Pharmacology:

Cardiovascular
System Drugs Part 1
Structure and
Function of
the Heart
Cardiac
Conduction
 occurs when the cell reaches a point of stimulation. The sodium gates

Phase 0 open along the cell membranes, and the sodium rushes into the cell,
resulting in a positive flow of electrons into the cell – an electrical
potential.

Phase 1 sodium ion concentrations are equal inside and outside the cell.

plateau stage) – the cell membrane is less permeable to sodium.

Phase 2 Calcium slowly enters the cell, and potassium begins to leave the cell.
The cell membrane is beginning to return to its resting state.

Phase 3 period of rapid repolarization as the gates are closed and potassium
moves out of the cell.

Phase 4 the cell comes to rest as the sodium – potassium pump returns the
membrane to its previous state.
 Coronary arteries and veins
Factors affecting the Heart’s use of
oxygen or oxygen consumption

 Heart rate
 Preload
 Afterload
 Ventricular stretch
Renin –
Angiotensin –
Aldosterone
System
ACE Inhibitors
 Act in the lungs to prevent ACE from converting
angiotensin I to angiotensin II, a powerful
vasoconstrictor and stimulator of aldosterone
release.
 Decreased cardiac workload by decreasing
peripheral resistance and blood volume.
 Contraindications: allergy, impaired renal function,
pregnancy, and lactation
 Caution: heart failure, salt/volume depletion,
women of child-bearing age
 Adverse effects: reflex tachycardia, chest pain,
heart failure, and cardia arrhythmia, GI irritation,
ulcers, constipation, liver injury, renal
insufficiency, renal failure and proteinuria
 Benazepril, enalapril and fosinopril – cough
 Captopril – fatal pancytopenia, cough and GI
distress
 Moexipril – GI distress, skin effects, cough and
cardiac arrhythmia, fatal MI and pancytopenia

Perindopril and lisinopril – fatal pancytopenia, fatal airway obstruction

 ARB selectively bind with the
angiotensin II receptors in vascular
smooth muscles and in the adrenal
cortex to block vasoconstriction and the
release of aldosterone.
 It slows down the progression of renal
disease in patients with HPN and DM.
 Contraindication: allergy, pregnancy,
lactation
 Caution: hepatic and renal dysfunction,
hypovolemia.
 Adverse effects: headache, dizziness,
syncope, weakness, hypotension, GI,
complain, diarrhea, abd pain, nausea,
dry mouth, tooth pain, cough, rash, dry
skin, alopecia, renal damage.
 Decrease serum level if taken with phenobarbital, indomethacin or rifamycin.
 Decrease antihypertensive effects if combined with ketoconazole, fluconazole
or diltiazem.
 Do not use with ACE inhibitor or Renin inhibitor
 Calcium channel blocker –inhibit the
movement of calcium ions across the
membranes of the myocardial and arterial
muscle cells, altering the action potential and
blocking muscle cell contraction.
 Contraindications: allergy, heart block, sick
sinus syndrome, renal and hepatic
dysfunction, pregnancy and lactation.
 Adverse effects: dizziness, light-headedness,
headache and fatigue, nausea, hepatic injury,
hypotension, bradycardia, peripheral edema
and heart block, skin flushing and rash
 Vasodilators – act directly on vascular smooth muscle to cause muscle relaxation, leading to vasodilation
and drop in BP. They are mostly reserved for use in severe hypertension, malignant hypertension, or
hypertensive emergencies.
 Contraindications: allergy, cerebral insufficiency, pregnancy
 Caution: PVD, CAD, heart failure or tachycardia
 Adverse effects: dizziness, anxiety, headache, reflex tachycardia, heart failure, chest pain, edema, skin
rash, abnormal hair growth (minoxidil), GI upset, nausea, vomiting.
 Cyanide toxicity – dyspnea, headache, vomiting, dizziness, ataxia, loss of consciousness, imperceptible
pulse, absent reflexes, dilated pupils, pink color, distant heart sounds, shallow breathing, hypothyroidism.
 Nonselective Adrenergic blocking Agents
MOA/ Indications Blocks alpha and beta receptors and used
primarily to treat cardiac-related conditions
Contraindications Bradycardia, AVB, asthma, shock or HF, lactation
Caution DM, bronchospasm,, pregnancy
Adverse Reaction Dizziness, paresthesia, insomnia, depression,
fatigue, vertigo, N/V, diarrhea, flatulence,
arrhythmia, hypotension, PE,CVA, cough,
hypoglycemia
Amiodarone - antiarrhythmic
Carvedilol – HPN and HF, LV dysfunction after
MI
Labetalol – pheochromocytoma, clonidine
withdrawal
Nonselective Alpha-Adrenergic Blocking
Agents
Blocks the post synaptic alpha1 adrenergic
receptors, decreasing sympathetic tone in the
vasculature and causing vasodilation . It also
blocks the presynaptic alpha receptors
preventing feedback control of NE release
leading to reflex tachycardia
CAD or MI
Pregnancy and lactation
Hypotension, angina, MI, CVA, flushing.
Tachycardia and arrhythmia, HA, weakness,
dizziness, N/V and diarrhea
Phentolamine
Alpha 1 selective adrenergic blocking agents
Blocks the postsynaptic alpha1 receptors sites
causing a decrease in vascular tone and
vasodilation. Doesn’t block the presynaptic alpha 2
receptor site. They block the smooth muscle
receptors in the prostate, prostatic capsule, urethra
and urinary bladder neck
Lactation
HF, RF, hepatic impairment , pregnancy
SNS blockage effects, priapism, nasal congestion
and reddened eyes
Alfuzosin
Doxazosin
Prazosin
Tamsulosin
Terazosin
 Nonselective Beta-Adrenergic Blocking Agents Beta 1- Selective Adrenergic Blocking Agents

MOA/ Indication Blocks the beta-receptors in the heart and in the JG apparatus. Selectively blocks beta 1 receptors in the SNS.
> Dec HR, contractility, excitability and membrane stabilizing >doesn’t prevent sympathetic bronchodilation
effects leading to dec arrhythmia, dec cardiac workload and dec o2
consumption.

Contraindication Bradycardia, AVB, shock, HF, bronchospasm, COPD, acute Bradycardia, AVB, cardiogenic shock, HF hypotension, lactation
asthma, pregnancy

Caution Diabetes, hypoglycemia, thyrotoxicosis, renal and hepatic DM, thyroid disease or COPD,pregnancy
dysfunction

Adverse reaction AR d/t blockage of receptors in the SNS AR related to blocking of beta 1 receptors in the SNS

Carteolol Acebutolol
Metipranolol Atenolol
Nadolol Betaxolol
Nebivolol Bisoprolol
Propranolol Esmolol
Sotalol – ventricular arrhythmia, AF, Aflut Metoprolol
Timolol - glaucoma
 Sympathetic Nervous System Blockers
 Beta-blockers block vasoconstriction, decrease heart rate, decrease cardiac muscle contraction, and tend to increase
blood flow to the kidneys, leading to a decrease in the release of renin. These drugs have many adverse effects and
are not recommended for all people. They are often used as monotherapy in step 2 treatment, and in some patients
they control BP adequately. Beta-blockers used to treat hypertension include the following agents: Acebutolol
(Sectral), atenolol (Tenormin), betaxolol (generic), bisoprolol (Zebeta), metoprolol (Lopressor), nadolol (Corgard),
nebivolol (Bystolic), pindolol (generic), propranolol (Inderal), and timolol (generic).
 Alpha- and beta-blockers are useful in conjunction with other agents and tend to be somewhat more powerful,
blocking all of the receptors in the sympathetic system. Patients often complain of fatigue, loss of libido, inability to
sleep, and GI and genitourinary disturbances, and they may be unwilling to continue taking these drugs. Alpha- and
beta-blockers used to treat hypertension include the following agents: Carvedilol (Coreg) and labetalol (Trandate).
 Alpha-adrenergic blockers inhibit the postsynaptic alpha1 -adrenergic receptors, decreasing sympathetic tone in the vasculature
and causing vasodilation, which leads to a lowering of BP. However, these drugs also block presynaptic alpha2 -receptors,
preventing the feedback control of norepinephrine release. The result is an increase in the reflex tachycardia that occurs when
BP decreases. These drugs are used to diagnose and manage episodes of pheochromocytoma, but they have limited usefulness
in essential hypertension because of the associated adverse effects. Alphaadrenergic blockers include the following agents:
Phenoxybenzamine (Dibenzyline) and phentolamine (Regitine).
 Alpha1 -blockers are used to treat hypertension because of their ability to block the postsynaptic alpha1 -receptor sites. This
decreases vascular tone and promotes vasodilation, leading to a fall in BP. These drugs do not block the presynaptic alpha2 -
receptor sites, and therefore the reflex tachycardia that accompanies a fall in BP does not occur. Alpha1 -blockers used to treat
hypertension include the following agents: Doxazosin (Cardura), prazosin (Minipress), and terazosin (generic).
 Alpha2 -agonists stimulate the alpha2 -receptors in the CNS and inhibit the CV centers, leading to a decrease in sympathetic
outflow from the CNS and a resultant drop in BP. These drugs are associated with many adverse CNS and GI effects, as well as
cardiac dysrhythmias. Alpha2 -blockers used to treat hypertension include the following agents: Clonidine (Catapres),
guanfacine (Tenex), and methyldopa (generic).
 Diuretics are drugs that increase the excretion of sodium and water from the kidney. Diuretics are very important for
the treatment of hypertension. These drugs are often the first agents tried in mild hypertension; they affect blood
sodium levels and blood volume. A somewhat controversial study, the Antihypertensive and Lipid-Lowering
Treatment to Prevent Heart Attack Trial, reported in 2002 and supported with follow-up studies that patients taking
the less expensive, less toxic diuretics did better and had better BP control than patients using other antihypertensive
agents. Replications of this study have supported its findings, and the use of a thiazide diuretic is currently
considered the first drug used in the stepped care management of hypertension. Although these drugs increase
urination and can disturb electrolyte and acid–base balances, they are usually tolerated well by most patients.
Diuretic agents used to treat hypertension include the following: Thiazide and thiazide-like diuretics: chlorothiazide
(Diuril), hydrochlorothiazide (HydroDIURIL), methyclothiazide (generic), chlorthalidone (generic), indapamide
(generic), and metolazone (Zaroxolyn) Potassium-sparing diuretics: amiloride (Midamor), spironolactone
(Aldactone), and triamterene (Dyrenium)
Antihypotensive agents
 Sympathomimetic fdrugs are the 1st
choice for treating severe hypotension
or shock.
 Midodrine – an alpha – specific agent
used to treat orthostatic hypotension.
  a condition that was once called “dropsy” or
decompensation, is a syndrome that usually involves
dysfunction of the cardiac muscle, of which the
sarcomere is the basic unit.
 Causes:
- CAD
Heart Failure - Cardiomyopathy
- Hypertension
- Valvular Heart Disease
> S/Sx – Left sided vs Right sided HF
Treatment of
CHF
 Vasodilators – ACE inhibitors and nitrates to decrease
cardiac workload, relax vascular smooth muscle to
decrease afterload, and allow pooling in the veins,
thereby decreasing preload.
 Diuretics decrease blood volume, which decreases
venous return and blood pressure, resulting in
decreased afterload, preload, and cardiac workload
 Beta Adrenergic agonist – stimulate the beta receptors
in the sympathetic nervous system, increasing calcium
flow into the myocardial cells and causing increased
contraction (positive inotropic effect)
 Human B type natriuretic peptide – produced by
myocardial cells and brain cells as a compensatory
response to increase workload and increased
stimulation by the stress hormones. They bind to
endothelial cells, leading to dilation and resulting in
decreased venous return, peripheral resistance and
cardiac workload. Nesiritide (Natrecor).
Cardiotonic
Agents
 Cardiotonic (Inotropic) drugs
affect the intracellular calcium
levels in the heart muscle, leading
to increased contractility.
 Cardiac glycoside Phosphodiesterase Inhibitor Hyperpolarization-Activated Cyclic
(Digoxin) (Milrinone) Nucleotide-Gated Channel Blocker
(Ivabradine)
Action Increases intracellular calcium and allows Blocks the enzyme phosphodiesterase which Blocking the HCNs slows the heart’s pacemaker,
more calcium to enter myocardial cells during leads to an increase in myocardial cyclic the sinus node, in the repolarizing phase of the
depolarization adenosine monophosphate (cAMP) thus action potential.
increasing calcium level in the cell

Effects (+) Inotropic (+) Inotropic (-) Chronotropic

Increase CO and renal perfusion
(-) Chronotropic
(-) Conduction velocity

Indications HF, Afib, A. flutter, Paroxysmal A. tach Short term treatment of HF that has not Stable symptomatic HF with a left ventricular EF
responded to digoxin and diuretics and of 35% or less, in sinus rhythm with a HR or 70 or
vasodilators more and with CI to beta blockers

Contraindications Vtach, vfib, heart block, SSS, idiopathic Severe aortic and pulmonic valvular disease, Active, decompensated HF, hypotension, SSS of
hypertrophic subaortic stenosis (IHSS), acute acute MI, FVD, ventricular arrhythmia AV blocks, resting HR of less than 60, on
MI, renal insufficiency, electrolyte pacemaker, severe hepatic impairment, lactation
abnormalities

Caution Pregnancy and lactation, pediatric and geriatric Elderly, pregnancy and lactation AF, moderate AVB, pregnancy (fetal toxicity)
clients

Adverse effects Headache, weakness, drowsiness, and vision
changes (yellow halo around objects); GI
upset: anorexia, N/V, diarrhea, arrhythmia,
digitalis toxicity – give digoxin immune fab
Ventricular arrhythmia, hypotension and chest Bradycardia, HPN, AF, luminous phenomena
pain. GI effects: anorexia, N/V and abd. Pain.
Hypersensitivity reaction: vasculitis,
pericarditis, pleuritis and ascites.
Thrombocytopenia and burning at IV site.
Antiarrhythmic
Agents
 Affect the action potential of the
cardiac cells by altering their
automaticity, conductivity, or both.
 Class I - Na channel blocker
 Class II beta blocker
 Class III K channel blocker
 Class I Class I II III IV

Ia Ib Ic Beta blocker K channel blocker Calcium channel blocker

Actions and Indications Stabilize the cell membrane by binding to Na channels, depressing phase Blocks beta receptors Blocks K channels and Blocks the movement of
0 of the action potential and changing its duration causing depression of slow the outward calcium ion across the
phase 4 AP. movement of K during cell membrane,
 Decrease HR Phase 3 of AP, depressing the generation
 depress phase 0  Depress phase 0  Markedly depress  Slowing of prolonging it. of action potentials and
 Prolong the duration  Shorten the duration phase 0 conduction through delaying phase 1 and 2
of action potential of action potential  Extreme slowing of the AV node, dec of repolarization,
conduction, little release of renin slowing automatic and
effects on AP SVT and PVC conduction.

VF and Pulseless VT
Ventricular arrhythmias

Contraindications Bradycardia, AVB, Ibutilide / dofetilide – SSS and AVB, pregnancy

Bradycardia, AVB, HF, hypotension, shock, electrolyte imbalance, lactation cardiogenic shock, HF, AVB and lactation, HF and
asthma, respiratory Sotalol - arrhythmia hypotension.
depression, pregnancy
and lactation

Caution Diabetes, thyroid, renal Shock, hypotension and Idiopathic hypertrophic

and hepatic dysfunction respiratory depression, subaortic stenosis,
Renal and hepatic dysfunction, pregnancy QTC prolongation, renal impaired renal and liver
and hepatic dysfunction function

Adverse Effects Dizziness, insomnia, N/V and GI distress, Dizziness, weakness,

hypotension, weakness, dizziness, fatigue, depression and
CNS depression, changes in taste, N/V, proarrhythmic, hypotension, hypotension, arrhythmia.
bradycardia, AVB, Amiodarone – fatal liver HA, N/V, hypotension,
vasodilation, cardiac arrest, respiratory depression, potential bone marrow bronchospasm, anorexia, toxicity, ocular abnormalities, HF, shock, arrhythmias,
depression N/V, loss of libido cardiac dysrhythmia edema