ATI Pharmacology Cardiovascular

Mechanisms regulating blood pressure
• 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 (Catecholamine Adrenergic Agonist)
Expected Action: • Binds to: α1 : vasoconstriction / β1 : Increased HR, contractility, & AV conduction
β2 –> Bronchodilation
Therapeutic Uses: • decreased absorption of local anesthetics or extravasated meds
• Manage superficial bleeding • decreased congestion of nasal mucosa • increased BP
• Treatment of AV block and cardiac arrest • Asthma
Adverse Effects: • Hypertensive crisis • Necrosis from extravasation
• Dysrhythmias / increased myocardial O2 demand leads to angina
Contraindications/Precautions: Pregnancy (C)
Interactions: • MAOIs = increased effect and duration • TCAs block uptake of epi.
• General anesthetics –> lead heart to be hypersensitive to epi which lead to dysrhythmias
• α-adrenergic blockers (phentolamine) • β-adrenergic blockers (propanolol)
Education: Stop infusion with evidence of extravasation; treat with α-blocker (phentolamine)

Dopamine
Expected Action:
• Low Dose (Dopamine receptors) –> Renal vasodilation
• Mod Dose (Dopamine, β1) –> Above + increased HR, increased contractility, increased AV conduction
• High Dose (Dopamine, β1, α1) –> Above + vasoconstriction
Therapeutic Uses: • Shock • Heart failure
Adverse Effects: • Necrosis can occur from extravasation of high doses
• Dysrhythmias / increased myocardial O2 demand –> angina
Contraindications/Precautions: Pregnancy (C) + Pheochromocytoma
Education: Stop infusion with evidence of extravasation; treat with α-blocker (phentolamine)

Adrenergic Receptor
α1 = Vasoconstriction of arterioles in skin, viscera, and mucous membranes, and veins
β1 = increased HR, increased contractility, increased AV conduction + Release of renin in kidneys
β2 = 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 (Catecholamine)
Expected Action: Binds to: α1 –> vasoconstriction / β1 –> increased HR, contractility, & AV conduction
β2 –> Bronchodilation
Therapeutic Uses: Heart failure
Adverse Effects: increased heart rate
Contraindications/Precautions: Pregnancy (B)
Education: Stop infusion ĉ evidence of extravasation; treat with α-blocker (phentolamine)

Alpha Adrenergic Blockers
Proto: Prazosin (Minipress) – Others: doxazosin mesylate (Cardura), Phentolamine (Regitine), ergotamine tartrate
Expected Action: Selective α1 blockade resulting in venous and arterial dilation
Therapeutic Uses: • Hypertension
• Phentolamine: Extravasation of adrenergic agonists
• Doxazosin mesylate: decreased symptoms of benign prostatic hypertrophy
Adverse Effects: First-dose orthostatic hypotension (monitor BP for 2 hrs post-treatment)
Contraindications/Precautions: Pregnancy (C)
Interactions:
• Antihypertensives additive hypotensive effect
• NSAIDs / clonidine antihypertensive effects of prazosin

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

Beta Adrenergic Blocker
Proto: Cardioselective: metoprolol (Lopressor), Nonselective: propanolol (Inderal) – Others: Cardioselective: atenolol, Nonselective: nadolol (Corgard)
Expected Action: • β1-adrenergic blockade –> decreased HR, decreased contractility, decreased AV conduction
Therapeutic Uses: • Hypertension • Dysrhythmias (block SA/AV cond.)
• Angina/MI (decreased O2 demand – increased diastole time // increased perfusion – decreased BP –> decreased O2)
• Heart failure (mechanism unknown, probably related to above)
• Hyperthyroidism, migraines, stage fright, pheochromocytoma, glaucoma
Adverse Effects: •
β1: • Bradycardia • decreased CO • AV block • Orthostatic hypotension
• Rebound myocardium excitation (d/c over 1-2 weeks)
β2: • Bronchoconstriction • Glycogenolysis inhibited
Contraindications/Precautions: • CI: AV block, sinus bradycardia
• Nonselectives are CI ĉ asthma, bronchospasms, heart failure
Interactions:
• β1: calcium-channel blockers verapamil (Calan) and diltiazem (Cardizem) intensify effects of β-blockers.
• β2: Insulin – prevents glycogenolysis

ACE Inhibitors
Proto: captopril (Capoten) — Others: enalapril (Vasotec), fosinopril (Monopril), lisinopril (Prinivil), ramipril (Altace)
Expected Action: • 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: • Heart failure • Hypertension
• MI (decreased risk of HF and mortality) • Peripheral neuropathy
• Ramipril can prevent MI, stroke, or death in high-risk patients
Adverse Effects: • Hyperkalemia • Cough • Neutropenia
• Angioedema (swelling in tongue/oropharynx) – treat with epinephrine
• First-dose orthostatic hypotension • Rash & dysgeusia
Contraindications/Precautions: Pregnancy (D) + bilateral renal stenosis, history of angioedema
Interactions: • Diuretics –> 1st-dose hypotension • Lithium –> increased [Lithium]
• AntihypertensivesAdditive effects • NSAIDs –> decreased antihypertensive eff.
• K+ supplements/K+ sparing diuretics –> hyperkalemia
Education: • Captopril 1 hr ac / others ĉ or ŝ food
• Should see increased renal function evidenced by decreased proteinuria

Angiotensin Receptor Blockers
Proto: Losartan (Cozaar) — Others: valsartan (Diovan), irbesartan (Avapro), candesartan (Atacand), olmesartan (Benicar)
Expected Action • Blocks action of angiotensin –> arteriole vasodilation, excretion of Na+ & H2O, retention of K+
• Change in ACE and ARB is that cough and hyperkalemia are not side effects of ARB.
Therapeutic Uses: • decrease hypertension (all) • Stroke prevention (losartan)
• Mgt of heart failure / mortality prevention after MI (valsartan)
• Delay progression of diabetic neuropathy (irbesartan, losartan)
Adverse Effects: • Angioedema • Fetal injury
Contraindications/Precautions: Pregnancy (D) + Renal stenosis + Caution ĉ Hx of angioedema
Interactions: Antihypertensives –> Additive effect ĉ ARBs
Pt Edu:
• ARBs can be taken with or without food
• Should see increased renal function evidenced by increased proteinuria

Calcium Channel Blockers
Proto: nifedipine (Adalat) — Others: amlodipine (Norvasc), felodipine (Plendil), nicardipine (Cardene), verapamil (Calan), diltiazem (Cardizem)
Expected Action: • Nifedipine: No vascular Ca2+channelsvasodilation peripheral & ♥ arterioles
• Verapamil, Diltiazem: Above + decreased contractility, decreased HR, decreased AV conduction
Therapeutic Uses: • All: Hypertension • All but Felodipine: Angina
• Verapamil, Diltiazem: Hypertension, Angina, Dysrhythmias
Adverse Effects: • Nifedipine: Tachycardia, peripheral edema, acute toxicity
• Verapamil, Diltiazem: Orthostatic hypotension, peripheral edema, constipation, cardiac suppression, dysrhythmias, acute toxicity
Contraindications/Precautions: heart block, hypotension, bradycardia, aortic stenosis, severe heart failure
Interactions: Verapamil, Diltiazem: • Grapefruit –> toxicity • Digoxin[digoxin]
• β-blockers: –> HF, AV block, bradycardia
Nifedipine: • Grapefruit –> toxicity • β-blockers: Used to decrease reflex tachycardia
Education: Administer IV over 2-3 minutes

Meds for Hypertensive Crisis
Proto: nitroprusside — Others: labetalol (Trandate), diazoxide (Hyperstat), fenoldopam (Corlopam), trimethaphan (Arfonad)
Expected Action: • Direct vasodilation of veins and arteries causing rapid decrease in BP (preload/afterload)
Therapeutic Uses: • Hypertensive emergencies •
• decrease bleeding during surgery by producing controlled hypotension
Adverse Effects: • Excessive hypotension •
• Cyanide poisoning: increases risk ĉ 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 Contraindications/Precautions: Pregnancy (C) Education: • Discard solutions that are blue, red, or green • Protect solutions from light • Do not mix other meds ĉ nitroprusside.

Organic Nitrates
Proto: nitroglycerine — Others: isosorbide dinitrate (Imdur)
Expected Action: •decreased cardiac O2 demand by dilating veins and decreasing venous return (preload)
• Relaxes or prevents spasms in coronary arteries thus increasing O2 supply
Therapeutic Uses: • Treatment of angina (acute, variant, and prophylaxis)
• IV perioperative BP control, HF d/t acute MI
Adverse Effects: • Headache • Tolerance • Orthostatic hypotension
• Reflex tachycardia – give metoprolol (Lopressor)
Contraindications/Precautions: traumatic head injury –> increased ICP
Interactions: • Sildenafil (Viagra) –> Acute or fatal hypotension
• EtOH, β-blockers, Ca-blockers, diuretics – additive hypotensive effects
Education: • Sublingual tab/translingual spray: R onset, S duration
• 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 & mfr’s tubing; Start at slow rate (5 mcg/min)

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

Antidysrhythmia (Class IA: Sodium Channel Blockers)
Sodium channel blockers: procainamide (Pronestyl), quinidine, disopyramide, tocainide, propafenone
Expected Action: decreased conduction / increased automaticity / decreased repolarization rate
Therapeutic Uses: • Supraventricular tachycardia • Atrial flutter
• Ventricular tachycardia • Atrial fibrillation
Adverse Effects: Systemic lupus syndrome (resolve with d/c medication)
• Blood dyscrasias • Cardiotoxicity (increased QRS, increased QT)
Contraindications/Precautions: Sens. to quinidine, complete ♥ block, lupus
Interactions: • Antihypertensives –> additive hypotensive effect
• Anticholinergics –> increased anticholinergic effects
• Antidysrhythmics –> increase in therapeutic effects / increased toxicity potential

Anticholinergic effects
• Dry Mouth
• Urinary retention
• Constipation
• Tachycardia
• Blurred vision
• Mydriasis

Lidocaine [Xylocaine] (Antidysrhythmias)
Expected Action:decreased conduction / decreased automaticity / increased repolarization rate
Therapeutic Uses: Short-term use only for ventricular dysrhythmias
Adverse Effects: • Respiratory arrest
• CNS effects (fatigue, paresthesias, seizures)-Tx seizures ĉ phenytoin (Dilantin)
Contraindications/Precautions: Stokes-Adams, Complete ♥ block
and Pregnancy (B)
Interactions:
• Cimetidine, phenytoin, β-Blockers –> increased effects of lidocaine.
• Never administer lidocaine that has epinephrine in it.
• Loading dose followed by maintenance dose of 1-4 mg/min.

Calcium Channel Blockers (Antidysrhythmias)
Calcium-channel blockers: verapamil (Calan), diltiazem (Cardizem)
Expected: •decreased force / decreased HR / decreased AV node conduction
Therapeutic Uses: • Atrial fibrillation • SVT • Atrial flutter
Adverse Effects: Orthostatic hypotension, peripheral edema, constipation, cardiac suppression, dysrhythmias, acute toxicity
Contraindications/Precautions: heart block, hypotension, bradycardia, aortic stenosis, severe heart failure
Interactions: • Digoxin –> increased[digoxin] • Grapefruit –>toxicity
• β-blockers:–> HF, AV block, bradycardia

Potassium Channel Blockers (Antidysrhythmias)
Potassium channel blockers: amiodarone (Cordarone), bretylium, sotalol, dofetilide
Expected Action: decreased conduction / decreased automaticity / decreased repolarization rate / decreased contractility
Therapeutic Uses: • Conversion of A-fib (oral)
• Recurrent V-fib • Recurrent V-tach
Adverse Effects: • Pulmonary toxicity • Visual disturbances (maybe blindness)
• Cardiac effects –> sinus bradycardia & AV block / may cause HF / Hypotension
• Liver/thyroid dysfunction • CNS effects • GI effects
• Phlebitis: Central venous line is indicated
Contraindications/Precautions: ****Pregnancy (D)**** (highly toxic)
• CI: AV block, bradycardia, newborns, infants
Interactions: • Grapefruit –> toxicity • Cholestyramine –> decreased [amiodarone]
• Quinidine, procainamide, digoxin, diltiazem, warfarin –> increased levels of these
• β-blockers, verapamil, diltiazem –> bradycardia
• Diuretics, antidysrhythmics, macrolide antibiotics –> increased risk dysrhythmias

Endogenous Glucoside (Antidysrhythmia)
Endogenous Glucoside: adenosine (Adenocard), ibutilide (Corvert)
Expected Action: decreased conduction through AV node
Therapeutic Uses: • Paroxysmal SVT • Wolff-Parkinson Syndrome
Adverse Effects: • Sinus bradycardia, dyspnea, flushed face (usually < 1 min) Contraindications/Precautions: • Pregnancy (C) • CI: 2/3º block, AV block, atrial flutter, atrial fibrillation Interactions • Methylxanthines (theophylline, caffeine) --> Adenosine receptors are blocked
• Dipyridamole (Persantine) –> Uptake is blocked leading to increased effects
Education: Very short life (< 1 min) + Administer by IV bolus, flushed with NS

HMG CoA Reductase Inhibitors (Statins) (Anti-lepemics)
Proto: atorvastatin (Lipitor) — Others: simvastatin (Zocor), lovastatin (Mevacor), pravastatin (Pravachol), rosuvastatin (Crestor)
Expected Action: • decreased LDL by increased LDL receptors in liver • decreased VLDL • increased HDL
• Promote vasodilation / decreased plaque-site inflammation / decreased thromboembolism risk
Therapeutic Uses: • 1º hypercholesterolemia • increased HDL
• Prevention of stroke and coronary events.
Adverse Effects: • Myopathy (monitor CK) • Peripheral neuropathy
• Hepatotoxicity evidenced by increased serum transaminase
Contraindications/Precautions: • Pregnancy (X) No rosuvastatin in Asians
• CI: Pregnant / viral or EtOH hepatitis • Caution ĉ ketoconazole
Interactions: • Fibrates –> increased risk of myopathy
• Med that suppress CYP3A4 (ketoconazole, erythromycin) –> increased statin levels
• Grapefruit juice and (lovastatin or simvastatin) –> Toxicity
Education: • Lovastatin ĉ evening meal (others OK ŝ food)
• Atorvastatin or fluvastatin should be used with renal insufficiency

Fibrates (Anti-lipemics)
Proto: gemfibrozil (Lopid) — Others: fenofibrate (Tricor)
Expected Action: •decreased Triglycerides by increased VLDL excretion • Promote HDL precursor production
Therapeutic Uses: •decreased plasma VLDL, increased plasma HDL
Adverse Effects: • Gall stones • Hepatotoxicity • Myopathy
Contraindications/Precautions: • Pregnancy (C) • Caution ĉ statins
• CI: liver disorders / severe renal dysfunction / gallbladder disease
Interactions: • Statins–> increased myopathy • Cholestyramine –> decreased absorption
• Warfarin –> increased risk of bleeding (monitor PT and INR)

Ezetimbie (Zetia) (Cholesterol Absorption Inhibitor)
Expected Action: Inhibit absorption of cholesterol secreted in the bile and from food.
Therapeutic Uses: • Adjunct to modified diet to help decrease LDL (alone or ĉ statin)
Adverse Effects: • Well-tolerated – no adverse effects
Contraindications/Precautions: • Pregnancy (X) • Caution ĉ breastfeeding
• CI: Renal dysfunction
Interactions: Bile acid sequestrants (cholestyramine) –> decreased absorption
• Use with fibrates (gemfibrozil) –> increased risk of gall stones and myopathy
• Cyclosporine –> increased levels of ezetimibe
Education: Taken once per day without regard to food

Bile Acid Sequestrants
Proto: cholestyramine (Questran) — Others: colestipol (Colestid)
Expected Action: •increased LDL receptors in liver promotes uptake of serum cholesterol –> decreased LDL
Therapeutic Uses: Adjunct with HMG CoA reductase inhibitor (eg atorvastatin) & diet –> decreased LDL
Adverse Effects: Constipation
Contraindications/Precautions: biliary disease or increased VLDL
Interactions: Digoxin, warfarin, thiazides, tetracyclines –> form complexes decrease absorption
Education: Dissolve in water or applesauce to prevent esophageal irritation or impaction.

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Pain and inflammation • Analgesics relieve pain • Narcotics / NSAIDs / Antimigraine agents • Anti-inflammatory medications relieve inflammation • Salicylates / Glucocorticoids / Antigout / Disease-modifying antirheumatics drugs (DMARDs) • Some are antipyretic (salicylates, ibuprofen) • Salicylates and NSAIDs …

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