diseases December 2007)

  • A new, interesting theory of hypertension—CMV infection in epithelial cells results in excess release of renin and angiotensin II, excess production of proinflammatory cytokines, and development of intimal hyperplasia and athersclerosis
to summarize ace inhibitors are used for22
To summarize…ACE inhibitors are used for:
  • Decrease the remodeling of the heart in heart failure patients and post-MI patients (clearly beneficial in MI patients 65-74 years of age, but not so clear in patients older than 75)
  • Beneficial in patients with anterior ST-elevation MIs and in patients with MIs complicated by HF or significant LV systolic dysfunction with LV ejection fractions less than 40%
  • Decrease the risk of 1st and 2nd myocardial infarctions in high-risk patients due to anti-inflammatory effects
  • Stroke prevention
  • Prevention of diabetic nephropathy
  • Decrease insulin resistance and reduce the risk of progression to type 2 diabetes
side effects of course
Side effects, of course…
  • Hypotension—start low and go slow
  • Hypoglycemia (low blood sugar)—only in diabetics on antiglycemic agents; not a problem in normoglycemic patients
side effects of course24
Side effects, of course…
  • Hyperkalemia (high potassium) (excreting sodium and water and retaining potassium)
  • Add a thiazide diuretic to the ACE inhibitor
  • Capozide (captopril + thiazide)
  • Vaseretic (enalapril +thiazide)
  • Prinizide (lisinopril + thiazide)
  • Zestorectic (as above)
  • Lotensin HCT (benazepril + hydrochlorothiazide)
what about k containing foods
What about K+ containing foods?
  • May also contribute to hyperkalemia and cardiac arrhythmias but usually only in patients with renal insufficiency so or in patients who are also on K+ sparing diuretics such as spironolactone (Aldactone) and eprelrenone (Inspra)
  • Avoid excessive potassium intake when on the above drugs or with renal insufficiency
  • Advise patients to decrease potassium intake until they can get their potassium checked
high k containing foods
High K+ containing foods
  • Potatoes
  • Prunes
  • Raisins
  • Apricots
  • Bananas
  • Halibut
  • Canteloupe
  • Oranges
  • Pasta sauce
  • for K+ content of 1,200 foods
side effects of course27
Side effects, of course…
  • Cough (gender differences)
  • ACE inhibitors block angiotensin converting enzyme; but as ACE is inhibited, bradykinin goes UP…bradykinin is a potent bronchoconstrictor
  • Women have more bradykinin to begin with, therefore the gender disparity in the cough
  • Rx? Stop drug; can try a nonspecific antitussive; consider indocin, baclofen, aspirin, or sulindac (Clinoril) if the cough persists (Rose BD)
side effects of course28
Side effects, of course…
  • Cough (gender differences)
  • Life-threatening angioedema (“Does my voice sound funny to you?”)
and one other thing ace inhibitors category d throughout pregnancy
And ONE OTHER THING:ACE inhibitors (category D) throughout pregnancy
  • Why?
  • Angiotensin 2 boosts growth factors
  • ACE inhibitors inhibit AT2 and inhibit growth; ACE inhibitors are teratogenic
  • Cooper WO et al. Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med 2006 Jun 8; 354:2498-500
sartans angiotensin ii receptor blockers
“Sartans”—Angiotensin II Receptor Blockers
  • Angiotensin receptor blockers (bypass ACE) and work by blocking the angiotensin II receptors on tissues
  • Who are they? The “Sartan Sisters”…
  • losartan—Cozaar
  • valsartan—Diovan
  • candesartan—Atacand
  • irbesartan—Avapro
  • telmisartan—Micardis
  • olmesartan—Benicar
  • azilsartan -- Edarbi
  • substitute if cough is unbearable on the ACE inhibitors
arbs as a safe haven for the side effects of the prils
ARBs as a safe haven for the side effects of the “prils”
  • Are the “sartans” safe for patients with a history of angioedema from the “prils”?
  • Appears to be about an 5 to 8% rate of cross-reactivity
  • Given this limited percentage, switching to an ARB should not be considered an absolute contraindication in all patients with ACE-inhibitor induced angioedema
  • Switch cautiously
  • (Prescriber’s Letter 2004; 11(7))
two other drug categories that influence the renin angiotensin aldosterone system
Two other drug categories that influence the renin-angiotensin-aldosterone system
  • The direct renin inhibitors -- aliskirin (Tekturna)
  • The aldosterone antagonists – spironolactone (Aldactone) and eplerenone (Inspra)—be careful with these drugs when used for CHF in combination with ACE inhibitors; potassium levels can increase to dangerous levels and life-threatening cardiac arrhythmias can occur
  • Keep checking the potassium levels
olols alols ilols beta blockers
“Olols, alols, ilols”—Beta blockers
  • atenolol (Tenormin)
  • betaxolol (Kerlone)
  • bisoprolol (Zebeta)
  • carvedilol (Coreg)
  • Esmolol (Brevibloc)
  • labetalol (Trandate)(Normodyne)—safe during pregnancy
  • metoprololsuccinate (Toprol XL, Lopressor)
  • nadolol (Corgard)
  • nebivolol (Bystolic)
  • propranolol (Inderal)(1968)(nonselective)
  • sotalol (Betapace)
  • timolol (Blocadren)
sympathetic nervous system sns fight flight system
Sympathetic Nervous System (SNS)—fight/flight system
  • In order to understand the beta blockers, a quick review of the SNS is in order
  • Lock and key theory
  • Receptors (lock) and neurotransmitters (key)
  • Receptors: beta-1, beta-2, alpha-1, alpha-2 receptors regulate the SNS
  • Neurotransmitters are the catecholamines: epinephrine, norepinephrine
  • Scenario: Visit Barb in Chicago
fight flight response
Fight/flight response
  • Heart rate goes up
  • BP goes up
  • Bronchioles dilate
  • Increased blood flow to arms and legs
  • Hair on arms and neck stands up
  • Tremor
  • What do your bowels WANT to do?
but you have a mother your frontal lobe
But you have a “mother”—your frontal lobe…
  • “Don’t even think about it…if I have told you once, I have told you twice…”
sns receptors and actions
SNS receptors and actions
  • B1—found on heart muscle; epinephrine binds to B1 and increases heart rate and strength of contraction (chronotropic and inotropic)
  • B2—skeletal muscle (tremor), bronchioles of the lungs (bronchodilation), large arteries of the legs (vasodilation), piloerection (hairs stand up on back of neck and arms)
alpha receptors and actions
Alpha receptors and actions
  • α1—arteriole smooth muscle (vasoconstriction to increase BP) (alpha 1 receptors are also located on the prostate gland)
  • α2 (hypothalamus)—regulates CNS output of SNS
  • Drugs can ‘selectively’ modulate the various receptors
same slide as the last one throw in alpha blockers
Same slide as the last one—throw in alpha blockers
  • α1—arteriole smooth muscle (vasoconstriction to increase BP) (alpha 1 are also located on the prostate gland)—the “osins”—(ALPHA-1 BLOCKERS including tamsulosin/Flomax, silodosin/Rapaflo; terazosin (Hytrin), doxazosin/Cardura)
  • Α2—hypothalamus—regulate CNS output of the SNS—clonidine/Catapres (consider this drug for women on Tamoxifen having hot flashes)
beta one receptors and cardioselective beta blockers
Beta one receptors and cardioselective beta blockers
  • B1—found on heart muscle; epinephrine binds to B1 and increases heart rate and strength of contraction (chronotropic and inotropic)—– cardiac output falls, heart rate falls (10-15%), blood pressure falls, workload of the heart decreases—angina, SVT, post-MI to protect the heart from remodeling and to reduce heart rate

atenolol (Tenormin), metoprolol (Lopressor), betaxolol (Kerlone); bisoprolol (Zebeta), nebivolol (Bystolic)@ doses <10 mg)


B2—skeletal muscle (tremor), bronchioles of the lungs (bronchodilation), large arteries of the legs (vasodilation), piloerection (hairs stand up on back of neck and arms)—NONSELECTIVE BETA BLOCKERS


Why don’t we pick just any old beta blocker? Because the non-cardioselective beta blockers block both the B1 AND B2 receptors and can wreak havoc in certain patient populations

  • B2 blockade can cause bronchoconstriction and exacerbate COPD & asthma as well as vasoconstrict the femoral artery {exacerbate [peripheral artery disease}

propranolol (Inderal), nadolol (Corgard), timolol (Blocadren), carvedilol (Coreg)

beta blockers other properties
Beta blockers…other properties
  • Water-soluble? (low lipophilicity)

atenolol (Tenormin), nadolol (Corgard), labetalol (Trandate), nebivolol (Bystolic)

  • Lipid-soluble? (high lipophilicity--cross the blood brain barrier)—CNS side effects—anhedonia (the “Blahs”)—BUT…the lipid-soluble can also “calm down” the brain
  • propranolol (Inderal), timolol (Blocadren), metoprolol (Lopressor, Toprol XL), pindolol
  • All of the others are moderately lipophilic
functions of beta blockers
Functions of beta-blockers
  • Decrease palpitations during panic attacks
  • Decrease heart rate in atrial fib
  • Decrease essential tremors
  • Decrease situational anxiety
  • Decrease symptoms of PTSD
  • Episodic dyscontrol syndrome
  • Decrease HR in patients with Grave’s disease
  • Decrease portal pressure in patients with cirrhosis and esophageal varices
  • Decrease migraine headaches by 50% in 50% of the patients (mechanism unknown)
  • Pre-operative beta-blockers—non cardiac surgeries—high risk pts
Beta-blocker eye drops for glaucoma—second-line therapy--Lower intraocular pressure by 20-25% with once or twice daily dosing
  • timolol (Timoptic), levobunolol (Betagan), carteolol (Ocupress), metipranolol (Optipranolol)
  • Timoptic + carbonic anhydrase inhibitor (Trusopt) = Cosopt
  • Highly lipid-soluble and cross the blood-brain barrier
  • Can cause bradycardia and anhedonia
  • So what can you use instead?
the oprosts first line therapy for glaucoma
The “oprosts”—first line therapy for glaucoma
  • The “oprosts”—bimatoprost (Lumigan), latanoprost (Xalatan), travoprost (Travatan)
  • And, unoprostone (Rescula)
  • Prostaglandin analogues—lower Intraocular pressure by 25-30%
  • *Latisse for thick, long eyelashes
long term use of topical prostaglandin analogs
Long-term use of topical prostaglandin analogs
  • **Latisse (bimatoprost) for thick, long eyelashes
  • Conjunctival hyperemia
  • Darkening of the iris
  • Increasing the length and number of eyelashes
  • Iris pigment changes occur most frequently in patients with green-brown, yellow-brown, or blue-gray-brown irides
calcium channel blockers 3 classes 1 st class
Calcium Channel Blockers…3 classes; 1st class …


  • Verapamil (Isoptin SR, Verelan and Verelan PM, Calan and Calan SR, Covera-HS)—block calcium channels primarily on the coronary vessels and the AV node—increasing blood flow to the heart and decreasing impulses through the AV node—used to decrease workload of heart and slow the heart rate; HTN, angina, atrial fib
  • Calcium channels in bowels (elderly)
2 nd class of calcium channel blockers benzothiazepines
2nd class of calcium channel blockers--benzothiazepines
  • Heart AND peripheral vasculature
  • Diltiazem—Cardizem LA and CD, Dilacor XR, Tiazac—dilates calcium channels on the coronary arteries and peripheral vessel calcium channels; decreases impulse transmission from atrium to ventricle

Clinical uses—

Atrial fibrillation, Hypertension, Angina, Vasospasm

Less constipation than verapamil

3 rd class dihydropyridines or the dipines peripheral vessel calcium channel blockers
3rd class--dihydropyridines or the “DIPINES”—Peripheral vessel calcium channel blockers
  • Amlodipine (Norvasc)
  • Felodipine (Plendil)**
  • Nifedipine (Procardia XL, Adalat)
  • Nicardipine (Cardene)
  • Isradipine (Dynacirc)
  • Nisoldipine (Sular)
  • Clevidipine (Cleviprex) for IV use vs. esmolol or IV nicardipine)
  • Amlodipine + benazepril=Lotrel
  • Amlodipine + Atorvastatin=CADUET
clinical uses of the dipines
Clinical uses of the “dipines”…
  • Hypertension
  • Vasospasm—Prinzmetal’s angina, Raynaud’s phenomenon, cocaine-induced vasospasms
  • Ureteral spasms in patients with small kidney stones
  • “male contraceptive”
side effects of ccbs
Side effects of CCBs…
  • Verapamil—significant constipation
  • Dipines—significant peripheral vasodilation with headaches; hypotension, and peripheral edema (swollen feet—pedal edema; (Plendil)
  • Diltiazem—less significant constipation than Verapamil
  • The GRAPEFRUIT connection
the liver drugs and the cytochrome p450 system cyp450
The liver, drugs and the cytochrome P450 system (CYP450)
  • Family of isoenzymes that metabolize drugs--CYP
  • CYP3A4—40-60% of total hepatic and extrahepatic enzymes; the extrahepatic enzymes are located primarily along the brush border of the small intestine
  • Drugs/foods can be either inducers or inhibitors of the enzyme system
  • The most famous inhibitor of this enzyme in the small intestines is grapefruit juice—if you inhibit the enzyme, drugs are absorbed in greater amounts resulting in a higher bioavailability and greater toxicity
the small intestine and metabolism of drugs
The small intestine and metabolism of drugs
  • When grapefruit juice or grapefruit inhibits CYP3A4, drugs are absorbed in a higher bioavailability
  • Interaction with grapefruit/grapefruit juice may last up to 72 hours—takes this long for CYP3A4 to recover from as little as 8 ounces of GJ
  • What is it in the grapefruit juice? The furanocoumarins

(American Journal of Clinical Nutrition May 2006)

grapefruit juice interactions increase bioavailability and increase the risk for toxicity
Grapefruit juice interactions increase bioavailability and increase the risk for toxicity
  • Amiodarone HCl—increased absorption with GFJ increasing risk of adverse effects and toxicities:

pulmonary toxicity, hypotension, and cardiac arrhythmias, (TSH). Avoid using Amiodarone in patients who may not understand the toxic potential of this interaction.

  • Felodipine (Plendil), nisoldipine (Sular), nicardipine HCl (Cardene), nifedipine (Procardia), isradipine (Dynacirc)—increased toxicity with headaches and peripheral edema
  • Simvastatin (Zocor)—300% increase in bioavailability with grapefruit vs. atorvastatin (Lipitor) 25% increase; rosuvastatin (Crestor)—no interaction
grapefruit juice grapefruit
Grapefruit juice/grapefruit
  • Avoid grapefruit juice and grapefruit with antibiotics
  • One interaction is especially dangerous
  • Interaction between grapefruit juice and erythromycin
  • Accumulates and may cause tachycardia
  • Prolongs QT interval and may cause death from “torsades de points”
the statin sisters
The “Statin Sisters”…

Who are they?

  • lovastatin (Mevacor)
  • simvastatin (Zocor)
  • atorvastatin (Lipitor)
  • fluvastatin (Lescol)
  • pravastatin (Pravachol)
  • rosuvastatin (Crestor)
  • pitavastatin (Livalo)
the statin sisters what do they do
The “Statin Sisters”…what do they do?
  • Inhibit an enzyme in the liver responsible for the production of the LDL-cholesterol; works primarily at night to reduce LDL, so the “statins” work the best when taken before bedtime (exception to the rule—atorvastatin/Lipitor)
  • LDL (low density lipoprotein) is the most atherogenic of the cholesterol bunch and puts fat right smack dab into all of the arterial walls; therefore, statins decrease LDL-cholesterol and reduce the risk of coronary artery disease, peripheral vascular disease and cerebrovascular disease; they also increase survival and improve the quality of life
the statin sisters59
The “Statin Sisters”
  • Anti-inflammatory effects
  • Reduce total cholesterol levels
  • Decrease fatty plaque formation in the arteries
  • Stabilize fatty plaques and prevent plaques from rupturing (an inflamed fatty plaque ruptures in a coronary artery triggers the coagulation cascade and clot formation)
  • Shrink plaques in all arteries (prevent strokes and heart attacks)
side effects
  • Myalgias **(other causes in elderly patients…)
  • About 1/20 patients experience muscle pain or weakness
  • Myositis; rhabdomyolysis (rare) (ASA is 100x more likely to cause a fatal side effect than taking a statin)
  • Simvastatin at higher doses is the riskiest “statin” for rhabdomyolysis—never use the 80 mg dose; lots of drug interactions; do NOT drink green tea with this statin
  • How about adding CoQ10 for muscle aches and pains? Either switch statins, lower the dose of statins, consider every other day dosing or take 50-100 mg/day of CoQ10
the afils the pfizer riser aka sildenafil viagra and friends for erectile dysfunction
The “afils”—the Pfizer Riser aka sildenafil (Viagra) and friends, for erectile dysfunction
  • Prior to November 1998
  • What are the causes of ED?
  • Athero, neuro, drugs, ↓testo, psychological (the stamp test)
  • Sildenafil (Viagra)(Revatio for pulmonary hypertension)
  • Vardenafil (Levitra)
  • Tadalafil (Cialis)—the “weekend warrior” (Adcirca for PH)
  • PDE5 inhibitors which in a round about way boost nitric oxide—potent vasodilator primarily below the belt
  • Can use in patients with stable CHD
can t use with nitroglycerin
Can’t use with nitroglycerin…
  • “When was your last dose of Viagra?
  • Can’t use Viagra or Levitra within 24 hours of receiving NTG; Cialis within 36 hours
  • Side effects
  • Hypotension
  • Headaches
  • GERD
  • Blue vision
  • Priapism
  • A surprise side effect of the “afils”…
Sexually transmitted diseases have increased by over 300% in the over 60 crowd since the release of Viagra…
  • More sex
  • No pregnancy worries
  • Swingin’ singles
  • Who cares what the neighbors think?
  • Swimming pools and golf courses
  • Can you have a heart attack during sex?
  • Only if…
drugs and reducing the size of the prostrate
Drugs and reducing the size of the “prostrate”
  • Alpha-one blockers

Tamsulosin (Flomax)

Silodosin (Rapaflo)

Doxazosin (Cardura)

  • Testosterone blockers

Dutasteride (Avodart)

Finasteride (Proscar)

  • Vitamin D for the prostate
the bisphosphonates for osteoporosis
The bisphosphonates for osteoporosis
  • The “dronates” for osteoporosis
  • Alendronate [Fosavance] (Fosamax + D), Risedronate (Actonel), ibandronate (Boniva)
  • zoledronic acid (Zometa) and pamidronate (Aredia)—hypercalcemia of cancer
  • Zoledronic acid – lower dose for osteoporosis—brand name Reclast
  • Trigger apoptosis of osteoclasts
  • Osteoblasts continue to build bone matrix but without remodeling
  • Any downside?
  • Subtrochanteric femur fractures? Very low risk
  • Can the patient FOLLOW directions with the oral bisphosphonates?
bisphosphnates dronates
Bisphosphnates— “dronates”
  • 1/100,000 patients per year on oral bisphosphonates
  • 94% of cases are on Zometa or Aredia for hypercalcemia of cancer
  • To minimize risk:

1) get dental exam before starting drugs

2) good dental hygiene reduces risk

3) might not help to do a drug holiday as these drugs stay in the bones for years (esp. Fosamax)

the prazoles proton pump inhibitors
The “prazoles”—Proton Pump Inhibitors*

Who are they?

  • Omeprazole (Prilosec)(first released as Losec in U.S.)
  • Lansoprazole (Prevacid)
  • Deslansoprazole (old-Kapidex)(new-Dexilant)
  • Rabeprazole (Aciphex)
  • Pantoprazole (Protonix)
  • Esomeprazole (Nexium)-- “the purple pill”
  • *BIGException:Aripiprazole/Abilify—antipsychotic—a dopamine system stabilizer
the prazoles proton pump inhibitors68
The “prazoles”—Proton Pump Inhibitors
  • MOA—Inhibition of the proton pump at the lumenal surface of the stomach…especiallyafter a meal

H+, Intrinsic Factor-B12

PPIs work here

Lumenal surface

Parietal cell

Basilar surface


H2 receptors

H2 blockers work here

the prazoles
The “prazoles”
  • Work within 4-7 days to reduce all acid in the stomach; take 30’-60’ before the first meal of the day or before the dinner meal (especially if nocturnal GERD is a problem)
  • BUT suppressing acid has been shown to have significant side effects:
  • Increased risk of hospital-acquired pneumonia and community acquired pneumonia (PPI use might be associated with 33,000 preventable deaths due to pneumonia in hospitalized patients)(Herzig)
  • Increased foodborne illness
  • Increased risk of osteopenia/osteoporosis with long-term use
  • Increased risk of B12 deficiency due to blocking the release of intrinsic factor
what happens when you have b12 deficiency
What happens when you have B12 deficiency?
  • B12 is necessary for the healthy production of RBCs and for the maintenance of the central and peripheral nervous system (cognitive function in the CNS and motor/sensory function of spinal cord and peripheral nerves)
  • B12 deficiency is the number one cause of nutritional dementia
  • B12 deficiency is one of the top 3 causes of peripheral neuropathy in the elderly
  • B12 deficiency causes macrocytic anemia (MCV greater than 120)
  • B12 is stored in theliver for ~ 5 years—takes a long time of PPI use to cause B12 deficiency
combine long term use of ppis with other risk factors
Combine long-term use of PPIs with other risk factors…
  • 39% of the population over 50 has a B12 deficiency
  • Patients on glucophage (Metformin) for longer than 3 years should also have B12 levels measured (and the peripheral neuropathy of diabetes may actually be a B12 deficiency neuropathy—give diabetics B12—improves any neuropathy they have)
  • Patients with malabsorption; gastrectomy; gastric surgery; atrophic gastritis
should we all be taking b12
Should we all be taking B12?
  • If so, how can we take it?
  • Supplements?
  • The 4 S’s…
  • How much? For dementia? For peripheral neuropathy?
  • For daily maintenance?
  • Can you overdose on B12? The one dreaded side effect is…
the tidines h2 blockers
The “tidines” (H2 blockers)
  • Cimetidine--Tagamet—can cause delirium in the elderly; increases the bioavailability of many drugs—beta blockers, morphine
  • Other H2 blockers—Ranitidine (Zantac); Nizatidine (Axid); Famotidine (Pepcid)
  • Best to give at night—decrease vagally-induced histamine release in stomach (double the OTC dose for best results)
  • (not to be confused with the “tadines”—amantadine and rimantadine which are the antiviral drugs, Symmetrel and Flumadine for Influenza A)
the antifungals the azoles
The antifungals--the “azoles”
  • Miconazole (Monistat)
  • Clotrimazole (Mycelex)
  • Fluconazole (Diflucan)
  • Itraconazole (Sporanox)
  • Ketoconazole (Nizoral)
  • Voriconazole (Vfend)
  • Posaconazole (Noxafil)—newest of the bunch (HIV)
  • “You have a yeast infection…”
the antiherpetics the cy i clovirs
The antiherpetics—the “cy{i}clovirs”
  • Acyclovir (Zovirax)
  • Famciclovir (Famvir)
  • Valacyclovir (Valtrex)
  • Ganciclovir (Cytovene) – CMV retinitis in HIV patients; CMV pneumonitis in transplant patients
the antiherpetics varicella zoster virus
The antiherpetics—Varicella Zoster Virus
  • Acyclovir (Zovirax)(4000/d)
  • Famciclovir (Famvir)(750/d)
  • Valacyclovir (Valtrex)(3000/d)

Tx must be started within 48-72 hours after the first signs of a rash appear.

  • +Prednisone
shingles prevention
  • Zostavax (Merck) to reduce the incidence of Herpes Zoster (shingles/Hell’s fire) in people over 50 (14 x stronger than Varivax)(risk reduction—50%); reduces severity and decreases post-herpetic neuralgia

“The FDA this week approved the first-ever transdermal patch for the treatment of depression. Simply remove the backing and press the patch firmly over your mother’s mouth.” Tina Fey, on Saturday Night Live (March 2006)

drugs for depression
Drugs for depression
  • Serotonin Reuptake Inhibitors (SRIs)—fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), citalopram (Celexa), escitalopram (Lexapro)
  • Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)—venlafaxine (Effexor), desvenlafaxine (Pristiq), duloxetine (Cymbalta)
drugs for depression80
Drugs for depression
  • The “other” category—mirtazapine (Remeron), buproprion (Wellbutrin)
  • “old” antidepressants—Tricyclic Antidepressants (TCAs) such as amitriptyline (Elavil), nortriptyline (Norpramin, Pamelor)—are actually SNRIs as they inhibit the re-uptake of both serotonin and norepinephrine;
  • Drugs that block the reuptake of serotonin and norepinephrine can be used for neuropathic pain (duloxetine/Cymbalta and amitriptyline (Elavil) are commonly used for neuropathic pain
is there a better ssri
Is there a better SSRI?
  • Top two are sertraline and escitalopram (Lancet, Jan. 09)
  • Sertraline/Zoloft—short half life; great for use in the elderly; few drug interactions—(cheapest)
  • Escitalopram/Lexapro—few drug interactions, not as many as Paxil
  • Citalopram/Celexa (not to be confused with Celebrex)—very few drug interactions
  • Fluoxetine/Prozac—half-life is too long for elderly
  • Paroxetine/Paxil—many, many drug interactions and not good for use in the elderly; is the most anti-cholinergic of all (interferes with cholinesterase inhibitors used for Alzheimer’s disease) and can cause anti-cholinergic side effects in elderly (see next slide)
ssris a major side effect
SSRIs—a major side effect
  • Boost serotonin
  • Makes ya’ happy
  • Blocks dopamine though and dopamine in the brain is responsible for sexual functioning (among other things)
  • Decreases libido, anorgasmia (50-75% of patients)
  • However, if premature ejaculation is your problem, the SSRIs are for you
i m here for my ssri prescription
I’m here for my SSRI prescription…
  • Low serotonin is part of the problem with patients with premature ejaculation
two other side effects of reduced dopamine from ssris
Two other side effects of reduced dopamine from SSRIs
  • Bruxism--morning headaches, jaw pain, a clicking sound in your jaw, sensitive teeth, and damaged teeth and crowns. Permanent long-term effects can include temporomandibular disorder, a painful condition affecting the jaw and facial muscles, and periodontal disease.
  • RLS (restless leg syndrome) due to low dopamine (check iron levels) (Rx? Dopamine agonists—ropinirole (Requip) or pramipexole (Mirapex) (p.s. dopamine and addiction)
the antibiotics the fluoroquinolones the floxacins
The antibiotics—the fluoroquinolones, the “floxacins”…
  • Ciprofloxacin (Cipro)*(2) (↑ INR)
  • Lomefloxacin (Maxaquin)(2)
  • Norfloxacin (Noroxin)*(2)
  • Ofloxacin (Floxin)(2)*

*uncomplicated UTI if resistance to TMP/SMX is ≥20%

  • Levofloxacin (Levaquin) (3)—too broad spectrum for UTI
  • Gemifloxacin (Factive)(4)
  • Moxifloxacin (Avelox)(4)—effective against TB
  • WARNINGS: C. difficile after the quinolones…
  • Acute tendonitis in elderly and patients on corticosteroids
the antibiotics the macrolides
The antibiotics—the macrolides
  • Erythromycin—dangerous with many other drugs due to prolongation of the QT interval
  • Azithromycin (Zithromax)—Z-pack (don’t take with food)
  • Clarithromycin (Biaxcin)—take with food!
  • Important drug/food interactions with the second generation macrolides;
  • Clarithromycin and digoxin toxicity
it s a mab mab mab monoclonal antibodies world immune system
It’s a “MAB, MAB, MAB” (monoclonal antibodies) world—immune system
  • Infliximab (Remicade)—targeted against TNF-α, the culprit in Crohn’s disease, RA, psoriasis; TB testing prior to use
  • Adalimumab (Humira)—as above
  • certolizumabpegol (Cimzia)—as above
  • Golimumab (Simponi)—as above
  • Palivizumab (Synagis)—RSV protection for developing lungs 34-week neonates have just 52% of the calculated lung volume of full-term infants at birth)
  • Omalizumab (Zolair)—mab to IgE
  • Belimumab (Benlysta)—SLE (targets B cell activating factor)
mabs for tumors
MABs for tumors
  • Trastuzumab (Herceptin)—HER2-neu+ Breast cancers; when given in early stages, prognosis improves significantly
  • Rituximab (Rituxan)—targets CD 20 receptor on B lymphocytes; used for Non Hodgkin’s Lymphoma
  • Cetuximab (Erbitux)—colon cancer (Martha Stewart)
it s a mab mab mab world
It’s a “MAB, MAB, MAB” world
  • Bevacizumab (Avastin)—inhibits angiogenesis; used to inhibit tumor growth; used to decrease neovascular growth in the retina; glioblastomamultiforme (with a tyrosine kinase inhibitor)
  • Abciximab (Reopro)—inhibits platelet aggregation
  • Ranibizumab (Lucentis)—wet macular degeneration
The “triptans”--5-HT (5-Hydroxytryptamine) (serotonin) 1B/1Dagonists-- vasoconstriction of peripheral arteries and coronary arteries
  • Sumatriptan (Imitrex)(64-70% response rate at 2°)
  • (Treximet—Imitrex (85 mg) + naprosyn (500 mg)
  • Naratriptan(Amerge)(fewer HA recurrences than Imitrex)(45% response rate at 2 hours)
  • Zolmitriptan (Zomig, Zomig ZMT)* (dissolves)
  • Rizatriptan (Maxalt,Maxalt MLT)* (dissolves)
  • Almotriptan (Axert)(dec. chest pain, tightness, pressure)
  • Eletriptan (Relpax)—faster acting than oral Imitrex
  • Frovatriptan (Frova) (longest half-life)(45% response rate at 2°
5 ht 3 serotonin receptors and n v
5-HT3 (serotonin) receptors and N & V
  • 5-HT3 in the CTZ (chemoreceptor trigger zone of the brain stem) is responsible for vomiting from chemo and post-anesthesia
  • 5-HT3 in the duodenum is responsible for nausea– “the organ of nausea”
serotonin antagonists for 5 ht 3
Serotonin antagonists for 5-HT3
  • The “setrons” for chemotherapy, reduced risk of anticipatory nausea and vomiting, postanesthesia-induced, and migraine-induced nausea and vomiting, morning sickness, and oral rehydration in kids
  • Granisetron (Kytril)
  • Ondansetron (Zofran, and generic)—also used for acute n and v
  • Dolasetron (Anzemet)
  • Palonesetron HCl (Aloxi)
thank you and remember
THANK YOU…and remember…
  • “Never under any circumstances take a sleeping pill and a laxative on the same night.”
  • Barb Bancroft, RN, MSN, PNP
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  • Cooper WO et al. Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med 2006 Jun 8; 354:2498-500
  • Codario RA. Do we use an ACE, an ARB, or both? What clinical trials tell us. Patient Care 2005 (April); 54-66.
  • Cramer C et al. Use of statins and incidence of dementia and cognitive impairment without dementia in a cohort study. Neurology 2008; 71:344.
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  • Evans RW. Migraine: A Question and Answer Review, Med Clin N Am 2009;245-263.
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  • Goh Sk, Yang KY, Koh JS, et al. Subtrochanteric insufficiency fractures in patients on alendronate therapy: a caution. J Bone Joint Surg BR 2007;89:349-53.
  • Herzig SJ et al. Acid-suppressive medication use and the risk for hospital-acquired pneumonia. JAMA 2009 May 27;301:2120.
  • How to start an ACE inhibitor. Guideline for medical practitioners from EdREN, the website of the Renal Unit, Royal Infirmary of Edinburgh
  • Friedman JM. ACE inhibitors and congenital anomalies. N Engl J Med 2006 (June 8);354:23.
  • Gaynes BN, et al. “The STAR*D Study: Treating depression in the real world,” Cleveland Clinic Journal of Medicine 2008; 75 (1):57-66.
  • Kramer JM et al. Comparative effectiveness of beta-blockers in elderly patients with heart failure. Arch Intern Med 2008 Dec 8; 168:2422
  • Nierenberg AA, et al. “A Critical Overview of the Pharmacologic Management of Treatment-Resistant Depression”, Psychiatric Clinics of North America 2007; 30(1):13-29.
  • Odvina CV, Zerwekh JE, Rao DS, Maalouif N, et al. Severely suppressed bone turnover; a potential complication of alendronate therapy. J Clin Endocrinol Metab 2005;90:1294-301.
  • Pilote L, Abrahamowicz M, Rodrigues E, et al. Mortality rates in elderly patients who take different angiotensin-converting enzymes inhibitors after acute myocardial infarction; a class effect? Ann Intern Med 2004 (141):102-112.
  • Tatro DS, ed. Drug Interaction Facts: Herbal supplements and Food. St. Louis, MO. A. Walters Kluwer Co; 2004; also available at
  • Nisbet BC, O’Conner RE. Atypical presentation of ACE Inhibitor-Induced Angioedema. Resident and Staff Physician October 2007;53(9):14-16.
  • Palmer M, Rosenbaum S. Clinical Practice Guideline of the American Academy of Emergency Medicine (AAEM); initial evaluation and management of patients presenting with acute urticaria or angioedema.
  • Rose BD, ed. UpToDate. UpToDate Web site.
  • Rosenson RS. Factors influencing the myotoxic potential of statins. The American Journal of Medicine 2004;116:408-16.
  • Sewers JR, Williams M, Epstein M, Bakris G. Hypertension in patients with diabetes. Postgrad Med April 2000; 107 (4):47-68.
  • Stoev B, Bohrn MA. Averting angioedema’s potentially dire consequences. Patient Care 2007 (October); 13-18.
  • How to start an ACE inhibitor. Guideline for medical practitioners from EdREN, the website of the Renal Unit, Royal Infirmary of Edinburgh
  • The Medical Letter. Antifungal Drugs. December 2009. 1000 Main St., New Rochelle NY 10801-7537
  • The Medical Letter. Drugs for Glaucoma. January 2010. 1000 Main St., New Rochelle, NY.
  • The Medical Letter.Golimumab and acetaminophen safety. July 13, 2009.