PHARMACOLOGY – simplify
don’t mystify
• “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…
• 35 years ago there were 900 drugs to choose
from in the PDR
• Today there are over 11,000…
• Plus….there are over 10,000 OTC drugs and
600 herbal products
• Rule #1…don’t PANIC
Organizing by Categorizing…
• Teach Generics NOT brand/trade names
• The “PRILs”—the ACE inhibitors
• The “SARTANs”—Angiotensin Receptor Blockers
(ARBs)
• The “OLOLs, ALOLs, ILOLs”—Beta Blockers
• The “DIPINEs”—The calcium channel blockers
• The “TRIPTANs”—serotonin agonists for migraines
• The “STATINs”—HMG Co-A reductase inhibitors
• The “NIBS”—tyrosine kinase inhibitors for cancer
• The “MABS”—monoclonal antibodies
• The “AZOLES”—antifungal drugs
• The “PRAZOLES”—anti-GERD drugs
Rule #2…Use a little humor in the
title of your lectures…
• Who is ACE and why do we want to inhibit him?
Or the story of “Angie and Al”
• Who is “Sara”(tonin) and why does she make us so
happy?
• Who put the “dope” in dopamine?
• Hormonal chaos
• Shove it up your acid-base…
• The “Statin Sister’s”—lova, simva, fluva, atorva, rosuva,
prava)
• From the devil weed to the poppy seed
• Corny, but…it WORKS
#3—Historical highlights and hysterical
highlights…nothin’ like a good story…
• Cows, sweet clover, rat poison, and the President of the
United States
• Dicumarol, WARFarin/Coumadin
• Rats in England
The “dropsy”…
• Serendipitous findings
• William Withering, M.D. and botanist treated his patients
with “dropsy” by leaching them
• Meanwhile, in the village of Shropshire, a local witch
brewed up a concoction that she dispensed to anyone
knocking at her door complaining of the “dropsy”
• 16 ingredients—one active
• The FOXGLOVE
“Witche’s brew”—atropine (deadly nightshade),
henbane (scopolamine— “twilight sleep”), mandrake
(+/- hemlock)
• 9th to the 13th century-- Surgical patients inhaled
“soporific” sponges infused with opium, marijuana,
hemlock, or henbane (scopolamine)
• Witche’s brew was also a popular analgesic and
hallucinatory potion—what was in it?
• Physician to Pope Julius III wrote that he used Witche’s
brew to anoint (from head-to-toe), the wife of a hangman
• How was it administered?
Historical highlights –36 years ago…PAIN
management in the early 70s
• The days of starting with the smallest dose
possible…RX: Demerol 50 to 150 mg q 3-4 PRN
• Patients waited too long to call nurse—wait and tolerate
pain
• Or, more likely, the nurse took too long to respond, OR
the dosing interval was inappropriate…
• The Limbic system --interpretation of
pain…Mutha…@!%&**(@!!!! I NEED IT NOW!!
• PRN took on a new meaning for me…PER
REGISTERED NURSE…
• “If we give ‘em too much, they’re going to become
addicts...”
The days of yesteryear…
• Around-the-clock vs. PRN
• Patient-controlled analgesia— “they will be
pushing that button all day and they’re going to
become addicts!!” (140 mg/24 vs. 48 mg/24)
• Pre-emptive analgesia—give ‘em something
before they even hurt…
Pain and newborns
• The circumcision decision
• Why bother giving the little guys something for
pain???
• “It’s such a short procedure and newborns don’t
feel pain anyway…”
• Babies circumcised without
anesthesia/analgesia experience more pain
during routine vaccinations 4-6 months later
• Pain and ADD??
• Sugar-coated pacifiers; EMLA cream
Historical highlights
• In the 2nd century AD the Greek physician
Galen prescribed opium for just about
anything that ails ya’—from asthma to
epilepsy; dropsy to diarrhea and for the…
• “troubles to which women are
subject..”
• All of the Asian countries started growing their
own poppy plants after introduction into their
countries
• Opium was used primarily as a sedative and as
a treatment for diarrhea when they weren’t
hanging around opium dens
Fast forward to today’s bowels…
• Codeine—not that great for pain management because
of its side effects; as the dose escalates, so do the side
effects; major side effect is constipation
• Morphine—major side effect is constipation
• Lomotil for diarrhea (atropine sulfate + diphenoxylate
HCl)
• “Lomotil is so good, it will…”
• Loperamide (Imodium)
• Undiarrhea (Taiwan)
• Stopit (Israel)
• New drug for opiate-induced constipation--RELISTOR
The approach…
• Divide and conquer
1) Prescription drugs—a Class Act; the
“statins”, the “prils”, the “sartans”, the
“azoles”, the “afils”, the “olols, alols, and
ilols”, the “triptans”…
2) OTC drugs—the most common;
acetaminophen, aspirin, NSAIDS, and
anti-histamines should top the list
3) Herbal products—the top 10
Let’s put all of the rules together…
•
•
•
•
Don’t panic…start with the basics
Use humor in the title
Tell a story
Let’s try it with the ACE inhibitors…
“The Prils”—The ACE inhibitors
(Brazilian pit viper—Bothrops jararaca))
• The Brazilian rain forest
• Pit viper venom and hypotension
• Tested in VA hospitals to
treat what was known in the 50’s and 60’s as “the
SILENT KILLER”, (hypertension)
Who are the ACE inhibitors? Pick a
“pril” any “pril”…
•
•
•
•
•
•
•
•
•
•
Captopril (Capoten)
Enalapril (Vasotec)
Lisinopril (Prinivil, Zestril)
Perindopril (Aceon)
Moxepril (Univasc)
Benazepril (Lotensin)
Quinapril (Accupril)
Trandolapril (Mavik)
Ramipril (Altace)
Etc…
A little refresher on the kidney…
• At any given moment, the
kidney is “sensing” the
pressure and volume of blood
flow throughout the body
• 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
1→angiotensin 2→ via
• Angiotensin Converting
Enzyme(ACE)
Angiotensin 2 triggers the release
of “AL” from the adrenal cortex
RENIN
ANGIOTENSIN 1
ANGIOTENSIN 2
What does “angie’ do?
•
•
•
“Tenses” your “angios”—vasoconstricts
(  BP)
Triggers release of “AL”—aldosterone (from
the adrenal cortex to save Na+ & H2O ( BP)
and excrete K+…but that’s not all…
ANGIOTENSIN 2 ALSO…
• Increases inflammation in the arteries
• Prothrombotic
• Increases tissue resistance to insulin
• Potent growth factor— “remodels tissues”
So, let’s get back to the original story…Who
is ACE and why do we want to inhibit him?
RENIN
ANGIOTENSIN 1
ACE --
ALDOSTERONE
ANGIOTENSIN 2
Functions of ACE Inhibitors
1.
2.
3.
4.
5.
6.
Anti-hypertensive agents via vasodilation and inhibition of
aldosterone (Na+ and H20 diuresis)
Treatment of heart failure by inhibiting renin-angiotensinaldosterone—CHF is a HYPER-RENINEMIC state—why? (low
volume/low pressure presented to the kidney from the failing heart
triggers renin release)
Anti-inflammatory
Anti-thrombotic
Hypoglycemic (be careful when starting ACE inhibitors in
diabetics)
Decreases “remodeling” of tissues
Is “remodeling” a good word? Hmmmmm….
Remodeling and angiotensin…
• Remodels myocardium and disrupts the
conduction system…
• Increases the risk of ventricular
dysrhythmias
• Increases vascular fibrosis—hypertension
• Increases intraglomerular blood pressure
resulting in intraglomerular hypertension
leading to CKD
“Angie” and the healthy kidney…
•
Afferent arteriole
(vasodilated via
(prostaglandins)
The analogy—3 lanes in
• Blood entering
glomerulus
• Glomerulus→filter
• Efferent arteriole
(vasoconstricted via
(angiotensin 2)
• Blood exiting
glomerulus-one lane out
PG
filter
AT2
Toilet
“Angie, the “prils” and the
Diabetic/hypertensive Kidney…hyperglycemia/HTN
•
Afferent arteriole
(  vasodilation by
(  prostaglandins)
• Blood entering
glomerulus
6 lanes in
• Glomerulus→filter
• Efferent arteriole
(  vasoconstriction via
 angiotensin-2)
Shoulder of the road exiting
Microalbuminuria**
Side effects…
•
•
•
•
Hypotension
Hypoglycemia
Cough
Angioedema (“Does my voice sound funny
to you?”)
• Hyperkalemia (excreting sodium and water
and retaining potassium)
Side effects…Rx of
hyperkalemia
Hyperkalemia-- Add a thiazide diuretic to the
“pril” and voilá!
• Capozide (captopril + thiazide)
• Vaseretic (enalapril +thiazide)
• Prinizide (lisinopril + thiazide)
• Zestorectic (as above)
• Lotensin HCT (benazepril +
hydrochlorothiazide)
Adding drugs that block aldosterone in CHF
patients—spironolactone (Aldactone) and
eprelrenone (Inspra)
• Be really careful to check K+ levels within the
first week after adding Aldactone or Inspra to an
ACE inhibitor
• RALES (1999) (Random Aldactone Evaluation
Study)—adding Aldactone postpones or
prevents 200 deaths/1000 people w/CHF
• BUT…For every 1000 new spironolactone RX in
heart failure patients, there are 50 more
hospitalizations for hyperkalemia
Decrease the intake of foods with high
potassium in patients on ACE-+ Aldactone…
•
•
•
•
•
•
•
•
•
Banana (1 m) 422 mg
Potatoes (with skin) 540 mg
French fries (1 med) 924 mg
Halibut (3 oz) 490 mg
Spinach (1c) 839 mg
Pasta sauce (1c) 940 mg
Oranges 1 m 237 mg
Prunes (elderly) 10 615 mg
Health.harvard.edu/heartextra for K+ content of 1,200
foods
Other potential K+ boosters…
• Stop taking any K+ supplements including salt
substitutes such as K+ iodide
• Go easy on the NSAIDS (decrease GFR) with
retention of fluids and electrolytes (including K+)
• Herbal or natural remedies with hefty doses of
potassium include noni juice, Siberian ginseng,
hawthorn berries
• Licorice can also “save” potassium (Harvard
Heart Letter, December 2004)
ACE inhibitors (category D) in
pregnancy
• Why?
• Inhibit growth factors
• Cooper WO, Hernandez-Diaz S, Arbogast PG,
Dudley JA, Dyer S, et al. Major congenital
malformations after first-trimester exposure to
ACE inhibitors. N Engl J Med 354;23:2443-51.
• Friedman JM. ACE inhibitors and congenital
anomalies. N Engl J Med 2006 (June 8); 354:23.
“Sartans”—ARBs
• Angiotensin Receptor Blockers (bypass ACE) and
work by blocking the tissue receptors
• Who are they? The “Sartan Sisters”…
•
losartan—Cozaar
•
valsartan—Diovan
•
candesartan—Atacand
•
irbesartan—Avapro
•
telmisartan—Micardis
•
olmesartan—Benicar
• Can use with “prils” for additive effect; Less side
effects—may substitute if cough is unbearable
“Olols, alols, ilols”—Beta
blockers
•
•
•
•
•
•
•
•
•
•
•
•
•
propranolol (Inderal)(1968)
nadolol (Corgard)
timolol (Blocadren)
atenolol (Tenormin)
metoprolol succinate and tartrate (Toprol XL, Lopressor)
betaxolol (Kerlone)
bisoprolol (Zebeta)
carvedilol (Coreg)
labetalol (Trandate)
acebutolol (Sectral),
penbutolol (Levatol)
pindolol (generic)
nebivolol (Bystolic)
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: dopamine, epinephrine,
norepinephrine
• Scenario: Visit Barb in Chicago
• B1—found on heart muscle; epinephrine binds to B1 and
increases heart rate and strength of contraction
(chronotropic and inotropic)
• B2—skeletal muscle, bronchioles of the lungs
(bronchodilation), large arteries of the legs (vasodilation)
• Alpha 1—arteriole smooth muscle (vasoconstriction to
increase BP)
• Alpha 2 (hypothalamus)—regulates CNS output of SNS
• Drugs can ‘selectively’ modulate the various receptors
“Olols, alols, ilols”…
• Cardioselective? (B1 receptors)—if you block
the B1 receptors on the heart, the heart rate and
contractile state decrease – cardiac output falls,
blood pressure falls, workload of the heart
decreases
atenolol (Tenormin), metoprolol (Lopressor),
betaxolol (Kerlone); bisoprolol (Zebeta),
nebivoloil (Bystolic)@ doses <10 mg)
• Used for blood pressure control, angina,
situational anxiety, hyperthyroidism (with heart
rates that can reach 200+)
Why don’t we pick just any old beta blocker?
Because the non-cardioselective block both the
B1 AND B2 receptors and can wreak havoc in
certain patient populations
• (bronchoconstrict { exacerbate COPD, asthma},
vasoconstrict the femoral artery {exacerbate
PAD})
propranolol (Inderal), nadolol (Corgard),
timolol (Blocadren), carvedilol (Coreg)
Beta blockers…other properties
• Water-soluble? (low lipophilicity)
atenolol (Tenormin), nadolol (Corgard), labetalol
(Trandate)
• 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—
anxiety (panic and situational) attacks, PTSD, episodic
dyscontrol, essential tremor
• propranolol (Inderal), timolol (Blocadren), metoprolol
(Lopressor, Toprol XL), pindolol
• All of the others are moderately lipophilic
Beta-blocker eyedrops
• Timolol (Timoptic), betaxolol (Betoptic),
levobunolol (Betagan), carteolol
(Ocupress)
• Highly lipid-soluble and cross the
blood-brain barrier
• Can cause bradycardia and anhedonia
• What can you use instead?
The “oprosts”…
• The “oprosts”—bimatoprost (Lumigan),
latanoprost (Xalatan), travoprost (Travatan)**
• Prostaglandin analogues for glaucoma
• **Not to be confused with the new “oprost”
(Iloprost or Ventavis)—it, too, is a synthetic
prostaglandin analogue (PG-12) but it dilates
the systemic and pulmonary vascular beds—
used for the treatment of pulmonary arterial
hypertension
Speaking of eye drops…one gtt or two?
• The volume of a single drop can vary with the viscosity
of the solution, the design of the dropper, and patient
technique.
• A second eye drop either washes out the first or
increases the possibility of systemic toxicity, and doubles
the cost
• When two different types of drops are being used, they
should be instilled at least 5 minutes apart.
• The Medical Letter, June 19, ‘06
Calcium channel blockers
• What are the calcium channel blockers?
• Where are the calcium channels located?
• Heart vessels and AV node, peripheral
blood vessels, bowels
3 Classes of Calcium Channel
Blockers…
1) Verapamil (Isoptin SR,
Verelan and Verelan PM,
Calan and Calan SR, ApoVerap, Novo-Veramil, NuVerap,)—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
2) Calcium channels in bowels
(elderly)
2) Diltiazem—Cardizem, Dilacor
XL—dilates calcium channels
on the coronary (1/5 affinity for
coronary channels) and
peripheral vessel calcium
channels;Clinical uses—
Atrial fibrillation,
Hypertension, Angina,
Vasospasm
Less constipation
3) “DIPINES”—Peripheral vessel
calcium channel blockers
•
•
•
•
•
•
•
Amlodipine (Norvasc)
Felodipine (Plendil)**
Nifedipine (Procardia)
Nicardipine (Cardene)
Isradipine (Dynacirc)
Nisoldipine (Sular)
MOA: Block the
peripheral vascular
calcium channels
• Amlodipine +
Atorvastatin=CADUET
Case study:
• 93-year-old male with severely edematous feet
• HCT given to decrease swelling—didn’t work
• Motrin (ibuprofen) given for the pain and
“edema”
• Taking felodipine (Plendil) for HTN
• Eating grapefruit or drinking grapefruit juice
every day for breakfast
• What is wrong with this picture?
What’s wrong?
• Motrin (ibuprofen)—vasoconstricts the
renal artery by blocking the vasodilating
prostaglandins—fluid retention
• felodipine is the most potent of all “dipines”
and therefore the most vasodilation
• Grapefruit juice increases the
bioavailability of felodipine and increases
toxicity
• What should be done?
Clinical uses of the “dipines”…
• Hypertension
• Vasospasm—Prinzmetal’s angina,
Raynaud’s phenomenon, cocaine-induced
vasospasms
• FYI: Ureteral spasm in patients with small
kidney stones (try slow release nifedipine
30 mg qd x 5-7 days)
• “male contraceptive”
Side effects of CCBs…
• Verapamil—significant constipation; blocks
Ca+ channels in bowel
• Dipines—significant peripheral
vasodilation with headaches; hypotension,
and peripheral edema (swollen feet—
pedal edema; (Plendil)
• Diltiazem—less significant constipation
than Verapamil
The “Statin Sisters”…
The weaker “sisters”…
• lovastatin (Mevacor)
• fluvastatin (Lescol)
• pravastatin (Pravachol)
The stronger “sisters”…
• simvastatin (Zocor)
• atorvastatin (Lipitor)
• rosuvastatin (Crestor)
The “Statin Sisters”…what do they
do? Reduce LDL cholesterol
• Inhibit the enzyme HMG-CoA reductase in the liver
• This enzyme in the liver is responsible for the production
of LDL-cholesterol;
• LDL 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
• Works primarily at night to produce LDL, so the “statins”
work the best when taken before bedtime (exception to
the rule is Lipitor—has a much longer half-life)
• Statins decrease CHD, PAD, CVD risk and increase
survival rates
• What else do the statins do?
The “Statin Sisters”
•
•
•
•
•
Reduce total cholesterol levels
Decrease plaque formation
Stabilize plaques and prevent plaque rupture
Shrink plaques in all arteries
Anti-inflammatory effects (other clinical
uses?)
• Atorvastatin and inflammation (RA, SLE,
MS)(Lancet 2004 June 19;363:2015-21)
• Stimulate neurogenesis-prevent DAT, improve
mood
• And the list goes on…and on…
The “Statin Sisters”—goals of
therapy
• LDLs less than 100 mg/dL (depending on your
risk of cardiovascular disease)
• Diabetics, CHD, PAD, CVD patients—goal is 70
mg/dL
• Instead of starting with the lowest doses, begin
with a dose that drops the LDL by 50%
SIDE EFFECTS
• Myalgias **(other causes in elderly patients…)
• Myositis; rhabdomyolysis (rare)
• About 1/20 patients experiences muscle pain or
weakness
• Reduce the dose, don’t stop the drug; add ZETIA
(ezetimibe)
• Check thyroid function;
• Are they drinking grapefruit juice? (simvastatin,
lovastatin, atorvastatin)
• Liver damage (Acute renal failure with rosuvastatin?)
• Draw CK and LFTs prior to starting statins** (PI says
yes—any evidence of liver dysfunction? No…)
The “glitazone” sisters—
Rosi/Pio
• Rosiglitazone—Avandia (BID)—may increase
TG levels up to 15%; 8-19% HDL↑
• Pioglitazone—Actos (QD)-- ↓TG by 9-12%;
↑HDL 12-19%
• MOA: insulin sensitizers—both lower HbA1c
equally
• Activating PPARs (peroxisome proliferatoractivated receptors) on skeletal muscle cells
and all cells of vasculature endothelium—
overcome insulin resistance
• Anti-inflammatory and immune-modulating
effects as well
The “glitazone” sisters—
Rosi/Pio
• Some evidence that these drugs slow the demise of
the pancreas when used early in Type 2 diabetes
• ANTI-INFLAMMATORY—reduce hs-CRP levels
• Watch out for fluid retention! Especially in patients
prone to chronic heart failure
• Can you use the “glitazones” in patients with known
CHF? (hmmm, maybe you can…Heart Failure
Society meeting, Toronto, 9/12-9/15, 2004)
• Weight gain—primarily subQ not visceral fat
• The brou-ha-ha over Avandia…
The “afils”—1998 and the Pfizer
Riser…Erectile dysfunction
• Prior to November 1998…
• Sildenafil (Viagra)
• Vardenafil (Levitra)
• Tadalafil (Cialis)—the “weekend warrior”
• Boost nitric oxide—potent vasodilator
• Can use in patients with stable CHD
• What are the causes of ED?
Athero, neuro, drugs, ↓testo
psychological (the stamp test)
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
• 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…
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…
• And, guys…there may be another
“surprise” side effect…
Nonarteritic anterior ischemic optic
neuropathy—NAION)
•
•
•
•
43 cases
38 in Viagra users
1/605,000 users
High risk males—over 50, diabetic, CVD,
HBP, high cholesterol, smokers, duh…
• (Diabetes Forecast, April 2006)
The “dronates” for osteoporosis
• The “dronates” for osteoporosis
• Alendronate (Fosamax) and Risendronate
(Actonel), ibandronate (Boniva)
• zoledronic acid (Zometa) and pamidronate
(Aredia)--cancer
• Trigger apoptosis of osteoclasts
• osteoblasts continue to build bone matrix
• Evidence that these drugs might also help
patients with osteoarthritis
• Any downside?
• Fractures? Osteonecrosis of jaw?
The “prazoles”**—Proton Pump
Inhibitors
• Who are they?
• Omeprazole (Prilosec)(first released as
Losec)
• Lansoprazole (Prevacid)
• Rabeprazole (Aciphex)
• Pantoprazole (Protonix)
• Esomeprazole (Nexium)-- “the purple pill”
• **Exception: Aripiprazole/Abilify—an new
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’ before the first meal of the day
• Blocking acid production also decreases the release of
intrinsic factor which is necessary for binding B12
• Do you need B12? YES. To maintain the health of the
central and peripheral nervous systems and to make
happy, healthy RBCs
• Do you need acid to digest food? NO
• Do you need acid to zap food-borne pathogens? YES
• Evidence that C. difficile is a higher risk if on PPIs
What about B12 deficiency with the
PPIs?
• 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)
• B12 deficiency is the number one cause of nutritional
dementia in the U.S.
• B12 is stored in the liver for 5 years or so
• 39% of the population over 50 has a B12 deficiency
• Should we all be taking B12?
• If so, how can we take it? Diet? Supplements?
• How much?
• Can you overdose on B12? The one dreaded side effect
is…
The “tidines” (H2 blockers)
• Cimetidine--Tagamet—can cause delirium in the
elderly;(400-800 po mg/qhs**) increases the
bioavailability of many drugs—beta blockers,
theophylline, morphine
• Ranitidine (Zantac)—20-40 mg qhs
• Nizatidine (Axid)—150-300 mg qhs
• Famotidine (Pepcid)--20-40 mg qhs
• Pepcid Complete—(famotidine +calcium carbonate +
magnesium hydroxide)—1 tab po PRN (not more than
2/day)
• Best to give at hs—decrease vagally-induced histamine
release in stomach
• (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”
•
•
•
•
•
•
Clotrimazole (Mycelex) • “You have a yeast
infection…”
Fluconazole (Diflucan)
Itraconazole (Sporanox)
Ketoconazole (Nizoral)
Miconazole (Monistat)
Voriconazole (Vfend)
The antiherpetics—the “cy{i}clovirs”
• Acyclovir (Zovirax)-• Famciclovir (Famvir)
• Valacyclovir (Valtrex)
• Can you get “hairpiece” from a “toe-lit”
seat?
The antiherpetics—the “cy{i}clovirs”
• 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
• Zostavax (Merck) to reduce the incidence of
Herpes Zoster (shingles/Hell’s fire) in people
over 60 (14 x stronger than Varivax)(risk
reduction—50%); reduces severity and
decreases post-herpetic neuralgia
Percent of individuals with shingles,
by age
•
•
•
•
•
•
•
•
•
•
10—0.5%
20—1.3%
30—2.7%
40—4.8%
50—7.5%
60—11.9%
70—19.7%
80—31.8%
90—46.1%
Donahue JG, et al. Archives of Internal Medicine, 1995.
The antibiotics--the “floxacins”…
• Ciprofloxacin (Cipro) (2nd)*
• Lomefloxacin (Maxaquin)
• Norfloxacin (Noroxin)*
• Ofloxacin (Floxin)*
*uncomplicated UTIs if resistance to TMP/SMX is ≥ 20%
• Levofloxacin (Levaquin) (3rd)—too broad spectrum for
UTI
• Gemifloxacin (Factive)**
• Moxifloxacin (Avelox)**--doesn’t reach suff. levels in
urine
• WARNING: C. difficile after the quinolones…
It’s a “MAB, MAB, MAB” world
• Cetuximab (Erbitux)—colon cancer (Martha
Stewart)
• Bevacizumab (Avastin)—inhibits angiogenesis
• Daclizumab (Zenapax)—anti-transplant rejection
• Natalizumab (Antegren)—inhibits the ability of
segs to migrate (MS and Crohn’s)
• Omalizumab (Zolair)—mab to IgE
It’s a “MAB, MAB, MAB” world
• Infliximab (Remicade)—targets TNF-α (TB testing prior
to use)
• Trastuzumab (Herceptin)—HER2-neu+ Breast
cancers—start early!
• Abciximab (Reopro)—inhibits platelet aggregation
• Rituximab (Rituxan)—NHL (SLE?)
• Palivizumab (Synagis)—RSV protection for developing
lungs (34-week infants have just 52% of the calculated
lung volume of full-term infants at birth)
• Efalizumab (Raptiva) for psoriasis—prevents T cells from
entering skin and becoming activated
• Ranibizumab (Lucentis)—for wet macular degeneration
The “triptans”--5-HT1D agonists-vasoconstriction of peripheral arteries + decrease
the release of neuropeptides from CN V
•
•
•
•
•
•
•
Suma (Imitrex)
Nara (Amerge)(fewer HA recurrences than Imitrex)
Zolmi (Zomig, Zomig ZMT)*
Riza (Maxalt,Maxalt MLT)*
Almo (Axert)(dec. chest pain, tightness, pressure)
Ele (Relpax)—faster acting than oral Imitrex
Frova (Frova)(longest half-life)
• *The “melt in your mouth” triptans contain aspartame
Herbal products
www.consumerlabs.com
•
1)
2)
3)
4)
The seven ten herbal products sold in the U.S. are:
Gingko biloba—inhibits platelet aggregation
St. John’s Wort—decreases effectiveness of drugs
Ginseng—sodium and water retention; bleeding/clotting
Kava**(adverse hepatic effects; FDA March 2002)—
liver failure
5) Saw Palmetto—questionable efficacy?
6) Garlic—inhibits platelet aggregation
7) Echinacea—immune enhancer
St. John’s Wort…
• “St. John’s wort is the most common herb
involved in drug interactions.”
• (Bonakdar RA. Herb-drug interactions: what physicians need to
know. Patient Care 2003; January: 58-69.)
Tatro DS, ed. Drug Interaction Facts: Herbal supplements and Food.
St. Louis, MO. A. Walters Kluwer Co; 2004; also available at
www.factsandcomparisons.com
St. John’s Wort for depression
• Does it work? Yes, it has been shown to be superior to
placebo.
• May boost serotonin, norepinephrine by mild MAO
inhibition; may also boost GABA and dopamine to
varying degrees
• Also appears to decrease cytokines and hormones of the
stress response (IL-6 and cortisol) that may be
responsible for mild depression
• Effective for mild depression…not moderate to severe
• Do NOT use with other anti-depressants—especially
SSRI’s
• Serotonin syndrome—agitation, hypertension,
tachycardia, seizures, coma
Say NO to St. John’s Wort for
patients on other drugs!
• Interacts with everyone and everything!
• Inducer of CYP3A4 (increases metabolism of
drugs and decreases effectiveness)
• Also pumps drugs out of cells (p-glycoprotein
pump) and reduces the effectiveness of
hundreds of drugs
St. John’s wort and other drugs
• SJW reduces Dig levels by 25%
• SJW decreases effectiveness of COCs by up to
50%
• SJW reduces effectiveness of transplant
rejection drugs, HAART drugs
• SJW and Gleevec--↓30-40%
(Pharmacotherapy, Nov.’05)
• Second degree sunburn – stay out of the sun
(SAD)
Plus…
• Over 10,000 over-the-counter (OTC) drugs that
can wreak havoc—2 examples:
• Cimetidine (Tagamet)
• Acetaminophen is in over 300 over-the-counter
products (Tylenol)—inadvertent overdoses (50%
of all acute cases of liver failure)
• Adding “cet” to an opiate =opiate +
acetaminophen
The many faces of
acetaminophen…
• Opiod-analgesic combinations:
Darvocet, Fioricet, Lorcet, Percocet, Propacet, Roxicet,
Ultracet
• Combos with “cet” as a suffix
• Use Rx combos w/ lowest dose of acetaminophen—325
mg/
• Advise patients of the combination so that they don’t
inadvertently overdose on Tylenol for sinuses, back pain,
headaches, joint pain, and whatever else ails ‘em.
• How many grams/d of acetaminophen is safe? 4 Gm or
less per day for adults
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;
• Bayer Select Pain Relief is ibuprofen
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
Origin of the word
• The word “digitalis” was first used by the
German botanist Leonhardt fuchs in 1542.
In Berman the name for foxglove flowers
was fingerhut, or thimble, and hence, the
Latin word for finger, digitus, was adapted
as the name for the plant species.
Historical Highlight
• In order to induce labor the Ebers papyrus
proposed that a woman should “apply
peppermint to her bare posterior” or take
“fennel, incense, garlic, sert-juice, fresh
salt, and wasp dung—make it into a ball
and insert it into the vagina. Works for me.
Historical highlight
• Searle marketed the first oral
contraceptive, ENOVID, in 1990. Between
1929 and 1935 the steroidal sex hormones
were isolated in pure form. Supplies were
scarce-- in order to obtain 12 mg of
estradiol, it was necessary to extract 4
tons of pig ovaries.
Bibliography
• Aronow WS. Hypercholesterolemia: The evidence
supports the use of statins. Geriatrics 2003; 58 (8): 1832.
• Codario RA. Do we use an ACE, an ARB, or both? What
clinical trials tell us. Patient Care 2005 (April); 54-66.
• Cooper WO, Hernandez-Diaz S, Arbogast PG, Dudley
JA, Dyer S, et al. Major congenital malformations after
first-trimester exposure to ACE inhibitors. N Engl J Med
354;23:2443-51.
• Friedman JM. ACE inhibitors and congenital anomalies.
N Engl J Med 2006 (June 8); 354:23.
• The Medical Letter. 1000 Main St., New Rochelle NY
10801-7537 www.medletter.com
• Moser M, Setaro JF. Resistant or difficult-to-control
hypertension. N Engl J Med 2006 July 27; 355(4):385392.
• Rosenson RS. Factors influencing the myotoxic potential
of statins. The American Journal of Medicine
2004;116:408-16.
• Stoev B, Bohrn MA. Averting angioedema’s potentially
dire consequences. Patient Care 2007 (October); 13-18.
• Wolf G and Ritz. E. Combination therapy with ACE
inhibitors and angiotensin II receptor blockers to halt
progression of chronic renal disease: pathophysiology
and indications. Kid Inter 2005;67:799-812
• Wade V and Gleason B. Dual blockade of the reninangiotensin system in diabetic nephropathy. Ann
Pharmacother 2004; 38:1278-82