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214 Cards in this Set

  • Front
  • Back
How many Americans have both hypertension and dyslipidemia?
30 million
Hypertension occurs along __% of the time, and it frequently occurs with ___.
<20%
dyslipidemia
Association with hypertension with other risk factors can have a ___ effect on CV risk.
multiplicative
MRFIT: Layering of both ___ and ___ can have a dramatic effect on __ mortality risk.
hypertension
dyslipidemia
CV
Many patients at risk will require ___ plus ___ modifications.
-pharmacologic treatment plus lifestyle modifications.
Pharmacologic treatments that can address __ risk factor will be in demand.
>1/more than one
JNC 7 Guidelines/Goals: What is the Primary goal?___
...to lower BP and decrease risk of CV morbidity & mortality
JNC 7 Goals: Achieve/maintain SBP at __ and DBP __ while controlling other ___ risk factors for CVD
<90 diastolic and <140 systolic; modifiable
JNC 7 Goals (cont.): In patients with diabetes or chronic kidney dsease: __
<130/80
Initial Drug Therapy: drug treatment when BP is __
>140/90
Initial Drug Therapy: Thiazide-type ___ as initial theraphy for most, either alone or with ___ inhibitors, ARBs, beta-blockers, CCBs.
diuretics; ACE
Initial Drug Therapy: may include __ drugs for patients with ___ hypertension
2; stage 2
JNC 7 achieving BP control: most pateints will require __ antyhypertensive medications to achieve __ goals
2; BP
JNC 7 Achieving BP control: ____ can be added to regimen when ___ fails to lower BP to goal value
second drug (from different class); single drug
ADA Hypertension Guidelines: pateints with diabetes and hypertension have __ the risk of CV than ___ with hypertension
twice; nondiabetics
Diabetic goal for BP
Preferred initial therapy: ___, ___, and ___.
<130/80
ACE inhibitors, diuretics, and beta-blockers
Benefits of treating hypertension...
Decrease morbidity/mortality, specifically decrease risk of CAD, MI, stroke, LVH, CHF, renal vascular disease, retinopathy
SHEP stands for?
What year?
What drug?
Patient type?
-Systolic Hypertension in the Elderly Program
-1991
-Diuretic chlorthalidone (w/w/o beta-clocker atenolol) vs placebo
-Patients >60 years with high systolic >140 and normal diastolic <90
SHEP outcomes: after __ years--
__% reduction in total stroke
__%reduction in risk for nonfatal MI or CHD
__% reduction in risk for all major CV events
-4.5 years
-36%
-27%
-32%
Syst-Eur stands for?
What year?
Drug used?
Years lasted?
-Systolic Hypertension in Eurpope trial
-1997
-CCB nitrendipine (w/w/o ACE inibitor enalapril and/or diuretic) vs placebo
-2 years
Syst-Eur outcomes:
__% reduction in stroke; __% reduction in nonfatal stroke
__% reduction in nonfatal cardiac endpoints
__% reduction in all CV endpoints
42%; 44%
33%
26%
31%
UKPDS 38 stands for?
What year?
Control measures?
Years lasted?
-UK Prospective Diabetes Study 38
-1998
-tight BP control (ACE inhibitor captopril and beta-blocker) vs less tight BP control in diabetics
-nine years
UKPDS outcomes:
__% reduction in risk for diabetes-related endpoint; __% reduction risk for diabetes related mortality
__% reduction risk for all stroke
__% reduction for microvascular disease
__% reduction risk for heart failure
24%; 32%
44:
37%
56%
HOPE?
Year?
Patient type?
Drug tested?
Years lasted?
Heart Outcomes Prevention Evaluation
2000
Patients at high risk for CV events
ACE inhibitor ramipril vs. placebo
5 years
HOPE outcomes:
-__% lower risk of CV death, stroke, MI
-Effect on primary outcome was ___ in various patient subgroups
-22% lower
-consistent
LIFE stands for?
Year?
Drug?
Patient type?
Years lasted?
-Losartan Intervention For Endpoint
-ARB losartan vs beta-blocker atenolol
-Patients with left ventricular hypertrophy (LVH)
-Four years
LIFE Outcomes:
-__% decrease risk for stroke
-__ decrease by __ for losartan and __ for atenolol
-__ DBP decrease by __ for losartan and __ for atenolol
-25% decrease in stroke
-SBP by 30.2 and 29.1
-DBP decrease by 16.6 and 16.8
ALLHAT stands for?
Year?
Drugs tested?
Antihypertensive and Lipid-Lowering Treatment to Prent Heart Attack Trial
-2002
-CCB Norvasc or lisinopril vs diuretic chlorthalidone
ALLHAT consisted of a ___ component and a ___ component
antyhypertensive and lipid-lowering
ALLHAT follow-up lasted __ years
4.9 years
Explaining the Multiplicative Effect
Association of hypertension with other risk factors (eg, dyslipidemia) can have a multiplicative effect on CV risk:
1+1 = 4
True or False
Most patients will require greater than/equal to 2 antihypertensive medications to achieve BP goals
True
What is the BP goal for patients with diabetes or renal disease
130/80
True or False: Patients with diabetes and hypertension have three times the risk of CV disease than nondiabetics with hypertension
False, it's TWICE vice three times
What are the 3 types of Diuretics?
Thiazide diuretics and thiazide-like diuretics
Loop diuretics
Potassium-sparing diuretics
What is the MOA for Diuretics?
Increase urinary fluid loss
Increase delivery of sodium chloride and water into urine
Reduce fluid volume, cardiac output, and blood pressure
Diuretics Efficacy
(3 C's)
-Complements efficacy of other agents
-Often used in combination therapy
-Recommended for patients with compelling indications of heart failure, high coronary disease risk, diabetes, and for recurrent stroke prevention
True or False:
Alpha blockers are typically used for the treatment of BPH
True
What is Caduet indicated for?
-Used for initial treatment for both hypertension/angina and dyslipidemia
-May be integrated into existing regimen
How does Lipitor work?
1) Atorvastatin calcium inhibits HMG-CoA reductase, resulting in
2) reduced synthesis of endogenous cholesterol and
3) increased expression of LDL-C receptors; this leads to
4) decrease in LDL-C in the blood
What is Norvasc's Cmax?
Cmax: 6 to 12 hours
True or False:
No Caduet dosage adjustment needed for patients with renal impairment
True
How many doses of caduet are available?
11 dosing combinations:
2.5 mg/10 mg-40 mg
5 mg/10-80 mg
10 mg/10-80 mg
(amlodipine/atorvastatin)
What are the different ways physicians can Rx Caduet?
-Substitute:
Receiving both amlodipine and atorvastatin
-Integrate:
On antihypertensive medication who also need lipid-lowering medication
On antihypertensive medication plus atorvastatin
On atorvastatin who also need antihypertensive medication
What are the 3 Key Clinical Trials Supporting Caduet?
Avalon
Gemini
Respond
What were the results of Avalon?
Percentage of patients who reached both JNC VI and NCEP ATP III goals:
45.5% with amlodipine besylate plus atorvastatin calcium
28.6% with atorvastatin calcium alone
8.3% with amlodipine besylate alone
More patients on both Norvasc and Lipitor reached both JNC VI and NCEP ATP III goals
What was the primary measure of Gemini?
Primary measure: % reaching JNC VI and NCEP ATP III goals
What were the results of Gemini?
82.1% reached NCEP ATP III LDL-C goal
65.5% reached JNC VI BP goal
57.7% achieved both goals
What are the benefits of treating hypertension?
Decreases morbidity/ mortality
Coronary artery disease (CAD)
Myocardial infarction (MI)
Stroke
Left ventricular hypertrophy (LVH)
Congestive heart failure (CHF)
Renal vascular disease
Retinopathy
What are the JNC 7 Treatment Goals:
Systolic BP
Diastolic BP

Goal for diabetic/renal disease:
Systolic BP
Diastolic BP
Systolic BP <140 mm Hg
Diastolic BP <90 mm Hg

Goal for diabetic/renal disease:
Systolic BP <130 mm Hg
Diastolic BP <80 mm Hg
JNC 7 BP Classifications are:
Normal:
Prehypertension:
Stage 1 hypertension:
Stage 2 hypertension:
Normal: SBP <120 and DBP <80
Prehypertension:
SBP 120-139 or DBP 80-89
Stage 1 hypertension:
SBP 140-159 or DBP 90-99
Stage 2 hypertension:
SBP >160 or DBP >100
According to JNC 7 therapy for a Prehypertensive patient should include:
Prehypertensive patient
Lifestyle modification
According to JNC 7 therapy for a Stage 1 and Stage 2 hypertensive patient should include…
Stages 1 and 2 hypertension:
Drug treatment as necessary in addition to lifestyle modification
What are examples of JNC 7 Lifestyle Modifications?
Reduce weight
Adopt Dietary Approaches to Stop Hypertension (DASH) eating plan
Restrict dietary sodium
Engage in regular physical activity
Limit alcohol consumption
Primary Hypertension is caused by ______and occurs in ______% patients.
Primary Hypertension is caused by UNKNOWN and occurs in 95% patients.
According to JNC 7 if a patient is NOT at their BP goal:
-Optimize dosages or add additional drugs until goal BP is achieved
-Consider consultation with hypertension specialist
If BP is 20/10 mm Hg above goal value:
Consider initiating therapy with 2 drugs
Types of Diuretics include:
Thiazide diuretics and thiazide-like diuretics
Loop diuretics
Potassium-sparing diuretics
What is the Mechanism of Action of Diuretics?
Increase urinary fluid loss
Increase delivery of sodium chloride and water into urine
Reduce fluid volume, cardiac output, and blood pressure
Which part of the blood pressure equation do diuretics effect?
BP=CO x TPR
What are the potential adverse effects of Diuretics?
Hypokalemia (low potassium)
Hypomagnesemia
Hyperlipidemia
Hyperuricemia
Hyperglycemia
Which patients are recommended for Beta-blockers?
Recommended for patients with compelling indications of:
Heart failure, post-myocardial infarction, high coronary disease risk, diabetes
How to Beta Blockers work?
Decrease cardiac output by blocking beta-adrenergic receptors
CO = HR X SV
Which part of the Blood Pressure equation do Beta Blockers effect?
The CO in:
BP=CO x TPR
Why are Beta Blockers classified as selective vs. non-selective?
Beta Blockers vary in terms of cardioselectivity
Degree of affinity for beta1 vs. beta2 receptors in the bronchi and peripheral blood vessels
What are the common adverse events associated with Beta-Blockers?
Adverse events: bradycardia, AV block, fatigue
Abrupt discontinuation may cause angina and myocardial infarction
Name some Beta-Blockers
Selective
Tenormin® (atenolol)
Lopressor®; Toprol-XL® (metoprolol)
Non-selective
Inderal® (propranolol)
Cogard® (Natalol)
Blockogen®(Tymolol)
Viscan®(Pindalol)
What part of the BP equation do Alpha Blockers effect?
Decrease peripheral resistance; the TPR in the following:
BP= CO x TPR
What is the MOA of ACE Inhibitors?
Decreased Arterial Pressure
Renin (kidney)
Angiotensin
Angiotensin I
ACE
Angiotensin II
Sodium/Water Retention
Vasoconstriction
System Arterial Pressure
Which part of the BP equation do ACE Inhibitors effect?
Reduce peripheral resistance
BP= CO x TPR
ACE Inhibitors are recommended for which patients?
Patients with the compelling indications of:
heart failure
post-myocardial infarction
high coronary disease risk
Diabetes
chronic kidney disease
recurrent stroke prevention
ACE Inhibitors are Less effective in which special population? Why?
African Americans
African Americans have low renin levels
What is renin?
Converts angiotensinogen to angiotensin I
What is the most common side effect of ACE Inhibitors?
COUGH
Angioedema
Other Adverse events: persistent cough, hyperkalemia, rash, loss of taste, leukopenia, hypotension, renal effects
Name some ACE Inhibitors...
Brand name® (generic name)
Accupril® (quinapril)
Altace® (ramipril)
Capoten® (captopril)
Lotensin® (benazepril)
Monopril® (fosinopril)
Prinivil®, Zestril® (lisinopril)
Univasc® (moexipril)
Vasotec® (enalapril)
How do ARBs work?
Renin (kidney)
Angiotensin I
ACE
Angiotensin II
**Angiotensin II Receptor Blocker (ARB)
Inhibition of AT1 Receptor Binding
Vasoconstriction
Name some ARBs
Brand name® (generic name)
Cozaar® (losartan)
Diovan® (valsartan)
Avapro® (irbesartan)
Atacand® (candesartan)
Micardis® (telmisartan)
What is the MOA of CCBs?
Inhibit calcium entry into cardiac and vascular smooth muscle cells
-Reduces peripheral resistance
Classified as dihydropyridines (DHPs) or non-dihydropyridines
How do CCBs effect the BP equation?
BP= CO x TPR
It depends on whether they are DHP or Non-DHP
What is a non-DHP CCB?
Non-dihydropyridines (eg, diltiazem, verapamil)
Decrease contractility more than DHPs
Can decrease heart rate/conduction
What is a DHP CCB?
Dihydropyridines (DHPs) (eg, amlodipine, felodipine)
Potent vasodilators
Little effect on cardiac conduction or contractility
Calcium Channel Blockers can be used effectively as:
a.First-line agent
b.Monotherapy
c.Combination therapy
d.All of the above
First-line agent
Monotherapy
Combination therapy
ALL OF THE ABOVE!
What are potential adverse effects of CCBs?
Potential adverse effects: headache, flushing, and localized ankle edema
Overall, should be used with caution in patients with CHF
What is Norvasc’s® MOA?
Mechanism of action:
Blocks receptors on slow calcium channels
Stops calcium from entering muscle cell
Inhibits vascular smooth muscle from contracting
Results in vasodilation
What is Norvasc’s ® Peak Plasma Levels?
6 to 12 hours after administration
What is Norvasc’s half-life?
Long half-life of 30 to 50 hours
Where is Norvasc metabolized and excreted?
Metabolized in liver and excreted via urine
Norvasc® is indicated for the treatment of…
Hypertension
Chronic stable angina
Confirmed or suspected vasospastic angina
TRUE or FALSE
Norvasc cannot be used in African-American patientse across a broad range of patient types
FALSE
Norvasc can be used in African-American patient
Norvasc is effective across a broad range of patient types
What is the discontinuation rate of Norvasc®?
1.5% of patients discontinued Norvasc® therapy due to adverse events
What is the rate of edema in Norvasc® 5 mg and 10 mg?
5 mg: 3%
10 mg: 10.8%
Norvasc should be used in caution in patients with...
Caution in patients with severe aortic stenosis
Caution in patients with severe hepatic impairment
Pregnancy category C
Not known if excreted in milk; nursing should be discontinued while Norvasc® is administered
What is the usual dose of Norvasc®?
Usual initial antihypertensive dose:5 mg qd
Maximum dose:10 mg qd
2.5 mg qd
TRUE or FALSE
The initial starting dose for patients with renal insufficiency is 2.5 mg QD
FALSE
The initial starting dose for patients with HEPATIC insufficiency is 2.5 mg QD
2.5 mg can be used for:
Small, fragile, or elderly patients
Patients with hepatic insufficiency
What are the key advantages of Norvasc?
Norvasc can be used safely and effectively:
With a broad range of patients
Alone or in combination with other antihypertensive therapies
ALLHAT findings
Norvasc and lisinopril comparable to chlorthalidone on: combined fata CHD and nonfatal MI; all-cause mortality; combined CHD
Unlike lisinopril, Norvasc was also comparable to chlorthalidone on: stroke; combined CVD
ASCOT stands for?
When?
Patients?
Comparisons?
Anglo-Scandinavian Cardiac Outcomes Trial
2003
Patients with hypertension, no history of CHD, and more than 3 risk factors
Compared effects of two regimens (Norvasc w/w/o ACE inhibitor and beta-blocker atenolol, w/w/o thiazide diuretic)
Stopped early due to superior CV benefits with Norvasc
VALUE stands for?
When?
Comparisons?
Valsartan Antihypertensive Long-term Use Evaluation Trial
2004
Valsartan regimen vs Norvasc
VALUE findings
After 4.2 years: no difference in time to first cardiac mortality/morbidity
-Norvasc better than valsartan in reducing BP
-Proportion of patients receiving monotherapy greater w/ Norvasc 35.3% than with valsartan 27%
BPLTCC stands for?
When?
Results?
Blood Pressure Lowering Treatment Trialists Collaboration
2000 and 2003
ACE inhibitor, CCB and ARB based reduced risk of CV events
No differences in total CV events between ACE CCB vs diuretic or beta-blocker regimens
Diuretics act in different parts of the ____.
kidney
Three types of diuretics
1. Thiazide diuretics and thiazide-like duretics
2. Loop diuretics
3. Potassium-sparing diuretics
Diuretics MOA: Increase ___ fluid loss
urinary
MOA (cont): Increase delivery of ____ and ____ into the urine.
NaCl (sodium chloride) and water
MOA (cont): ___ fluid volume, cardiac output and blood pressure
Decrease
Diuretics efficacy:
___ efficacy of other agents.
Often used in ___ therapy.
-Complements
-combination
Diuretics efficacy: recommended for patients with compelling indications of __, high ___ disease risk, ___, and for recurrent ___ prevention.
heart failure; high coronary disease risk; diabetes; stroke prevention
Diuretics safety and dosing: potential adverse effects (name 5)...
Hypokalemia, hypomagnesemia, hyperlipidemia, hyperuricemia, hyperglycemia
Dosing comes in...
12.5 mg or 25 mg
Dosing in thisazide is ___ daily.
once
Dosing in potassium-sparing diuretics usually prescribed in ___ with ___ diuretics.
combination; thiazide
Beta-blockers: recommended for patients with compelling indications of __, __, high __, and ___.
heart failure; post-MI; high coronary disease risk; diabetes
How do beta-blockers impact the BP equation?
BP=COxTPR: decrease CO by blocking beta-adrenergic receptors
Beta-blockers pharmacology: vary in terms of _____.
cardioselectivity
Degree of affinity for beta, located in the ___ vs. beta2 receptors located in the ___ and peripheral blood vessels.
heart; bronchi
How are beta-blockers classified?
Either selective or non-selective.
Adverse events of beta-blockers (name three)
Bradycardia; AV block; fatigue
What may abrupt discontinuation of beta-blockers cause?
Angina; MI
Beta-blockers are contraindicated in patients with ___, untreated ___ and AV block __ and __.
bronchial asthma; untreated left ventricular failure; AV block II and III.
Beta-blockers should be used with caution in patients with __, since these agents can mask symptoms of ___.
diabetes; hypoglycemia
Beta-blocker dosing is __or __ daily.
once or twice
Alpha blockers decrease ___ ___.
peripheral resistance
Alpha blockers are effective in ___ therapy.
combination
Alpha blockers are useful in abnormal lipid profiles, diabetes, or ____.
BPH (benign prostatic hypertrophy)
Alpha blockers adverse events (name five):
headache, dizziness, weakness, fatigue, mild fluid retention
Alpha blockers first-dose postural ___ and ___ can occur.
hypotension; syncope
Alpha blockers dosing is __ or __ daily in __ inital dose, titrated.
once or twice, small
How are Alpha blockers available in the USA? (name three)
Prazosin; Hytrin (terazosin); Cardura (doxazosin)
For benign prostatic ___ only: (name two)
hypertrophy
Flomax (tamsulosin); Uroxatral (alfuzosin)
Combined Alpha and Beta Blockers: decrease ___ resistance; effective as ___ and in ____.
peripheral; monotherapy AND IN combination
Combined Alpha and Beta blockers used to treat ___ patients with hypertension, ___ emergencies, hypertension with concomitant ___ failure.
pregnant; hypertensive; heart
Types of combined Alpha and Beta Blockers: name two...
Coreg (carvedilol, used for CHF) and Normodyne, Trandate (labetalol hydrochloride)
ACE Inhibitors: reduce ___ resistance.
peripheral
ACE Inhibitors are recommended for patients with: (name six)
heart failure; post-MI; high coronary disease risk, diabetes, chronic kidney disease, and recurrent stroke prevention.
Are ACE Inhibitors less or more effective in African Americans?
LESS effective
ACE Inhibitors MOA:
Decreased peripheral resistance
Renin (kidney)-->Angiotensin I-->ACE-->Angiotensin II-->decrease in Na, H20, vasoconstriction, arterial pressure
ACE Inhibitors adverse events: (name six)
cough; hyperkalemia; rash; loss of taste; leukopenia; hypotension; renal effects
ACE Inhibitors black box warning regarding ___.
Pregnancy
ACE Inhibitors dosing:
Once daily to three times daily; qd to tid
What type of drug is Norvasc?
CCB DHP (Selective in vasodialation in the peripheral); MOA happens in the cardiac muscle cells
Examples of ACE inhibitors:
-Acccupril (quinpril): Pfizer
-Altace (ramipril)
-Mavik (trandolapril)
-As generics: Capoten/captopril, Lotensin/benazepril, Monopril/fosinopril, Prinivil, Zestril/lisinopril, Vasotec/enalapril
Angiotensin II Receptor Blockers: what do they block?
Angiotensin II, which STOPS vasoconstriction; does not allow the Ang II to travel to endothelial/blocks the receptor from binding on the cell
What are ARBs recommended for?
Patients with heart failure, diabetes, and chronic kidney disease; preserves HEART function
What side effects come with ARBs?
No real side effects; may have unfavorable effects on pts with renovascular disease
Dosing with ARBs:
Once or twice a day
Calcium Channel Blockers MOA
Inhibit calcium entry into cardiac and vascular smooth muscle cells; they REDUCE peripheral resistance
Three classifications of CCBs
Verapamil (non-DHP); Diltiazem (non-DHP);
Dihydropyridine (DHP)
DHP vs Non-DHP CCBs: what is the main difference?
DHPs have little effect on cardiac conduction while Non-DHP decreases contractility and decrease rate/conduction
Which CCB is a potent vasodilator?
DHP
Name two types of DHP
amlodipine and felodipine
CCBs are effective as a ___ agent and in both __ and ___ therapy.
first-line; monotherapy; combination
CCBs are recommended for these type of patients:
Those with DIABETES and those with CORONARY DISEASE RISK
CCBs effective in __, __, and __.
Elderly; African-Americans; Caucasians
CCB safety
Edema (ankle); headache; flushing; used in caution with CHF
Procardia XL generic...
nifedipine
Who makes Procardia?
DHP or Non-DHP?
Indications?
Dosing?
Pfizer; DHP; for hypertension, vasospastic angina and stable angina
Dosing: starting 30 or 60 mg with max daily of 120 mg
Norvasc generic
amlodipine besylate
Norvasc indications
Hypertension, chronic stable angina, vasospastic angina
Norvasc dosing
-5 mg initial dose, max 10
-small, fragile, elderly, hepatic issues: 2.5
-children 2.5-5 mg
Inotropic
contractility
Chronotropic
heart rate
Norvasc is considered both...
Non inotropic and non chronotropic: has no effect on heart rate or contractility
Norvasc is ___ with other drugs
synergistic (no drug to drug interactions)
Norvasc effectiveness
Effective in ALL degrees of hypertension; 24-hour control; across a broad range of patient type
Discontinuation rate in Norvasc
1.5%
Contraindication with Norvasc
Known sensitivity to amlodipine
Plendil generic
Plendil marketed by...
DHP or non-DHP...
Indication...
Higher or lower rates of edema/headache...
Felodipine
DHP
Hypertension
Higher
Plendil dosing
Starting: 5 mg
Maintenance: 2.5-10 mg
Cardizem LA
Indication
Contraindications
Dosing
diltiazem
Hypertension (alone or combo)
Contraindicated: CV conditions, SSS, AV block
Starting dose: 180-240
Max dose: 540 mg
Three other types of CCBs (brand name and generic)
1. Plendil (felodipine) by AstraZeneca
2. Cardizem LA (diltiazem)
3. Cover-HS (verpamil) by Pfizer
Covera-HS (verapamil)
Pfizer brand for hypertension/angina; warnings: CV condictions; contraindications: CV, SSS, AB block; serious adverse events in pts w/ hypertrophic cardiomyopathy
Dosing: qd
Caduet used to treat:
initial treatment for both hypertension/angina and dyslipidemia
Can caduet be integrated into existing condition?
YES!
Caduet MOA
Antihypertensive: dihyropyrdine calcium antagonist amlodipine besylate
Cholesterol-lowering agent: HMG-CoA reductase inhibitor atorvastatin calcium
Amlodipine Besylate Component: what specifically does it do?
It prevents calcium ions from entering muscle cells and it causes both peripheral and coronary blood vessels to dilate to increase blood flow
Lipitor component works this way...
inhibits HMG-CoA resulting in reduced synthesis of cholesterol in liver and in
Lipitor component review
1. it inhibits HMG-CoA resulting in 2.reduced syntheses of endogenous cholesterol and 3.increased expression of LDL, this leads to 4. decrease in LDL in the blood
C max of lipitor
1-2 hours; food decreases rate of absorption
C max of Norvasc
6-12 hours; not affected by food
Geriatric patients
Norvasc decreases clerance, increases AUC
Lipitor increases Cmax and AUC; greater degree of lower LDL
Pediatric patients
Norvasc: clearance and distribution similar to adults
Lipitor: no data in children under 10
Pharmacokinetics:
Increase in AUC __ to __%; may need ___ initial dose
40-60%
Lower
Gender differences with Lipitor: increased Cmax about __%; lowered AUC about __% in women
20% and 10%
Caduet Dosing
Starting dose
11 combinations: 5/10 up to 10/80
Starting dose: 5/10 or 5/20 (if pt needs >45% then start at 5/40)
What is the key difference in LDL reduction between men and women?
There is NO difference in LDL reduction
Is Caduet proven safe for Class III and IV heart failure?
YES!
Are dosage adjustments needed for patients for renal insufficiency?
NO!
Does hemodialysis enhance clearance of either agent?
NO
Hepatic insufficiency in Norvasc: patients may have ___ clearance, with ___ in AUC of __ to __%.
decreased clearance; increased; 40-60%
Hepatic insufficiency in Lipitor chronic liver disease ___ in plasma concentrations.
increase
Hep insufficiency Lipitor: Child-Pugh B disease--Cmax and AUC...?
Cmax 16-fold more; AUC 11 fold more
Indications of Caduet:
Norvasc and Lipitor...
Norvasc: hypertension, chronic stabel angina, vasopastic angina
Lipitor: prevent CV disease, het.hypercholesterolemia, elevated TG, dysbetalipoproteinemia, homo FH, pediatric w/ hetero FH, stroke
Is there data in the Package Insert to support switching a patient from statins other than atorvastatin to Caduet?
NO!
Caduet is contraindicated in patients with ___ disease or unexplained _____.
Liver; persistent elevations of serum transaaminases; women who are pregnant/breastfeeding; known hypersensivity
Caduet warnings (only due to Norvasc)
increased angina; MI
Caduet warnings (only due to Lipitor)
Liver dysfunction; skeletal muscle destruction
Caduet precautions (with Norvasc component)
caution in pts with CHF; no protection against abrupt beta-blocker withdrawal
Caduet precautions (Lipitor component)
may blunt adrenal/gonadal steroid production; CNS toxicity in dogs; need to report myopathy
Other Caduet precautions
Hypotension, Pregnancy catagory X, no studies in kids/elderly; remember: need to add in TLC with drug!
How much does the 10/80 dose of Caduet increase the atorvastatin calcium AUC by?
18%
What interactions with Norvasc?
NONE!!
Atorvastatin calcium interacts with...
antacid, colestipol, digoxin, erythromycin, oral contraceptives, fibrates, nitrates, antifungals
Caduet adverse events:
mild to moderate: well tolerated, similar only to those reported in Norvasc and Lipitor
Adverse events of Norvasc
headache, edema
discontinuation=1.5%
Adverse events of Lipitor
constipation, flatulence, dyspepsia, ab pain, discontinuation=<2%
What is common in Avalon, Gemini and Respond?
All patients have hypertension and dyslipidemia
Three different groups in the studies
Group I, Group II, Group III
Group I
No add'l risk factors; BP<140/90 and LDL<160
Group II
>/= CV risk factor; BP<140/90 and LDL<130
Group III
CHD, diabetes, other CV risk equivalents; BP<130/85 and LDL <100
Were patients receiving BP or lipid medications?
NO!
Primary outcome measure...
the percent of patients who reached their JNC VI BP goal, their NCEP ATP III LDL-C goal, or both goals
Response results
SBP, DBP, and LDL were significantly lowered on the Norvasc/Lipitor; safety profile comparable to previously mentioned
Is Norvasc indicated to treat CHF?
No: it is indicated for hypertension; if they have CHF they can use Norvasc and it won't worsen the symptoms