Cardiac Pharmacology Update

Report
 Common
Cardiac Medications by
Class
› Examples
› Mechanism of Action (MOA)
› Side Effects
 Common Interactions
 Questions
Examples:
› Enalapril (Vasotec), Lisinopril (Prinivil/Zestril), Captopril
(Capoten), Benazepril (Lotensin), Fosinopril
(Monopril), Quinapril (Accupril), Ramipril (Altace)
 MOA:
› suppresses the renin-angiotensin-aldosterone system;
prevention of the conversion of Angiotensin I (AT I) to
Angiotensin II (AT II, which is a vasoconstrictor)
 Vasodilation (↓ afterload, ↓ BP);
 Prevents cardiac remodeling after MI (prevent
development heart failure); Renal protective in DM
 Side Effects:
› ↓BP, ↑ K+, Cough, Angioedema, ↑ SCr & BUN,
neutropenia, hepatotoxicity; teratogenic


Examples:
› Candesartan (Atacand), Irbesartan (Avapro),
Losartan (Cozaar), Olmesartan (Benicar),
Telmisartan (Micardis), Valsartan (Diovan)

MOA:
› blocks Angtiotensin II, a vasoconstrictor, at the
receptor sites, effect similar to ACE I
› Vasodilation (↓ afterload, ↓ BP); Prevents cardiac
remodeling after MI (prevent development
heart failure); Renal protective in DM

Side Effects:
› ↓BP, ↑ K+, ↑ SCr & BUN, teratogenic
› Same as ACE-I, except w/o cough

Examples:
› Selective BB
 Metoprolol (Lopressor/Toprol XL), Atenolol
(Tenormin), Betaxolol (Corgard), Bisoprolol
(Zebeta), Nebivolol (Bystolic)
› Non-Selective BB
 Propranolol (Inderal), Labetalol (Trandate),
Carvedilol (Coreg), Nadolol (Corgard)

MOA: ↓HR, ↓BP, and ↓ force of contraction
› Selective BB block the beta1 adrenergic
receptors of the heart—blocking of
catecholemines
› Non-Selective BB blocks both beta1 receptors
(heart) and beta2 receptors (bronchial and
vasculature sites)
 Side
Effects:
› bradycardia, hypotension, masks
symptoms of hypoglycemia, fatigue,
lethargy, wheezing/dyspnea
nightmares, insomnia, impotence
 Non-Selective BB:
 Bronchospasm and vasoconstriction
 Use w/ caution in asthma, COPD, PVD,
DM

Examples:
› Non-Dihydropyridines—Verapamil
(Calan/Covera/Verelan/Isoptin), Diltiazem
(Cardizem/Tiazac/Diltia/Cartia/Diltzac/Dilacor);
› Dihydropyridines—Amlodipine (Norvasc),
Felodipine (Plendil), Isradipine (DynaCirc),
Nicardipine (Cardene), Nifedipine
(Procardia/Adalat), Nisoldipine (Sular)

MOA: ↓ HR, ↓ Contractility, vasodilation
› inhibits influx Ca+ into cardiac and vascular
smooth muscle cells

Side Effects:
› ↓ HR, ↓BP, edema, angioedema, gingival
hyperplasia, HA, flushing, dizziness
› Constipation (verapamil), CHF
exacerbation (verapamil/diltiazem), drug
interactions (verapamil/diltiazem)

MOA:
› Increases force of heart contractions, ↓ HR

Side Effects:
› Manifestations of Toxicity:
 Anorexia, N/V/D, visual changes, arrhythmias
(PVCs), bradycardia
› Increased Risk of Toxicity:
 Renal impairment, low K+/Mg+, elderly,
hypothyroid; Drug interactions
• Examples:
 Loop—
 Furosemide (Lasix), Bumetanide (Bumex), Torsemide
(Demedex), Ethacryinic Acid
 Thiazide—
 Hydrochlorothiazide (HCTZ), Chlorthiazide (Diuril),
Chlorthalidone, Metolazone (Zaroxolyn)
 Potassium Sparing—
 Amiloride, Triamterene;
 Aldosterone Antagonists—
 Spironolatone (Aldactone), Eplerenone (Inspra)
• MOA: eliminates extracellular fluid
 Loop: inhibits Cl- reabsorption in loop of Henle
 Thiazide: inhibits reabsorption of Na+ and water,
vasodilation
 Potassium Sparing: inhibits K+ channels
 Aldosterone Antagonists: block aldosterone
 Loop:
 ↓K+, ↓Na+, ↓Ca+, ↓Mg+; Ototoxicity,
Photosensitivity, Dehydration
 Thiazide:
 ↓K+, ↓Na+, ↓Mg+; Hyperglycemia, ↑
Lipids, ↑Ca+, dehydration
 Triamterene/Amiloride:
 ↑ K+, GI upset, photosensitivity
 Spironolactone, etc.:
 ↑ K+, Gynecomastia, drowsiness, GI
upset
Examples: Hydralazine, Minoxidil
 MOA:

› Relaxation smooth muscle, lowering pressure
needed to push blood through vessels

Side Effects:
› Hydralazine:
 Headache, drug fever, peripheral neuropathy, hepatitis,
skin reactions
› Minoxidil:
 Hair growth, fluid overload, use with BB to prevent reflex
tachycardia

Examples:
› Nitroglycerin, Isosorbide Mononitrate (ISMO,
Monoket, Imdur), Isosorbide Dinitrate (Isordil)

MOA:
› Relaxation of smooth muscle, lowering pressure
needed to push blood through vessels

Side Effects:
› Headache, flushing, hypotension, syncope,
cyanosis (blue) may indicate
methemiglobinemia
Examples
› Alpha-1 Receptor Blocker—Doxazosin, Prazosin,
Terazosin
› Centrally Acting Agents—Clonidine, Methyldopa,
Guanabenz, Guanfacine
 MOA
› Alpha-1 Receptor Blocker
 Peripheral relaxation of smooth muscle causing
vasodilation
› Centrally Acting Agents
 Stimulates alpha-2 adrenergic receptors in brain
causing a peripheral reduction in sympathetic
tone—↓ HR, ↓CO, ↓ peripheral resistance
 Side Effects
› Dizziness, drowsiness, syncope/hypotension,
depression, dry mouth, rebound HTN


Examples
› Aspirin, Clopidrogel (Plavix), Prasugrel
(Effient), Dipyridimole, Ticlodipine (Ticlid)

MOA
› Inhibits platelet aggregation and clot
formation

Side Effects
› Bleeding
› GI upset, thrombocytopenia
Heparin, Enoxaparin (Lovenox), Dalteparin
(Fragmin)
 MOA—disruption of clotting cascade
(antithrombin III)
 Side Effects—bleeding, thrombocytopenia

Warfain (Coumadin)
 MOA—disruption of vitamin K dependent
clotting factors
 Side Effects—bleeding, skin necrosis



Statins (Atorvastatin, Fluvastatin, Lovastatin,
Pravastatin, Rosuvastatin, Simvastatin)
› MOA: blocks cholesterol synthesis and increases
catabolism
› Side Effects: HA, GI upset, elev LFT’s, myopathy,
rhabdomyolysis;
› **New FDA Warning not to exceed 40mg/day
Simvastatin unless previously stable on dose
without side effects. Do not increase patients
beyond 40mg.
Fibric Acid Analogs (Gemfibrozil, Fenofibrate)
› MOA: Decreases VLDL synthesis; increases
VLDL/Triglyceride removal
› Side Effects: elev LFT’s, myopathy, GI upset,
diarrhea, cholelithiasis, rash/itching




Cholesterol Absorption Inhibitor (Ezetimibe)
› Side Effects: headache, angioedema
Omega 3 Fatty Acids (Lovaza)
› Side Effects: halitosis, GI upset, weight gain,
prolonged bleeding time
Niacin
› Side Effects: flushing, itching, GI upset,
hyperglycemia, elev LFT’s, elevated uric acid,
myopathy w/ high dose statins/fibrates
Bile Acid Sequestrants
› Side Effects: GI upset, bloating, constipation,
drug interactions (decreases absorption)


Class Ia Anti-Arrhythmic Agents
Depresses pacemaker rate, conduction and
excitability
› Quinidine
 Side Effects: syncope, TdP, ↓ BP, n/v/d, HA,
dizziness, tinitis, fever, thrombocytopenia
› Procainamide
 Side Effects: hypotension, TdP, SLE, n/v/d,
fever, rash, hepatitis, agranulocytosis, HA,
mood changes

Class Ib—Lidocaine
 Depresses abnormal cardiac activity, shortens
action potential duration, prolongs diastole
(extending time for recovery)
 Side Effects: Hypotension, parasthesias,
nausea, tremor, syncope, hearing
disturbances, slurred speech, seizures

Class Ic—Propafenone
 Similar to Quinidine, weak BB
 Side Effects: metalic taste, proarrhythmias

Class II—Beta-Blockers

Class III
› Amiodarone
 Broad spectrum of activity: lengthens action
potential, weak CCB, non-competitive BB,
alpha-receptor blocker
 Effects: vasodilatation, bradycardia, heart
block, TdP, pulmonary fibrosis, corneal
deposits, visual disturbances, sun sensitivity, skin
discoloration, constipation, hepatic
dysfunction, ataxia, HA, tremor, drug
interactions
• Class III, cont.
› Dronedarone

 Similar to amiodarone
 Effects: bradycardia, TdP, GI upset, weakness,
rash, liver injury, hepatic failure; new agent
› Sotolol
 Non-selective BB, prolongs action potential
 Side Effects: fatigue, bradycardia, dizziness,
dyspnea, proarrhythmias
Class IV—CCBs (Verapamil/Diltiazem)
› Drugs affecting Absorption
 Antibiotics alter GI Flora, affecting Warfarin
› Drugs affecting Protein Binding
› Drugs affecting Metabolism
 Increases Metabolism of Medication
 Rifampin ↑ warfarin metabolism, decreasing INR
 Decreases Metabolism of Medication
 Amiodarone inhibits hepatic enzymes from
metabolizing key medications
› Drugs affecting Excretion
 Amiodarone decreases digoxin clearance

Cialis/Viagra/Levitra potentiate
Nitrates/Vasodilators = Hypotension!
› Important to know if patients are taking
these medications

Warfarin—Everything!
› “the biggies”
 Amiodarone
 Sulfamethoxazole (Septra/Bactrim)
 Metronidazole (Flagyl)
 Quinolones (Cipro, etc)
 Rifampin
Medications
Effect on PT/INR Mechanism
Estrogens, Vitamin K
↓
Methimazole, Propylthiouracil
Barbituates, carbamazepine, chronic ETOH,
dicloxacillin, nafcillin, rifampin, phenytoin
↓
Increased synthesis of clotting factors
Reduced catabolism of clotting
factors
↓
Increased warfarin metabolism
cholestyramine, colestipol, sucralfate
azathioprine, cyclophosphamide, cyclosporine,
mesalamine
↓
Reduced warfarin absorption
↓
thyroid hormones
↑
cetotetan, vitamin E
↑
Broad spectrum antibiotics
acute ETOH, allopurinol, amiodarone, azithromycin,
ciprofloxacin, erythromycin, clarithromycin,
fluconazole, fluorouracil, fluoxetine, ketoconazole,
metronidazole, omeprazole, phenytoin,
sulfamethoxazole, propafenone
acetaminophen, androgens, vitamin C, clofibrate,
corticosteroids, gemfibrozil, statins
↑
Unexplained
Increased catabolism of clotting
factors
Decreased synthesis of clotting
factors
Impaired Vitamin K production by GI
flora
↑
Decreased warfarin metabolism
↑
Unexplained
aspirin, clopidrogel, NSAIDs, SSRIs, ticlodipine
0
Increased bleeding risk

NSAIDs & ACE-I
› Can reduce the antihypertensive effect of
ACE-I or cause/worsen renal failure

Digoxin & Amiodarone
› May need less digoxin if on chronic
amiodarone

Drugs prolonging QT interval
› Can cause arrhythmia when combined with
other drugs prolonging QT interval
Anti-arrhythmic medications known to prolong QT
Interval
› Amiodarone
› Dofetilide
› Procainamide
› Quinidine
 Other medications with potential to prolong QT Interval
› Droperidol
› Erythromycin
› Clarithromycin
› Haloperidol
› Methadone
› Ziprasidone
› Many others…


????

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