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Transcript
Drugs Affecting the
Cardiovascular System
Felix Hernandez, M.D.
Diuretics

Thiazide Diuretics

Chlorothiazide
MOA: inhibits sodium and chloride reabsorption in the
distal tubule
 Indication: is the ideal starting agent for HTN. Is also
used to treat chronic edema and hypercalcuria
 Side Effects: hypokalemia, hyponatremia,
hyperglycemia,
 Contraindications: pregnancy, anuria

Diuretics

Loop Diuretics

Furosemide (Lasix)
MOA: inhibits chloride reabsorption in the thick
ascending loop. Causes high losses of potassium in
the urine.
 Indications: preferred diuretic for patients with a low
GFR and in hypertensive emergencies. Is also used
for edema and to lower serum potassium levels
 Side Effects: hyponatremia, hypokalemia,
hypocalcemia, dehydration, hypotension, ototoxicity
 Contraindications: anuria and electrolyte depletion

Diuretics

Potassium Sparing Diuretics

Amiloride





MOA: directly increases sodium excretion and decreases
potassium secretion in the DCT
Indications: used in conjunction with other diuretics to treat
HTN
Side Effects: Hyperkalemia, glucose intolerance in DM patients
Has a more rapid onset than Spironolactone
Spironolactone (Aldactone)



MOA: Antagonist of Aldosterone
Indications: Used with thiazides for edema related to CHF,
cirrhosis and nephrotic syndrome. Also used to diagnose and
treat hyperaldosteronism
Side Effects: Same as Amiloride plus endocrine imbalances
(hirsutism, oily skin, acne)
Diuretics

Osmotic Diuretics

Mannitol
MOA: osmotically inhibits sodium and water
reabsorption
 Indications: ARF, brain edema, removing OD of some
drugs
 Side Effects: headache, dizziness, polydipsia,
confusion, chest pain

Presynaptic Adrenergic Blockers


Clonidine  alpha 2
Methyldopa  methylnorepinephrine
Peripheral Anti-adrenergics

Reserpine




MOA: partially depletes catecholamine stores in
the PNS and CNS causing a decrease in TPR, HR
and CO
Indications: seldom used for mild to moderate
HTN
Side Effects: parasympathetic predominance
Contraindications: CHF, asthma, bronchitis, PUD,
depression. All related to the parasympathetic
predominance
Alpha and Beta Blockers

Alpha-1 Blockers



Prazosin
Doxazosin (Cardura)
Mixed alpha and beta blockers


Labetolol
Carvedilol (Coreg)


Can cause further suppression of a failing heart
Beta Blockers

Atenolol



Preferentially blocks Beta-1 receptors
Metoprolol (Lopressor)
Timolol
Vasodilators

ACE Inhibitors





MOA: Inhibit angiotensin converting enzyme in the lung
which reduces the production of angiotensin II a
vasoconstrictor. Also suppresses aldosterone.
Indications: HTN, DOC for HTN with DM, CHF, MI for
reperfusion
Side Effects: first dose hypotension, dizziness, dry
hacking cough
Contraindications: pregnancy, bilateral renal artery
stenosis
Drugs:



Captopril
Lisinopril
Enalapril
Vasodilators

Angiotensin Receptor Blockers (ARB)





MOA: antagonist at angiotensin II receptor
Indications: HTN
Side Effects: hypotension and dizziness
Contraindications: pregnancy
Drugs:
Losartan (Cozaar)
 Valsartan (Diovan)

Direct Vasodilators

Hydralazine

MOA: relaxes arterioles (not veins) independent
of sympathetic interactions.




Causes a decrease in BP with a reflex tachycardia,
increased CO and increased renal blood flow
Indications: moderate HTN, can be used in
pregnant women with HTN
Side Effects: reflex tachycardia, fluid retention,
Lupus like syndrome, peripheral neuritis with
long term treatment due to vit. B6
Contraindications: patients with ischemic heart
disease
Direct Vasodilators

Nitroprusside




MOA: is converted to nitric oxide which induces
cGMP which then relaxes smooth muscles by
dephosphorylating myosin
Indications: Hypertensive crisis
Side Effects: severe hypotension, cyanide
toxicity and hepatotoxicity
Contraindications: none
Calcium Chanel Blockers

Verapamil (Isopten)




MOA: blocks calcium influx causing dilation of
peripheral arterioles and reducing afterload.
Indications: DOC for acute paroxysmal
supraventricular tachycardia, DOC to slow
ventricular response in A-fib
Side Effects: constipation, hypotension,
bradycardia, edema, dizziness
Contraindications: patients on IV Beta blockers
or Digitalis, A-V node blocks, heart failure,
hypotension
Calcium Chanel Blockers

Diltiazem (Cardizem)




MOA: dilates peripheral arterioles leading to a
decreased afterload, increases oxygen supply to
the myocardium by preventing sympatheticinduced coronary artery spasm.
Indications: reduction of angina episodes,
increased exercise tolerance in stable angina,
HTN
Side Effects: edema, headache, rash
Contraindications: AV node block, SSS,
hypotension, pulmonary congestion
Calcium Chanel Blockers

Nifedipine (Procardia)




MOA: more potent peripheral vasodilation,
doesn’t dilate coronary arteries, causes a reflex
in crease in HR and CO
Indications: no longer used as a single agent
due to toxicity
Side Effects: MI, peripheral edema, pulmonary
edema, transient hypotension, reflex tachycardia
Contraindications: hypotension
Anti-anginal Agents

Nitrates

Nitroglycerin
MOA: dilates large myocardial arteries to increase
blood flow to the heart. Reduces cardiac preload by
reducing venous tone which allows pooling of blood
in the periphery
 Indications: DOC for angina. Used immediately
before exercise or stress to prevent ischemic episodes
 Side Effects: hypotension with rebound tachycardia,
cerebral ischemia, contact dermatitis with
transdermal, aggravation of peripheral edema


Isosorbide Dinitrate
Used for prophylaxis of angina not for acute attacks
 Has a faster onset of action sublingual than oral

Cardiac Glycosides

Digoxin

MOA: inhibits sodium/potassium ATPase and increases
the inward current of calcium. This leads to an increased
contraction, increased CO and decreased heart size,
venous return and blood volume.






Causes diuresis by increased renal perfusion.
Slows ventricular rate in A-fib by increased sensitivity of AV
nodes to vagal inhibition.
Increases peripheral resistance
Indications: heart failure, A-fib, paroxysmal tachycardia
Side Effects: bradycardia, nodal blocks, arrhythmias
Contraindications: V-fib, severe bradyacrdia, allergic
reactions to drug class
Drugs for Lipid Disorders

Cholestyramine



MOA: forms insoluble complexes with bile salts
allowing them to be excreted in feces. The body
compensates by increasing the number of LDL
receptors and oxidizing cholesterol to bile acids
Indications: LDL>190 or 160 with 2 risk factors
Lipid Profile Effects:
decreases TC, and LDL
 Increases Triglycerides, VLDL and HDL

Drugs for Lipid Disorders

Niacin



MOA: unclear, may reduce VLDL synthesis and
secretion
Indications: same as Cholestyramine
Profile changes:
Decreases TC, triglycerides, VLDL, and LDL
 Increases HDL

Drugs for Lipid Disorders

Ezetimibe (Zetia)



MOA: inhibits cholesterol absorption in the GI
Indications: hypercholesterolemia
Profile Changes:
Decreases LDL and triglycerides
 Increases HDL

Statins



MOA: inhibit HMG-CoA reductase in the liver which
is the enzyme that catalyzes the rate limiting step
in cholesterol synthesis.
Indications: Same
Profile Changes:




Decreases TC, LDL, VLDL and Triglycerides
Increases HDL
Side Effects: Myalgia
Drugs:



Simvastatin (Zocor)
Atorvastatin (Lipitor)
Rosuvastatin (Crestor)
Anticoagulants

Heparin




MOA: binds to antithrombin III forming a
complex which then binds to and inhibits
activated clotting factors.
Indications: DVT and PE prophylaxis post-op,
maintaining extracorporeal circulation with open
heart surgery and dialysis, and achieving
immediate anticoagulation
Side Effects: bleeding, hemorrhage,
thrombocytopenia, necrosis at injection site
Notes: Protamine Sulfate inactivates it and can
be used as an antagonist if severe bleeding
occurs. Monitor PTT
Anticoagulants

Warfarin




MOA: antagonizes vitamin K and inhibits the
synthesis of vitamin K dependent clotting factors
(II, VII, IX, and X)
Indications: DVT, IHD, PE, artificial heart valves,
A-fib
Side Effects: bleeding, hemorrhage, necrosis
Notes: Monitor PT
Antiplatelet Agents

Aspirin/Ibuprofen




MOA: inhibits cyclooxygenase thus blocking platelet
aggregation
Indications: to reduce the risk of recurrent TIA or stroke,
reduce risk of MI in patients with unstable angina or
prior infarction
Side Effects: GI ulceration, bleeding hemorrhage
Clopidogrel (Plavix)



MOA: blocks platelet aggregation by inhibiting ADP
receptor
Indications: reduction of atherosclerotic events
Side Effects: neutropenia and same as aspirin
Thrombolytic Agents

Streptokinase



MOA: activates plasminogen to plasmin.
Plasmin digests fribrin and fibrinogen into
degradation products which also cause
anticoagulation by inhibiting the formation of
fibrin.
Indications: to lyse thrombi in ischemic coronary
arteries after infarction. PE, DVT, occluded
cannula
Side Effects: bleeding, bruising, rare but can
have an anaphylactic response (strep toxin)
Thrombolytic Agents

Tissue Plasminogen Activator (TPA)




MOA: binds to fibrin, then activates fibrin-bound
plasminogen to plasmin
Indications: to reperfuse coronary arteries that
are occluded
Side Effects: hematoma at catheterization site
Alteplase/Reteplase



MOA: recombinant form of TPA
Indications: Acute MI, Ischemic stroke, PE
Side Effects: Bleeding