CARDIOVASCULAR

PHARMACOLOGY
A Study Guide

Pharmacology
Touro College of Osteopathic
Medicine

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 FACULTY
Arthur Prancan, Ph.D., Course Director
329 Touro College Building (646) 981-4612
Arthur.Prancan@touro.edu

Kamilah Ali, Ph.D., Assistant Professor

442 Touro College Building (646) 981-4614
Kamilah.Ali6@touro.edu

Clifford Knapp, Ph.D., Associate Professor

60 Prospect Avenue, 845-648-1000, ext. 60257
Clifford.Knapp@touro.edu

Tanchun Wang, Ph.D., Assistant Professor

60 Prospect Avenue, 845-648-1000, ext. 60228
Tanchun.wang4@Touro.edu

STUDY GUIDE CONTENTS

1. Essential Objectives for Focused Learning p. 3
2. Diuretics p. 4
3. ACE Inhibitors, ARBs, and Aliskiren p. 10
4. Vasodilators p. 13
5. Calcium Channel Blockers p. 14
6. Angina Pectoris p. 14
7. Molecular Mechanisms of Arrhythmias p. 16
8. Antiarrhythmic Drugs p. 23
9. Sympatholytics p. 29
10. Acute Myocardial Infarction p. 36
11. Congestive Heart Failure p. 42
12. Antihypertensive therapy p. 45
13. Hyperlipidemia p. 46
14. Study Objectives p. 48
15. Study Quiz p. 50

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 Essential Objectives for Focused Learning

Drug Classification

Drug Mechanism of Action

Mechanism of Usefulness

Mechanism of Toxicity

Drug Classification

All drugs belong to a GROUP

Identify a group according to chemical characteristics, mechanism of action or

clinical application

Learn the drug classes and individual drugs in the group

Then, a subsequent review can have an end point, establishing confidence.

Mechanism of Action

Each drug involves itself in the biology of the patient or infective agents

Identify EXACTLY what the drug does

This may not be the mechanism of usefulness, but it can start the ball rolling in the
right direction

EVERYONE WILL DETERMINE WHETHER OR NOT YOU KNOW THIS!

Mechanism of Usefulness

This will differ with the disease

For each application, how does the mechanism of action become useful?

This is also known as THERAPY

Mechanism of Toxicity

All drugs can cause trouble

Many side effects are simply TOO MUCH THERAPY

Additional side effects must be learned

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 DIURETIC AND ANTIDIURETIC MOA, USE, TOXICITY

Subclass, Site of Action MOA, Use Major Usefulness

DRUGS Major Toxicities
Carbonic Anhydrase Blocks carbonic Tox: Systemic acidosis
Inhibitor anhydrase, blocks
Proximal Tubule Urinary alkalosis
reentry of bicarbonate
and sodium
Acetazolamide Uses:
Methazolamide Glaucoma, Altitude
sickness Alkalinization
of urine
Loop Diuretics Inhibition of the Na+ - Hypokalemia, Metabolic
Ascending Loop of K+ -2Cl- cotransport alkalosis
Henle system
Rapid hypovolemia
20 to 30% of the
Ototoxicity by
Furosemide filtered Na+
Ethacrynic Acid may be
Torsemide reabsorption may be irreversible (Therefore,
Bumetanide blocked limited use)
Ethacrynic Acid Hyperuricemia
Torsemide is longer
acting than furosemide. Diabetogenic
Bumetanide is 40x hyperglycemia
more potent than Cross-sensitive to other
furosemide. sulfonamide derivatives
(Furosemide, Torsemide
Use: CHF, edema, and Bumetanide)
hypertension,
Hypocalcemia
hypercalcemia
Thiazides Inhibition of Na+-Cl- Hypokalemia and
Distal convoluted cotransport alkalosis
tubule Hyperuricemia

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 Use: Hypertension, Hyperglycemia
Hydrochlorothiazide CHF, osteoporosis,
Increase of plasma
Indapamide nephrogenic diabetes cholesterol and
Chlorthalidone insipidus triglycerides
Sulfa sensitivity,
Photosensitivity, skin
rash
Hypercalcemia
Potassium-sparing Uses: Antagonize
Late distal tubule and Spironolactone is an aldosterone during
collecting duct aldosterone antagonist renin-angiotensin
and androgen hypertension and
Spironolactone and congestive heart failure.
antagonist.
Eplerenone (less Combine with Loops or
androgenic) Thiazides to offset
Triamterene and
Amiloride and hypokalemia.
amiloride
Triamterene Block sodium
transport, and retain Tox: Hyperkalemia and
potassium. Acidosis
Osmotic It is filtered at the Tox: Hyponatremia and
Mannitol glomerulus but poorly acute hypovolemia.
reabsorbed from the Hypotension
tubule. Thus mannitol
Use: Cerebral edema,
holds water in the
renal failure maintain
lumen by virtue of its
volume, dilute toxic
osmotic effect.
drugs.

ADH Agonists Vasopressin(ADH): V1, Tox:

(Antidiuretics) V2; V1 is arterial Vasospasm,
Vasopressin(ADH) vasoconstriction. hypertension, coronary
Desmopressin ischemia and anginal
Desmopressin
pain are likely with
:V2>>>>V1

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Use: Both reduce urine vasopressin, not
volume. Desmopressin desmopressin.
preferred for
nephrogenic diabetes
insipidus no
vasoconstriction. V2
only.

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 Mechanisms for Side Effects of Diuretics

A. Hypokalemia and Alkalosis (Loops and Thiazides)

Nephron NaCl
Blood
Blood
Cell HOH

Na+ Na+
Na+
K+,H+
K+, H+ K+,H+
Hypokalemia Urine
Alkalosis

This happens in the Collecting Tubule when a diuretic (Loop or

Thiazide) sends a load of sodium downstream. The greater recovery
of sodium is exchanged for potassium and hydrogen ion, leaving loss
of potassium from plasma and increased pH.

B. Hyperkalemia and Acidosis (Spironolactone, Amiloride and

Triamterene)

The opposite of A (above) can happen when these drugs prevent

sodium recovery at the same site. Because no potassium is lost, they
are classified as Potassium Sparing. These drugs are useful in two
ways: 1) Aldosterone antagonist (Spironolactone) when aldosterone
is known to be involved, as in congestive heart failure. Aldosterone
promotes sodium recovery. 2) Prevent hypokalemia and alkalosis
when used in combination with Loop or Thiazide diuretics (Amiloride
or Triamterene).
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C. Sulfa-sensitivity (Acetazolamide, most Loops, all Thiazides)

Sulfonamide structure drugs share cross allergenicity. Symptoms can

be photosensitivity, generalized dermatitis (rash), hemolytic anemia,
thrombocytopenia and acute necrotizing pancreatitis.

D. Hyperglycemia (Loops and Thiazides)

This problem is partly or mostly due to the structural similarity

between vasodilators that open potassium channels (Diazoxide) and
diuretics. The Beta-Islet Cell of the pancreas is continuously
stabilized by potassium conductance (in to out) at a potassium
channel, which can be closed by metabolic signaling when the plasma
glucose concentration becomes elevated. At that time, a calcium-
mediated signal is allowed to release insulin. Diuretic-related
maintenance of a open Beta-Cell potassium channel results in a higher
rate of potassium conductance and a more stable cell, which requires
much higher glucose concentration in the plasma to activate release of
insulin hyperglycemia.

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E. Hypovolemia and Hyponatremia (Loops and Thiazides)

Loss of sodium is the primary mechanism for the loss of extracellular

fluid, which is quickly seen as a shrinking plasma volume. As long as
the loss of sodium is balanced by fluid loss, the concentration of
sodium remains in the normal range.

Big However, excessive and rapid decrease in volume triggers ADH

(Vasopressin, Antidiuretic Hormone) release, causing water recovery
at the collecting duct. Also, these conditions activate an intense thirst
mechanism, driving the patient to consume a limitless quantity of
water. Now we have a serious expansion of plasma volume with no
additional sodium intake. The outcome is dilutional hyponatremia,
which can quickly lead to irritability, confusion, N/V, ventricular
arrhythmias, convulsions, stupor, coma and death. Limiting water
intake in these patients is critical. In non-drug treated individuals, this
same scenario can take place during extreme physical exercise, during
which sodium is lost through sweat and water intake is not controlled.

F. Hyperuricemia (Loops and Thiazides)

These drugs enter the nephron via the organic acid excretion site in
the proximal tubule. That is where organic acids from filtered plasma
must enter the nephron, as well. Competition for these sites causes
accumulation of uric acid, causing hyperuricemia and contributing to
exacerbation of gouty arthritis. Other acids that do this: Lactic acid
during alcohol metabolism. Salicylic acid following deacetylation of
acetylsalicylic acid (aspirin). Gout-related ankle pain can become
worse when alcohol or aspirin are used to suppress the symptoms.

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 ANGIOTENSIN CONVERTING ENZYME INHIBITORS
ANGIOTENSIN RECEPTOR BLOCKERS (ARBs) and ALISKIREN

Here are two classes of drugs which are used to treat high blood pressure and
congestive heart failure. The ACE inhibitors (ACEI) prevent synthesis of
angiotensin II while preserving bradykinin. Angiotensin II antagonists block
the receptor. The value of these drugs lies in their focus on a system that
offers compensatory regulation of vascular resistance, extracellular water
volume and the sympathetic nervous system.

ACE Inhibitors
ACE Inhibitor Subclass The ACE Inhibitors

Direct-acting drugs Captopril and Lisinopril

Prodrugs Enalapril, Ramipril, Quinapril,

Benazepril, Fosinopril., Perindopril,
Zofenopril

Active metabolites Enalaprilat, Ramiprilat

Sulfur containing drugs Captopril, Zofenopril

ACTIONS OF ANGIOTENSIN II

1. Vasoconstriction. Angiotensin directly causes vascular smooth muscle to

contract. The
angiotensin II receptor on the arteriole (AT-1) is coupled to the Gq regulatory
protein
and phospholipase C, the effector, which mediates generation of inositol
triphosphate(IP3) and
diacylglycerol (DAG). Smooth muscle contraction proceeds as it does for M3 and
Alpha-1 receptor sites.
2. Aldosterone release. Adrenocortical zona glomerulosa is stimulated by
angiotensin II to cause increased synthesis of aldosterone. The resulting

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conservation of sodium at the renal collecting tubule produces increased
extracellular and blood volume, and may cause loss of potassium.

3. Antidiuretic hormone release. Water recovery at vasopressin (ADH) receptor

sites in the collecting tubule contributes to vascular volume expansion.

4. Sympathetic Nervous System activation. Sympathetic ganglia, neurons and

the adrenal medulla are directly activated by angiotensin II.

5. Hypertension. Add up all of the above.

ACTIONS OF BRADYKININ

1. Vasodilation. Bradykinin is a powerful (10x histamine) arteriolar vasodilator.

This action is mediated by nitric oxide and perhaps by prostaglandins E2 and I2.
Therapeutic Benefit, Decreases Blood Pressure.

2. Inflammation. This peptide can produce all signs of inflammation, including

localized edema and pain. Angioedema: use ARB.

3. Smooth muscle contraction. Respiratory structures respond to bradykinin.

Bronchoconstriction, cough and aggravation of asthma are probable outcomes.
Cough: use ARB.

CLINICAL USEFULNESS OF ANGIOTENSIN CONVERTING ENZYME

INHIBITORS

1. Lower blood pressure in hypertensive patients who have elevated renin.

2. Identify responsive hypertensives who do not have elevated renin.

3. Improve congestive heart failure.

Note: Clinical benefits are due to decreased angiotensin II, increased

bradykinin and decreased aldosterone and vasopressin.

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POTENTIAL TOXICITIES OF THE ACE INHIBITORS

1. Cough is caused by bradykinin stimulating bronchi. It is intractable and

progressively worsens over a long course of drug administration. Discontinuation
of the drug reverses this symptom.

2. Hypotension can occur immediately following introduction of ACE inhibitors

to a patient. This is especially likely to happen if the patient is hypovolemic due to
diuretics or salt restriction as in antihypertensive therapy or during management of
congestive heart failure. Under these conditions the blood pressure may bepropped
up by angiotensin II, alone.

3. Acute renal failure is associated with ACE inhibitors in patients with bilateral
renal artery stenosis.

4. Hyperkalemia is probably associated with a decrease of aldosterone

5. Angioedema is caused by bradykinin. Note: Toxicities are due to

decreased angiotensin II,
6. Altered taste and allergic skin rash.
increased bradykinin and
CONTRAINDICATIONS decreased aldosterone.

1. Pregnancy (second and third trimester). These drugs risk fetal renal failure and
hypotension.

2. Renal insufficiency may be associated with neutropenia and proteinuria.

ANGIOTENSIN II RECEPTOR BLOCKERS (ARBs)

The Drugs: Losartan (Cozaar), Valsartan (Diovan), Candesartan (Atacand)

Irbesartan (Avapro) , Telmisartan (Micardis) - plus others.

These drugs are angiotensin II antagonists at the AT-1 receptor, and can be used to
prevent or reverse AII actions at all sites of angiotensin action. Primary usefulness
is antihypertensive with some benefits seen in diabetic nephropathy and congestive
heart failure.

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Side Effects: Because bradykinin is inactivated in the usual way, some side
effects associated with ACE inhibitors are not seen. No angioedema, no cough.
This is an advantage in some patients. All other actions listed for ACE Inhibitors
are seen with ARBs.

RENIN ANTAGONIST

Aliskiren

MOA: Binds renin. Renin, a peptidase, is unable to convert Angiotensinogen to

Angiotensin I. Therefore, no A II.

Diuretics, ACE Inhibitors and Angiotensin Receptor Blockers reduce blood

pressure, but increase renin release. Therefore, adding a direct renin blocker may
suppress the renin increase which opposes antihypertensive drug action.

Toxicity: Same toxicities and pregnancy caution as ACEIs and ARBs.

Vasodilators
Drug MOA Use Toxicity
Hydralazine Unknown Powerful Hypotension, headache,
Arteriole decrease in dizzy, high HR, chest pain,
Blood Pressure Drug-induced lupus
Minoxidil Open K+ Same Never alone due to potent
Channel hypotension and reflexive
Arteriole tachycardia, chest pain
Use with Beta Blocker
Hypertrichosis
Diazoxide Open K+ Same Hypotension, tachycardia,
Channel chest pain, hyperglycemia
Arteriole (see open K+ channel in
Beta Islet Cell)
Hypertrichosis
Sodium Nitric Oxide Unstable, short- Many of the above, except
Nitroprusside (NO) acting, iv for no hair growth. Mostly
Venules high BP low BP, high HR, dizziness,
Arterioles emergency. headache.
Fenoldopam D1 agonist Improves
Decreases

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 arteriolar
resistance

Calcium Channel Blockers

Drug MOA Use Toxicity
Dihydropyridines: Block L Vasodilator Only Hypotension,
Nifedipine Type Antihypertensive Hyperglycemia
Amlodipine Calcium Antianginal Reflexive tachycardia
Plus approx. 20 Channel Possible angina
Arteriole pectoris
Only Possible MI
Verapamil Block L Vasodilator Hypotension
Diltiazem Type Antihypertensive No Reflexive
Calcium Antianginal tachycardia
Channel Antiarrhythmic (Blocks Cardiac
Arteriole Calcium)
and Heart Cardiac Depression
SA Node is slowed
(lower slope on Phase
4)
AV Node depression

DRUGS FOR ANGINA PECTORIS

Drug Class
Drugs MOA Use Toxicity
NITRATES Donate Typical Hypotension
Short acting (min): Nitric Oxide Angina Headache
Nitroglycerin, sublingual (NO) Less Tachycardia
10-30 Vasodilate Cardiowork Rebound Angina
Isosorbide dinitrate, cheek venules, lower Rapid tolerance
10-60 preload.
Amyl nitrite, inhaled
3-5

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 NITRATES Same Atypical Note: MOA, USE
Long acting (hrs): Prinzmetals and TOXICITY
Nitroglycerin, oral Stop for all
6-8 coronary NITRATES are
Nitroglycerin, dermal spasm the SAME.
3-10
Isosorbide dinitrate, oral
2-6
Isosorbide mononitrate
6-10
BETA BLOCKERS Adrenergic Typical Fatigue
Non-Selective: Beta-1 Angina
Propranolol Receptor Only Drowsiness
Nadolol Less CNS Blocker Avoid in:
depression. (Also Beta-2)
Asthma Cardiac
Pindolol (ISA) No Diabetes depression
rebound, less Decrease HR, Peripheral
cardiodepression. SV Vascular AV Node
(Heart Work) Dis. depression

Cardioselective: Adrenergic Safer in Rebound

Atenolol Beta-1 Asthma, Phenomenon
Metoprolol Receptor Diabetes
Acebutolol (ISA) As Blocker and Vasc.
above. Disease
CALCIUM CHANNEL All: All: Dihydropyridines:
BLOCKERS Block L type Typical Hypotension
Dihydropyridines: calcium Angina Reflexive
Nifedipine channel in Less tachycardia
Amlodipine arterioles. Cardiowork Possible angina
Nicardipine pectoris
Vasodilate. Atypical Possible MI
Lower Prinzmetals
Non-Dihyropyridines afterload. Stop Non-D:
Verapamil coronary Hypotension
Diltiazem Non-D types spasm No Reflexive
also: tachycardia.
Decrease SA Node is slowed
heart work. (lower slope on
Relieve Phase 4)
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 coronary AV Node
vasospasm. depression.

ARRHYTHMIAS

MOLECULAR MECHANISMS of ARRHYTHMIAS

The therapy of arrhythmias targets basic molecular mechanisms in the heart

which underlie both normal and abnormal function. This section reviews the
primary functional mechanisms in the heart and portrays arrhythmias as extensions
of those activities.

Learning Objectives for Arrhythmias and Antiarrhythmics:

1. Identify the terms: automaticity, conduction, refractoriness,

EAD, DAD, reentry.

2. Identify the main ions that are associated with the phases of the
action potential in the pacemaker and in the Purkinje system.

3. Define actions of the SANS and PANS on SA nodal function.

4. Define the effects of the SANS and PANS on AV nodal

function.

5. Define SANS and PANS effects on the ventricles.

6. Describe influences that affect automaticity.

7. Describe afterdepolarizations.

8. Characterize changes in AV nodal conduction.

9. Characterize reentry.

10. List drugs in each class of drugs.

11. Define the specific Mechanism of Action for each class of

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drugs.

12. Define primary uses and contraindications for each class of

drugs.
13.Identify prominent toxicities for each drug class.

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Phase 0 Initiated by opening of sodium channels and entry of sodium into the cell via ion
channels and down a concentration gradient.

Phase 1 Overshoot. Sodium channels close

Phase 2 Calcium channels open and allow calcium entry via ion channels down the concentration
gradient.

Phase 3 Potassium channels open as calcium channels are closing, thereby creating the Phase 2-3
"shoulder". Most of Phase 3 is due to K+ conductance via ion channels
down a concentration gradient.

Phase 4 Potassium remains the major conductive ion as the sodium-potassium pump resets the
concentration gradient for each ion. Also, the Na+-Ca++ antiporter is busy re-
establishing the appropriate Ca+ concentrations.

NOTE: This is a busy phase for the cell, even though it is known as a "resting" phase. The
N+, K+ and Ca++ gradientn are re-established and maintained. A
pacemaker cell, such as SA or AV node, or even a Purkinje cell, is also
busy during Phase 4. This is the spontaneous depolarization phase for
these cells, wherein Ca++ "leaks" across the membrane, depolarizing the
cell until it reaches threshold and spontaneously fires itself. Because the
SA node does this first, it remains the only functional pacemaker in a
normal heart.

(Drawing taken from Katzung, 6th edition, Chapter 14)

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 ANTIARRHYTHMIC DRUGS

Class Mechanism Prototype Analogs

+
Ia Block Na Channels Quinidine Procainamide
(Most used) Disopyramide (like Quinidine)
+
Ib Block Na Channels Lidocaine Mexiletine, Tocainide
(Short-acting) Phenytoin (vs Digoxin)
+
Ic Block Na Channels Flecainide Moricizine
(Long-acting)

II Beta Blockers Propranolol Acebutolol, Metoprolol

Atenolol, Esmolol
+
III K Channel Blockers Amiodarone Sotalol
(Increase Action Potential
Duration)
++
IV Ca Channel Blockers Verapamil Diltiazem
(Cardiac and arterial)

Special AV Node Stabilizers Digoxin Adenosine

(Also II and IV)

Class I - SODIUM CHANNEL BLOCKERS

Class Drugs Usefulness/Actions Toxicity
Ia Quinidine Slows conduction vel. M2 block unloads the
Increases Effective AV Node
Refractory Period (ERP) Alpha-1 block, BP
Used for serious atrial down and HR up
arrhythmias Afib. Long Q-T, Torsade
Ia Procainamide Slows conduction vel. Lupus-like syndrome
Ib Lidocaine Short-acting, iv, used for Safe, short action and
V. Tach, extrasystole iv admin. May cause
cardiac depression
Class Drugs Usefulness/Actions Toxicity

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 Ib Phenytoin Increases AV Nodal conduction. So, possible for
Digoxin tox. Dig. Causes AV depression and V.
extrasystole, tachycardia.
Ic Flecainide, Very potent Na blockers. Limited usefulness,
Encainide and My cause Ventricular except in very short
Moriczine Arrhythmias. duration.

Class II BETA BLOCKERS

Class Drugs Usefulness/Actions Toxicity
II Propranolol Nonselective Beta-1 Cardiac depression,
and Beta-2 Rebound Phenomenon,
antagonist Beta-2 block in asthma,
Used for all SA, AV diabetes and peripheral
and V arrhythmias. vascular disease
II Atenolol, po, iv Selective Beta-1 Cardiac depression,
Metoprolol, po, iv antagonists Rebound
Esmolol, iv
II Acebutolol ISA and selective No Rebound

Class III POTASSIUM CHANNEL BLOCKERS

Class Drugs Usefulness/Actions Toxicity
III Amiodarone Blocks K+ channels, Pulmonary fibrosis
Blocks Na+ channels Hypothyroidism due to
Blocks Ca++ channels similarity in structure
Blocks Beta-1 receptors with thyroxine plus a
Used for V. tach, not load of iodine
polymorphic V. tach, A. Blue-grey skin and eye
fib. deposits
Long Q-T, Torsade
III Sotalol Beta-1 and 2 block Cardio depression,
Blocks K+ channels Long Q-T, Torsade

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 Class IV CALCIUM CHANNEL BLOCKERS
Class Drugs Usefulness/Actions Toxicity
IV Verapamil Block calcium channel AV depression
Diltiazem in arteriole, SA, AV, SA asystole
Ventricle. Constipation
Vasodilation, no reflex. Dizzy-low BP
Suppress rate of
conduction at AV node,
protect ventricle during
atrial arrhythmias.
Drug of choice vs AV
origin atrial
tachycardia.

SPECIAL CLASS
Drugs Usefulness Toxicity
Digoxin AV Nodal Depressant Ventricular extrasystoles
Used to protect Ventricle leading to V. tach and fib.
from Atrium during A. AV nodal block
tach, and A. fib. when a
drug may unload the AV
Node.
Adenosine Action = 8 sec. iv to stop Bronchoconstrictor, cough.
A. tach due to reentry in Anti-asthmatic theophylline is
AV Node. an adenosine antagonist

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 ANTIARRHYTHMIC CLINICAL APPLICATION OVERVIEW
1. Impulse-conducting pathways (sodium channel depolarizing cells) in
atrium or ventricle respond to Class I and to Class III. Most
tachycardia is a reentry of the wall in atrium or ventricle. Sodium
channel blockers decrease depolarization velocity and stop the rapid
response to a repeat signal. Potassium channel blockers expand the
Action Potential Duration (APD) to increase Effective Refractory
Period (ERP). The cell is not ready to fire when adjacent cell action is
taking place. In both cases, the rapid recycling of action is extinguished.
2. Arrhythmias of calcium conductance depolarization in SA Node and
AV Node respond to drugs in Class II and Class IV. The nodal
pacemaker tissues depolarize slowly via calcium conductance, driven by
Beta-1 agonists and suppressed by Beta-1 blockers and calcium channel
blockers. Muscarinic agonists also suppress these sites by stimulating
K+ conductance.
3. The Sympathetic Nervous System acts via Norepinephrine at Beta-1
receptors, causing increase in Heart Rate at SA Node, increase in AV
conduction velocity at AV Node and increased ventricular contractility
and arrhythmias. All of these are suppressed by Class II Beta Blockers.

ATRIAL ARRHYTHMIAS
1. Digoxin is used to protect the ventricle by causing AV nodal depression.
Also verapamil or a Beta-Blocker.
2. Ectopic focus or active sites are sodium depolarization actions and are
suppressed by Class Ia.
3. Reentry in the atrium wall is a conducting pathway. Blocked by Class
Ia or by Class III.

SUPRAVENTRICULAR TACHYCARDIA
1. AV Node reentry. AV nodal depressants stop the recycling action:
verapamil (IV), propranolol (II), digoxin or adenosine.
2. AV Node Reciprocating with the Accessory Pathway, Wolff-Parkinson-
White. Avoid AV nodal depression. Avoid the drugs in 1. Use
procainamide (Ia) or cardioversion.

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PREMATURE VENTRICULAR CONTRACTIONS (PVC)
1. Extra Systoles, Early After Depolarizations (EADs), Delayed After
Depolarizations (DADs).
2. Caused by high calcium via digoxin or SANS, high sodium via
aldosterone or low potassium via diuretics.
3. Stop and prevent with lidocaine (Ib) or amiodarone (III).
4. Use Beta Blockers (II) if a high Sympathetic NS Activity as in
hyperthyroidism.

VENTRICULAR TACHYCARDIA
1. Ectopic depolarizations or a reentry in a conducting circuit.
2. Life threatening, use cardioversion.
3. Lidocaine (Ib)
4. Class Ia or Class III

VENTRICULAR FIBRILLATION
1. Cardioversion to synchronize depolarizations.
2. Stabilize with Class Ib, Ia or III.

DIGITALIS-INDUCED ARRHYTHMIAS
1. Phenytoin (Ib) increases AV conduction against digoxin-induced AV
depression. It also suppresses extrasystoles.
2. Procainamide (Ia) has no AV nodal action. Therefore, no added AV
nodal depression and suppression of extrasystoles.
3. Must avoid AV depressants: Class II, Class III (Class II and IV
activity), Class IV and adenosine.

What Have We Learned About Sodium Channel Blockers (Class I)?

1. They suppress and prevent arrhythmias by raising threshold for
depolarization (reluctant action potential) and by decreasing conduction
velocity (slow, lazy action potential).
2. Most likely to act on conducting pathways, wall reentry circuits and
single cells (sodium channel-based depolarization).
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3. Quinidine has Ia, III (ERP up), antimuscarinic (AV Node unloaded),
and alpha-1 blocking activity (Low BP, HR up)
4. Procainamide causes Lupus when not metabolized (Slow Acetylator
phenotype) and Long Q-T, Torsades when metabolized to NAPA (Fast
Acetylator phenotype).
5. Lidocaine is special: iv, short-acting, few or no side effects, used for
suppression of extra systoles in MI or post-MI ischemic hearts.
6. Phenytoin is special: Actually increases AV Nodal impulse conduction.
Therefore, it is useful in controlling Digoxin-induced ventricular extra
systoles AND AV depression.
7. Flecainide, Encainide and Moriczine are potent sodium channel
blockers which may promote arrhythmias under some conditions. Can
be used in limited treatment plans.

What Have We Learned About Beta Blockers (Class II)?

1. Same Beta Blockers as Antihypertensive and Antianginal drugs.
2. Same action: Antagonize NE at Beta-1, Target SA Node, AV Node,
Ventricle.
3. Suppress SANS HR and Arrhythmias, Protect ventricle from atrium
(AV Node).
4. Same Tox.: Cardiac depression, AV node depression, rebound, 3
patients (Beta-2).

What Have We Learned About Potassium Channel Blockers (Class III)?

1. Expand APD, ERP.
2. Amiodarone acts as Ia, II, III, IV, Alpha X Skin deposits, long t1/2,
pulmonary fibrosis, hypothyroidism. Common use, very effective.
3. Sotalol is a beta blocker.
4. All can cause Torsades.
5. Same usefulness as Class I.

What Have We Learned About Calcium Channel Blockers (Class IV)?

1. Target SA Node, AV Node, Ventricle.
2. Verapamil and Diltiazem, not Nifedipine
3. Remember that these are vasodilators.
4. Side effects are negative cardiac and hypotension. Loss of smooth
muscle action in other organ sites.

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What About Digoxin and Adenosine?
1. Digoxin is antiarrhythmic because it suppresses AV Node.
2. Protects Ventricle. # 1 job in cardiology.
3. Adenosine, injectable, super short action, stops AV Node reentry right
now.
4. Bronchial irritant.

SYMPATHOLYTICS

Note: Focus on the Sympatholytics. Secondarily, most other autonomic

drugs affect cardiac performance, blood pressure or vascular
performance. Take a look.

Alpha-1 Adrenergic Receptor

Site of Action Receptor Stimulation Receptor Blockade
Iris Radial Muscle Mydriasis Miosis; Loss of -1, M3
Big Pupil dominates, Pinpoint Pupil
Arteriole Vasoconstriction Vasodilation
Resistance Vessel Blood pressure is maintained or Blood pressure decreases due
increased due to increased total to lowered resistance.
peripheral resistance (TPR). Decreased TPR. Lower
Diastolic Pressure Diastolic Pressure
Venule Capacitance Venoconstriction Venodilation
Vessel Blood pressure is supported or Blood pressure is decreased due
increased due to increased venous return, to venous pooling (increased
increased stroke volume, increased capacitance), less venous return,
cardiac output (CO). lower CO.
GI Sphincter Contraction of sphincter smooth Relax sphincter smooth
muscle. No movement of contents. muscle, movement.
Urinary Bladder Urinary Retention Less control, Incontinence.
Sphincter

29
Alpha-1 Adrenergic Agonists
Agonist Receptor Actions Uses
Norepinephrine Alpha-1, Beta-1 Vasoconstrictive increase in blood
pressure.
Epinephrine Alpha-1, Beta-1, Beta-2 Vasoconstrictive benefit to retain local
anesthetics in the injection site. Other
uses are Beta-1 and 2 related.
Ephedrine Alpha-1, Beta-1, Beta-2 Vasoconstrictive decongestant in past;
as herb, included in weight-control
mixtures, now banned due to Beta-1
cardiac toxicity.
Pseudoephedrine Alpha-1, Beta-1 Vasoconstrictive decongestant
Phenylephrine Alpha-1 Vasoconstrictive decongestant
Vasoconstrictor in cases of hypotension
due to anesthesia in surgery. Raise BP
Methoxamine Alpha-1 Vasoconstrictor in cases of hypotension
due to anesthesia in surgery. Raise BP
Alpha-1 Adrenergic Antagonists
Antagonist Receptor Actions Uses
Prazosin, Doxazosin Alpha-1 Anti hypertensive
Terazosin Alpha-1 Anti hypertensive
Benign Prostatic Hypertrophy (BPH)
Tamsulosin, Alfuzosin Alpha-1 Benign Prostatic Hypertrophy (BPH)
Phentolamine Alpha-1, Alpha-2 Diagnostic for
Short-acting, Pheochromocytoma Management
Phenoxybenzamine Alpha-1, Alpha-2 Management of Pheochromocytoma
Long-act.,

Alpha-2 Adrenergic Receptor

Site of Action Receptor Stimulation Receptor Blockade
Vasomotor Center Autoreceptor; Negative Allow uncontrolled release of
(VMC) in the Decrease further release of NE NE from presynaptic neuron,
medulla oblongata; from same presynaptic terminal, hypertension, tachycardia.
Presynaptic Neuron decrease SANS activity, decrease
blood pressure.

Alpha-2 Adrenergic Agonists

Agonist Receptor Actions Uses
Clonidine Alpha-2 Anti hypertensive
-Methyl DOPA Alpha-2 Anti hypertensive
Guanabenz Alpha-2 Anti hypertensive

30
Alpha-2 Adrenergic Receptor Antagonists
Antagonist Receptor Actions Uses
Yohimbine Alpha-2 Improve SANS
Phentolamine Alpha-1, Alpha-2 Anti hypertensive
Alpha-2 block increases
reflexive tachycardia
when BP becomes too
low
Phenoxybenzamine Alpha-1, Alpha-2 Anti hypertensive
Alpha-2 block increases
reflexive tachycardia
when BP becomes too

Beta-1 Adrenergic Receptor

Site of Action Stimulate Receptor Block Receptor

Cardiac Increase rate of spontaneous
SA Node depolarization of pacemaker and
thereby increase heart rate.
Cardiac Increase rate of impulse
AV Node conductance from atrium to
ventricle
Cardiac Improve myocyte contractility,
Ventricle increase myocardial contractility
and systolic ejection fraction.
Renin release at Renin release, leading to increased
the Kidney synthesis of angiotensin II and
Juxtaglomerular subsequent release of aldosterone.
Apparatus
Decrease rate of spontaneous
depolarization and thereby
decrease heart rate.
Antihypertensive.
AV nodal depression.
Antiarrhythmic
Depress ventricular contractility
and excitability. Antiarrhythmic.
Inhibit rennin release.
Antihypertensive.

Beta-2 Adrenergic Receptor

Site of Action Stimulate Receptor Block Receptor
Bronchiole Bronchodilate Allow bronchoconstriction
Arteriole Vasodilate (No agonist)
Smooth muscle Relax smooth muscle. Allow increased activity leading
GI tract Decrease tone and peristalsis. to distress.
Smooth muscle Relax smooth muscle. Allow increased bladder tone
Urinary Bladder Urinary retention. and urgency.
Liver Glucose production Block glycogenolysis, may cause
Glycogenolysis or deepen hypoglycemia.

31
 Beta-1 and 2 Adrenergic Agonists (Nonselective)
Agonist Receptor Actions Uses
Norepinephrine Alpha-1, Beta-1 Vasoconstrictive increase in blood pressure.
Epinephrine Alpha-1, Beta-1, Beta-2 Vasoconstrictive benefit to retain local
anesthetics in the injection site. Cardiac
Stimulant (Beta-1). Bronchodilator (Beta-
Ephedrine Alpha-1, Beta-1, Beta-2 Vasoconstrictive decongestant in past; as herb,
included in weight-control mixtures, now
banned due to Beta-1 cardiac toxicity. Some
use as a long-acting bronchodilator (Beta-2)

Isoproterenol Beta-1, Beta-2 Bronchodilator (Beta-2) with a strong cardiac

(Beta-1) side effect. Cardiac stimulant (Beta-

Beta-1 Selective Adrenergic Agonists

Agonist Receptor Actions Uses
Dobutamine Beta-1 Cardiotonic, improves ventricular
contractility in heart failure.
Dopamine Beta-1, D-1, D-2 Improves cardiac performance in shock states
and also improves renal blood flow via regional
vasodilation (D-1, D-2).

Beta-2 Selective Adrenergic Agonists

Agonist Receptor Actions Uses
Metaproterenol Beta-2 (inhalation, po) Bronchodilat
Albuterol Beta-2 (inhalation) short acting Bronchodilat
Terbutaline Beta-2 (inhalation) short acting Bronchodilat
Pirbuterol Beta-2 (inhalation) short acting Bronchodilat
Salmeterol Beta-2 (inhalation) long acting Bronchodilat
Formotorol Beta-2 (inhalation) long acting Bronchodilat
Beta-1 and 2 Adrenergic Antagonists (Nonselective)
Antagonist Receptor Actions Uses
Propranolol Beta-1, Beta- Antihypertensive, Antianginal,
Timolol Beta-1, Beta- Glaucoma, Hypertension
Nadolol Beta-1, Beta- Hypertension, Antianginal,
2 Antiarrhythmic Migraine Headache

32
 Beta-1 Adrenergic Antagonists (Cardioselective)
Antagonist Receptor Uses
Atenolol Beta- Antihypertensive, Antianginal
Metoprolol Beta- Antihypertensive, Antianginal
Acebutolol Beta- Antihypertensive, Antiarrhythmic

Partial Agonists at the Beta-1 Adrenergic Receptor (Functional Beta

Antagonists) Intrinsic Sympathomimetic Activity (ISA)
ISA Partial Agonist Receptor Actions Uses
Antihypertensive
Pindolol Beta-1, Beta-2
Acebutolol Beta-1 selective Antihypertensive
Antiarrhythmic

Nicotinic Neuronal (Nn) Ganglionic Receptors

Site of Action Receptor Stimulation Receptor Blockade

Autonomic Post-Ganglionic action in Loss of action in
Ganglia all systems. predominant
systems.
Sympathetic N.S.
Parasympathetic
N.S. Adrenal
Medulla

Nicotinic Agonists at the Ganglion

Agonist Receptor Actions Uses
Acetylcholine Nn Mediator of indirect
Nicotine (Natural
Agonists) agonists Natural toxin
Physostigmine Anticholinesterase Antimuscarinic poisoning
Neostigmine Anticholinesterase Myasthenia gravis (Nm)
Pyridostigmine Anticholinesterase Myasthenia gravis (Nm)
Sarin (War Gas, Nerve Anticholinesteras Toxin
Gas) e Irreversible

33
 Nicotinic Antagonist (Ganglionic Blocker)

Antagonist Receptor Action Uses

Mecamylami Nn (Ganglionic Antihypertensi

Nicotinic Neuromuscular Receptors (Nm)

Site of Action Receptor Stimulation Receptor Blockade

Neuromuscular Skeletal fasciculation, Skeletal muscle
Junction contraction, fatigue, relaxation
paralysis (depolarization
blockade).

Neuromuscular Agonists (Nm)

Agonist Receptor Actions Uses
Acetylcholine Nm Mediator of indirect
Nicotine (Natural agonists Natural toxin
Agonists)
Physostigmine Anticholinesterase Antimuscarinic poisoning
Neostigmine Anticholinesterase Myasthenia gravis (Nm)
Pyridostigmine Anticholinesterase Myasthenia gravis (Nm)
Edrophonium Anticholinesterase (Short) Diagnostic, Myasthenia
Sarin (War Gas, Nerve Anticholinesterase Toxin
Gas) Irreversible, (Super
l )
Neuromuscular Blockers (Nm)
Antagonist Receptor Actions Uses
Curare Nm Skeletal muscle
(Competitive antagonist) Non-depolarizing Blocker relaxation
Succinylcholine Nm Skeletal muscle
(Persistent depolarization) Depolarizing Blocker relaxation

34
 Muscarinic M-2 Receptors
Site of Action Receptor Stimulation Receptor Blockade
Cardiac Slowed rate of Allows increased heart
Pacemaker SA pacemaker depolarization, rate
Node lower heart rate
Cardiac AV Allows increased
Slowed rate of impulse
Node impulse conductance
conductance A to V.
A to V.

Muscarinic M-3 Receptors

Site of Action Receptor Stimulation Receptor Blockade

Smooth Pupil Contraction Mydriasis (Big
Muscle (Gq, (Miosis) pupil)
PLC) Bronchoconstriction Bronchodilation
GI, Urinary bladder tone increases GI, Urinary bladder relax
Smooth Arterioles dilate (NO) Vasoconstrict (Alpha-1)
Muscle (Nitric GI and Bladder Sphincters open Sphincters contract (Alpha-
Oxide) (NO) 1)
Exocrine Salivation, Airway Indirect
Glands secretions Generalized Agonists
sweating Myasthenia

Muscarinic M-2, M-3 Agonists

Agonists Receptor Actions Uses
Bethanechol M-3 GI and Urinary Stasis
Pilocarpine M-3 Glaucoma
Echothiophate Anticholinesterase, Long-acting Glaucoma
Acetylcholine (Ach)M-2, M-3, Nn, Nm Neurotransmitter
Anticholinesterases M-2, M-3, Nn, Nm, Reversible Indirect Agonists (via
Ach) Myasthenia gravis

Sarin (Nerve Gas) Anticholinesterase, Irreversible Toxin

35
 Muscarinic Antagonists (M-2, M-3)
Antagonist Receptor Uses
Actions
Atropine M-2, M-3 Opthalmic: Mydriasis and
Plus Cycloplegia. GI, Bladder
others relaxation.
Counteracts Anticholinesterase
Tropicamide M-3 Opthalmic: Mydriasis and Cycloplegia.
Cyclopentolat
e
Scopolamine M-3 Motion sickness
Ipratropium M-3 Bronchodilator in asthma and COPD

ACUTE MYOCARDIAL INFARCTION

When a patient proceeds past angina and experiences ischemic damage,
additional requirements for pharmacologic intervention become evident. Here
is an outline of drug therapy which may be effective in aspects of acute
myocardial infarction, heart failure and cardiogenic shock.

Pharmacologic Strategies Following Myocardial Infarction

A. Coronary Flow

1. Anticoagulation. Acute blood coagulation and persistent

hypercoagulability are clearly associated with acute myocardial
infarction. Heparin is the immediate benefit drug, given intravenously
or subcutaneously, which potentiates the natural antitarombotic action of
Antithrombin III. Overuse results in excessive bleeding and can be
reversed by using protamine sulfate to bind heparin and stop its action.
Warfarin requires more time to demonstrate a benefit. It blocks
synthesis of clotting factors, most of which are pre-made and
circulating with long half-lives. This drug is orally available; offers
benefit by 3-5 days, and can suppress coagulation for many weeks or
months. Overuse results in bleeding which can be reversed with vitamin
36
 K (the missing co-factor for clotting factor synthesis) or by infusing the
depleted clotting factors.

2. Fibrinolysis. Clinical studies have revealed that drugs designed to

digest fibrin clots improve survival following acute myocardial
infarction about 20%. Streptokinase, alteplase and urokinase can be
infused IV to lyse newly formed clots. They act by promoting the
conversion of plasminogen to plasmin, the natural proteolytic enzyme
that digests, fibrin and retracts clots.

3. Platelet Stabilization. Aspirin is the most prominent drug iri this

category and is known for its ability to prevent platelet events when
used in a low dose. Aspirin is also used during the MI to suppress any
further involvement of platelets in the ongoing occlusion. Aspirin
irreversibly acetylates cyclooxygenase (COX) to block synthesis of
thromboxane, the endogenous platelet aggregant in platelets.
Ticlopidine and clopidogrel suppress platelets by inhibiting the ADP-
mediated platelet activation pathway. Abciximab targets the platelet
surface recognition molecules (glycoproteins) which are essential for
platelet - platelet adhesion.

The Drugs for Improvement of Coronary Flow

Class Drug Mechanism Toxicity

Anticoagulants Heparin Potentiates Bleedin
Antithrombin III g
Warfarin
Inhibits Vitamin K Bleeding
epoxide reductase
Fibrinolytics Streptokinase Activate Plasmin Bleeding
Alteplase
Urokinase

37
 Antiplatelet Aspirin Acetylates
COX GI distress,
Clopidogrel bleeding
Blocks ADP
Abciximab
Heparin: reverse bleeding with protamine sulfate; Warfarin use vitamin K

B. Control of Arrhythmias
1. Acute MI can be accompanied by ventricular extra-systoles,
which can become ventricular tachycardia or fibrillation. Class lb
lidocaine is short-acting, iv administered, relatively non-toxic
drug that effectively suppresses arrhythmias in ischemic ventricle.
Class III, amiodarone is also useful.

2. Bradycardia is caused by abnormally high vagal activity during acute

MI.
Atropine is the drug of choice for restoring normal sinus
rhythm.

The Antiarrhythmic Drugs

Class Drug Mechanism Toxicity

Na+ Channel Minimal due to short act.,

Class IB Lidocaine
Blocker IV
Class III IC- Channel Blocker Many. Heart block,
Amiodarone pulmon. fibrosis, corneal
deposits, blue skin, thyroid
dysfunction, constipation,
liver necrosis. Limit use to
IV, short-term.
Antimuscarinic Atropine M2 Receptor Mydriasis, anhydrisis,
Antagonist xerostomia,
constipation, urinary
retention.

C. Pulmonary Congestion. Acute heart failure may occur during and

following acute MI, causing venous volume and pressure increase to the point
of pulmonary and systemic edema. This symptom can be managed to
maintain pulmonary function.

38
 1. Volume Management. Reduction of intravascular volume can
decrease left ventricular filling pressure. Furosemide can rapidly
improve vascular compliance, increasing venous capacitance,
reducing venous return and ultimately decreasing ventricular filling
pressure.

2. Pulmonary Congestion and Pain. Morphine reduces pulmonary

congestion and relieves the pain of acute myocardial infarction.

3.. Bronchodilation. Bronchospasm may be prominent and can be

resolved using a
bronchodilator. The rational approach to bronchorelaxation in this
patient leads to aminophylline. It is bronchodilator, vasodilator and
cardiotonic.
Methylxanthines have positive inotropic and chronotropic cardiac
action due to release of norepinephrine. In addition, they inhibit
phosphodiesterase, improving cAMP signalling associated with
beta-1and beta-2 receptors. Finally, they antagonize adenosine on
smooth muscle, probably the bronchodilating mechanism.

Drugs to Improve Pulmonary Congestion

Class Drug Mechanism Toxicity

Diuretic Furosemide Loop Diuretic Hypovolemia hyponatremia

hyperkalemia, alkalosis
hyperglycemia, hyperuricemia

Analgesic Morphine Mu Agonist Euphoria, sedation,

respiratory depression,
constipation, N/V
Bronchodilator Aminophylline PDE Inhibitor Irritability, tremor, convulsions
Adenosine
Antagonist

39
D. Low Blood Pressure and Low Cardiac Output. Shock Syndromes. This is
acute heart failure with high ventricular filling pressure. The goals are to
improve cardiac output and to reduce venous volume and pressure.

1. Vasodilation. Nitroprusside is used because of its combined dilating

effects on
venules and arterioles. It can increase venous capacitance to maintain
reduced venous return, resulting in lowered ventricular filling
pressure. Nitroprusside can also dilate arterioles with the benefit of a
reduced requirement for left ventricular systolic ejection pressure.
Cardiac Output will increase. Nitroprusside dose is limited by the
degree of arterial hypotension produced.

2.. Cardiotonic Benefit. Direct improvement of cardiac output can be

attained with dopamine agonist at Beta-1 myocardial receptors and a
DA-1 receptor vasodilator in peripheral vasculature. Renal blood flow
and urine production will be restored and maintained. Dopamine and
nitroprusside can be useful in combination. Other inotropic drugs can
also be useful: inamrinone, milrinone and dobutamine.

Drugs to Improve Cardiac Output and Blood Pressure

Class Drug Mechanism Toxicity

Vasodilators Nitroprusside NO Hypotensio
Dopamine donator n
Cardiotonics Dopamine Beta-1 Tachycardia
Dobutamine agonist
Inamrinone
(Amrinone)M PDE N/V,
ilrinone inhibitors thrombocytopenia
Dobutamine Tachycardia

40
E.. Right Ventricle Infarction and Failure. Low blood pressure and low
cardiac output. This problem is focused on the right ventricle and its inability
to move sufficient blood volume to the left ventricle, allowing cardiac output
and blood pressure to suffer. The goal in this area is to improve left ventricle
filling pressure.

1.Volume replacement. Adding circulating volume can drive volume and pressure
through the ineffective right ventricle to the left side of the heart,
improving cardiac output and blood pressure.

2. Cardiotonics. Increased left ventricle contractility can augment the

benefits of volume replacement. Dopamine, dobutamine, inamrinone
and milrinone can be used to provide short-term benefit.

F. Prophylaxis against the "Second Myocardial Infarction"

1. Low Dose Aspirin. Aspirin is at the heart of the MI prevention strategy. Low
dose aspirin has been accepted as an important method for preventing
platelet aggregation leading to MI or stroke. Since aspirin
irreversibly acetylates cyclooxygenase (COX) and platelets cannot
synthesize new enzyme, platelets are permanently unable to produce
Thromboxane A2, an important agonist for platelet aggregation. A low
dose of aspirin is all that is necessary for this effect on platelets;
and it does not suppress synthesis of endothelial prostacyclin, a
defensive anti-aggregant. In this way, platelets are selectively
inactivated. Aspirin doses range from 80 - 160 mg/ day.

2. Antiplatelet Drugs. Ticlopidine and Clopidogrel stabilize platelets in

acute coronary syndromes. These drugs are used for short-term avoidance
of myocardial infarction during unstable angina pectoris.

3. Beta Blockers (non-ISA). These drugs improve survival when given

early following an MI and with continuous use over the subsequent 2-3
years. The mechanism of benefit is probably the suppression of
catecholamine-mediated ventricular arrhythmias, which can cause
sudden cardiac arrest. Timolol was shown to reduce deaths following
the first infarction in a multicenter study.
4. Reduce Risk Factors.
Smoking
Weight
Stress
Diet

41
 CONGESTIVE HEART FAILURE
Drug MOA Use Toxicity
Thiazide Diuretics Block sodium Loss of body Hypokalemia
recovery at Distal water. Resolve Alkalosis
Hydrochlorothiazide Convoluted peripheral Hyperuricemia
Chlorthalidone Tubule. Sodium edema, lung Hyperglycemia
Indapamide and water congestion and Hypercalcemia
diuresis. expanded blood
volume.
Loop Diuretics Block sodium Rapid loss of Hypokalemia
Furosemide recovery at body water. Alkalosis
Torsemide ascending Loop Resolve Hyperuricemia
Bumetanide of Henle. peripheral Hyperglycemia
Ethacrynic Acid Sodium and edema, lung Hypocalcemia
(No S, Ototox.) water diuresis. congestion and
expanded blood
volume.
Potassium Sparing Aldosterone Stops volume Hyperkalemia
diuretics Antagonist expansion by Acidosis
Block sodium Aldosterone as
Spironolactone recovery at it drives
Eplerenone collecting tubule, recovery of
less potassium sodium and
loss in exchange water at
collecting
tubule.
Potassium Sparing Not Aldo. In combination, Hyperkalemia
diuretics Antagonist they counteract Acidosis
Block sodium hypokalemia of
Amiloride recovery at Loop and
Triamterene collecting tubule, Thiazide
less potassium diuretics.
loss in exchange.
ACE Inhibitors Block Decrease Hypotension
Prils Angiotensin II vascular Hyperkalemia
Captopril synthesis resistance and Cough
Lisinopril aldosterone Angioedema
Enalapril Retain release
Ramipril Bradykinin (BK) (Volume
42
 expansion).
Add a
vasodilator.
ARBS Block Relieve effects Hypotension
Sartans Angiotensin II of angiotensin II Hyperkalemia
Losartan Receptors and aldosterone (Advantage: No
Valsartan BK)
Vasodilators Arteriolar Relieve Cardiac Hypotension
vasodilator workload:
Hydralazine Afterload
Venular dilation
Isosorbide dinitrate Preload
Beta Blockers Beta-1 Suppress high Heart Failure
Antagonists heart rate and Cardiodepressant
Atenolol potential for V. AV Nodal
Metoprolol arrhythmias Depression

Beta Blockers Alpha and Beta Vasodilation

blockade minus reflexive
Carvedilol tachycardia
Labetalol
Beta blocker Beta Blocker Vasodilation
With minus reflexive
Nebivolol Nitric oxide tachycardia
action
Digoxin Blocks Na+ K+- Improve Ventricular
ATPase cardiac Arrhythmias
contractility (Ca++,
Improved Ca++ in Automaticity)
cell Cardiotonic
AV Nodal
Depression
(Vagus, Ach, M-
2)
Dobutamine Beta-1 Agonist Improve Possible
Also: NE, Epi, cardiac ventricular
Isoproterenol contractility arrhythmias

Cardiotonic Possible high BP

43
 (Alpha-1: NE,
Epi)
Phosphodiesterase Increase cAMP, Improve
Inhibitors Beta-1 cardiac cardiac
signal contractility
Inamrinone
Milrinone Cardiotonic
Brain Natriuritic cGMP Lower Preload
Peptide (BNP) Relax Smooth and Afterload
Muscle
Nesiritide Vasodilate IV short-term
Arterioles and
Venules

44
 ANTIHYPERTENSIVE THERAPY
The Eighth Report of the Joint National Committee on Prevention,
Detection, Evaluation, and Treatment of High Blood Pressure (JNC8) provides
the current guideline for hypertension prevention and management. It supplements JNC7,
which has a comprehensive recommendation. The following are the reports key
messages:

In persons older than 60 years, the guideline is to maintain BP less than 150/90
mmHg. Younger than 60, the goal is less than 140/90 mmHg. For all patients with
kidney disease or diabetes, goal is 140/90 mmHg.

African American: Thiazide diuretic, Calcium Channel Blocker (CCB)

Non-African American under 55: Thiazide, CCB, ACEI, ARB

Non-African American over 55: Thiazide, CCB

Pregnancy: Methyldopa, labetalol, hydralazine

MI and CHF: Beta blocker (BB), ACEI, ARB, spironolactone

Angina: BB, CCB

Kidney disease or Type II diabetes: ACEI, ARB

Asthma: CCB, ACEI, ARB, avoid non-selective BB

BPH: Alpha-1 blocker

Migraine: BB, CCB

Osteoporosis: Thiazide diuretic

Hypertensive crisis: Nitroprusside, hydralazine, labetalol, fenoldopam

45
 Drugs Used For Hyperlipidemia
Drug Use MOA Toxicity
BILE ACID RESINS LDL-C blood Bind bile acids in Nausea, bloating, constipation or
levels decrease the gut and diarrhea. These drugs have a gritty
Cholestyramin 30%. prevent their texture and must be mixed well in 8
eColestipol resbsorption. ounces of water.
Colesevalam Not to be used in Interfere with drug and vitamin
patients with These drugs are absorption:
high not absorbed. thiazides, digoxin, warfarin, estrogens,
triglycerides and fat-soluble vitamins. Drugs and
Oral vitamins must be spaced several
Bioavailability is hours when giving a bile acid resin.
zero
Effective against Decreases Intense flushing and itching, which is
hypertriglyceridem production of reversible and preventable with
NIACIN ia VLDL in the liver. aspirin. Peptic ulcer, Hyperglycemia,
Hyperuricemia (gout).
Decreases VLDL Myositis and
(TG) assembly. Rhabdomyolysis can also occur.
HMG CoA Circulating HMG CoA Hepatic toxicity (increased liver function
REDUCTASE LDL-C reductase is the tests)
INHIBITORS decreases by rate-limiting step Myopathy, and
25- 45%. in cholesterol Rhabdomyolysis.
Lovastatin, synthesis by liver. Drug interactions: enzyme inhibitors
Simvastatin, Statins The statin drugs (erythromycin, ketoconazole) and
Pravastatin, stimulate and competitively grapefruit juice may increase levels and
Fluvastatin, increase LDL bind this enzyme toxicity of the Statin drug. These drugs
Atorvastatin, receptors. and decrease should never be used in pregnancy.
Rosuvastatin LDL
FIBRATES Triglyceride PPAR-alpha Myositis, gallstones, and liver toxicity.
levels decrease by agonist which (Especially when given with a statin
Gemfibrozi 35%. Degrade drug).
increases
lFenofibrat VLDL(TG). lipoprotein lipase
e
activity.
Fibrates
degrade VLDL-
triglycerides.
Inhibitor of intestinal Reduction of LDL Inhibits Small increase in hepatic dysfunction
sterol absorption intestinal when given with a statin drug.
absorption of GI distress
Ezetimibe (Zetia) cholesterol and
For homozygous Oral availability
familial Inhibits VLDL
Lomitapide
hyperlipidemia, assembly
LDL over 500

46
 For homozygous Injected weekly
familial Inhibits apoB
Mipomersen
hyperlipidemia, synthesis
LDL over 500

47