NPLEX Combination Review Cardiovascular Part 1 Paul S. Anderson, ND Medical Board Review Services...

NPLEX Combination ReviewCardiovascular Part 1

Paul S. Anderson, ND

Medical Board Review Services

Copyright MBRS

• SGOT / AST “A sick heart can beat f-AST”– Identify and monitor HEART!!! , Kidney,hepatocellular damage– Increased in early MI (peak at 24-36 hrs.)

• SGPT / ALT “L is for Liver”– Identify and monitor hepatocellular damage.– ALT>AST Mainly = Liver Dz.

• GGT / GGTP– Useful in detecting space-occupying lesions, biliary dysfunction

and ETOH abuse – Chemical toxicity.

• CPK– Most often performed to document an acute MI; should be

performed upon admission to hospital (after 12 hours but before 24 hours).

– CPK-MB elevation also may be associated with pulmonary embolism.

LDH (118.0 – 273IU/ml)Principle measurement to diagnose conditions in which there is tissue damage.

• Isoenzymes:– LDH-1 Normally Lower than LDH-2– In MI: LDH-1>LDH-2!– Liver Dz: LDH< AST&ALT– Pernicious Anemia LDH may be 50X Normal– LDH-5 Increase in Muscle Dz’s

• LDH ELEVATIONS– Acute MI– Myocarditis– Liver disease– Tissue necrosis– CHF– Shock– Pancreatitis– Acute renal infarction– Hemolysis– Skeletal muscle disease– Trauma– Multi-system disease– Collagen-vascular disease

MI

– Troponin-1Increase 2-4 hours post-MI

– CK / MB Increase 4-6 hours post

– Myoglobin Increase 4-8 hours post

– AST 6- 36 hours post

– LDH-1>LDH-2! 12-48 hours post

Plasma Lipid ProfileUsed to determine cardiac risk and to aid in the diagnosis of

lipoprotein metabolism disorders:

• Total cholesterol (< 200mg/dL)– HDL (< 35 mg/dL confer increased myocardial risk)– LDL (> 100mg/dL associated with increased myocardial risk)

• Triglycerides (< 250mg/dL)• Apolipoprotein A1 (> 140mg/dL) Lipoprotein portion of HDL.

(Higher = better) may be more useful than HDL cholesterol to identify patients with CAD

• Apolipoprotein B (70 –110 mg/dL) major apoprotein of LDL and VLDL; elevated levels indicate increased myocardial risk

• Lipoprotein (a) (< 30mg / dL)– Correlates CAD risk; concentrations > 30mg/dL correlate 2X greater risk

of developing CAD. (<20 desirable range). Used in predicting stent closure post-surgery.

Plasma Lipid Profile

• Genotyping HyperlipidemiaFredrickson’s Types:– Sub Types I, II, III, IV (Definitive dx with lipid

electrophoresis)– IV Most Common

• Chol. = / > 200• HDL = Low / LDL = High• TG > Chol.

– II Second Most Common• Chol. > 200• TG Normal

• Homocysteine – Increased levels in serum may confer increased myocardial risk.

• Ammonia (NH3) (5-50mmol/l)– Severe liver disease is the most common cause of elevated levels.

• Vitamin B12 (> 200pg/ml)– Decreased values in pernicious anemia and alcoholism.

• Folate (200 – 640ng/ml)– DECREASED in megaloblastic anemia and alcoholism.– INCREASED in acute renal failure and liver disease.

• TIBC (% Transferrin saturation) 255 –450mcg/dL

– Usually performed in conjunction with serum iron in the evaluation and diagnosis of iron-deficiency anemia, chronic disease anemia and thalassemias.

– INCREASED: Fe deficiency anemia, PG and OBC.– DECREASED: Anemia chronic disease, sideroblastic anemia and

hemochromatosis.• Serum Iron:

– VERY labile! Changes quickly.• Ferritin (20 – 300ng/ml)

– Detection of iron deficiency and anemia by reflecting storage of iron.

Calculating % Fe. SaturationSerum Iron (mcg/dL) / TIBC

(mcg/dL)

Vascular Studies• ARTERIAL

– AORTA: Performed when working-up probable aneurysms – CAROTID: Performed to ensure normal vascular anatomy of common carotid

artery, internal and external carotids; ruling out stenos is or occlusion– LEA: Examining extremity arterial anatomy, normal triphasic blood flow, plaques

or other pathological lesions and normal segmental blood pressure.• VENOUS

– LEV: Normal venous anatomy with spontaneous, phasic blood flow pattern, normal venous augmentation with no pathological valves present.

• Advantages – Noninvasive without radiation risk.– May obviate need for costly hospitalization.– Structural image therefore useful for patients with organ function dysfunction.– Does not require ingestion of contrast dyes.

• Disadvantages– Requires skilled technician to operate transducer.– Air-filled structures cannot be studied with this procedure.– Obese & restless patients cannot be adequately studied.

• Interfering factors– Bowel gas (air) complicates procedure.– No open wound or dressing can be used to visualize deep structures.

Electrocardiogram• Resting ECG

– Performed to establish baseline ECG.

• Stress / exercise ECG– Graded exercise tolerance test. Systolic values usually

increase. Diastolic usually remains unchanged.– Test measures the efficiency of the heart during a dynamic

exercise stress period.– Valuable for diagnosing IHD, underlying pathophysiological

functioning.

• Holter monitor – Method of continuously recording the ECG; often for 24

hours.– Provides documentation of suspected cardiac rhythm

disturbances.

ECG Findings• Infarction

– Pathologic Q-Waves• .04 sec or > & 1/3 as deep as R-Wave is high (all but AVR)

– S-T Segment changes• Tall T’s, (S-T elevations)

– Age of infarct• Hyperacute: Normal Q, ST Elevation, upright T• Acute: Q MB Pathologic, ST Less Elevated, T inverted• Recent: Q-Change, Isoelectric S-T, Symmetrical T inv.• Old: Significant Q- changes, Isoelectric T waves

• Drug / Electrolyte changes– Digitalis: Scooped S-T’s– Hyperkalemia: Wide P & QRS, Peaked T– Hypokalemia: Flat T wave, U wave present– Hypercalcemia: Short Q-T– Hypocalcemia: Long Q-T

• Pericarditis: P-R Depression, S-T elevation

Clinical Considerations: ECG• Interfering factors:

– Race: ST elevation with T-wave inversion more common in people of African decent.

– Food Intake: High CHO may shift electrolytes and induce ST depression and T-wave inversion.

– Anxiety: May induce ST depression and/ or T-wave inversion.

– Pre-testing activity may alter results.

• Procedural preparation and aftercare– Proper lead placement– Instruct patient regarding procedure– Recognize limitations of ECG

Stress EKG• Indications

– Definite indications • Atypical symptoms in men or menopausal women • Assess prognosis in patient with known CAD • Assess patient with Exercise-induced

dysrhythmia – Possible indications:

• Typical or atypical symptoms in menopausal women

• Assess response to therapies • Evaluate variant Angina • Serial testing in patient with known CAD

Family Practice Notebook

Stress EKG• Contraindications

– Aortic Dissection – Critical Aortic Stenosis – Critical Left Ventricular outflow-tract obstruction – Idiopathic Hypertrophic Subaortic Stenosis (IHSS) – Inability to Exercise to adequate level of exertion – Uninterpretable Electrocardiogram

• Left Bundle Branch Block (Adenosine Nuclear needed) • Electronically paced rhythm (Pacemaker) • WPW Syndrome • Abnormal ST segments (>1 mm ST abnormality)

– Recent or active cerebral ischemia – Severe uncontrolled Hypertension – Uncompensated Congestive Heart Failure – Unstable Angina – Digoxin Use (Class IIB Recommendation) – Cardiac revascularization within last 5 years


Ankle Brachial Index• Technique

– Measure highest systolic reading in both arms • Record first doppler sound as cuff is deflated • Record at the radial pulse • Use highest of the two arm pressures

– Measure systolic readings in both legs • Cuff applied to calf • Record first doppler sound as cuff is deflated • Use doppler ultrasound device

– Record dorsalis pedis pressure – Record posterior tibial pressure

• Use highest ankle pressure (DP or PT) for each leg – Calculate ratio of each ankle to brachial pressure

• Divide each ankle by highest brachial pressure


Ankle Brachial Index

• Interpretation – Ankle-Brachial ratio >0.95: Normal – Ankle-Brachial ratio <0.95: Peripheral Vascular

Disease – Ankle-Brachial ratio <0.6: Intermittent

Claudication – Ankle-Brachial ratio <0.5: Multi-level disease – Ankle-Brachial ratio <0.26: Resting ischemic pain

• Ankle-Brachial ratio <0.2: Gangrenous extremity


Carotid Evaluation / Ultrasound

• Interpretation of carotid bruit – Degree of stenosis by atherosclerotic Plaque

• Minimum stenosis causing bruit: 50% (<3 mm lumen) • Prolonged, high-pitched bruit: >75% (1.5 mm lumen)

– Location • Plaque involves posterior wall of common carotid • Affects bifurcation and flow into internal carotid • Risk of distal thrombus formation in internal carotid

– Carotid bruit associated risk of stroke at 1 year • Asymptomatic carotid bruit: 1% risk at 1 year • Transient Ischemic Attack history: 1.7% risk • Other studies question bruit significance


Carotid Evaluation / Ultrasound

• Evaluation – Carotid Artery Duplex Ultrasonography

• Standard diagnostic tool for carotid stenosis • Less expensive than MRA • Accuracy for diagnosing severe carotid stenosis

– Test Sensitivity: 86%

– Test Specificity: 87%

– Carotid Magnetic Resonance Angiography (MRA) • Better than ultrasound at defining carotid anatomy • Accuracy for diagnosing severe carotid stenosis

– Test Sensitivity: 95%

– Test Specificity: 90%


Echocardiogram

• Indication – Every patient with Congestive Heart Failure! – Distinguishes

• Systolic Dysfunction • Diastolic Dysfunction

– Identify underlying valve disease – Identify underlying ischemic heart damage – Quantify Congestive Heart Failure severity

Echocardiogram

• Assessment – Chamber size (diastolic and end-systolic dimensions)

• Left Ventricular Hypertrophy • Left Atrial Enlargement

– Ejection Fraction (EF) • Systolic Dysfunction: EF < 45% • Diastolic Dysfunction (isolated): EF > 50% • Echocardiogram accuracy is +/- 5% at best

– Heart Valve Function and dysfunction – Wall thickness and wall motion abnormalities


Thrombolysis• Needed when the intrinsic clotting

mechanisms are activated– Arrhythmias– Fibrillation– Prosthetic valves– Hyper-coaguable (thick) blood

• High Fibrinogen• Dehydration

• Multiple sites in the clotting cascade can be affected

Anti-thrombotics

Outpatient

MOA Uses Adverse Effects

Other

Warfarin[Coumadin]

Vitamin K antagonist

(Extrinsic) Factors 2,7,9,10

Thrombosis, rheumatic heart disease, embolism, ischemic heart disease

Prolonged bleeding, hemorrhage, diarrhea, fever,rash

Monitor pro-thrombin time

Antithrombotics

Mainly IV / inpatient


Other

Heparin Inhibits clotting factors by binding to antithrombin III (AT3) and ENHANCING the thrombin blockade of AT3.

Prevention of deep vein thrombosis, embolism, DIC

Hemorrhage, cutaneous necrosis, chills, pruritus, fever

Administer cautiously in men-struating women, patients with liver disease or blood disease

CLOTTING PATHWAYS

Measured by: PTT

Drugs: Heparin

Measured by PT/INR

Drugs: Warfarin, ASA, Vitamin-E, EFA’s

Factors 2-7-9-10

PROTHROMBIN ACTIVATOR made up of V&X: Started by X alone and V becomes active with + feedback

Extrinsic Pathway: Damage outside of blood vessels.

Intrinsic Pathway:

Blood trauma (turbulence and viscosity) or collagen and blood contact.

Antithrombin III keeps Thrombin INACTIVE

Antithrombotics MOA Uses Adverse Effects

Clopidogrel[Plavix]

Aspirin (ASA)

Prevent formation of platelet aggregating substance: thromboxane A2 (TxA2) – The pro-inflammatory cytokine produced by COX activity along with PG2 in the arachadonate cascade.

Reduce risk of MI, Stroke

Salicylism (ASA), GI distress, bleeding, tinnitus, rash, occult blood

TTP(Plavix)

ASA for Prevention• Most patients use 75-162mg / day “low dose ASA”

– Average is one 81mg ASA (baby aspirin)

• Am J Cardiol 2008;102:396-400 compared the effects of aspirin 300 mg/day and combined therapy with aspirin 100 mg/day and clopidogrel 75 mg/day on platelet function – Both strategies significantly decreased ADP- and collagen-induced

platelet aggregation, the authors report: • 18 of 30 patients treated with aspirin 300 mg/day and • 25 of 30 treated with aspirin 100 mg/day and clopidogrel 75 mg/day had

adequate platelet inhibition.

• "Increasing the aspirin dose to 300 mg/day or adding clopidogrel to aspirin can provide adequate platelet inhibition in a significant number of those patients with impaired responses to low-dose aspirin," the investigators conclude.

Clopidogrel (Plavix) Rx:

• 75 mg Tablets

• Preventive: 75mg qd

• Acute (STMI): 300mg loading dose then 75mg qd

• Literature lists continuing ASA Rx as well

Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events.

N Engl J Med. 2006; 354(16):1706-17 (ISSN: 1533-4406)

• CONCLUSIONS: In this trial, there was a suggestion of benefit with clopidogrel treatment in patients with symptomatic atherothrombosis and a suggestion of harm in patients with multiple risk factors. Overall, clopidogrel plus aspirin was not significantly more effective than aspirin alone in reducing the rate of myocardial infarction, stroke, or death from cardiovascular causes.

Cardiac Function - Basics

Cardiac Function

• Electrical function– Creates the rhythmic pumping of blood via muscular

contraction– When irregular creates

• Arrhythmias• Extra beats

• Hydraulic function– Mass movement of blood through the chambers– Pushed by muscle contraction– Controlled by valves in the system– When irregular creates

• Murmurs• Aberrant blood flow

Cardiac Muscle Physiology

EPI

EPIB-1

Adrenergicreceptor

Beta blockers

Ca++

CA++ Channels CA++

Influx

Adenylate cyclase

Cyclase-a

ATP

cAMP

Prot. Kinase

Prot.Kinase-a

“Phosphorylation”

Tension Generation

Cross Bridge Formation

CA++

Channel Blockers

Cardiac AP and Ca++ Channel

Ca++ Channel Open

Carnitine at the Mitochondrial Membrane

Drugs to correct rhythm disturbances:

• These drugs are used to “calm” the electrical impulses in the heart.

• This “calming” creates less aberrant heart beating

• These drugs come in four classes– Two classes are also anti-hypertensive drugs– Two classes are specifically rhythm agents

Class I Anti-arrhythmics

MOA Uses Adverse Effects Other

Digoxin Cardiac Glycoside

(also)Lidocaine

Inhibits the sodium/potassium pump to increase intracellular calcium.

Calcium drives the cardiac AP plateau.

CHF,

paroxysmal atrial tachycardia,

atrial fibrillation,

atrial flutter,

Fatigue

arrhythmias

muscular weakness

agitation

blurred vision

anorexia

nausea

Monitor blood levels.

Toxicity may be life threatening.

Yellow halo around vision may develop.

Quinidine

**NOT Quinine!

Decreases automaticity, conduction velocity and prolongs refractory periodHas anticholinergic effects

Atrial flutter

atrial fibrillation

premature atrial and ventricular depolarization

Arrhythmia, nauseavomiting diarrhea cinchonism fever vertigoheadache

Prolongs QRS and QT intervals on EKG

Cinchonism!

• Quinine AND Quinidine:

• Tinnitus / Hearing Loss

• Headache / Nausea

• Dizziness / Vertigo

• Visual changes

Digitalis / Quinidine Rx:

• Digitalis:– (Capsules 0.05, 0.1, 0.2mg::Tabs 0.125, 0.25 mg)– Dose 0.05 to 0.35mg bid– Therapeutic dose levels in 7-21 days– Measure trough level; Effective level 0.8-2 ng/mL

• Quinidine:– (Sulfate; 200, 300mg:: Gluconate; 324mg ER)– Dose 300-400mg sulfate q-6hrs– Dose 324 ER q-8-12hrs– Measure trough level 30-35 hours after starting or

changing therapy; Effective level 2-6 mcg/mL

Class IIBeta Blockers

Class IIIAmiodarone

Class IVCalcium Channel Blockers

•delay in repolarization

•prolongation in AP

•slowing of electrical conduction

•reduction in SA node fct.

•decreased conduction through accessory pathways

•About 7 out of every 10 patients will experience some type of reaction, and between 1 in 20 and 1 in 5 will experience side effects that are severe enough to stop the medication. •The most severe side effect related to the lungs. These reactions can be fatal. (One in 10 of those that develop lung toxicity will die.) •rare, fatal liver toxicity has occurred

Antiarrhythmics MOA Adverse Effects Other

Diuretics

Na+ HANDLING ALONG THE NEPHRON• Numbers = % Na• Arrows = Direction of flow• PROXIMAL TUBULE

– Reabsorbs 67% (2/3) Na & H2O– Reabsorbs all Glucose, HCO3, &

Amino Acids– Reabsorbs Na via Cotransport with

Glucose, AA’s, PO4; And via Countertransport in the Na+ / H+ Exchange.

– Site of Carbonic Anhydrase Inhibitor activity (Blocks HCO3 reabsorption)

• THICK ASC. LOOP of HENLE– Reabsorbs 25% of Na– Na-K-Cl cotransporter– Site of Loop Diuretic action

• DISTAL TUBULE / COLL. DUCT

– Reabsorbs 8% Na via. Na-Cl cotransporter

– Site of thiazide diuretic action

Na+ HANDLING ALONG THE NEPHRON• PROXIMAL TUBULE

– Reabsorbs 67% (2/3) Na & H2O

– Site of Carbonic Anhydrase Inhibitor activity (Blocks HCO3 reabsorption)

• THICK ASC. LOOP of HENLE– Reabsorbs 25% of Na– Site of Loop Diuretic action

• DISTAL TUBULE / COLL. DUCT

– Reabsorbs 8% Na via. Na-Cl cotransporter

– Site of thiazide diuretic action

Antihypertensive/Diuretics


Chlorothiazide

(Hydrochloro-thiazide – HCTZ)

Inhibits sodium and chloride re-absorption in distal tubule resulting in a decrease in the glomerular filtration rate

HTNEdema

Hypokalemia, oliguria, anuria, GI disturbance, hypercalcemia, hyperglycemia, hyperuricemia, renal failure

C.I. in patients with hypersensitiv-ity to thiazide or

sulfonamide drugs

Furosemide[Lasix]

Loop diuretic, inhibits sodium and chloride re-absorption in the Loop of Henle

Edema, HTN

Hypokalemia, oliguria, anuria, GI disturbance, hypercalcemia, hyperglycemia, hyperuricemia, ototoxic, hypovolemia

Triamterene

(Often in combination with HCTZ as “Maxzide”

Spironolactone

Potassium sparing diuretic acts on distal tubules

Aldosterone antagonist

Edema, HTN

EdemaHTN

Some endocrine uses (PCOS…)

**Hyperkalemia, nausea, vomiting, diarrhea

Same, plus breast deformity and tenderness

May turn urine blueFolic Acid Base

Multiple toxicities

Antihypertensive/Diuretics


ALDOSTERONE

Spironolactone

BLOCKS!

Leads to Na EXCRETION (in urine) and K retention (in blood)

Diuretics• HCTZ

– 12.5mg capsules; 25, 50, and 100mg tablets• Edema: 50-100mg qd until edema resolved

– Short term only

– Max Dose 200 mg acutely

• HTN:– 12.5 – 50mg qd

• HCTZ / Triamterene– 25mg / 37.5mg - Maxzide; 50mg / 75mg – Maxzide-25

• Furosemide– 20, 40, and 80mg Tablets

• Edema: 80 mg qd (may increase as required up to 600mg total daily)

• HTN: 40mg bid

Antihypertensive Drugs:• Beta Blockers

–END IN “-OLOL”• ACE Inhibitors

–END IN “-PRIL”• ARB’s (Angiotensin Receptor Blockers)

–END IN -SARTAN• Catecholamine Agent

– ONLY ONE: Reserpine

• Calcium Channel Blockers– All the rest!

Beta-Blockers


EPI

EPIB-1

Adrenergicreceptor

Beta blockers

Ca++

CA++ Channels CA++

Influx

Adenylate cyclase

Cyclase-a

ATP

cAMP

Prot. Kinase

Prot.Kinase-a


Tension Generation


CA++

Channel Blockers

AntihypertensivesBeta Blockers


AtenololAcebutololBetaxololBisoprololEsmololMetoprolol

1 adrenergic receptor blocker, decreases cardiac output and renin release

Hypertension, angina

Fatigue, drowsiness, vertigo, dizziness, bradycardia, hypotension, bronchospasm, CHF

Enhance effects of digitalis

PropranololCarteololNadololPindololSotalolTimolol

Blocks both 1 and 2 adrenergic receptors

Hypertension, angina, arrhythmias, migraines, essential tremors

Fatigue, bradycardia, hypotension, lethargy, nausea, vomiting, diarrhea, CHF

Abrupt discontinuation may cause tachycardia and rebound hypertension

Beta Blockers

• Atenolol (Tenormin)– 25, 50 or 100mg tablets– HTN:

• 50 mg qd• Increases to 100 mg qd maximun

– Migraine Prophylaxis• 100mg qd

Calcium Channel Blockers


EPI

EPIB-1

Adrenergicreceptor

Beta blockers

Ca++

CA++ Channels CA++

Influx

Adenylate cyclase

Cyclase-a

ATP

cAMP

Prot. Kinase

Prot.Kinase-a


Tension Generation


CA++

Channel Blockers

Cardiac AP and Ca++ Channel

Ca++ Channel Open

Antihyper-tensivesCa++ Channel Blockers


BepridilMibefradil

Verapamil[Isopten]

Calcium channel blocker

Angina, hypertension

Constipation, hypotension, dizziness, edema, nausea, CHF

Increased levels with cimetidine

Diltiazem[Cardizem]


Angina, hypertension, atrial fibrillation or flutter

Headache, edema, dizziness, arrhythmias, CHF, nausea, constipation, rash

Increased levels with cimetidine

AmlodipineFelodipineNicardepineNefidipineNifedipine[Procardia]


Angina, hypertension

Dizziness, CHF, MI edema, headache, weakness, nausea,

Capsule passed in stool, medicine released in gut


• Amlodipine (Norvasc)– 2.5, 5 and 10mg tablets

– Angina• 5 to 10 mg qd

– HTN• 2.5 to 5 mg qd• Maximum dose is 10 mg qd

Angiotensin Agents

ALDOSTERONE – RENIN – ANGIOTENSIN SYSTEM

ACE-I - BLOCK

ARB BLOCK

Antihypertensives MOA Uses Adverse Effects Other

ACE Inhibitors

CaptoprilBenazeprilEnalaprilLisinoprilFosinapril

Inhibits ACE [angio-tensin converting enzyme] in the lungs.

Hyper-tension, heart failure

Dry persistent cough Tachycardia, hypotension, urticaria, rash, Renal dysfunction headache Hyperkalemia

Contra-indicated in preg-nancy

Antihypertensives MOA Uses Adverse Effects

ARB’sCandi-/ Irbe-Epro- / Lo-Telme- / Val- (sartan)

Blockade of ANG-2 Receptors

Hyper-tension in those with ACE intolerance due to Cough

HypotensionRenal DysfunctionHyperkalemia

Angiotensin Agents• ACE Inhibitors

– Quinapril (Accupril)• 5, 10, 20 and 40mg tablets• Dose for HTN 10-20 mg to start• Maximum dose 80 mg qd

• ARB’s– Candesartan (Atacand)

• 4, 8, 16 and 32 mg tablets• 16 mg qd starting dose• Often used 8 – 16 mg bid

No "clinically meaningful difference" in hypertension

• "With the exception of rates of cough, the available evidence does not strongly support the hypothesis that ACE inhibitors and ARBs have clinically meaningful differences in benefits or harms for individuals with essential hypertension," according to the report's authors, led by Dr David B Matchar (Duke Center for Clinical Health Policy Research, Durham, NC).

• He and his colleagues analyzed 69 reports based on 61 randomized and observational studies that lasted at least three months and directly compared an ACE inhibitor and an ARB in adults with essential hypertension and evaluated meaningful end points like blood pressure control, treatment compliance, and adverse events.

Peripheral Anti-Adrenergic

Peripheral anti-adrenergic


Reserpine Depletes catecholamine stores in PNS [and maybe CNS]

Essential hypertension

Drowsiness, sedation, nervousness, depression, Decr. HR, nasal congestion, nausea / diarrhea Parasympathetic Predominance

Do NOT administer MAO inhibitors and Reserpine within two weeks of each other

Rx of Reserpine:

Available in 0.1 and 0.25mg tablets

Common Rx’s:

- 0.1 qd to bid

- 0.25 qd to bid

Do not use in catecholamine responsive depressives.

Overdose symptoms include hyper-parasympathetic activity.

But doesn’t Rauwolfia and Reserpine use make people

kill themselves?

Lets go through this now:

Peripheral anti-adrenergic


Reserpine Depletes catecholamine stores in PNS [and maybe CNS]

Essential hypertension

These are RARE in hyper-catecholamine patients.Drowsiness, sedation, nervousness, depression, Decr. HR, nasal congestion, nausea / diarrhea Parasympathetic Predominance

Do NOT administer MAO inhibitors and Reserpine within two weeks of each other

Rauwolfia and Reserpine

• Reserpine Tablets:– 0.1 and 0.25mg available– Dose is 0.1 – 0.25 qd – bid

• Rauwolfia:– Watch tincture concentration– Average dose 1-3 mL qd - bid

Anti-Anginal Drugs

Anti-anginal drugs


Nitroglycerin Increases blood supply to heart; decreases preload and afterload

Angina Headache, dizziness, hypotension, tachycardia, bradycardia, rash

Amyl Nitrate Unknown, thought to be dilation of arterial and venous system

Angina Throbbing headache, dizziness, hypotension, tachycardia, bradycardia,

Antidote for cyanide poisoning

Papaverine HCl

“Cardiac vessel dilation”

Angina Similar to Nitro. No longer used


See above Angina

Nitrate Rx:

• NTG – SL-Tablets 0.3, 0.4 or 0.6mg– Acute angina:

• Dose 1 SL tablet up to 1 tablet every 5 minutes for 3 doses

• Other dose forms available:– Spray, Cream, Long Acting Capsules

• L-Arginine PO dose– 1000 – 2000mg bid

• Magnesium Glycinate PO dose– 100-300mg bid

• Zinc PO dose– 20-50mg bid (taken in the middle of a meal to

decrease nausea!)

Angina Rx:

Lipid Management

Basics:• HDL:

– “Good” although there are better and worse forms.• Acts more like a hormone than a lipid molecule

• LDL:– “Bad” although there are better (larger) and worse

(smaller) forms.– Carry OXIDANTS!– Generally LOWERING these makes one less

inflammatory

• Triglycerides:– Stimulated in production by CHO intake– Elevations often indicate Pro-Inflammatory status and

disorders of Insulin – Sugar biochemistry

LDL Oxidation: The LDL has the potential to carry an incredible load of free radical.Anti-Oxidant effects of Vitamins E, C, GSH and the RBC - Lipid – Plasma Interaction

Reduced Glutathione

Oxidized Glutathione

Plasma

ASC

ASC RDHA

LDLRBC

TocoToco R

LDL + R = “oxidized LDL”

Cholesterol Transport

Cellular Cholesterol Balance

High Cholesterol Types• Lipoprotein Electrophoresis

– 5 Sub categories of hyperlipidemia• Fredrickson’s Genotypes

– Types 2 & 4 are most common• Type 4 is 1-2 X more common than Type 2

– Generally High TC, TG’s (higher than TC), and LDL– Responds to carbohydrate restriction– Poor response to low fat diets

• Type 2– generally High TC, LDL, and NORMAL TG’s– Responds better to reduced fat diets

Sugar / Insulin and TG Synthesis

BLOOD

CYTOSOL

MITOCHONDRIA

CHO AcetylCoA

[AcetylCoA Carboxylase] Insulin(+)

Malonyl CoA

Palmitate

CPT-1

(-)

Acyl Units

Beta Oxidation

Energy

Acyl Units

Esterify to TG’s

TG’s to

Blood

Lipid Lowering Agents


Other

Lovastatin[Mevacor]

Simvastatin[Zocor]

Atorvastatin [Lipitor]

Fulvistatin [Lescol]

Pravistatin [Pravacol]

HMG CoA reductase inhibitor

Hyperlipidemia GI distress, headache, dizziness, abdominal cramps, rash, liver toxic, rhabdo-myaloysis

Monitor liver function

Check AST and ALT prior to Rx, and at 6 weeks post-Rx.

Rx along with 75-100 mg Co-Q10 minimum.

Discontinue if patient has muscle pain concomitant to Rx – EVEN if LFT’s are normal.

Statin Rx:

• Atorvastatin (Lipitor)– 10, 20, 40 and 80mg tablets

• Dose 10 to 20mg qd• Start at 40mg qd if LDL reduction need is greater

than 45%• Maximum dose 80mg qd

• Draw Lipids and LFT’s 4 weeks after therapy initiation or does adjustment

A Multicenter Placebo Controlled Dose Ranging Study of Atorvastatin

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 3, No. 2, 119-123 (1998)

• Patients received placebo or atorvastatin 10, 20, 40, 60, or 80 mg once daily.

• Adjusted mean decreases in LDL cholesterol for patients receiving atorvastatin 10, 20, 40, 60, and 80 mg were 37%, 42%, 50%, 52%, and 59%, respectively, compared with a mean increase of 0.3% for patients receiving placebo

Cholestyramine[Questran]

Combines with bile acid to form an insoluble compound that is excreted

Hyper-lipidemia

Constipation, fecal impaction, abdominal pain, nausea

Reduces absorp-tion of fat soluble vitamins



Other

Niacin Stimulates hepatic lipid metabolism

Hyper-lipid-emia

Niacin flush, rash, GI distress

Give with B-Complex and Vitamin C to avoid Hepatic Effect.



May be Rx’d alone or in a combination of Niacin and a low dose statin.

Rx a high potency B-Complex AND Vitamin C (gram per gram of Niacin).

Rx takes at least 1500 – 2000 mg daily to have any significant effect on lipids.

SLOW release is generally better tolerated.

Slow release is NOT more dangerous than immediate release if Rx’d properly.

LOWERS: TC, LDL AND TG

RAISES: HDL

Niacin Rx:

• Niacin Extended Release (Niaspan)– 250, 500, 750 or 1000mg tablets

• Start with 1000 mg hs, work up to 1500 – 2000mg hs– Avoid spices, tannins etc with medication– 81mg ASA taken with the Niacin reduces

flushing

Advicor Rx:

• Lovastatin / Niacin combination:

– 20/500, 20/750, 20/1000 or 40/1000mg

– Dose is 1 po qhs

Fibrates

• Fenofibrate (TriCor…)– Multiple dose formats

• To lower Triglycerides– 48 – 145 mg qd – Maximum dose 145mg

Lovaza

• Omega-3-acid ethyl esters (1 gram capsules)– Normal Sig is 2 capsules bid

• Indicated alone or with Statins in patients with high (200-499) or very high (>500) triglycerides.– Alone in very high TG– With 40 mg Statin in high TG

Cardiovascular (CV) causes of chest pain

• Angina: Covered later

PERICARDITIS

• Usually more localized, sternal or over cardiac apex

• sharp, stabbing, knife-like pain• lasts hours to days • aggravated by deep breathing or lying supine

and relieved by sitting up and leaning forward • may auscultate friction rub

DISSECTING AORTIC ANEURYSM

• anterior chest pain, may radiate to back

• excruciating, tearing pain; sudden onset, lasts hours to days

• pain unrelated to anything

• BP lower in left arm

Noncardiac causes of chest pain

• GI disorders: peptic ulcer, esophageal reflux, hiatal hernia, cholecystitis; pain usu burning, cramping, aching; worse supine; may be meal related

• Musculoskeletal disorders: variable location; aching pain, made worse with movement or palpation; touching surface of chest aggravates the pain.

• Spontaneous Pneumothorax: unilateral location; sharp, localized; sudden onset lasting many hrs; dyspnea, SOB, painful breathing

Noncardiac causes of chest pain

• Pulmonary Embolism: pleurisy type pain, dyspnea, pleural rub, pain over area of infarction; hemoptysis with lg infarction

• Pulmonary Hypertension: substernal pain, pressure, dyspnea, accentuated pulmonary second heart sound

• Anxiety States: localized pain, sharp, burning; moves from place to place, brief duration, with emotional situations; frequent sighing

NPLEX Combination Review Cardiovascular Part 1 Paul S. Anderson, ND Medical Board Review Services...

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Transcript of NPLEX Combination Review Cardiovascular Part 1 Paul S. Anderson, ND Medical Board Review Services...