Mechanisms Regulating Arterial Pressure

N203 ATI (Unit 6) Cardiovascular System -

 ANS helps control pressure by adjusting cardiac output (HR x SV) and peripheral resistance. The renin-angiotensin-aldosterone system helps control arterial pressure by: Releasing angiotensin II potent vasoconstrictor of arterioles and veins Releasing aldosterone promotes Na+ and H2O retention by kidneys Vasopressin (ADH) is a potent vasoconstrictor and water reabsorption. Atrial natriuretic peptide (ANP) is a vasodilator and causes excretion of Na+ and H2O by kidneys. It also inhibits renin secretion. Decreasing blood volume and dilating arterioles and veins help control BP

Epinephrine

N203 ATI (Unit 6) Cardiovascular System -

Epinephrine (Adrenaline) Catecholamine Adrenergic Agonist Binds to: 1 vasoconstriction / 1 HR, contractility, & AV conduction 2 Bronchodilation absorption of local anesthetics or extravasated meds Therapeutic Uses: Manage superficial bleeding congestion of nasal mucosa BP Treatment of AV block and cardiac arrest Asthma Hypertensive crisis Necrosis from extravasation Adverse Effects: Dysrhythmias / myocardial O2 demand angina Pregnancy (C) Contraindications/Precautions: MAOIs effect and duration TCAs block uptake of epi. Interactions: General anesthetics lead heart to be hypersensitive to epi dysrhythmias -adrenergic blockers (phentolamine) -adrenergic blockers (propanolol) Education: Stop infusion with evidence of extravasation; treat with -blocker (phentolamine)
Expected Action:

Dopamine

N203 ATI (Unit 6) Cardiovascular System -

Expected Action:

Dopamine (Intropin) Catecholamine Adrenergic Agonist

Low Dose (Dopamine receptors) Renal vasodilation Mod Dose (Dopamine, 1) Above + HR, contractility, AV conduction High Dose (Dopamine, 1, 1) Above + vasoconstriction Shock Heart failure Therapeutic Uses: Necrosis can occur from extravasation of high doses Adverse Effects: Dysrhythmias / myocardial O2 demand angina Pregnancy (C) Contraindications/Precautions: CI: Pheochromocytoma Interactions: Education: Stop infusion with evidence of extravasation; treat with -blocker (phentolamine)

Adrenergic Receptors

N203 ATI (Unit 6) Cardiovascular System -

1 1

Vasoconstriction of arterioles in skin, viscera, and

mucous membranes, and veins

HR, contractility, AV conduction Release of renin in kidneys Vasodilation of arterioles in heart, lungs, and

skeletal muscle

Bronchodilation Relaxation of uterine smooth muscle Glycogenolysis in liver Skeletal muscle contraction

Dopamine

Vasodilation of renal blood vessels

Dobutamine

N203 ATI (Unit 6) Cardiovascular System -

Expected Action:

Dobutamine (Dobutrex) -- Catecholamine

Binds to: 1 vasoconstriction / 1 HR, contractility, & AV conduction 2 Bronchodilation Therapeutic Uses: Heart failure Adverse Effects: heart rate Pregnancy (B) Contraindications/Precautions: Interactions: Education: Stop infusion evidence of extravasation; treat with -blocker (phentolamine)

-Adrenergic Blockers

N203 ATI (Unit 6) Cardiovascular System -

Expected Action:

Proto: Prazosin (Minipress) Others: doxazosin mesylate (Cardura),

Phentolamine (Regitine), ergotamine tartrate

Selective 1 blockade resulting in venous and arterial dilation Hypertension Phentolamine: Extravasation of adrenergic agonists Doxazosin mesylate: symptoms of benign prostatic hypertrophy Adverse Effects: First-dose orthostatic hypotension (monitor BP for 2 hrs post-treatment) Pregnancy (C) Contraindications/Precautions: Interactions: Antihypertensives additive hypotensive effect NSAIDs / clonidine antihypertensive effects of prazosin Education:
Therapeutic Uses:

Centrally Acting 2 Agonists

N203 ATI (Unit 6) Cardiovascular System -

Expected Action:

Proto: clonidine (Catapres) Others: guanfacine (Tenex), methyldopa (Aldomet)

sympathetic outflow in CNS bradycardia, CO, vasodilation, BP Hypertension Severe cancer pain (epidural) Investigational: Migraine, flushing from menopause, withdrawal management Dry mouth (usually resolves in 2-4 weeks) Adverse Effects: Drowsiness & sedation Rebound hypertension Pregnancy (C) Contraindications/Precautions: Antihypertensives: Additive hypotensive effect Interactions: Prazosin, MAOIs, TCAs: Counteract effects of clonidine. CNS Depressants: Additive CNS depressant effect Apply patch to hairless skin on torso or upper arm Education:
Therapeutic Uses:

-Adrenergic Blockers

N203 ATI (Unit 6) Cardiovascular System -

Proto: Cardioselective: metoprolol (Lopressor), Nonselective: propanolol (Inderal) - Others: Cardioselective: atenolol, Nonselective: nadolol (Corgard) 1-adrenergic blockade HR, contractility, AV conduction Hypertension Dysrhythmias (block SA/AV cond.) Therapeutic Uses: Angina/MI ( O2 demand - diastole time perfusion - BPO2) Heart failure (mechanism unknown, probably related to above) Hyperthyroidism, migraines, stage fright, pheochromocytoma, glaucoma Adverse Effects: 1: Bradycardia CO AV block Orthostatic hypotension Rebound myocardium excitation (d/c over 1-2 weeks) 2: Bronchoconstriction Glycogenolysis inhibited CI: AV block, sinus bradycardia Contraindications/Precautions: Nonselectives are CI asthma, bronchospasms, heart failure Interactions: 1: calcium-channel blockers verapamil (Calan) and diltiazem (Cardizem) intensify effects of -blockers. 2: Insulin prevents glycogenolysis Expected Action:

Lisinopril; Prinivil
Classification: Angiotensin-Converting Enzyme (ACE) Inhibitors

Expected Dose/Route: Initial: 10 mg/day; increase doses 5-10 mg/day at 1- to 2-week intervals; Action: maximum daily dose: 40 mg
Block production of angiotensin II arteriole vasodilation, excretion of Na+ and H2O, retention of K+, and possible pathological changes to vessels and heart

Therapeutic Uses:
Treatment of hypertension, either alone or in combination with other antihypertensive agents; adjunctive therapy in treatment of CHF (afterload reduction); treatment of hemodynamically stable patients within 24 hours of acute myocardial infarction, to improve survival; treatment of acute myocardial infarction within 24 hours in hemodynamically stable patients to improve survival; treatment of left ventricular dysfunction after myocardial infarction

Adverse Effects:

Hyperkalemia

Cough

Neutropenia

Angioedema (swelling in tongue/oropharynx) treat with epinephrine First-dose orthostatic hypotension

Rash & dysgeusia

Implications:
May cause depression in some patients; discontinue if angioedema of the face, extremities, lips, tongue or glottis occurs; watch for hypotensive effects within 1-3 hours of first dose or new higher dose

Education:
Take exactly as directed; do not discontinue without consulting prescriber. Take first dose at bedtime. This drug does not eliminate need for diet or exercise regimen as recommended by prescriber. Do not take potassium supplements or salt substitutes containing potassium without consulting prescriber. May cause dizziness, fainting, lightheadedness (use caution when driving or engaging in tasks that require alertness until response to drug is known); postural hypotension (use caution when rising from lying or sitting position or climbing stairs);

Angiotensin Receptor Blockers (ARBs)

N203 ATI (Unit 6) Cardiovascular System -

(Avapro), candesartan (Atacand), olmesartan (Benicar) Blocks action of angiotensin arteriole vasodilation, excretion of Na+ & H2O, retention of K+ ACE and ARB is that cough and hyperkalemia are not side effects of ARB. hypertension (all) Stroke prevention (losartan) Therapeutic Uses: Mgt of heart failure / mortality prevention after MI (valsartan) Delay progression of diabetic neuropathy (irbesartan, losartan) Angioedema Fetal injury Adverse Effects: Pregnancy (D) CI: Renal stenosis Contraindications/Precautions: Caution Hx of angioedema Antihypertensives Additive effect ARBs Interactions: ARBs can be taken with or without food Education: Should see renal function evidenced by proteinuria

Expected Action:

Proto: Losartan (Cozaar) Others: valsartan (Diovan), irbesartan

Calcium Channel Blockers

N203 ATI (Unit 6) Cardiovascular System -

Proto: nifedipine (Adalat) Others: amlodipine (Norvasc), felodipine (Plendil), nicardipine (Cardene), verapamil (Calan), diltiazem (Cardizem) Nifedipine: vascular Ca2+channelsvasodilation peripheral & arterioles Verapamil, Diltiazem: Above + contractility, HR, AV conduction All: Hypertension All but Felodipine: Angina Therapeutic Uses: Verapamil, Diltiazem: Hypertension, Angina, Dysrhythmias Nifedipine: Tachycardia, peripheral edema, acute toxicity Adverse Effects: Verapamil, Diltiazem: Orthostatic hypotension, peripheral edema, constipation, cardiac suppression, dysrhythmias, acute toxicity Contraindications/Precautions: CI: heart block, hypotension, bradycardia, aortic stenosis, severe heart failure Interactions: Verapamil, Diltiazem: Grapefruittoxicity Digoxin[digoxin] -blockers: HF, AV block, bradycardia Nifedipine: Grapefruittoxicity -blockers: Used to reflex tachycardia Education: Administer IV over 2-3 minutes
Expected Action:

Meds for Hypertensive Crisis

N203 ATI (Unit 6) Cardiovascular System -

Expected Action:

Proto: nitroprusside Others: labetalol (Trandate), diazoxide

(Hyperstat), fenoldopam (Corlopam), trimethaphan (Arfonad)

Direct vasodilation of veins and arteries causing rapid BP (preload/afterload) Hypertensive emergencies Therapeutic Uses: bleeding during surgery by producing controlled hypotension Excessive hypotension Adverse Effects: Cyanide poisoning: risk liver dysfunction; Give slowly (5 mcg/kg/min) along with thiosulfate to deactivate cyanide. Thiocyanate poisoning: Can manifest as altered mental state/psychosis. Avoid prolonged use (>3 d). Plasma thiocyanate should be <0.1 mg/mL Pregnancy (C) Contraindications/Precautions: Discard solutions that are blue, red, or green Education: Protect solutions from light Do not mix other meds nitroprusside.

Organic Nitrates

N203 ATI (Unit 6) Cardiovascular System -

Proto: nitroglycerine Others: isosorbide dinitrate (Imdur) cardiac O2 demand by dilating veins and decreasing venous return (preload) Relaxes or prevents spasms in coronary arteries thus O2 supply Treatment of angina (acute, variant, and prophylaxis) Therapeutic Uses: IV perioperative BP control, HF d/t acute MI Headache Tolerance Orthostatic hypotension Adverse Effects: Reflex tachycardia - give metoprolol (Lopressor) CI: traumatic head injury ICP Contraindications/Precautions: Sildenafil (Viagra)Acute or fatal hypotension Interactions: EtOH, -blockers, Ca-blockers, diuretics additive hypotensive effects Sublingual tab/translingual spray: R onset, S duration Education: Transmucosal: R onset, L duration SR caps: S onset, L duration Transdermal: S onset, L duration (hairless area, min 8 hr/day without med to lower risk of developing tolerance. Topical: S onset, L duration IV: Use glass bottle & mfrs tubing; Start at slow rate (5 mcg/min) Expected Action:

Cardiac Glycosides

N203 ATI (Unit 6) Cardiovascular System -

Expected Action: Therapeutic Uses:

Proto: digoxin

(+) inotropicSV, CO (-) chronotropic > fill time SV, CO Tx of HF Dysrhythmias, A-Fib GI effects CNS effects (fatigue, vision changes) Adverse Effects: Dysrhythmias, cardiotoxicity: risk fromK+, [digoxin], disease CI: v-fib, v-tach, 2/3 blocks Contraindications/Precautions: Quinidine dig toxicity Verapamil [digoxin] Interactions: Sympathomimetics add to inotropic effect Loop & thiazide diuretics K+ risk of digoxin dysrhythmia ACE inhibitors / ARBs risk K+ therapeutic digoxin effects Check apical pulse: hold < 60 (adults), < 70 (kids), < 90 (infants) Education: Therapeutic levels = 0.5-2 ng/mL Treat bradycardia atropine Treat dysrhythmias phenytoin or lidocaine Activated charcoal or cholestyramine can bind digoxin to prevent absorption.

Antidysrhythmics
(Class IA: Na+-Channel Blockers)

N203 ATI (Unit 6) Cardiovascular System -

Sodium channel blockers: procainamide (Pronestyl), Expected Action:

quinidine, disopyramide, tocainide, propafenone Supraventricular tachycardia Atrial flutter

conduction / automaticity / repolarization rate

Therapeutic Uses: Adverse Effects:

Ventricular tachycardia Blood dyscrasias

Interactions:

Atrial fibrillation

Systemic lupus syndrome (resolve with d/c medication) Cardiotoxicity (QRS, QT) CI: Sens. to quinidine, complete block, lupus

Contraindications/Precautions:

Antihypertensives additive hypotensive effect

Anticholinergics anticholinergic effects Antidysrhythmics in therapeutic effects / toxicity potential

Education:

Anticholinergic Effects

N203 ATI (Unit 6) Cardiovascular System -

Dry Mouth Urinary retention Constipation Tachycardia Blurred vision Mydriasis

Antidysrhythmics
(Class IB: Na+-Channel Blockers)

N203 ATI (Unit 6) Cardiovascular System -

Expected Action:

Sodium channel blockers: lidocaine (Xylocaine)

conduction / automaticity / repolarization rate

Therapeutic Uses: Adverse Effects:

Short-term use only for ventricular dysrhythmias Respiratory arrest CI: Stokes-Adams, Complete block Pregnancy (B)

CNS effects (fatigue, paresthesias, seizures)Tx seizures phenytoin (Dilantin)

Contraindications/Precautions: Interactions:

Cimetidine, phenytoin, -Blockers effects of lidocaine.

Education:

Never administer lidocaine that has epinephrine in it.

Loading dose followed by maintenance dose of 1-4 mg/min.

Antidysrhythmics
(Class IV: Ca2+-Channel Blockers)

N203 ATI (Unit 6) Cardiovascular System -

Calcium-channel blockers: verapamil (Calan), Expected Action:

diltiazem (Cardizem) Atrial fibrillation SVT Atrial flutter

force / HR / AV node conduction

Therapeutic Uses: Adverse Effects:

Orthostatic hypotension, peripheral edema, constipation, cardiac suppression, dysrhythmias, acute toxicity
Contraindications/Precautions: Interactions: Education:

CI: heart block, hypotension, bradycardia, aortic stenosis, severe heart failure Digoxin[digoxin] Grapefruittoxicity -blockers: HF, AV block, bradycardia

Antidysrhythmics
(Class III: K+-Channel Blockers)

N203 ATI (Unit 6) Cardiovascular System -

Potassium channel blockers: amiodarone (Cordarone), Expected Action:

bretylium, sotalol, dofetilide

conduction / automaticity / repolarization rate / contractility Conversion of A-fib (oral) Recurrent V-tach Pulmonary toxicity Visual disturbances (can blind) Adverse Effects: Cardiac effects sinus bradycardia & AV block / may cause HF / Hypotension Liver/thyroid dysfunction CNS effects GI effects Phlebitis: Central venous line is indicated Highly Pregnancy (D) Contraindications/Precautions: Toxic CI: AV block, bradycardia, newborns, infants Grapefruit toxicity Cholestyramine [amiodarone] Interactions: Quinidine, procainamide, digoxin, diltiazem, warfarin levels of these -blockers, verapamil, diltiazem bradycardia Diuretics, antidysrhythmics, macrolide antibiotics risk dysrhythmias
Therapeutic Uses:

Recurrent V-fib

Antidysrhythmics
(Endogenous Glucoside)

N203 ATI (Unit 6) Cardiovascular System -

Expected Action:

Endogenous Glucoside: adenosine (Adenocard), ibutilide (Corvert)

conduction through AV node

Therapeutic Uses: Adverse Effects:

Paroxysmal SVT

Wolff-Parkinson Syndrome

Sinus bradycardia, dyspnea, flushed face (usually < 1 min) Pregnancy (C)

Contraindications/Precautions:

CI: 2/3 block, AV block, atrial flutter, atrial fibrillation

Interactions:

Methylxanthines (theophylline, caffeine) Adenosine receptors are blocked Dipyridamole (Persantine) Uptake is blocked leading to effects
Education:

Very short life (< 1 min)

Administer by IV bolus, flushed with NS

Atorvastatin; Lipitor
Classification:Antilipemics HMG CoA Reductase Inhibitors (Statins)

Expected Route/Drug: PO Start with 1040 mg q.d., may increase up to 80 mg/d Action:

LDL by LDL receptors in liver VLDL HDL Promote vasodilation / plaque-site inflammation / thromboembolism risk HDL Therapeutic Uses: 1 hypercholesterolemia Prevention of stroke and coronary events. Myopathy (monitor CK) Peripheral neuropathy Adverse Effects: Hepatotoxicity evidenced by serum transaminase
Implications:
Monitor for therapeutic effectiveness which is indicated by reduction in the level of LDL-C. Lab tests: Monitor lipid levels within 24 wk after initiation of therapy or upon change in dosage; monitor liver functions at 6 and 12 wk after initiation or elevation of dose, and periodically thereafter. Assess for muscle pain, tenderness, or weakness; and, if present, monitor CPK level (discontinue drug with marked elevations of CPK or if myopathy is suspected). Monitor carefully for digoxin toxicity with concurrent digoxin use.

Education:
Report promptly any of the following: Unexplained muscle pain, tenderness, or weakness, especially with fever or malaise; yellowing of skin o eyes; stomach pain with nausea, vomiting, or loss of appetite; skin rash or hives. Do not take drug during pregnancy because it may cause birth defects. Immediately inform physician of a suspected or known pregnancy. Inform physician regarding concurrent use of any of the following drugs: erythromycin, niacin, antifungals, or birth control pills. Minimize alcohol intake while taking this drug. Do not breast feed while taking this drug.

Antilipemics Fibrates

N203 ATI (Unit 6) Cardiovascular System -

Expected Action:

Proto: gemfibrozil (Lopid) Others: fenofibrate (Tricor)

TG by VLDL excretion
Therapeutic Uses: Adverse Effects:

Promote HDL precursor production

plasma VLDL, plasma HDL Gall stones Hepatotoxicity Pregnancy (C) Myopathy Caution statins

Contraindications/Precautions:

CI: liver disorders / severe renal dysfunction / gallbladder disease

Interactions:

Statins myopathy

Cholestyramine absorption

Warfarin risk of bleeding (monitor PT and INR)

Antilipemics Cholesterol Absorption Inhibitor

N203 ATI (Unit 6) Cardiovascular System -

Expected Action:

Proto: ezetimibe (Zetia)

Inhibit absorption of cholesterol secreted in the bile and from food.

Therapeutic Uses: Adverse Effects:

Adjunct to modified diet to help LDL (alone or statin) Well-tolerated no adverse effects Pregnancy (X) Caution breastfeeding

Contraindications/Precautions:

CI: Renal dysfunction

Interactions:

Bile acid sequestrants (cholestyramine) absorption

Use with fibrates (gemfibrozil) risk of gall stones and myopathy Cyclosporine levels of ezetimibe
Education:

Taken once per day without regard to food

Antilipemics
Bile-Acid Sequestrants
N203 ATI (Unit 6) Cardiovascular System -

Expected Action:

Proto: cholestyramine (Questran) Others: colestipol (Colestid)

LDL receptors in liver promotes uptake of serum cholesterol LDL

Therapeutic Uses:

Adjunct with HMG CoA reductase inhibitor (eg atorvastatin) & diet LDL
Adverse Effects:

No systemic effects (not absorbed in GI tract)

Contraindications/Precautions: Interactions:

Constipation

CI: biliary disease or VLDL

Digoxin, warfarin, thiazides, tetracyclines form complexes absorption

Education:

Dissolve in water or applesauce to prevent esophageal irritation or impaction.