Pharmacology

MAURICE LEE B. SANTOS, RN, DNM

FACULTY MEMBER
 Cardiac Glycosides
• Left sided HF - left ventricle does not contract sufficiently to pump
the blood returned from the lungs and LA out through the aorta
into the peripheral circulation.
• Right-sided HF - occurs when the heart does not sufficiently pump
the blood returned into the RA from the systemic circulation. Left-
sided heart failure may lead to right-sided failure and vice versa.

Cardiac Glycosides
A. Digitalis
B. Digoxin
 Cardiac Glycosides
A. Digitalis
• Naturally occurring are found in a number of plants like digitalis
(digitalis glycosides).
• Inhibits the NA-K pump, resulting in an increase in intracellular
sodium. This ↑ leads to an influx of calcium, causing the cardiac
muscle fibers to contract more eJiciently.
• Three eJects on ♥ muscle: (1) + inotropic action (↑ myocardial
contraction stroke volume), (2) - chronotropic action (↓ ♥ rate),
and (3) - dromotropic action (↓ conduction of ♥ cells).

Cardiac Glycosides
A. Digitalis
• ↑ in myocardial contractility strengthens cardiac, peripheral, and
kidney function by enhancing cardiac output, ↓ preload, improving
blood flow to the periphery and kidneys, ↓ edema, and promoting
fluid excretion. As a result, fluid retention in the lung and
extremities is ↓.
 Cardiac Glycosides
• Digoxin is a secondary drug for HF. Used to treat acute HF include
intravenous inotropic agents (dopamine and dobutamine) and
phosphodiesterase inhibitors (milrinone).
• Cardiac glycosides - correct atrial fibrillation (cardiac
dysrhythmia with rapid uncoordinated contractions of atrial
myocardium) and atrial flutter (cardiac dysrhythmia with rapid
contractions of 200 to 300 beats/ min).
• When digoxin cannot convert atrial fibrillation to normal ♥
rhythm, the goal is to slow the ♥ rate by decreasing electrical
impulses through the AV node.

Cardiac Glycosides
B. Digoxin
• Pharmacokinetics: Absorption (tablet – 70% to 80%, liquid -75 to
85%). Half-life – 30 to 40 hours, kidney dysfunction – alter metabolism,
hyperthyroidism - ↑ dose, hypothyroidism - ↓ dose.
• Pharmacodynamics: ↓ conduction in AV node = ↓ hear rate,
therapeutic serum level – 0.5 to 1.0 ng/ml, for HF - ↓ serum levels, for
atrial fibrillation - ↑ serum levels, digoxin therapeutic serum level – 0.8
to 2.0 ng/ml
• SE and AE: Digitalis toxicity
• Nursing Process: Drug and herbal history, VS (full minute), assess for
signs and symps, determine peripheral and pulmonary edema, monitor
serum potassium and digoxin level, advise to eat foods high in
potassium, report side effects
 Cardiac Glycosides
Digitalis Toxicity (Digoxin)
Sx and Symp: Anorexia, diarrhea, N and V, bradycardia, PVC, cardiac
dysrhythmias, headaches, malaise, blurred vision, visual illusions, confusion,
and delirium. Older adults - prone to toxicity.
Cardiotoxicity: serious adverse rxn to digoxin; ventricular dysrhythmias result.
3 cardiac-altered fxns can contribute to digoxin-induced ventricular
dysrhythmias: (1) suppression of AV conduction, (2) ↑ automaticity, and (3) a ↓
refractory period in ventricular muscle. Phenytoin and lidocaine (short-term)
are for digoxin-induced ventricular dysrhythmias.

Cardiac Glycosides
Antidote for Cardiac/Digitalis Glycosides
Digoxin immune Fab (Digibind): For severe digitalis toxicity,
digitalis toxicity may result in first-degree, second-degree, or
complete ♥ block.
 Cardiac Glycosides
Drug Interactions: Diuretics - furosemide and hydrochlorothiazide
promote the loss of K from the body. Hypokalemia (low serum
potassium level) ↑ the eJect of digoxin at its myocardial cell site of
action - digitalis toxicity. Cortisone promote NA retention and K
excretion or loss and can cause hypokalemia. Patient with digoxin
plus K-wasting diuretic or a cortisone drug should consume foods ↑
in K. Antacids can ↓ digitalis absorption.

Cardiac Glycosides
• Phosphodiesterase inhibitors - + inotropic group of drugs given
to treat acute HF. This drug group inhibits the enzyme
phosphodiesterase promoting + inotropic response and
vasodilation. Milrinone lactate - ↑ stroke volume and cardiac
output and promotes vasodilation. Administered IV - no longer
than 48 to 72 hours.
• Patient’s ECG and cardiac status should be monitored because of
the risk of severe cardiac dysrhythmias.
 Cardiac Glycosides and Inotropic Agents
Generic Example
Rapid Acting Digitalis Digoxin
Phosphodiesterase Inhibitors Milrinone lactate
Atrial Natriuretic Peptide Nesiritide
Hormones
Antidote for Digitalis Toxicity Digoxin immune Fab (Digibind)

Antianginals
• Antianginal drugs are used to treat angina pectoris.
• It is a condition of acute cardiac pain caused by inadequate blood flow to the
myocardium due to either plaque occlusions within or spasms of the
coronary arteries. ↓ blood flow = ↓ in O2 to the myocardium, which results in
pain. Anginal pain is tightness, pressure in the center of the chest and pain
radiating down the left arm. Referred pain felt in the neck and left arm
commonly occurs with severe angina pectoris.
• Anginal attacks may lead to MI, lasts for only a few minutes.
• Tests: Stress tests, echocardiogram, cardiac profile laboratory tests, and
cardiac catheterization.
 Types of Angina Pectoris
• The frequency of anginal pain depends on many factors, including the type of
angina.
• Three types of angina:
A. Classic (stable) - predictable stress or exertion
B. Unstable (preinfarction) - frequently with progressive severity unrelated to
activity; unpredictable regarding stress/exertion and intensity
C. Variant (Prinzmetal, vasospastic) - during rest
• First two types - narrowing or partial occlusion of the coronary arteries
• Variant angina - vessel spasm (vasospasm)
• It is common for a patient to have both classic and variant angina. Unstable
angina often indicates an impending MI. Emergency that needs immediate
medical intervention.
 Nonpharmacologic Measures to Control
Angina
• " heavy meals, smoking, extreme weather changes, strenuous
exercise, and emotional upset.
• Proper nutrition, moderate exercise, rest and relaxation
techniques

Types of Antianginal Drugs

• Antianginal drugs increase blood flow either by ↑ O2 supply or by ↓ O2
demand by the myocardium. Three types of antianginals: nitrates, beta
blockers, and CA channel blockers.
• Nitrates is a reduction of venous tone, which ↓ the workload of the ♥ and
promotes vasodilation.
• Beta blockers and CA channel blockers ↓ the workload of the ♥ and ↓ O2
demands.
• Nitrates and CA channel blockers for variant angina pectoris. Beta blockers
are not eZective for this type of angina and may aggravate but it is eZective
against stable angina for prevention of angina attacks. Unstable angina -
immediate medical care is necessary.
 Types of Antianginal Drugs
Nitrates - SL and IV as prn. If the cardiac pain continues, a beta
blocker is given IV, and if the patient is unable to tolerate beta
blockers, a CA channel blocker may be substituted.

Antianginal Drugs
A. Nitrates - used to relieve angina. They aZect coronary arteries and blood
vessels in the venous circulation. Nitrates cause generalized vascular and
coronary vasodilation, which ↑ blood flow through the coronary arteries to the
myocardial cells. This group of drugs ↓ myocardial ischemia but can cause
hypotension.
• SL nitroglycerin tablet - average prescribed dose is 0.4 mg following cardiac
pain. If pain has not subsided or worsened, then 911 should be called. The
eZects of SL nitroglycerin last for 30 - 60 minutes. The SL tablets decompose
when exposed to heat and light - original airtight glass containers.
• After a dose of nitroglycerin, the patient may experience dizziness, faintness,
or headache - peripheral vasodilation. If pain persists - call for medical
assistance.
 Antianginal Drugs
• SL nitroglycerin – most common used nitrate. Absorbed into the
circulation through the SL vessels. Nitroglycerin other forms:
topical (ointment, transdermal patch), translingual, oral extended-
release capsule and tablet, aerosol spray (inhalation), and IV.
• Types of organic nitrates. Isosorbide dinitrate - SL tab, chewable
tab, immediate-release tab, and sustained-release tab and
capsules. Isosorbide mononitrate can be given orally in
immediate-release and sustained-release tablets.

Antianginal Drugs
Nitroglycerin
• Pharmacokinetics: SL – rapid and into internal jugular vein and RA. Ointment
and patch – slowly through the skin
• Pharmacodynamics: Nitroglycerin acts directly on the smooth muscle of
blood vessels, causing relaxation and dilation. ↓ cardiac preload and
afterload and reduces myocardial O2 demand. Onset - SL and IV – 1 to 3 mins
while transdermal method – 40 to 60 mins. Transdermal patch – 18 - 24 hrs.
Decline in use of ointment – 4 to 8 hrs and need to reapplied 3 to 4 times a
day, patch remove nightly – to avoid tolerance (allow 8 to 12 hrs nitrate free).
• SE and AE: Headache (most common), hypotension, dizziness, weakness,
and faintness. Ointment or transdermal patches are D/C - the dose should be
tapered, Reflex tachycardia - nitrate is given too rapidly
 Antianginal Drugs
Nitroglycerin
• Drug interactions: Beta blockers, CA channel blockers,
vasodilators, and alcohol can enhance the hypotensive eJect of
nitrates. IV nitroglycerin may antagonize the eJects of heparin.

Antianginal Drugs
B. Betablockers
• Beta-adrenergic blockers block the beta1- and beta2-receptor sites. ↓ the
eZects of the SNS by blocking the action of the catecholamines (epinephrine
and norepinephrine), thereby ↓ the HR and BP.
• As antianginal, antidysrhythmic, and antihypertensive drugs. Useful for
classic (stable) angina. Should not be abruptly D/C . The dose should be
tapered over a specified number of days to avoid reflex tachycardia and
recurrence of anginal pain.
• Patients " ↓ HR and BP and have second- or third-degree AV block
 Antianginal Drugs
B. Betablockers
• Nonselective – propranolol, nadolol, and pindolol.
• Cardioselective - act more strongly on the beta1 receptor, which decreases ♥ rate but
avoids bronchoconstriction (none for beta2 receptor). Examples of selective - atenolol and
metoprolol. Choice for controlling angina pectoris.
• Pharmacokinetics: Orally, half-life (propranolol – 2 to 6 hours, atenolol – 6 to 7 hours, and
metoprolol – 3 to 7 hours)
• Pharmacodynamics: ↓ force of myocardial contraction and O2 demand by myocardium is
reduced. EHective for classic angina. Nonselective = onset – 30 mins while peak is 2 to 4
hours and duration is 12 to 24 hours. Selective (atenolol) = onset - 60 mins, peak – 2 to 4 hrs,
duration – 24 hrs. Selective (metoprolol) = onset – 30 to 60 mins and duration is 3 to 6 hrs.
• SE and AE: Both ↓ HR and BP, Nonselective – bronchospasm, agitation, confusion, tapered 1
to 2 weeks, VS

Antianginal Drugs
C. CA Channel Blockers
• CA channel blockers (CCB) - stable and variant angina pectoris,
certain dysrhythmias, and hypertension. CA activates myocardial
contraction, ↑ the workload of the ♥ and the need for more O2.
CCBs relax coronary artery spasm (variant angina) and relax
peripheral arterioles (stable angina), ↓ cardiac O2 demand. They
also ↓ cardiac contractility (- inotropic eJect that relaxes smooth
muscle), ↓ afterload, ↓ peripheral resistance, and reduce the
workload of the ♥, which ↓ the need for O2.
 Antianginal Drugs
C. CA Channel Blockers
• Pharmacokinetics: CCBs - verapamil, nifedipine, and diltiazem
for the long-term treatment of angina. 80% to 90% are absorbed
through GI. First- pass metabolism by the liver ↓ the availability of
free circulating drug, and only 20% of verapamil, 45% to 65% of
diltiazem, and 35% to 40% of nifedipine are bioavailable. Highly
protein- bound (80% to 90%), and their half-lives are 2 to 9 hours.
• Other CCBs - nicardipine HCl, amlodipine, felodipine, and
nisoldipine. All are highly protein-bound (greater than 95%).
Nicardipine - shortest half-life at 5 hours.

Antianginal Drugs
C. CA Channel Blockers
• Pharmacodynamics: Bradycardia - use of verapamil, the first
calcium blocker. Nifedipine - most potent CA blockers, promotes
vasodilation of the coronary and peripheral vessels, and
hypotension can result.
• Onset - 10 mins for verapamil and 30 minutes for nifedipine and
diltiazem. Verapamil’s duration - 6 to 8 hours for PO and 10 to 20
mins for IV. Duration of nifedipine and diltiazem – 6 to 8 hours.
 Antianginal Drugs
C. CA Channel Blockers
• SE and AE: headache, hypotension, dizziness, and flushing of the
skin. Reflex tachycardia - result of hypotension. Peripheral edema
due to CCBs. CCBs - changes in liver and kidney function. CCBs -
antianginal drugs such as nitrates to prevent angina.
• Nifedipine - immediate-release form (10-and 20-mg capsules) -
associated with an ↑ incidence of sudden cardiac death when
prescribed in high doses as outpatient. Hence, immediate-release
nifedipine is usually prescribed only as PRN in the hospital for
acute ↑ in BP.

Antianginal Drugs
• Nursing Process: VS, drug history, sips of H2O before SL, for
nitroglycerin use in ointment, " touch nitroglycerin patch, "
apply nitro ointment and patch place of defibrillator, " alcohol,
educate about meds
 Antianginals
Generic Example
Short Acting Nitroglycerin
Long Acting Isosorbide dinitrate, Isosorbide
mononitrate
Beta Adrenergic Blockers Atenolol, Metoprolol tartrate,
Propranolol
Calcium Channel Blockers Amlodipine, Diltiazem,
Nicardipine HCl, Nifedipine

Antidysrhythmic Drugs
• Cardiac dysrhythmia (arrhythmia) - deviation from the normal♥ rate or
pattern of the heartbeat. This includes ♥ rates –bradycardia, tachycardia, or
irregular. The terms dysrhythmia (disturbed heart rhythm) and arrhythmia
(absence of heart rhythm) are used interchangeably.
• ECG identifies the type of dysrhythmia. P wave - atrial activation, QRS
complex - ventricular depolarization, and the T wave - ventricular
repolarization. The P-R interval - AV conduction time, and the Q-T interval -
ventricular action potential duration.
• Atrial dysrhythmias - prevent filling of the ventricles and ↓ cardiac output by
33%.
• Ventricular dysrhythmias - ineZective filling of the ventricle and ineZective
pumping results in ↓ or absent cardiac output.
 Antidysrhythmic Drugs
• Ventricular tachycardia, ventricular fibrillation = followed by
death. CPR is necessary!
• Cardiac dysrhythmias follow an MI or can result from hypoxia (lack
of O2 to body tissues), hypercapnia (↑ CO2 in the blood), thyroid
disease, CAD, cardiac surgery, excess catecholamines, or
electrolyte imbalance.
 Cardiac Action Potential
• Electrolyte transfer occurs through the cardiac muscle cell
membrane. When NA and CA enter the cardiac cell,
depolarization (myocardial contraction) occurs. NA enters rapidly
to start the depolarization, and CA enters later to maintain it. CA
influx leads to ↑ release of intracellular CA from the sarcoplasmic
reticulum, resulting in cardiac contraction. Myocardial ischemia
contraction - irregular.

Cardiac Action Potential

• Cardiac action potentials are transient depolarizations followed
by repolarizations of myocardial cells.
• Five phases. Phase 0 - rapid depolarization caused by an influx of
NA ions. Phase 1 is initial repolarization - termination of NA ion
influx. Phase 2 - plateau and is characterized by the influx of CA
ions, which prolong the action potential and promote atrial and
ventricular muscle contraction. Phase 3 - rapid repolarization
caused by influx of K ions. Phase 4 is the resting membrane
potential between heartbeats.
 Types of Antidysrhythmic Drugs
• Desired action of antidysrhythmic (antiarrhythmic) drugs is to
restore the cardiac rhythm to normal.
• Four classes: (1) NA (fast) channel blockers IA, IB, and IC; (2) beta
blockers; (3) drugs that prolong repolarization; and (4) CA (slow)
channel blockers.

Types of Antidysrhythmic Drugs

A. Class I
• Class I: NA Channel Blockers – SCBs ↓ NA influx into cardiac cells.
Responses to the drug are ↓ conduction velocity in cardiac
tissues; suppression of automaticity, which ↓ the likelihood of
ectopic foci; and ↑ recovery time.
• Three subgroups of NA channel blockers. Class IA slows
conduction and prolongs repolarization. Class IB slows
conduction and shortens repolarization. Class IC prolongs
conduction with little to no eJect on repolarization.
 Types of Antidysrhythmic Drugs
• Lidocaine, a Class IB SCBs - treat acute ventricular dysrhythmias.
It slows conduction velocity and ↓ action potential amplitude.
Onset - IV is rapid. 1/3 of lidocaine reaches the general
circulation. A bolus of lidocaine is short-lived.

Types of Antidysrhythmic Drugs

Class II: Beta Blockers
• ↓ conduction velocity, automaticity, and recovery time. Beta blockers are
more frequently prescribed for dysrhythmias than SCBs.
• Pharmacokinetics: cardioselective beta drug acebutolol is well absorbed in
the GI. It is metabolized in the liver to active metabolites; 80% to 100% of the
drug is eliminated in the bile via feces, and urine. The half-life for the drug is 3
to 4 hours.
• Pharmacodynamics: Acebutolol for ventricular dysrhythmias, angina
pectoris, and HPN. Onset – 1 to 2 hours; peak – 2.5 to 3.5 hours, and duration
– 12 - 24 hours.
 Types of Antidysrhythmic Drugs
Class III: Drugs that Prolong Repolarization
• Used in emergency treatment of ventricular dysrhythmias when other
an6dysrhythmic are ineffec6ve. Amiodarone ↑ the refractory period
and prolongs the ac6on poten6al dura6on.

Types of Antidysrhythmic Drugs

Class IV: CCBs
• Fourth class - Verapamil is a slow CCBs blocks CA influx, thereby
↓ the excitability and contractility (- inotropic) of the myocardium.
It ↑ the refractory period of the AV node, which ↓ ventricular
response. Verapamil is contraindicated for patients with AV block
or HF.
 Antidysrhythmic Drugs
• SE and AE: Quinidine - first drug for cardiac dysrhythmias, N and V diarrhea,
confusion, hypotension, ♥ block, and neurologic and psychiatric symptoms.
Procainamide causes less cardiac depression than quinidine.
• ↑ doses of lidocaine - cardiovascular depression, bradycardia, hypotension,
seizures, blurred vision, and double vision. Others - dizziness,
lightheadedness, and confusion. Contraindicated - patients with advanced
AV block. Caution in patients with liver disorder and HF.
• Mexiletine and tocainide similar SE to lidocaine. Contraindicated for use in
patients with cardiogenic shock or in those with second- or third-degree ♥
block.

Antidysrhythmic Drugs
• SE and AE: Beta blockers - bradycardia and hypotension.
Bretylium and amiodarone – N and V, hypotension, and neurologic
problems. CCBs – N and V, hypotension, and bradycardia.
• All antidysrhythmic drugs are potentially prodysrhythmic. The
pharmacologic activity of the drug on the ♥ and the inherently
unpredictable activity of a diseased ♥ , with or without the use of
drugs.
• Life-threatening ventricular dysrhythmias can result from
appropriate and skillful attempts at drug therapy to treat
patients with heart disease.
 Antidysrhythmic Drugs
• Nursing Process: Health and drug history, VS, ECG, cardiac
enzymes, IV push or bolus for 2 to 3 mins, " (alcohol , caJeine,
and tobacco), report side eJects

Antidysrhythmic Drugs
Generic Example
Class I
Sodium Channel Blockers IA Disopyramide phosphate
Sodium Channel Blockers IB Lidocaine, Mexiletine HCl
Sodium Channel Blockers IC Flecainide, Propafenone
Class II
Beta-Adrenergic Blockers Acebutolol HCl, Esmolol,
Propranolol
 Antidysrhythmic Drugs
Generic Example
Class III: Drugs that prolong Adenosine, amiodarone HCl,
repolarization ibutilide
Class IV: CCBs Verapamil, diltiazem

Hypertension
• HPN leads to MI, renal failure, and death.
• Essential HPN – most common, 95% of persons with ↑ BP. Origin
unknown, contributing factors may include family Hx of HPN,
hyperlipidemia, African-American, diabetes, aging, stress,
excessive alcohol ingestion, smoking, and obesity.
• Ten percent of HPN - renal and endocrine disorders and are
classified as secondary HPN.
 Selected Regulators of Blood Pressure
• Kidneys and blood vessels - maintain a “normal” BP. Kidneys regulate BP by
control of fluid volume and the RAAS. Kidneys control NA and H2)
elimination/retention, which aZects cardiac output and systemic arterial BP.
• Renin (from the renal cells) stimulates production of angiotensin II (a potent
vasoconstrictor), which causes the release of aldosterone.
• Baroreceptors in the aorta and carotid sinus and the vasomotor center in the
medulla also assist in the regulation of BP. Catecholamines such as
norepinephrine, released from the sympathetic nerve terminals, and
epinephrine, released from the adrenal medulla, ↑ BP through
vasoconstriction activity.
 Selected Regulators of Blood Pressure
• Other hormones that contribute to BP regulation are antidiuretic hormone
(ADH), atrial natriuretic peptide (ANP) hormone, and brain natriuretic peptide
(BNP) hormone.
 Selected Regulators of Blood Pressure
• Physiologic Risk Factors: High in saturated fat and carbohydrate alcohol,
obesity (2/3 of obese are HPN)
• Normal weight loss and mild to moderate sodium restriction.
• Cultural Responses to Antihypertensive Agents: Beta blockers and ACE
inhibitors is less effective for the control of HPN in African Americans unless
combined or given with a diuretic. Effective for African Americans are alpha1
blockers and CCBs, diuretics as the initial monotherapy for controlling HPN.
• Asian Americans are twice as sensitive as whites to beta blockers and other
antihypertensives. A reduction in antihypertensive dosing is frequently
needed.
 Selected Regulators of Blood Pressure
• Hypertension in Older Adults: Both systolic and diastolic HPN are
associated with ↑ cardiovascular morbidity and mortality. Antihypertensive
therapy ↓ in cardiovascular disorders is 34% for stroke and 19% for coronary
♥ disease.
• Frail or institutionalized persons is orthostatic hypotension - episode of
sudden low BP presents dizziness due to blood pooling in lower extremities.
Older adults – SNS does not respond as quickly especially when potentiated
by antihypertensive drug administration. Older adults with HPN - modify
lifestyle activities, restricting dietary NA to 2400 mg daily, " tobacco,
modifying diet, exercising, and ↓ stress.

Nonpharmacological Control of
Hypertension
• Stress-reduction techniques, exercise, salt restriction, ↓ alcohol
ingestion, and smoking cessation.
• Nonpharmacologic + antihypertensive drugs
 Pharmacological Control of Hypertension
• Individualized approach but often more than one antihypertensive
is used to control BP, which also may lead to less adverse eJects.
• Antihypertensive drugs are classified into six categories: (1)
diuretics, (2) sympatholytics (sympathetic depressants), (3)
direct-acting arteriolar vasodilators, (4) ACE inhibitors, (5)
angiotensin II receptor blockers (ARBs), (6) direct renin inhibitors,
and (7) CCBs.

Pharmacological Control of Hypertension

1. Diuretics - Diuretics promote sodium depletion, which
decreases extracellular fluid volume (ECFV). Diuretics are effective
as first- line drugs for treating mild hypertension.
(Another Slide for Diuretics)
• HCTZ - controlling mild HPN by ↓ excess fluid volume.
• Thiazide diuretics are not recommended for patients with renal
insufficiency (creatinine clearance <30 mL/min).
• Loop (high-ceiling) diuretics such as furosemide are usually
recommended, because they do not depress renal blood flow.