Download Evaluation and Treatment of Hypertension

Evaluation and Treatment
Practical Pearls for Clinical
Dilemmas in Primary Care
of Hypertension
When Thiazides Are Not A
Good Choice
A 58 yo man is diagnosed with
hypertension. His BP’s are 160/96, 160/100,
and 158/96 on 3 outside readings. He has
been on a low sodium diet and he is not obese.
PMH- hyperlipidemia, GERD and gout. What
would be the most appropriate treatment?
A) Low salt diet and exercise
B) Hydrochlorathiazide
C) Doxazosin
D) ACE inhibitor
History of Gout
Creatinine > 1.6
 Lithium use
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Are Beta blockers efficacious
antihypertensive therapy in the elderly?
Diuretic Choice
Strongly consider chlorthalidone
 Long acting, great data
 Major drawback has been hypokalemia
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Meta analysis of 10 randomized trials (at least 1 year
in duration)
16, 164 elderly ( 60 yr) patients included
2/3 of patients on diuretics controlled on
monotherapy, < 1/3 patients on b-blockers well
controlled
Diuretics effective in CVA, CAD, cardiovascular
mortality and all cause mortality. B-blockers only
decreased cerebrovascular events.
JAMA 1998; 279:1903-1907
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A 60 yo man presents for follow-up of
hypertension. He has been taking medication
(Lisinopril) for the past 3 months. His most recent
outside blood pressure readings are 156/94, 150/96,
158/92. PMH: Type 2 DM, GERD, depression. Meds:
Lisinopril 20mg qd, Rabeprazole 20mg qd, Sertraline
50 mg qd, Glyburide 10 mg qd.
What do you recommend?
A) No changes in therapy
B) Increase Lisinopril to 20 mg BID
C) Add Hydrochlorathiazide 12.5 mg qd
D) Add Amlodipine (Norvasc) 5mg qd
E) Add Clonidine .1mg BID
Combination Therapy
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Combining a thiazide with B blocker or an
ACE has a synergistic effect, controlling BP in
up to 85%
Combination of ACEI with amlodipine may be
superior to ACEI + diuretic in patients with
diabetes (less CV events)
Low doses of thiazide can be very effective in
combination with ACE inhibitors (12.5 mg of
thiazide)
Thiazide ACE combination can be further
enhanced by moderate dietary salt restriction
Outcomes with Different Combination Regimens
for Hypertension (ACCOMPLISH)
6946 patients with diabetes and HTN
randomized to benazapril and HCTZ or
Benazapril and amlodipine,in addition 4,559
patients without DM were also studied.
 BP lowering same with both combinations,
reduced CV events in patients on B +A (HR .79,
CI .68-.92, p <.003)
J AM Coll Cardiol 2010;56 (1): 77-85.
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A 58 yo woman is seen for treatment of hypertension. She
has not ever had good control of her hypertension since
treatment was started 2 years ago. She has been taking her
medications faithfully. Meds: Felodipine (Plendil), Atenolol ,
Clonidine, and Losartan (Cozaar). On exam her BP is 200/106
P-55.Labs- BUN 30, Cr 2.0, Na 137, K 4.0. ECG- LVH
What would you recommend?
A) Increase felodipine from 10mg a day to 10mg BID
B) Increase losartan from 50mg BID to 100mg BID
C) Add hydrochlorathiazide 12.5 mg qd
D) Add hydrochlorathiazide 25 mg qd
E) Add furosemide 40 mg BID
Treatment of Refractory
Hypertension
Refractory Hypertension
Occurs in 5% of hypertensive patients
Always carefully evaluate for medication
adherence.
 Worse with increasing obesity
 Think of secondary causes
 Sleep apnea
 Ingestion of substances that interfere with
treatment (especially NSAIDS)
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Most have too much volume.
Furosemide extremely useful, especially
if renal insufficiency present
 Consider spironolactone
 Simplify regimens if possible to improve
adherence
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AHA Recommendations For
Treatment of Hypertension
Indication
BP goal
Initial therapy
B Blocker
Hypertension Pearls
Losartan can lower uric acid
A low potassium level in a patient with
untreated hypertension suggests a
hyperaldosterone state ( hyperaldosteronism
due to adrenal hyperplasia > renal artery
stenosis)
 Treat renal artery stenosis medically, not
surgically or with stents
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Low risk
<140/90 ACE/CCB/Thi
High risk
<130/80 ACE/CCB/Thi
With CAD <130/80 BB and ACE
CHF
< 120/80 BB/ACE/Aldo
Diuretics
No
No
Yes
Yes
How Can You Tell What
Kind Of Headache It Is?
A 29 yo woman is evaluated for headaches.
She reports having headaches about twice a
month. She feels pain behind her right eye
and frequently pain on her forehead. Her
headaches often get better with 550 mg of
Naprosyn. She has never had visual problems
or nausea with her headaches. The
headaches are worse with exercise. About
once a month the headache is bad enough to
force her to leave work early.
What is the Most Likely Type of
Headache?
Clinical Features of Tension Type
Headache
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Mild Headache
Often described as tightness, vice like
 Neck to forehead can be involved
 Often helped by NSAIDS
 Worse during times of stress
 Not disabling
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A)Migraine
B)Cluster
C)Muscle tension
D)Nitrate headache
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Clinical Features of Migraine
Headaches
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Family history common
Pulsating quality
Worse with activity
Mild to Severe in intensity
Can be disabling
History of motion sickness common
Nausea, photophobia, phonophobia may
occur
Diagnosing Migraine
POUNDing Pneumonic
 Pulsating
 Duration 4-72 hOurs
 Unilateral
 Nausea
 Disabling
If 4 criteria met LR is 24 for migraine
If 3 met LR 3.5
If 2 or fewer LR.41
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JAMA 2006: 296: 1274-1283
Role of Metoclopramide
Frequency of Headache Types
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Tension Type – Most common
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Migraine - Common
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Cluster - Rare
Metoclopramide vs Hydromorphone
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Retrospective cohort study to evaluate metoclopramide vs
hydromorphone for initial ED treatment of migraine
200 patients, 51 received IV or IM hydromorphone, 95
received IV metoclopramide and 54 received a different
medication.
Using a 1-10 pain scale, mean pain scale reductions were
2.3 for hydromorphone, 3.7 for metoclopramide and 2,8 for all
other meds (p<.001).
Less rescue meds and faster ED discharge with
metoclopramide
J Pain 2008;9 (1): 88-94.
Good efficacy when combined with
NSAID. Equivalent to sumatriptan oral if
patient has nausea.
 My boost effect of oral triptan or other
oral migraine treatments
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Oral treatment protocol for
moderate to severe HA
NSAID + motility drug (Metoclopramide)
no relief
Oral triptan
no relief
Oral narcotic
no relief
ER/office visit for IV therapy
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Vascular Headache
Prophylaxis
Effective
 B Blocker (propranolol, metoprolol)
 Tricyclic antidepressant (amitriptyline)
 Riboflavin
 Valproate/Topiramate> Gabapentin
Migraine Prophylaxis
Options for the patients who fail standard
prophylaxis
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Leukotriene inhibitors
ACE inhibitors (Lisinopril 10-20 mg)
Calcium channel blockers (Candesartan 16 mg)
Less Effective
Calcium channel blocker
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Memantine for Prevention of Refractory
Migraine
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Patients with refractory migraine studied (8-14
headache days per month or failure of 2 previous
preventive treatments in patients with transformed
migraine) received 10-20 mg of memantine daily for 3
months
28 patients in this open labeled study. HA frequency
reduced from 21.8 days to 16.1 days (p<.01), Days
with severe pain reduced from 7.8 to 3.2 (p<.01).
Side effects in 37.5 %, with 5.5% drop out due to side
effects.
Headache 2008;48 (9): 1337-42
Prophylaxis of migraine headaches
Riboflavin
No response x 3 months
B-blocker
No response x 3 months
Add TCA
No response x 3 months
Valproate/topir>gaba
Topiramate And Acidosis
Topiramate acts as a carbonic anhydrase
inhibitor
 Metabolic non anion gap hyperchloremic
acidosis can occur
 Average drop in bicarbonate is 4, but can be
severe, especially in the setting of surgery
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Lipid Treatment
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Rosuvastatin To Prevent Vascular
Events With High CRP
A 36 yo man comes to clinic for an annual
evaluation. He does not smoke and has no
history of diabetes. He exercises for 45 minutes
each day. His father had an MI at age 75 last
year. His exam is normal (BP 120/70). Lipid
testing shows TC 170, Tri 150 , HDL 45, LDL
120 HSCRP 2.1. What would you recommend
for him?
A) Niacin
B) Fenofibrate
C) Rosuvastatin
D) No treatment
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17,802 men and women (men >50, women > 60)
with LDL less than 130 and HSCRP >2 randomized
to Rosuvastatin 20 mg or placebo
Primary end point (MI/Stroke/Unstable
angina/revasc/death from CV) .77/100 person years
treatment vs 1.36 / 100 in placebo, p<.00001
NNT= 82
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NEJM 2008;359 (21): 2195-2207.
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Statins Alone or With Niacin or
Ezetimibe
Should We Use Niacin?
Lowers LDL by 8%
Lowers Lp(a ) by 20%
 Raise HDL-C cholesterol by 29%
 Side effects of niacin
FLUSHING (about 1/3 have severe flushing, and 25%
D/C because of it) (1)
increased uric acid
Slight effect on glucose
1) Clin Ther 2009; 31 (1):130-140.
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A)
B)
C)
D)
E)
A 70 yo man presents for primary care. He has a
history of CAD with an MI 2 years ago. His current
medications include Atorvastatin, Aspirin, Isosrbide
mononitrate, Omeprazole, Metoprolol, Folate,
Vitamin E, Calcium, Multiple vitamin, Fish Oil. What
do you most strongly recommend stopping in this
patient?
Aspirin
Folate
Vitamin E
Calcium
Multiple Vitamin
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Open label, 12-week study of 292 patients who qualified for lipid
lowering therapy
Patients randomized to 4 arms, atorvastatin/niacin ER,
Rosuvastatin/niacin ER, simvastatin/ezetimibe or rosuvastatin
alone.
All groups lowered LDL cholesterol by 50% or more, statin ER
niacin combinations raised HDL cholesterol by 20%, where non
niacin combinations raised HDL by 8% , p<.001
90% in simvastatin ezetimibe and rosuvastatin arms completed
the study, only 75% in the niacin arms
Atherosclerosis 2007;192:432-437.
Vitamin E and Statins Don’t Mix
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Methods: Double blind trial of 160 patients with
CAD, low HDL, normal LDL randomly assigned
to simvastatin + niacin, antioxidents,
simvastatin+ niacin +antioxidants , or placebo.
Endpoints were arteriographic evidence of a
change in coronary stenosis and occurance of
1st cardiovascular event
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Vitamin E and Statins Don’t Mix
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How to Use Niacin
The protective increase in HDL 2 with simvastatin
plus niacin was attenuated by antioxidant use.
Average stenosis increased by 3.9% with placebo,
1.8% with antioxidants, .7% with
simvastatin/niacin/antioxidants and regressed by .4%
with simvastatin-niacin.
Cardiovascular events: 24% placebo, 21%
antioxidants, 14% simvastatin/niacin antioxidants and
3% simvastatin/niacin
NEJM 2001; 345:1583-1592
Rarely useful by itself (limited by
flushing at higher doses)
 If you are going to use it by itself, best
for patients with low HDL, normal LDL
 Very underused in combination with
statins (can use lower doses of niacin
and get good effect)
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Tricks to Using Niacin
 Use
ER product
 Dose it at night!
 Give it with ASA
Side Effects of Statins
 Rhabdomyolysis
(rare) 3.4/100,000 py
 Hepatotoxicity (rare)
 Liver failure .1-.5/ 100,000 py
 Myalgias 10-15%
Drugs That Increase Risk of
Statin Toxicity
Fibrates (Gemfibrozil >> Fenofibrate)
 Azole antifungals
 Amiodarone
 Erythromycin/Clarithromycin
 Protease inhibitors
 Verapamil/Diltiazem
 Niacin (do not use high doses)
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Approach To Statin-Related
Muscle Symptoms
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Use lowest possible statin dose
Use lower doses in Asians
Discontinue medicine and report sudden onset of
symptoms
No need to monitor CK levels in asymptomatic
patients(except in patients with drug interaction)
If myalgias are severe, stop drug ,let symptoms
resolve, then start different statin
In muscle cell toxicity studies pravastatin and
rosuvastatin least toxic, simvastatin the most.
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A 49 yo woman with a recent history of breast cancer
comes to clinic with worsening hot flashes. She is
waking up several times at night with symptoms. Her
breast cancer was diagnosed 18 months ago. She had
2 positive axillary lymph nodes. The cancer was ER+.
She was placed on tamoxifen.
 What do you recommend for her hot flashes?
A) Estrogen + Progesterone
B) Estrogen
C) Sertraline
D) Paroxetine
E) Citalopram
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Some Important Drug Interactions
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Hot Flashes in Women on
Tamoxifen
SSRI’s and Tamoxifen
All women started on Tamoxifen over a 30 month period and
continued for 2 years were studied (National Medco
intergrated database)
1,298 women were identified. Divided into 2 groups, those
who took a CYP2D6 inhibitor (353, 27%) and those who didn’t
(945,73%)
Of those who took an SSRI (60%), those who took a potent
inhibitor ,213 (fluoxetine, sertraline ,paroxetine) had a
recurrence rate of 16% compared to those who took a less
potent inhibitor, 137 (citalopram, escitalopram or fluvoxamine)
8.8%
Aubert RE et al Increased risk of breast cancer recurrence in women taking
tamoxifen and CYP2D6 inhibitors, ASCO annual meeting ,May 2009
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A)
B)
C)
D)
Pharmacist calls to tell you that you are
prescribing a triptan for a patient who is on
an SSRI (citalopram 20 mg a day). She is
on no other meds. What should you do?
Switch to another migraine treatment
Have patient not take citalopram for 24
hours after taking the triptan
Cut the dose of triptan by 50 %
Don’t worry
Avoid fluoxetine, sertraline and paroxetine (if
you must use one of these, could switch
tamoxifen to an aromatase inhibitor
 If you choose an SSRI, use citalopram,
escitalopram or fluvoxamine
 Venlafaxine
 Gabapentin
 Clonidine
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Triptans and SSRI’s
Concern for serotonergic syndrome
Extremely unlikely if only a triptan + SSRI
(especially at lower doses of SSRI)
 Beware of patients on multiple drugs that can
trigger serotonergic syndrome ( tramadol,
linezolid,meperidine, dextromethorphan, TCA,
MAOI, buspirone, trazadone)
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A)
B)
C)
D)
Pharmacist calls you to tell you that she did
not fill the Tadalafil (10mg) prescription you
wrote for your patient because he is on
tamsulosin. What do you do?
Switch Tamsulosin to Finaseride
Switch Tamsulosin to Alfuzosin
Switch Tadalafil to Sidenafil
Ask that the prescription be filled
Alpha blockers and Tadalafil
.4 mg of tamsulosin was given for 7 days in
healthy volunteers, then tadalafil 10mg,20 mg
or placebo were given two hours after
tamsulosin dose
 No significant difference in standing SBP with
either dose of tadalafil and placebo, no one had
a SBP < 85, no dizziness.
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Managing Drug Interactions with
PDE5 Inhibitors
Nitrates
Ok to give NTG > 4 hours after sildenafil use, 24 hours
after vardenafil use and 48 hours after tadalafil use
 Alpha Blockers
Ok to use in patients who are on stable alpha blocker
therapy. For patients on doxazosin or terazosin, should
not take within 4 hours of a dose to avoid potential
drop in BP

What medication was he placed on?
a) Amoxicillin
b) Codeine
c) Cefixime
d) Azithromycin
e) TMP/Sulfa
J Urol 2004; 172: 1935-1940.
A 72 y.o. male S/P AVR replacement two years ago
for aortic stenosis presents with wide spread
bruising on his back/legs and some bruising on
the back of both hands. His last INR was three
weeks ago and was 3.0. He states he saw an
M.D. six days ago for a cough and was put on a
medication described as a “white tablet.” His
chronic medications include: Coumadin 5 mg qd,
Albuterol inhaler 2 puffs 4 times a day and
Nortryptiline 25 mg qhs.
Warfarin Interactions
Decrease metabolism (increase PT)
Most Severe
TMP/Sulfa
Erythromycin
Amiodarone
Propafenone
Ketoconazole/fluconazole
Itraconazole
Metronidazole
Possible*
Quinolones
Omeprazole
Clarithromycin
Azithromycin
* Especially in elderly
and polypharmacy
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Antibiotics and Warfarin
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Retrospective cohort study 104 patients on stable
warfarin therapy. Effect on INR of Terazocin (control),
Azithromycin (32 patients), Levofloxacin (27) and
TMP/Sulfa (16)
Mean change in INR: Terazocin -.15, Azithromycin +
.51 , Levofloxacin + .85, TMP/Sulfa +1.76
Percent patients having a INR > 4: Terazocin 5%,
Azithromycin 31%, Levofloxacin 33%, TMP/Sulfa
69%
JGIM 2005;20 (7);653-6.
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