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280 Cards in this Set

  • Front
  • Back
what do vasodialators target?
Arteries
Calcium Channel Antagonist drugs
verapamil, diltiazem
dihydropyridines: amlodipine, felodipine, isradipine, nicardipine, nifedipine, nimodipine, nisoldipine
What are the 2 types of calcium channel?
Receptor operated channels (ROCs)

Voltage operated channels (VOCs)
In order for ROCs (calcium channels) to open what must happen?
alpha 1 must be activated
what do VOCs open in response to?
membrane depolarization so if you give a drug that hyperpolarizes the membrane the channel will not open
List of the four type of VOCs
1. T (transient)- short opening time, in cardiac and skeletal muscle
2. L (long lasting)- opens for a longer time on vascular smooth muscle and cardiac muscle
3. N (neural)- on nerve terminals
4.P (purkinje)- don't need to know
Channels exist in 3 states
1. resting- which is closed but able to open
2. active- depolarized so channle opens
3. inactive- closed (different conformation that resting) unable to open and cannot respond to depolarization. The membrane has to become sufficiently repolarized to return to resting state
verapamil and diltiazem bind strongly to the _______ state and cause...
inactive--> to slow recovery of the channel from the inactive state going to resting state
prolongation of the recovery stae is most obvios at _______ stimulation rates
(verapamil and diltiazem)
high stimulation rates becasue the more likely the membrane is depolarized the more likely to see
use dependence
prolongation of the recovery state is most obvious at high stimulation rates

(verapamil and diltiazem)
what do calcium channel blockers do to vascular smooth muscle?
relax vascular smooth muscle (aterioles>veins) by blocking Ca channels
CCB decrease Ca influx leading to what?
a decrease in intracellular [Ca]--> decreasing contraction of vasculature sm--> vasodilation
Ateriole dilation causes
Decrease in PVR--> decrease BP
Verapamil and Diltiazem effecrs of the sa node
both cause SA node depression causing a decreas in HR
How do verapamil and diltiazem cause sa node depression?
Because they slow down the conduction of the heart by blocking the calcium channels in the heart
Do verapamil and diltiazem cause reflex tachycardia?
no becasue of SA node depression
do the dihydropyridines casue sa node depression
no, therefore they produce reflex tachycardia because the body is trying to compenstate to the reduction in BP by increasing the HR
dihydropyridines (CCB) and cardiac blocking activity
they have little cardiac blocking activity--> therefore they cause refelx tachycardia
Do CCB cause fluid retention?
no, there is an increae in BF to the kidneys so they do not try to retain fluid it is not well understood
Diltiazem and verapamils properties
cause vasodialtion, decrease cardiac contractility, decrease SA node automaticity and decrease AV node conduction

They block CA channels in the heart and vessels
dyhydropyridines properties
cause vasodilation only becasue only blocking the Ca channels in the vessels not in the heart
SE of calcium channel blockers
* dizziness, hypotension, HA, flushing (all caused by vasodilation), cardiac depression (esp verapamil and diltiazem) constipation (verapamil because blocking Ca channels in the GI tract)
CHF consideration with verapamil and diltiazem
Cardiac depression
- SA and AV node abnormalities (decrease conduction)
therefore HR would decrease even more than it already has
what does a decrease in AV node conduction cause?
AV node block
A mismatch in atrium and ventricular contraction
Intravenous verapamil and propanolol should not be used together because...
both depress the heart causing AV block and severe ventricular depression
Which agents should not be used in patients with DM, HTN, asthma, and Hyperlipidemia?
non-selective beta blockers
hydralazine
one of the first anti-HTN agents
Relaxes ateriolar smooth muscle
Does hydralazine have effects on veins
NO
Hydralzines MOA on ateriole smooth muscle
A. endothelium-dependent mechanism which is mediated by NO
B. hyperpolarization of vascular sm by inhibiting voltage gated Ca channels from opening thus causing vasodilation
Hydralazines class
Voltage gated Ca channel blocker
(direct vasodilator)
what does Hydralazine ultimately cause?
decrease in PVR--> decrease in BP
When using hydralazine how does the body respond to the decrease in BP?
increase in sympathetic refelx to increase BP
and
increase in fluid retention throug the kidneys

As a result hydralazine is used in combo with a diuretic to block fluid retention and a B-Blocker to block the increase in HR
SE OF HYDRALAZINE
HA, flushing, dizziness (all from vasodilation)
First pass metabolism by N-acetylation--> low boiavailbility (10-35%)
acetylator phenotypes: 50% slow acetylator, 50% fast acetylator
Drug induce lupus syndrome (rare): autoimmune disease where T cells target normal cells in the body) incidence in 4x higher in men
Secondary tachyphylaxis
When some one is a fast acetolator what does that mean?
That the dose will need adjustment becaue they will need more of the med because they metabolize it faster than a slow acetylator would (who would need less of the drug)
what is secondary tachyphylaxis and what drug causes it?
the same dose of drug is given which results in less effects

the body is using physiological mechanisms to compenstate for a decrease in BP
Hydralazine
How is secondary tachyphylaxis caused?
Intially there is a decrease in BP which causes the body to retain fluid and increase CO

Both of the above cause a reverse of the pressor effects and gives the apperance of tacyphylaxis
indications of hydralazine
never used as sole therapy for long term treatment of HTN because of SE and tachyphalaxis

it is used in combination with diuretics and b-blockers
Minoxidil
is a prodrug that is converted to its active compound by hepatic sulfotransferase
Minoxidil MOA
artety selective
relaxes arteriolar sm by hyper polarization of vascular sm

open K channels--> K flows out of the cell--> cell hyperpolarization--> inhibition of VO Ca channels--> inbition of contraction
Minoxidil class
Calcium channel blocker (Blocks VOC)
what are the overall effects of minoxidil?
decrease in PVR--> decrease in BP
How does the body respond to the decrease in BP caused by minoxidil?
a decreease in BP causes and increase in the sympathetic reflex thus increasing HR

increase in fluid retention in the kideney

you don't see secondary tachyphylaxis

therefore give in combo with B-blockers and diuretics
SE of minoxidil
Potent stimulant of renin secretion
- indirect by increae in sympathetic drive
- activation of intrinsic renal mechanism

Na and water retention (use with care in patient s with CHF)
hypertrichosis (hairgrowth)
- increase in cutaneous blood flow-- harigrowth on face, back, arms
expalin activation of intrinsic renal mechanism a se of minoxidil
increase in renin release--> will increase BP so minoxidil does not have as great of effects but it still drops BP
What is the issue with drugs that cause fluid retention and CHF?
there is alread a decrease in HR, BP, and CO and fluid is already being retained to compenstate
is sodium nitroprusside selective for arteries?
No it effects veins and arteries
Sodium nitroprusside
nitoso moiety necessary for activity
relaxation is mediated by releae of nitric oxide
sodium nitroprusside effects on veins and arteries
casues vasodilation of both leading to a decrease in PVR, VR and BP
What are sodium nitroprussides effcts on the heart
causes only modest increase in HR and decrease in myocardial oxygen requirements
what are refelx sympathetic activation effects on the heart?
increase HR therefore increases O2 demand of the cardiac muscles which is a problem in coronary ishemia becasue the heart is already deprived of O2
description of the sodium nitroprusside molecule
Fe is in the middle attahed to 5 Cn molecules and 1 NO
SE of sodium nitroprusside
if infuse too quickly cyanide accumulates and thiocyanate in the blood
promotes ventialtion/profusion mismatching in COPD
ventalation/perfusion mismatch
there are areas of the lung that are not well ventilated and which causes hypoxi pulmonary vasoconstriction

when there is a mis matchblood goes to both well ventilated and poorly ventilated areas of the lung resulting in a decrease in oxygen concentration in the blood
hypoxic pulmonary vasoconstriction
areas of the lung that are not well ventilated have a decease blood supply going to them
ACE inhibitor drug names
catoPRIL, enalaPRIL, enalaPRILate, moexiPRIL, benzaPRIL, perindoPRIL, fosinoPRIL, quinaPRIL, ramiPRIL, trandoPRIL
what step do ACE inhibit?
They block angiotensin I form being converted to angiotensin II by blocking angiotensin converting enzyme
what does the inhibtion of conversion of angiotensin I to angiotensin II cause?
a decrease in the pressor effects ( a decrease in the blood pressure effects of angiotensin II)
what is the rate limiting step in the formation of angiotensin II?
renin
relative pharmacological activites of angiotensins:
angiotensin I 1
angiotensin II 100
angiotensin III 10-25
pharmacological actions of angiotensin II and aldosterone
increase aldosterone synthesis and secretion--> increase Na and water retention --> increase VR--> BP
pharmacological actions of angiotensin II and arterioles
directly constrincts the arterioles (potent vasoconstrictor of the efferent ateries

indirectly constricts blood vessels
pharmacological actions of angiotensin II and sympathetic nervous system
increase sympatheic nervous system activity
1. central action
2. presynaptic facilitation of NE release
3. CCA release from adrenal medulla
4. ganglionic stimulant (high concentrations) --> increase CCA release
5. post-synaptic facilitation of alpha adrenoceptor response ( make vasculature sm more constricted) (enhances the effeccts of alpha 1)
pharmacological actions of angiotensin II and cardiac
increase cardiac contractility

diret: myocardial
indirect: increase sympathetic effects
pharmacological actions of angiotensin II and vascular and myocardial hypertrophy
stimulates vasculature and myocardial hypertrophy by:

the induction of protooncogenes c-fos and c-jun
--> increase in cell proliferation
--> hypertrophy

muscle becomes bigger so vessels constrict more because vasculature (blood supply) to the larger muscles has not increased
pharmacological actions of angiotensin II and cns
stimulates drinking, increase ADH, increases ACTH
on a molar basis angiotensin is ___ times more potent than NE at increasing _______
40
BP
anti-HTN effects of ACE relate to inhibition of:
1. angiotensin II formation (major)
2. bradykinin degradation
bradykinin
a vasodilator that is an analgesic substance that stimulates sensory nerve endings

it contributes to the ACE inhibitor effects to decrease BP
what are the initial effects of ACE inhibitors?
anti-HTN actions are related directly to plasma renin concentrations
what are the chronic effects of ACE inhibitors?
there is no relationship with renin concentrations

there is a decrease in PVR--> decrease in BP

there is a small increase in CO and a small increase in HR ( the synpathetic ns has been toned down so not as a great of a response from the body trying to compenstate because blocking both side of the system)
SE of ACE inhibitors
Dry cough/wheezing (due to increase in bradykinin)
severe hypotension in hypovolemic patients or in patients who are Na depleted or treated with diuretics
ARF
angioedema
hyperkalemia
How do ACE inhibitors cause ARF?
a decrease in A II--> increase in dilationof efferent arteriole--> decrease in golmerular pressure--> decrease in GFR--> ARF
what is the problem with ACE inhibitors and severe hypotension in hypovolemic patients or those who are NA depleted or treated with diurectics?
their BP my be critically maintained by A II, so removing it would cause a severe decrease in BP
How do ACe inhibitors cause angioedema?
ACE inhibitors cause swelling of the throat causing difficulty breathing
how do ACE inhibitors cause hyperkalemia?
decrease in A II--> decrease aldosterone-->decrease in K secretion-->hyperkalemia
do ARBs cause angioedema?
no, only ace inhibitors
ARBs drugs
losartan, irbesartan, candesartan, olmesartan, valsartan, telmisartan, eprosartan
SE of ARBs
no dry cough/wheezing
hyperkalemia
ARF
Severe hypotension in hypovolemic patients or in patients who are Na depleted or treated with diuretics
diarrhea, dizziness, insomnia, nasal congestion
not to be administered to pregnant women (losartan is passed in breast milk
what do arbs inhibit?
inhibit angiotensin II tpye 1 receptors which causes a decrese in pressor effects af A II
why don't ARBs cause dry cough or wheezing?
because they do not effect bradykinin levels
Omapatrilat
a vasopeptidase inhibitor

inhibit angiotensin converting enzyme and neutral endopeptidase therefore prevent the formation of A II
Vasopeptidase inhibitors ______ levels of vasoconstrictors and ______ levels of vasodilators
decrease
increase
do vasopeptidase inhibitors effect bradykinin levels?
yes, they cause and increase in bradyknin levels more than ACEs
SE of vasopeptidase inhibitors
dry cough/wheezing
facial redness, flushing, dizziness (from vasodilation)
severe angioedema (more common than ACEs
are vasopeptidase cliically used?
no because of the angioedema
Renin inhibitors
block the formation fo angiotensin I and therefore angiotensin II
aliskiren
renin inhibitor
inhibits the formation of angiotenisn I from angiotensinogen
Renin
an enzyme released from the juxtaglomerulus apparatus in response to low BP
SE of renin inhibitors
diarrhea, dyspepsia
cough (less than ACE inhibitors)
angioedema (rare)
poor absorption 9F=2.5%
what do you need to have available in order to remove CN
glucathione
SCN causes/effects
anorexia, nausea, fatigue, toxic psychosis, disorientation
how is CN normally broken down?
CN (hepatic rhodonase)--->SCH---->urine

essentailly CN is attached to a thiol group and excreted in the urine

that is why you do not want to infuse sodium nitroprusside too quickly
endothelin receptor antagonist drug names
ambrisentan, bosentan, darusentan
MOA of endothelin receptor antagonist
blockade of ETa receptor--> decreases contraction--> PVR--> decreses BP

Not good to block becasue tempers vasoconstriction (slows it down)
endothelin 1-->
endothelin 1--> vassoconstriction to increase PVR and Increase BP
SE of endothelin receptor antagonist
swelling of ankles, legs and nasal congestion, facial flushing (caused from vasodilation)
liver injury (monitor liver enzymes monthly)
contraindicated in pregnancy
Have to use 2 forms of birth control
uses of endothelin receptor antagonist
in pulmonary HTN (approved) resistant HTN (under investigation)
Ar
are endothelin receptor antagonist desirable to treat HTN
no because of the SE
stage 1 hypertension treatment
start with 1 or 2 drugs:
first line: thiazides (A-1)
second line:ACE,ARB,CCB or combination (A-2)
Stage 2 hypertension
Start with 2 drugs (A-3)
usually a thiazide-type diuretic or ARB, ARB, or CCB (A-2)
AHA first line treatment (4 choices)
ACE
ARB
CCB
Thiazide
Strengths of recomendations
level of evidence
A- overwhelming info, convincing evidence
A is better than C
1 is better than 3
are patients treated the same if the have compelling indications or non?
No, those with compelling indications are treated more taylored, whereby those without complications are treated from the choice of the 4 treatment therapies
What drug class has landmark data?
Thiazides
(A-1)

placedo vs. treatment
Thiazides and key point 7
have been classified as first-line agents for treating most patients with HTN. This recommendation is supported by clinical trials showing reduced CV morbidity and mortality with thiazide diuretic therapy. Comparitive data from the landmark clinical, the ALLHAT, confirm the first-line role of thiazide diuretics

Thiazides have the highest level of outcomes data supporting their use
The antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT)
Objective: Compared CV events with CCB (amlodipine), ACE inhibitor
(lisinopril), and alpha-blocker (doxazosin) based therapy to a thiazide
diuretic (chlorothalidone) based therapy
• Prospective, double-blind, randomized trial; 42,448 patients for 4-9 yrs
Results of the ALLHAT
• Results:
- Alpha-blocker vs. thiazide: Alpha-blocker treatment terminated
early after 3.3 yrs due to significantly more heart failure
- CCB vs. thiazide: No difference in nonfatal MI and CHD death; less
heart failure with the thiazide
- ACE inhibitor vs. thiazide: No difference in nonfatal MI and CHD
death; less heart failure and less stroke with the thiazide

Alpha blocker were not as good as thiazides

Overall there was no difference with thiazides
Conclusion of ALLHAT
Conclusion: Thiazide-type diuretics remain unsurpassed in their ability
to reduce hypertension-associated complications
Key point 8- guidelines regarding ACE, ARB CCB
An angiotensin-converting enzyme (ACE) inhibitor, angiotensin II receptor
blocker (ARB), or calcium channel blockers (CCB) may be used in patients without
compelling indications. Clinical trials have demonstrated that these agents
reduce the risk of CV events when used to treat hypertension.

This is treatment of primary HTN not a patient with complications
Beta-Blockers and CV events
B-blockers do not reduce CV risk to the extent that thiazides diuretics do.

Therefore not a first line therapy they are add on therapies
Key point 9:b-blockers
Beta-blockers do not reduce CV events to the extent that thiazide-type diuretics,
ACE inhibitors, ARBs, or CCBs do when used as the primary antihypertensive
agent in patient with hypertension but without a compelling indication for betablocker
therapy.
Compelling Indications
Left Ventricular Dysfunction
Post-Myocardial Infarction
Coronary Artery Disease
DM
CKD
Recurrent Stroke Prevention
LVD goal Bp
120/80
LVD treatment for HTN
Standard treatment: Diuretic with ACE (A-1) then add a B-blocker

Add on therapy: ARB (A-2) or aldosterone antagonist (A-2)
Post MI treatment HTN
Standard treatment: B-blocker (A-1) then add ACE (A-1) ot ARB (A-2) after b-blocker

Add on therapy: aldosterone antagonist (A-2) if patient also has LVD
Coronary artery disease treatment HTN
Standard treatment: B-blocker (A-1) then add ACE (A-1) or ARB (A-2)

add on therapy: CCB (B-1), diuretic (B-2)
DM treatment of HTN
Standard: ACE (A-1) or ARB (A-2)

Add on treatment: Diuretics (B-2) next add a b-blocker (B-2), or CCB (B-2)
CKD treatment of HTN
Standard treatment: ACE (A-1) or ARB (A-1)

no preference for add on treatments
Reccurent stroke prevention treatment HTN
Standard treatment: Diuretic with the ACE (A-2) or ARB (A-2)

no preference for add on treatments
key point 10: compelling indications
10 Compelling indications are comorbid conditions where specific drug therapies have
been shown in outcome trials to provide unique long-term benefits (reducing the risk
of CV events). Drug therapy recommendations for compelling indications are either in combination with or in place of a thiazide-type diuretic.
What special population is eplernone used in?
Eplerenone may be added to beta-blocker and ACE inhibitor therapy to ↓ CV
risk, but this is only for patients with left ventricular dysfunction immediately
after their MI
Post MI
Although beta-blocker and ACE inhibitors are both needed, the beta-blocker
is standard first therapy to minimize risk of recurrent MI followed by ACE
inhibitors as add-on therapy

This patient has no symptoms of ischemia, but they do have damage to the heart

Eplerenone may be added to beta-blocker and ACE inhibitor therapy to ↓ CV
risk, but this is only for patients with left ventricular dysfunction immediately
after their MI
Coronary artery disease
Describes patients with chronic stable angina, acute MI or unstable angina

Beta-blocker therapy is first-line for management of both elevated BP and to
decrease cardiac ischemia; followed by an ACE inhibitor or ARB to further ↓
CV risk.
What type of CCB are used in Coronary artery disease?
DIhydropryidines because they do not affect the contractility of the the heart
What benefit do ACEs provide to a damaged heart?
they help with the re-molding of the heart by improving endothelial function (decrease BP and RAAS)
Key point 11-Diabetes
Patients with diabetes are at very high risk for CV events. All patients with
diabetes and hypertension should be managed with either an ACE inhibitor or an
ARB. These are typically in combination with one or more other antihypertensive
agents because multiple agents frequently are needed to control BP.
The American Diabetes Association Position Statement -- Treatment of
Hypertension in Diabetes (Diabetes Care 2008):
ACE inhibitor, ARB, diuretic, beta-blocker or CCB can all be used as initial
drug therapy for hypertension in diabetes
What is the first line treatment for of HTN for Type I DM at any level of proteinuria?
ACE
What is the treatment of HTN for type 2 DM with microalbuminuria?
ACE or ARB
What is the treatment of HTN for type 2 DM with macroalbuminuria?
ARB
CKD and HTN
Significant (similar to stage 3, 4 or 5 CKD) is defined by the JNC7 as:
what is considered severe proteinuria?
> 1 gm/day of protein in urine
as kidney function declines what changes in their therapy?
thiazides are used when GFR is 30-60

loops are used when GFR is < 30
what is the BP goal for CKD
130/80
Recurrent Stroke prevention
o Specifically referring to ischemic stroke, not hemorrhagic stroke
o Start antihypertensive therapy only after patients are very stable after an
acute stroke to minimize risk decreasing cerebral perfusion
o ACE inhibitors in combination with a thiazide diuretic is a compelling
indication since this combination ↓ risk more than each drug individually
o ARB therapy has been shown to reduce risk of recurrent stroke and is
considered a compelling indication
When do you start an anti-HTN in a patient that has had a stroke?
When the patient is stable to minimize risk of decreasing cerebral perfusion

want patient to be slightly hypertensive
If a patients BP decreases too much during a stroke what is the monotherapy option?
ARB
Left Ventricular Dysfunction (Systolic Heart Failure):
Diuretics (possibly a thiazide, often a loop) are first-line to relieve symptoms
of edema along with an ACE inhibitor as standard therapy to ↓ CV risk
o After ACE inhibitor is started, add a beta-blocker as standard therapy to ↓ CV
morbidity and mortality
− Very important…. beta-blockers can reduce mortality if used correctly; but
may cause death if started/dosed inappropriately:
What are the 3 drugs used to treat HTN with LVD?
Diuretics
ACE
B-blocker
What are the 3 B-blockers are used in LVD and HTN?
Bisoprolol
Caredilol
Metoprolol XL
How are B-blockers dosed for HTN and LVD?
Start at very low doses, much lower than the recommended starting
doses for hypertension
what is the MOA of B-blockers for HTN and LVD?
the b-blockers block the B1 receptors on the heart causing them to up-regulate resulting in an increase in contractility and increasing EF)
Bisoprolol starting dose and target dose for HTN in LVD
1.25 mg qd--> 10md/qd
Carvedilol starting dose and target dose for HTN in LVD
3.125 mg bid--> 25-50 mg bid
metoprolol XL starting dose and target dose for HTN in LVD
12.5-25 mg qd-->200 mg qd
add on therapies for HTN in LVD
aldosterone antagonist to further ↓ CV risk
Why are ACEs always used in HTN in LVD?
Because they help remoldel the damaged heart and the increase in bradykinin causes even more vasodilation
what is the order of therapy of HTN in LVD?
Diuretic and ACE and then slowly add a B-Blocker
When do you intitate a B-blocker with HTN in LVD?
only initiate in stable LVD
when there are no signs of exacerbation
goal bp for LVD and rate of therapy
120/80
Initiate all agents using slow titration’s to minimize complications
o Since many agents have been shown to ↓ risk of CV events in left ventricular
dysfunction, agents are often added even if goal BP values are attained.
Orthostatic hypotension or side effects are usually the limiting factors to
utilizing these multiple agents together.

slowly initiating the therapy to prevent dizziness mainly because decreasing BP to low values
Age and HTN
Most have ↑ SBP but at goal DBP (a.k.a., Isolated Systolic Hypertension [ISH], Hypertension

Systolic BP increase and diastolic remains low or slighly decreases as a result PP is wide (there is a big difference b/w SBP and DBP)
Hypertension in the Very Elderly Trial
(HYVET)
● 3845 patients
age 80 years or older with
hypertension
● Randomized, double-blind
trial
● Trial stopped early after 1.8
years because people were dying more frequently w/ placebo treatment and those with the drug treatment were living longer
Landmark data
what is the stage 2 rule and the exception?
a patient with stage 2 hypertension is started on 2 drugs
But, for those > 75 start with 1 drug because do not want to reduce BP to quickly to prevent dizziness and a fall
what was the goal BP in the HYVET study for the elderly?
150/80
Dosing considerations for the elderly
Older patients with isolated systolic hypertension are often at risk for orthostatic
hypotension when antihypertensive drug therapy is started, particularly with
diuretics, ACE inhibitors, and ARBs. Although overall treatment should be the
same, low initial doses should be used and dosage titrations should be gradual to
minimize risk of orthostatic hypotension.
Children and Adolescents HTN
have different cut off values
goals are based on percentiles
lifestyle modifications are key
African Americans
Control rates are generally lower
o African Americans compared to Caucasians:
Women and Pregnancy
o Estrogen containing oral contraceptives can ↑ BP
o Gestational hypertension (i.e., Pregnancy-induced)
o Chronic Hypertension in Pregnancy
Preferred agent for HTN in pregnancy
methyldopa (1st line)
What agents are contraindicated for HTN in pregnancy
ACE, ARB, renin inhibitors
Primary Prevention Patients (those without compelling indications): HTN
Thiazide-type diuretic, ACE Inhibitor, ARB, or CCB
Patients with compelling indications: HNT
Tailored and specifically ordered regimens consisting of thiazidetype
diuretic, ACE Inhibitor, ARB, CCB or beta-blockers
Situations that favor thiazide diretics
Osteoporosis or
at increased risk for
osteoporosis, highnormal
potassium
situations that do not favor thiazide diuretics
Gout (because increases uric acd), hyponatremia,
prediabetes (because increase glucose), low-normal
potassium
situations that favor ACE
Low-normal potassium,
prediabetes
situations that do not favor ACE
High-normal potassium or
hyperkalemia
contraindications for ACE
Pregnancy, bilateral
renal arterty
stenosis, history of
angioedema
situations that favor ARB
Low-normal potassium,
prediabetes
situations that do not favor ARB
High-normal potassium or
hyperkalemia
contraindications for ARB
Pregnancy, bilateral
renal arterty
stenosis
Situations that favor CCBs- dihydropyridines
Raynaud's syndrome,
elderly patients with
isolated systolic
hypertension,
cyclosporine induced
hypertension
situations that do not favor CCBs- dihydropyridines
Peripheral edema, , highnormal
heart rate or
tachycardia
contraindications for CCBs-dihydropyridines
Left ventricular
dysfunction (all
except amlodipine
and felodipine)
situations that favor CCB- nondihydropryidines
Raynaud's syndrome,
migraine headache,
arrhythmias, high-normal
heart rate or tachycardia
situations that do not favor CCBs- nondihydropyridines
Peripheral edema, lownormal
heart rate
contraindications for CCBs- nondihydropyridines
Second or thrid
degree heart block,
left ventricular
dysfunction
MAP =
(SBP * 1/3) + (DBP * 2/3)
hypertensive crisis
when BP is above 180/120
CV risk doubles with every ______ increase
20/10
in patients over 50 what is a stronger predictor of CV disease
SBP
in patients under 50 what is a stronger predictor of CV disease
DBP
ISH is a result of
pathophysiological changes in the arterial vasculature consistant with aging

these changes decrease the compliance of the arterial wall
what receptor mediates most responses that are critical to CVD A1 or A2?
A1
thiazide diuretics
HCTZ
chlorthalidone
idapamide
metolazone
Loop diuretics
furosemide
torsemide
ethacrinic acid
bumetanide
Potassium sparing diuretics
amiloride
triamterene
Diuretics Se
Mostly dose dependent
Diuretics place in therapy
Diuretic drug interactions
May ↑ lithium concentrations
Diuretics are contraindicated in
Acute gouty arthritis (this is an active gout atack) (esp thiazides); Hypotension;
Dehydration; Hyponatremia
diuretic dosing considerations
What are the considerations in pre-diabetic patients and thiazides?
Patients with prediabetes (elevated fasting blood glucose ≥100 mg/dL) or
at risk for prediabetes may experience increases in glucose:
what can you do to minimize onset of DM II when using a thiazide
To minimize risk of progressing to type 2 diabetes maintain serum
potassium between 4.0-5.0 mEq/L by: 1) using a thiazide with an ACE
Inhibitor, ARB or potassium sparring diuretic; 2) adding potassium
supplementation; or 3) using the lowest effective thiazide dose.
what happens when thiazides decrease K?
it impairs the bodies ability to utilize insulin

you don not have to be hypokalemic to see a decrease in insulin utilization
Diuretics and CKD
Patients with severe chronic kidney disease (estimated GFR <30), or
patients with significant edema (e.g., in heart failure) sometimes require a
loop diuretic instead of a thiazide. Torsemide is the only loop diuretic than
can be dosed one daily for hypertension.

furosemide is dosed bid because shorter half life
Triamterene and amiloride
(potassium sparing diuretics) do not provide
significant BP lowering, but are used with a thiazide to minimize
hypokalemia. Using a potassium sparing diuretic with and ACE inhibitor, or
ARB in chronic kidney disease requires careful monitoring for
hyperkalemia.
ACE Inhibitors
benazepril
captopril
enalapril
fosinopril
lisinoprl
moexipril
perindopril
quinapril
ramipril
trandolapril
ACE inhibitors place in therapy
first line agents for primary prevention and all compelling indications

they work well and have long term data
SE ACE
Monitoring for diuretics
BP response, electrolyte, renal function test
Monitoring for ACE
BP response; Electrolytes; Renal function tests
when monitoring BP what part of therapy are you looking at?
efficacy
When you are monitoring electrolytes and renal function tests what part of drug therapy are you looking at?
toxicities
ACE drug interactions
May ↑ lithium concentrations
ACE contraindications
a decrease in bradykinin breakdown causes?
The ↓ breakdown of bradykinin, which can causes a dry cough, may ↑
vasodilatation and ↑ effectiveness in left ventricular dysfunction, diabetes
and kidney disease
do ace inhibitors affect serum creatinine?
Can ↑ serum creatinine due to dilation of the efferent arteriole in the
kidney resulting in an “altered GFR”, but only stop if serum creatinine
increases > 35% from baseline
When do you want to carefully monitor patients on ACE?
Using an ACE inhibitor with a potassium sparing diuretic, or aldosterone
antagonist, or ARB, or in patients with chronic kidney disease requires
careful monitoring for hyperkalemia
dosing considerations for ACE
Half the usual starting dose should be selected for those with left
ventricular dysfunction, hyponatremia or volume depletion, and in the
very elderly (age ≥ 75 years) to minimize the first dose hypotension
ARBs
candesartan
eprosartan
irbesartan
losartan
olmesartan
temisartan
valsartan
ARBs place in therapy
First-line agents for primary prevention; certain compelling indications
SE of of ARBs
Fewest side effects of all antihypertensive drug classes
Monitoring of ARBs
BP response; Electrolytes; Renal function tests
ARBs contraindicated in
Comments on ARBs
do ARBs affect bradykinin
No
so there is no dry cough
CCBs non dihydropyridines
verapamil
diltiazem
pharmacological actions of verapamil and diltiazem
cause periperal vasodialtion, decrease in HR, decrease in cardiac contractility, decrease in SA/AV nodal conduction and an increase in coronary blood flow
pharmacological actions of dihydropyridine CCBs
increase in peripheral vasodilation more than nondihydropyridines, increase in HR, no change in cardiac contractility and a increase in cardiac blood flow more than verapamil adn diltiazem
Dihydropyridines CCB and dosing
Amlodipine, immediate-release (Norvasc) 2.5-10 1
Felodipine, extended-release (Plendil) 2.5-10 1
Isradipine, immediate-release (DynaCirc) 5-10 2
Isradipine, controlled-release (DynaCirc CR) 5-10 1
Nicardipine, immediate-release (Cardene) 60-120 3
Nicardipine, sustained-release (Cardene SR) 60-120 2
Nifedipine, sustained-releasea (Procardia XL, Adalat CC) 30-120 1
Nisoldipine, extended-release (Sular) 10-40 1
a Immediate release nifedipine should be avoided.
Shoud immeidate release nifedipine be use
should be avoided/never used
DCCB place in therapy
SE DCCB
monitoring of DCCB
BP response, HR
contraindications of DCCB
Left Ventricular Dysfunction (except amlodipine,
felodipine)
what does the concurrent use of DCCB and ACE or ARB do?
Concurrent ACE inhibitor or ARB therapy minimizes peripheral edema caused by the ccb

this is becasue arteries not veins are dilating so more pressure is in the cappilaries and ACE/ARB decrease A II causing vasodilation and decreased pressure in the capillaries
NDCCB
Diltiazem and verapamil

many different formulations
NDCCB place in therapy
SE NDCCB
monitoring of NDCCB
BP response; HR
drug interactions with NDCCB
NDCCB are contraindicated in
what CCBs are better in diabetic nephropathy
NDCCB
are the different formulations of diltiazem and verapamil AB rated?
dosing considerations for CCB
Cardio selective B-blockers
atenolol
betaxolol
bisoprolol
metoprolol
metoprolol extended-release
Non-selective B-blockers
nadalol
propanolol
propanolol long acting
timolol
ISA B-blockers
Acebutolol
carteolol
penbutolol
pindolol
mixed alpha/beta blockers
carvedilol
labetalol
vasodilatory b-blocker
nebivolol
(also cardio selective)
B-blockers place in therapy
SE of b-blocker
(more prominent with non-selective agents):
at what HR do you not want to use a B-blocker in?
< 60 bpm
monitoring for b-blockers
BP response
HR (do not want to drop below 60)
B-blockers drug interactions
B-blockers contraindicated in
Comments on B-blockers
dose considerations of B-blockers
aldosterone antagonists (AA)
eplerenone
spironolactone
AA place in therapy
Compelling Indications: Left Ventricular Dysfunction and post Myocardial
Infarction (but only when accompanied by left ventricular dysfunction)

not 1st line
SE of AA
Monitoring of AA
BP response; Electrolytes; Renal function tests
drug interactions AA
May ↑ lithium concentrations
AA contraindicated in
comments on AA
Patient/Clinician Discussions
− Treatment is to control, not to cure hypertension
− Chronic treatment is usually necessary to control BP
− Multiple agents are often needed
− Establish appropriate long-term and short-term goals
− Review potential hypertension-related hypertension-associated complications
− Presence or absence of symptoms are not helpful (unless it is a hypertensive crisis)
− Treatment should not be discontinued without medical consultation
− Appropriate education regarding drug side effects that do not scare patients
Enhance Patient Education and Improve Patient Adherence by
− Ask open-ended questions
− Provide encouragement for achieving goals
− Encourage patients to openly discuss their medications and any problems or side effects
− Involve patients' families or caregivers in the treatment process
− Encourage self-BP monitoring
− Simplify treatment regimens to maximize adherence (once daily medications are
preferred)
− Keep therapy inexpensive if possible
− Provide oral and written instructions and information on drug regimens and goals
− Provide assistance to non-adherent patients (i.e., pill boxes)
− Contact patients who fail to either refill medications
− Collaborate with other health care professionals
starting drug therapy
Administer once daily medications in the morning (except alpha-blockers
and chronotherapeutic CCBs)
o Consider initial therapy with two drugs for:
avoid starting a 2 drug therapy in what patients?
initial two-drug therapy in patients at risk for orthostatic
hypotension, or in unstable patients

>75
when is BP re-evaluated after starting therapy in stable patients
Evaluate BP response in 2 to 4 weeks in clinically stable patients
when is BP re-evaluated after starting therapy in unstable patients
Evaluate BP response within 1 to 7 days in unstable patients or those with
very high BP values (i.e., > 200/110 mm Hg)
how does self monitoring differ from clinic values
Self-BP monitoring may be helpful, but anticipate home values to be lower (5 mm Hg)
than what is measured in clinic for most patients
combination therapy key point
Most patients require combination therapy to achieve goal BP values. Combination
regimens should include a diuretic, preferably a thiazide-type. If a diuretic was not the
first drug used, it should be the second drug add-on therapy for most patients.
when BP goals are <140/90 how many agents are usually needed?
> or equal 2
when BP goals are <130/80 how many agents are usually needed?
> or equal to 3
Combination Regimens
- A diuretic is additive with most other agents
- Start with low dose when initiating two drugs together to minimize orthostasis
ACCOMPLISH Trial
Recommended in patients with stage 2 hypertension
- The ACCOMPLISH (N Engl J Med 2008;359:2417-28) demonstrated that
initial two drug therapy is very effective in attaining goal BP values, and that
some combinations may be more effective in lowering CV events than others:
• Randomized, double-blind, controlled trial
• Fixed dose combination of benazepril/amlodipine or benazepril/HCTZ
with dose increased based on BP lowering
• 11,506 patients with hypertension and:
- Age ≥ 60 years; 55-59 years eligible if ≥ 2 CV diseases or target
organ damage
- SBP ≥ 160 mm Hg or on BP medication
- Evidence of CV disease, kidney disease, or target organ damage
• 1° endpoint: composite measure of CV morbidity or mortality
results of accomplish trial
proved that when you start with 2 drug therapies patients are more likely to reach goal BP
- Incidence of the primary endpoint was ~20% lower with
benazepril/amlodipine than with benazepril/HCTZ
ideal combination regimens
should an ACE and an ARB be combined
The combination of an ACE Inhibitor with an ARB should not be used for
managing hypertension based on the results from the ON-TARGET trial
ONTARGET trial
● 31,546 high-risk
patients with HTN
● Randomized,
double-blind trial
● Combination vs
ramipril:
– Hypotension:
4.8 vs 1.7%
(p<0.001)
– Renal dysfunction:
13.5 vs 10.2%
(p<0.001)

there was no difference in the ability to reduce CV events between an ACE and an ARb

the combinatin of an ACE and an ARB proved to be unecessary
CLINICAL CONTROVERSIES
• Treatment of white coat hypertension
• Ambulatory BP measurements versus clinic BP measurements
• Treating prehypertension patients with pharmacotherapy
• Thiazide-type diuretics in severe CKD
• Atenolol compared with other beta-blockers
• Hydrochlorothiazide versus chlorthalidone
• Goal BP values in the very elderly (≥ 80 yrs)

controversies becasue we know some ways to treat and then there are aspects of particular treatments that are unkown
o Evidence demonstrates pharmacists can improve management of
hypertension
the pharmacists role in HTN
Collaborative drug
therapy management
Assuring effective therapy
Measure and/or monitor BP
Improve compliance
Increase patient awareness
Patient education
Complete prescription fulfillment
criteria for metabolic syndrome (most have 3 or more)
abdominal obesity
increase in TG
decrease in HDL
Increase in BP
increase in fasting glucose
metabolic complications of obestiy
adipose tissue releases-->
free fatty acids, cytokines nd proinflamitory , prothrombotic mediators
Consequences of free fatty acids
basal lipolysis is increased (lipotoxity)
high levels of FFA overload the ____ and ______ which inhances insulin resistance
muscle
liver
role of intra abdominal adiposity and FFA in metabolic syndrome
increase in hepatic glucose output
increase in TG rich vldl wich in turn increases LDL and decreases HDL
In the musle it decrese insulin sensitivity
insulin resistance causes ____ and leads to atherosclerosis
casues:
HTN
hyperinsulinemia
DM
High TG
small dense LDL
low HDL
hypercoagulability

All leading to atherosclerosis