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
• Today there are over 11,000…
• Plus….
The numbers….
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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….
• 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…
• 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
• 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)
Plus…
• 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-thecounter 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???
• When you hear “Bayer” what do you think?
• ASPIRIN OF COURSE!
• 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
• “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
Ketoprofen
• 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
• 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….
• 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
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”
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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…
• 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”…
So if you were an ACE inhibitor, what would you do?
Inhibit ACE? Inhibit the formation AT angiotensin II
1.
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)
1. Treatment of heart failure by inhibiting renin-angiotensinaldosterone—CHF is a HYPER-RENINEMIC state
2. Anti-inflammatory
3. Anti-thrombotic
4. Hypoglycemic (be careful when starting ACE inhibitors in
diabetics)
5. Decrease growth of tissues or “remodeling”
Is “remodeling” a good word? Hmmmmm….
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
• BOTTOM LINE?
“Angie” and the healthy kidney…
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Afferent arteriole
(vasodilated via
(prostaglandins)
Blood entering
glomerulus
Glomerulus→filter
Efferent arteriole
(vasoconstricted via
(angiotensin II)
Blood exiting
glomerulus
PG
filter
AT II
Toilet
“Angie, the “prils” and the Diabetic/hypertensive
Kidney…hyperglycemia/HTN
•
Afferent arteriole
( ↑ vasodilation by
( ↑ prostaglandins)
• Blood entering
glomerulus
• Glomerulus→filter
• Efferent arteriole
( ↑ vasoconstriction via
( ↑ angiotensin II)
• Blood exiting
glomerulus
PRILS inhibit ATII/vasodilate the efferent arteriole
Microalbuminuria
**
To summarize…ACE inhibitors are used
for:
• Hypertension (*night time dosing of antihypertensive 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
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…
• 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 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?
• 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
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Potatoes
Prunes
Raisins
Apricots
Bananas
Halibut
Canteloupe
Oranges
Pasta sauce
Health.harvard.edu/heartextra for K+ content of
1,200 foods
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 course…
• Cough (gender differences)
• Life-threatening angioedema (“Does my
voice sound funny to you?”)
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
• 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”
• Are the “sartans” safe for patients with a history
of angioedema from the “prils”?
• Appears to be about an 5 to 8% rate of crossreactivity
• 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
• 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
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atenolol (Tenormin)
betaxolol (Kerlone)
bisoprolol (Zebeta)
carvedilol (Coreg)
Esmolol (Brevibloc)
labetalol (Trandate)(Normodyne)—safe during
pregnancy
metoprolol succinate (Toprol XL, Lopressor)
nadolol (Corgard)
nebivolol (Bystolic)
propranolol (Inderal)(1968)(nonselective)
sotalol (Betapace)
timolol (Blocadren)
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
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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…
• “Don’t even think about it…if I have told you
once, I have told you twice…”
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
• 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
• 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
• 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
• 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 lipidsoluble 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
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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”—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
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**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;
1st class …
DIPHENYALKYLAMINES
• 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)
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
3rd class--dihydropyridines or the “DIPINES”—
Peripheral vessel calcium channel blockers
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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”…
• 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…
• 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)
• 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
• 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
• 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
• 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”…
Who are they?
• lovastatin (Mevacor)
• simvastatin (Zocor)
• atorvastatin (Lipitor)
• fluvastatin (Lescol)
• pravastatin (Pravachol)
• rosuvastatin (Crestor)
• pitavastatin (Livalo)
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 Sisters”
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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
• 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…
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“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…
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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”
• 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 “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”
• 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*
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”
• *BIG Exception: Aripiprazole/Abilify—antipsychotic—a
dopamine system stabilizer
The “prazoles”—Proton Pump
Inhibitors
• MOA—Inhibition of the proton pump at the lumenal
surface of the stomach…especially after a meal
H+, Intrinsic Factor-B12
PPIs work here
Lumenal surface
Parietal cell
Basilar surface
H2 receptors
H2
H2 blockers work here
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 longterm use
• Increased risk of B12 deficiency due to blocking the
release of intrinsic factor
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 the liver for ~ 5 years—takes a long time of
PPI use to cause B12 deficiency
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?
•
•
•
•
•
•
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)
• 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”
•
•
•
•
•
•
•
Miconazole (Monistat)
Clotrimazole (Mycelex)
Fluconazole (Diflucan)
Itraconazole (Sporanox)
Ketoconazole (Nizoral)
Voriconazole (Vfend)
Posaconazole (Noxafil)—newest of the bunch
(HIV)
• DRUG INTERACTIONS
• “You have a yeast infection…”
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
• 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
• PREVENTION?
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
DEPRESSION
“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
• 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 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?
• 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
• 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…
• Low serotonin is part of the problem with
patients with premature ejaculation
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”…
•
•
•
•
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
• 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
• Infliximab (Remicade)—targeted against TNF-α,
the culprit in Crohn’s disease, RA, psoriasis; TB
testing prior to use
• Adalimumab (Humira)—as above
• certolizumab pegol (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
• 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
• Bevacizumab (Avastin)—inhibits
angiogenesis; used to inhibit tumor
growth; used to decrease neovascular
growth in the retina; glioblastoma
multiforme (with a tyrosine kinase
inhibitor)
• Abciximab (Reopro)—inhibits platelet
aggregation
• Ranibizumab (Lucentis)—wet macular
degeneration
The “triptans”--5-HT (5-Hydroxytryptamine) (serotonin) 1B/1D
agonists-- 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-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-HT3
• The “setrons” for chemotherapy, reduced risk of anticipatory
nausea and vomiting, postanesthesia-induced, and migraineinduced 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)
And last, but not least, an all in one pill
for stress…
THANK YOU…and remember…
• “Never under any circumstances take a
sleeping pill and a laxative on the same night.”
• Barb Bancroft, RN, MSN, PNP
• www.barbbancroft.com
• BBancr9271@aol.com
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• Bonakdar RA. Herb-drug interactions: what physicians need to know.
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• Cooper WO et al. Major congenital malformations after first-trimester
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• Codario RA. Do we use an ACE, an ARB, or both? What clinical trials tell us.
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• Cramer C et al. Use of statins and incidence of dementia and cognitive
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• Cayley WE. Are beta blockers effective first-line treatments for
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