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214 Cards in this Set
- Front
- Back
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How many Americans have both hypertension and dyslipidemia?
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30 million
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Hypertension occurs along __% of the time, and it frequently occurs with ___.
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<20%
dyslipidemia |
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Association with hypertension with other risk factors can have a ___ effect on CV risk.
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multiplicative
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MRFIT: Layering of both ___ and ___ can have a dramatic effect on __ mortality risk.
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hypertension
dyslipidemia CV |
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Many patients at risk will require ___ plus ___ modifications.
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-pharmacologic treatment plus lifestyle modifications.
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Pharmacologic treatments that can address __ risk factor will be in demand.
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>1/more than one
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JNC 7 Guidelines/Goals: What is the Primary goal?___
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...to lower BP and decrease risk of CV morbidity & mortality
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JNC 7 Goals: Achieve/maintain SBP at __ and DBP __ while controlling other ___ risk factors for CVD
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<90 diastolic and <140 systolic; modifiable
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JNC 7 Goals (cont.): In patients with diabetes or chronic kidney dsease: __
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<130/80
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Initial Drug Therapy: drug treatment when BP is __
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>140/90
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Initial Drug Therapy: Thiazide-type ___ as initial theraphy for most, either alone or with ___ inhibitors, ARBs, beta-blockers, CCBs.
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diuretics; ACE
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Initial Drug Therapy: may include __ drugs for patients with ___ hypertension
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2; stage 2
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JNC 7 achieving BP control: most pateints will require __ antyhypertensive medications to achieve __ goals
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2; BP
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JNC 7 Achieving BP control: ____ can be added to regimen when ___ fails to lower BP to goal value
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second drug (from different class); single drug
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ADA Hypertension Guidelines: pateints with diabetes and hypertension have __ the risk of CV than ___ with hypertension
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twice; nondiabetics
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Diabetic goal for BP
Preferred initial therapy: ___, ___, and ___. |
<130/80
ACE inhibitors, diuretics, and beta-blockers |
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Benefits of treating hypertension...
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Decrease morbidity/mortality, specifically decrease risk of CAD, MI, stroke, LVH, CHF, renal vascular disease, retinopathy
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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 |
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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% |
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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 |
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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% |
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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 |
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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% |
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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 |
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HOPE outcomes:
-__% lower risk of CV death, stroke, MI -Effect on primary outcome was ___ in various patient subgroups |
-22% lower
-consistent |
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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 |
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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 |
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ALLHAT stands for?
Year? Drugs tested? |
Antihypertensive and Lipid-Lowering Treatment to Prent Heart Attack Trial
-2002 -CCB Norvasc or lisinopril vs diuretic chlorthalidone |
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ALLHAT consisted of a ___ component and a ___ component
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antyhypertensive and lipid-lowering
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ALLHAT follow-up lasted __ years
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4.9 years
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Explaining the Multiplicative Effect
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Association of hypertension with other risk factors (eg, dyslipidemia) can have a multiplicative effect on CV risk:
1+1 = 4 |
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True or False
Most patients will require greater than/equal to 2 antihypertensive medications to achieve BP goals |
True
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What is the BP goal for patients with diabetes or renal disease
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130/80
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True or False: Patients with diabetes and hypertension have three times the risk of CV disease than nondiabetics with hypertension
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False, it's TWICE vice three times
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What are the 3 types of Diuretics?
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Thiazide diuretics and thiazide-like diuretics
Loop diuretics Potassium-sparing diuretics |
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What is the MOA for Diuretics?
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Increase urinary fluid loss
Increase delivery of sodium chloride and water into urine Reduce fluid volume, cardiac output, and blood pressure |
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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 |
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True or False:
Alpha blockers are typically used for the treatment of BPH |
True
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What is Caduet indicated for?
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-Used for initial treatment for both hypertension/angina and dyslipidemia
-May be integrated into existing regimen |
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How does Lipitor work?
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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 |
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What is Norvasc's Cmax?
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Cmax: 6 to 12 hours
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True or False:
No Caduet dosage adjustment needed for patients with renal impairment |
True
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How many doses of caduet are available?
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11 dosing combinations:
2.5 mg/10 mg-40 mg 5 mg/10-80 mg 10 mg/10-80 mg (amlodipine/atorvastatin) |
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What are the different ways physicians can Rx Caduet?
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-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 |
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What are the 3 Key Clinical Trials Supporting Caduet?
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Avalon
Gemini Respond |
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What were the results of Avalon?
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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 |
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What was the primary measure of Gemini?
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Primary measure: % reaching JNC VI and NCEP ATP III goals
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What were the results of Gemini?
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82.1% reached NCEP ATP III LDL-C goal
65.5% reached JNC VI BP goal 57.7% achieved both goals |
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What are the benefits of treating hypertension?
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Decreases morbidity/ mortality
Coronary artery disease (CAD) Myocardial infarction (MI) Stroke Left ventricular hypertrophy (LVH) Congestive heart failure (CHF) Renal vascular disease Retinopathy |
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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 |
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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 |
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According to JNC 7 therapy for a Prehypertensive patient should include:
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Prehypertensive patient
Lifestyle modification |
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According to JNC 7 therapy for a Stage 1 and Stage 2 hypertensive patient should include…
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Stages 1 and 2 hypertension:
Drug treatment as necessary in addition to lifestyle modification |
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What are examples of JNC 7 Lifestyle Modifications?
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Reduce weight
Adopt Dietary Approaches to Stop Hypertension (DASH) eating plan Restrict dietary sodium Engage in regular physical activity Limit alcohol consumption |
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Primary Hypertension is caused by ______and occurs in ______% patients.
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Primary Hypertension is caused by UNKNOWN and occurs in 95% patients.
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According to JNC 7 if a patient is NOT at their BP goal:
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-Optimize dosages or add additional drugs until goal BP is achieved
-Consider consultation with hypertension specialist |
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If BP is 20/10 mm Hg above goal value:
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Consider initiating therapy with 2 drugs
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Types of Diuretics include:
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Thiazide diuretics and thiazide-like diuretics
Loop diuretics Potassium-sparing diuretics |
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What is the Mechanism of Action of Diuretics?
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Increase urinary fluid loss
Increase delivery of sodium chloride and water into urine Reduce fluid volume, cardiac output, and blood pressure |
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Which part of the blood pressure equation do diuretics effect?
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BP=CO x TPR
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What are the potential adverse effects of Diuretics?
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Hypokalemia (low potassium)
Hypomagnesemia Hyperlipidemia Hyperuricemia Hyperglycemia |
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Which patients are recommended for Beta-blockers?
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Recommended for patients with compelling indications of:
Heart failure, post-myocardial infarction, high coronary disease risk, diabetes |
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How to Beta Blockers work?
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Decrease cardiac output by blocking beta-adrenergic receptors
CO = HR X SV |
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Which part of the Blood Pressure equation do Beta Blockers effect?
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The CO in:
BP=CO x TPR |
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Why are Beta Blockers classified as selective vs. non-selective?
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Beta Blockers vary in terms of cardioselectivity
Degree of affinity for beta1 vs. beta2 receptors in the bronchi and peripheral blood vessels |
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What are the common adverse events associated with Beta-Blockers?
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Adverse events: bradycardia, AV block, fatigue
Abrupt discontinuation may cause angina and myocardial infarction |
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Name some Beta-Blockers
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Selective
Tenormin® (atenolol) Lopressor®; Toprol-XL® (metoprolol) Non-selective Inderal® (propranolol) Cogard® (Natalol) Blockogen®(Tymolol) Viscan®(Pindalol) |
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What part of the BP equation do Alpha Blockers effect?
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Decrease peripheral resistance; the TPR in the following:
BP= CO x TPR |
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What is the MOA of ACE Inhibitors?
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Decreased Arterial Pressure
Renin (kidney) Angiotensin Angiotensin I ACE Angiotensin II Sodium/Water Retention Vasoconstriction System Arterial Pressure |
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Which part of the BP equation do ACE Inhibitors effect?
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Reduce peripheral resistance
BP= CO x TPR |
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ACE Inhibitors are recommended for which patients?
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Patients with the compelling indications of:
heart failure post-myocardial infarction high coronary disease risk Diabetes chronic kidney disease recurrent stroke prevention |
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ACE Inhibitors are Less effective in which special population? Why?
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African Americans
African Americans have low renin levels |
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What is renin?
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Converts angiotensinogen to angiotensin I
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What is the most common side effect of ACE Inhibitors?
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COUGH
Angioedema Other Adverse events: persistent cough, hyperkalemia, rash, loss of taste, leukopenia, hypotension, renal effects |
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Name some ACE Inhibitors...
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Brand name® (generic name)
Accupril® (quinapril) Altace® (ramipril) Capoten® (captopril) Lotensin® (benazepril) Monopril® (fosinopril) Prinivil®, Zestril® (lisinopril) Univasc® (moexipril) Vasotec® (enalapril) |
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How do ARBs work?
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Renin (kidney)
Angiotensin I ACE Angiotensin II **Angiotensin II Receptor Blocker (ARB) Inhibition of AT1 Receptor Binding Vasoconstriction |
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Name some ARBs
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Brand name® (generic name)
Cozaar® (losartan) Diovan® (valsartan) Avapro® (irbesartan) Atacand® (candesartan) Micardis® (telmisartan) |
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What is the MOA of CCBs?
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Inhibit calcium entry into cardiac and vascular smooth muscle cells
-Reduces peripheral resistance Classified as dihydropyridines (DHPs) or non-dihydropyridines |
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How do CCBs effect the BP equation?
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BP= CO x TPR
It depends on whether they are DHP or Non-DHP |
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What is a non-DHP CCB?
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Non-dihydropyridines (eg, diltiazem, verapamil)
Decrease contractility more than DHPs Can decrease heart rate/conduction |
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What is a DHP CCB?
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Dihydropyridines (DHPs) (eg, amlodipine, felodipine)
Potent vasodilators Little effect on cardiac conduction or contractility |
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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! |
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What are potential adverse effects of CCBs?
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Potential adverse effects: headache, flushing, and localized ankle edema
Overall, should be used with caution in patients with CHF |
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What is Norvasc’s® MOA?
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Mechanism of action:
Blocks receptors on slow calcium channels Stops calcium from entering muscle cell Inhibits vascular smooth muscle from contracting Results in vasodilation |
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What is Norvasc’s ® Peak Plasma Levels?
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6 to 12 hours after administration
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What is Norvasc’s half-life?
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Long half-life of 30 to 50 hours
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Where is Norvasc metabolized and excreted?
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Metabolized in liver and excreted via urine
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Norvasc® is indicated for the treatment of…
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Hypertension
Chronic stable angina Confirmed or suspected vasospastic angina |
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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 |
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What is the discontinuation rate of Norvasc®?
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1.5% of patients discontinued Norvasc® therapy due to adverse events
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What is the rate of edema in Norvasc® 5 mg and 10 mg?
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5 mg: 3%
10 mg: 10.8% |
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Norvasc should be used in caution in patients with...
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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 |
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What is the usual dose of Norvasc®?
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Usual initial antihypertensive dose:5 mg qd
Maximum dose:10 mg qd 2.5 mg qd |
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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 |
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What are the key advantages of Norvasc?
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Norvasc can be used safely and effectively:
With a broad range of patients Alone or in combination with other antihypertensive therapies |
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ALLHAT findings
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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 |
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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 |
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VALUE stands for?
When? Comparisons? |
Valsartan Antihypertensive Long-term Use Evaluation Trial
2004 Valsartan regimen vs Norvasc |
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VALUE findings
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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% |
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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 |
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Diuretics act in different parts of the ____.
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kidney
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Three types of diuretics
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1. Thiazide diuretics and thiazide-like duretics
2. Loop diuretics 3. Potassium-sparing diuretics |
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Diuretics MOA: Increase ___ fluid loss
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urinary
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MOA (cont): Increase delivery of ____ and ____ into the urine.
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NaCl (sodium chloride) and water
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MOA (cont): ___ fluid volume, cardiac output and blood pressure
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Decrease
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Diuretics efficacy:
___ efficacy of other agents. Often used in ___ therapy. |
-Complements
-combination |
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Diuretics efficacy: recommended for patients with compelling indications of __, high ___ disease risk, ___, and for recurrent ___ prevention.
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heart failure; high coronary disease risk; diabetes; stroke prevention
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Diuretics safety and dosing: potential adverse effects (name 5)...
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Hypokalemia, hypomagnesemia, hyperlipidemia, hyperuricemia, hyperglycemia
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Dosing comes in...
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12.5 mg or 25 mg
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Dosing in thisazide is ___ daily.
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once
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Dosing in potassium-sparing diuretics usually prescribed in ___ with ___ diuretics.
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combination; thiazide
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Beta-blockers: recommended for patients with compelling indications of __, __, high __, and ___.
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heart failure; post-MI; high coronary disease risk; diabetes
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How do beta-blockers impact the BP equation?
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BP=COxTPR: decrease CO by blocking beta-adrenergic receptors
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Beta-blockers pharmacology: vary in terms of _____.
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cardioselectivity
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Degree of affinity for beta, located in the ___ vs. beta2 receptors located in the ___ and peripheral blood vessels.
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heart; bronchi
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How are beta-blockers classified?
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Either selective or non-selective.
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Adverse events of beta-blockers (name three)
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Bradycardia; AV block; fatigue
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What may abrupt discontinuation of beta-blockers cause?
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Angina; MI
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Beta-blockers are contraindicated in patients with ___, untreated ___ and AV block __ and __.
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bronchial asthma; untreated left ventricular failure; AV block II and III.
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Beta-blockers should be used with caution in patients with __, since these agents can mask symptoms of ___.
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diabetes; hypoglycemia
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Beta-blocker dosing is __or __ daily.
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once or twice
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Alpha blockers decrease ___ ___.
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peripheral resistance
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Alpha blockers are effective in ___ therapy.
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combination
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Alpha blockers are useful in abnormal lipid profiles, diabetes, or ____.
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BPH (benign prostatic hypertrophy)
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Alpha blockers adverse events (name five):
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headache, dizziness, weakness, fatigue, mild fluid retention
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Alpha blockers first-dose postural ___ and ___ can occur.
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hypotension; syncope
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Alpha blockers dosing is __ or __ daily in __ inital dose, titrated.
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once or twice, small
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How are Alpha blockers available in the USA? (name three)
|
Prazosin; Hytrin (terazosin); Cardura (doxazosin)
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For benign prostatic ___ only: (name two)
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hypertrophy
Flomax (tamsulosin); Uroxatral (alfuzosin) |
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Combined Alpha and Beta Blockers: decrease ___ resistance; effective as ___ and in ____.
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peripheral; monotherapy AND IN combination
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Combined Alpha and Beta blockers used to treat ___ patients with hypertension, ___ emergencies, hypertension with concomitant ___ failure.
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pregnant; hypertensive; heart
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Types of combined Alpha and Beta Blockers: name two...
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Coreg (carvedilol, used for CHF) and Normodyne, Trandate (labetalol hydrochloride)
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ACE Inhibitors: reduce ___ resistance.
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peripheral
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ACE Inhibitors are recommended for patients with: (name six)
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heart failure; post-MI; high coronary disease risk, diabetes, chronic kidney disease, and recurrent stroke prevention.
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Are ACE Inhibitors less or more effective in African Americans?
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LESS effective
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ACE Inhibitors MOA:
|
Decreased peripheral resistance
Renin (kidney)-->Angiotensin I-->ACE-->Angiotensin II-->decrease in Na, H20, vasoconstriction, arterial pressure |
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ACE Inhibitors adverse events: (name six)
|
cough; hyperkalemia; rash; loss of taste; leukopenia; hypotension; renal effects
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ACE Inhibitors black box warning regarding ___.
|
Pregnancy
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ACE Inhibitors dosing:
|
Once daily to three times daily; qd to tid
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What type of drug is Norvasc?
|
CCB DHP (Selective in vasodialation in the peripheral); MOA happens in the cardiac muscle cells
|
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|
Examples of ACE inhibitors:
|
-Acccupril (quinpril): Pfizer
-Altace (ramipril) -Mavik (trandolapril) -As generics: Capoten/captopril, Lotensin/benazepril, Monopril/fosinopril, Prinivil, Zestril/lisinopril, Vasotec/enalapril |
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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
|
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What are ARBs recommended for?
|
Patients with heart failure, diabetes, and chronic kidney disease; preserves HEART function
|
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What side effects come with ARBs?
|
No real side effects; may have unfavorable effects on pts with renovascular disease
|
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Dosing with ARBs:
|
Once or twice a day
|
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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) |
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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
|
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Which CCB is a potent vasodilator?
|
DHP
|
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Name two types of DHP
|
amlodipine and felodipine
|
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CCBs are effective as a ___ agent and in both __ and ___ therapy.
|
first-line; monotherapy; combination
|
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CCBs are recommended for these type of patients:
|
Those with DIABETES and those with CORONARY DISEASE RISK
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CCBs effective in __, __, and __.
|
Elderly; African-Americans; Caucasians
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CCB safety
|
Edema (ankle); headache; flushing; used in caution with CHF
|
|
|
Procardia XL generic...
|
nifedipine
|
|
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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 |
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Norvasc generic
|
amlodipine besylate
|
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Norvasc indications
|
Hypertension, chronic stable angina, vasospastic angina
|
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Norvasc dosing
|
-5 mg initial dose, max 10
-small, fragile, elderly, hepatic issues: 2.5 -children 2.5-5 mg |
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Inotropic
|
contractility
|
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Chronotropic
|
heart rate
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Norvasc is considered both...
|
Non inotropic and non chronotropic: has no effect on heart rate or contractility
|
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Norvasc is ___ with other drugs
|
synergistic (no drug to drug interactions)
|
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Norvasc effectiveness
|
Effective in ALL degrees of hypertension; 24-hour control; across a broad range of patient type
|
|
|
Discontinuation rate in Norvasc
|
1.5%
|
|
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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 |
|
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Plendil dosing
|
Starting: 5 mg
Maintenance: 2.5-10 mg |
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Cardizem LA
Indication Contraindications Dosing |
diltiazem
Hypertension (alone or combo) Contraindicated: CV conditions, SSS, AV block Starting dose: 180-240 Max dose: 540 mg |
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Three other types of CCBs (brand name and generic)
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1. Plendil (felodipine) by AstraZeneca
2. Cardizem LA (diltiazem) 3. Cover-HS (verpamil) by Pfizer |
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Covera-HS (verapamil)
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Pfizer brand for hypertension/angina; warnings: CV condictions; contraindications: CV, SSS, AB block; serious adverse events in pts w/ hypertrophic cardiomyopathy
Dosing: qd |
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Caduet used to treat:
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initial treatment for both hypertension/angina and dyslipidemia
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Can caduet be integrated into existing condition?
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YES!
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Caduet MOA
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Antihypertensive: dihyropyrdine calcium antagonist amlodipine besylate
Cholesterol-lowering agent: HMG-CoA reductase inhibitor atorvastatin calcium |
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Amlodipine Besylate Component: what specifically does it do?
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It prevents calcium ions from entering muscle cells and it causes both peripheral and coronary blood vessels to dilate to increase blood flow
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Lipitor component works this way...
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inhibits HMG-CoA resulting in reduced synthesis of cholesterol in liver and in
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Lipitor component review
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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
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C max of lipitor
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1-2 hours; food decreases rate of absorption
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C max of Norvasc
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6-12 hours; not affected by food
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Geriatric patients
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Norvasc decreases clerance, increases AUC
Lipitor increases Cmax and AUC; greater degree of lower LDL |
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Pediatric patients
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Norvasc: clearance and distribution similar to adults
Lipitor: no data in children under 10 |
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Pharmacokinetics:
Increase in AUC __ to __%; may need ___ initial dose |
40-60%
Lower |
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Gender differences with Lipitor: increased Cmax about __%; lowered AUC about __% in women
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20% and 10%
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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) |
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What is the key difference in LDL reduction between men and women?
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There is NO difference in LDL reduction
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Is Caduet proven safe for Class III and IV heart failure?
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YES!
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Are dosage adjustments needed for patients for renal insufficiency?
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NO!
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Does hemodialysis enhance clearance of either agent?
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NO
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Hepatic insufficiency in Norvasc: patients may have ___ clearance, with ___ in AUC of __ to __%.
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decreased clearance; increased; 40-60%
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Hepatic insufficiency in Lipitor chronic liver disease ___ in plasma concentrations.
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increase
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Hep insufficiency Lipitor: Child-Pugh B disease--Cmax and AUC...?
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Cmax 16-fold more; AUC 11 fold more
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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 |
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Is there data in the Package Insert to support switching a patient from statins other than atorvastatin to Caduet?
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NO!
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Caduet is contraindicated in patients with ___ disease or unexplained _____.
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Liver; persistent elevations of serum transaaminases; women who are pregnant/breastfeeding; known hypersensivity
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Caduet warnings (only due to Norvasc)
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increased angina; MI
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Caduet warnings (only due to Lipitor)
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Liver dysfunction; skeletal muscle destruction
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Caduet precautions (with Norvasc component)
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caution in pts with CHF; no protection against abrupt beta-blocker withdrawal
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Caduet precautions (Lipitor component)
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may blunt adrenal/gonadal steroid production; CNS toxicity in dogs; need to report myopathy
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Other Caduet precautions
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Hypotension, Pregnancy catagory X, no studies in kids/elderly; remember: need to add in TLC with drug!
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How much does the 10/80 dose of Caduet increase the atorvastatin calcium AUC by?
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18%
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What interactions with Norvasc?
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NONE!!
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Atorvastatin calcium interacts with...
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antacid, colestipol, digoxin, erythromycin, oral contraceptives, fibrates, nitrates, antifungals
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Caduet adverse events:
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mild to moderate: well tolerated, similar only to those reported in Norvasc and Lipitor
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Adverse events of Norvasc
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headache, edema
discontinuation=1.5% |
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Adverse events of Lipitor
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constipation, flatulence, dyspepsia, ab pain, discontinuation=<2%
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What is common in Avalon, Gemini and Respond?
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All patients have hypertension and dyslipidemia
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Three different groups in the studies
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Group I, Group II, Group III
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Group I
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No add'l risk factors; BP<140/90 and LDL<160
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Group II
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>/= CV risk factor; BP<140/90 and LDL<130
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Group III
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CHD, diabetes, other CV risk equivalents; BP<130/85 and LDL <100
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Were patients receiving BP or lipid medications?
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NO!
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Primary outcome measure...
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the percent of patients who reached their JNC VI BP goal, their NCEP ATP III LDL-C goal, or both goals
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Response results
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SBP, DBP, and LDL were significantly lowered on the Norvasc/Lipitor; safety profile comparable to previously mentioned
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Is Norvasc indicated to treat CHF?
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No: it is indicated for hypertension; if they have CHF they can use Norvasc and it won't worsen the symptoms
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