Cardiovascular Pharmacology – Pharmacotherapy Review
Edward JN Ishac. Ph.D.
Professor, Dept. Pharmacology & Toxicology
Office: Smith Bldg, Room 742
Email: eishac@vcu.edu Tel: (804) 828 2127
Table 1. Pregnancy Drug Classification (FDA, 1979)
Category: A
These drugs are the safest. Well-designed studies in people show no risks to the
fetus. (eg. Folic acid, Vitamin B6)
Category: B
Studies in animals show no risk to the fetus, and no well-designed studies in
people have been done. OR
Studies in animals show a risk to the fetus, but well-designed studies in people
do not. (eg. alpha-methyl dopa, clopidogrel, insulin, acetaminophen)
Category: C
No adequate studies in animals or people have been done. OR
In animal studies, use of the drug resulted in harm to the fetus, but no
information about how the drug affects the human fetus is available.
(most drugs, 60%)
Category: D
Evidence shows a risk to the human fetus, but benefits of the drug may
outweigh risks in certain situations. For example, the mother may have a lifethreatening disorder or a serious disorder that cannot be treated with safer drugs
(eg. Amiodarone, lithium, phenytoin, ACEIs).
Category: X
Risk to the fetus has been proved to outweigh any possible benefit
(eg. Statins, warfarin, misoprostol, thalidomide).
1. Proven safety in pregnancy (A, B):
a. Alpha-methyl dopa (B)
b. Clopidogrel (B)
2. Need to weigh risk vs Benefit for use in pregnancy: (C)
a. Nifedipine (C)
b. Spirolactone (C)
c. Beta-blockers (C)
d. Labetalol (C)
e. Prazosin (C)
f. Hydralazine (C)
g. Heparin (C)
h. Ezetimibe (C)
i. Nitroglycerin (C)
j. Verapamil (C)
k. Cholestyramine (C)
l. Quinidine (C)
m. Hydrochlorothiazide (B)
n. Sildenafil (B)
3. Not advised or Contraindicated in pregnancy (D or X):
a. ACE inhibitors (D)
b. Atenolol (D)
c. ARBs (D)
d. Statins (X)
e. Aliskiren (D)
f. Warfarin (X)
g. Amiodarone (D)
h. Phenytoin (D)
i. Aspirin (D)
j. Clofibrate (C)
Figure 1. Sites of Action of Lipid-Lowering Agents
6
3
1
4
2
5
1. Resins
2. Statins (best ↓LDL)
3. Niacin (best ↑HDL)
4. Fibrates (best ↓TGs)
5. Ezetimibe
6. Omega-3 Fatty acids
Table 2. Adult Treatment Panel (ATP) III Lipid Guidelines (2004)
Desirable
mg/dl
Borderline
to high
Total Cholesterol
< 200
200-239
> 240
0-1 RF, 10 yr <10% - <160 mg/dl
LDL Cholesterol
< 130
130-159
> 160
2 RF, 10 yr 11-20% - <130 mg/dl
> 60
CHD or CHD equivalent (ie. PAD,
diabetes), 10 yr > 20% - <100 mg/dl
(optimal < 70mg/dl)
> 200
↑Risk → ↑Pharmacotherapy
HDL Cholesterol:
Men
Women
Triglycerides
> 40
> 50
<120-150
120-199
High
LDL-C Goals
RF = Risk factors
Risk Factors: age > 45 (male) and 55 (females), family history of early vascular disease or
hyperlipidemia, current smoker, elevated BP, obesity, diabetes, high LDL and low HDL.
Total-C = LDL-C + HDL-C + VLDL-C;
VLDL-C = TGs/5
Table 3. Summary of Drug Classes used in Hyperlipidemia
Lipid-Lowering Agents
LDL HDL
Resins (Sequestrants)
 Bile acid reabsorption
Cholestyramine


Statins [-statins]
HMG-CoA reductase inhibitors
Atorvastatin


Niacin: inhibit adipose lipolysis
(Nicotinic A. + Vit. B3)
 VLDL release


Fibrates: activate PPARs
Lipoprotein lipase stimulators.
Fenofibrate, Gemfibrozil


Ezetimibe
Inhibit. Cholesterol absorption.




Omega-3 Fatty acids
Inhibit VLDL-TG synthesis
TGs
Notes

Patients hate it, gritty taste, GI discomfort,
constipation.,  LDL-Rec.,  VLDL,  fat
soluble Vits A,D,E,K, warfarin, thiazide,
digoxin absorption
 Liver toxicity, myopathy,  mylination CI:
pregnancy, children.  LDL-Rec, most
substrates 3A4
 Flushed face (with aspirin), GI, glucose
intolerance (diabetes), gout, liver toxicity,
ulcer
 Nausea, skin rash, headache,  statin
myopathy (fenofibrate safer).  LDL
synthesis,  gallstone risk
Newest class: No major adverse effects
noted (↑cancer risk?), clinical benefit not
proven, not frontline
 ↑bleeding, fishy aftertaste, diabetes,
thrombocytopenia, GI disorders
Table 4. Drug Nomenclature – Suffixes, Infixes
Drug Class
HMG-CoA inhibitors
Suffix
Examples
-vastatin
Atorvastatin, simvastatin, lovastatin
Fibrates
-fibr-
Fenofibrate, gemfibrozil, clofibrate
Beta-blockers (A-M: β1)
-olol
Propranolol, metoprolol, atenolol, [sotalol]
Alpha1-blockers
-osin
Prazosin, doxazosin, tamsulosin
ACE inhibitors
-pril
Captopril, lisinopril, enalapril
ARBs
-sartan
Losartan, valsartan, irbesartan
Renin inhibitors
-kiren
Aliskiren, remikiren
Dihydropyridines (CCBs)
-dipine
Nifedipine, amlodipine, nimodipine
PDE 5 inhibitors (cGMP)
-afil
Sildenafil, vardenafil, tadalafil
Thrombin inhibitors
-rudins
Hirudin, bivalirudin, lepirudin
LMW Heparins
-parin-
Enoxaparin, dalteparin, fondaparinux
Thrombolytic agents
-plase
Alteplase, retaplase, [streptokinase]
Drug Class
Hypertens.
HF
Arrhyth.
Angina
Notes / Contraindications / Cautions
E. ISHAC 2010.3
Beta-Blockers (BBs)   

Glycosides: Digoxin 
Vasodilators

Many Rx interactions, [K+] important, low K+toxicity, use HF

Flushing, dizziness, headache, nausea, reflex tachycardia

Effects enhanced in depolarized, damaged tissue, Phase.0, CV

 NO/cGMP, tolerance (off periods), hypotension, flushing, dizziness,
HF (CI: unstable HF, bronchospasm, bradycardia, depression);
insomnia, Raynaud D. Caution in diabetes, asthma (use 1-)
Ca++-Blockers (CCBs) 
  HF, constipation, edema, rash, reflex HR (Nifed.), gingival h.
ACEI/ARB/Aliskiren   
Angioedema, hyperkalemia, tetrogenic, glossitis, cough (acei), taste

Diuretics (Thiazides)   
GFR >30, hypokalemia (CG); diabetes (↓glucose tol), plasma[Ca]





Na+-Channel blockers

Nitrates




headache, reflex tachycardia, many forms oral, iv, spray, patches
AGENT (Trade Name®)
ANTIHYPERTENSIVE AGENTS
NOTES
Diuretics
I = drug interactions
S = side effects CI = contraindications/cautions HT = Hypertension HF = Heart failure
Thiazides: Hydrochlorothiazide (Esidrix) Hypertension, HF, Nephrogenic DI (with
Na reabsorb, K+ loss, Blood volume, CG
Metolazone, Chlorthalidone, Indapamide low Na), act on Distal tube, plasma[Ca++] toxicity, less effective in lean individual. Loop D.
more powerful than thiazides and usually for acute
Loop Diuretics: Furosemide
(Lasix) HF, acute hypertension, edema, act on
use (ie edema) S: hypokalemia, glucose tolerance
Bumetanide, Torsemide, Ethacrynic acid Loop of Henle, plasma[Ca++]
Thz), photosensitivity, hearing loss (loop)
Potassium Sparing
Hypertension, Heart failure (HF)
Act on Collecting tube, no K+ loss, VG combo Rx,
Spironolactone
(Aldactone) (others Eplerenone, Triamterene)
block ALD (Spiro & Epler.), block Na chan (Triamt)
Acetazolamide
(Diamox) Glaucoma, reverse alkalosis, mountain s. Proximal tube, Carbonic A inhibitor, low use
Mannitol
(Osmitrol) Acute renal failure, cranial p. Rx excretion Proximal tube, freely filtered, increase osmolarity
Angiotensin Converting Enzyme Inhibitors (ACEI) & Angiotensin Receptor Blockers (ARBs)
SNS = Sympathetic nervous system
Captopril
[-opril]
(Capoten) Hypertension (HT), Heart failure (HF)
(Prinivil) ACE inhibitors (ACEI)
Lisinopril
Enalapril
(Vasotec) HF, Hypertension (acute & chronic)
Losartan
[-sartan]
Aliskiren
(Cozaar) HT, HF, (others Irbesartan, Valsartan)
(Tekturna) Hypertension (VG if high plasma [renin])
Beta-Adrenoceptor Antagonists
Propranolol
[ –olol]
(A-M 1-selective)
Pindolol
Timolol
AT-II, TPR, Aldosterone, SNSbradykinin
S: cough, hyperkalemia, altered taste (Zn), glossitis,
food reduces absorp. CI: Low GFR, pregnancy (all)
ACEI, iv emergency HT, prodrug, T1/2 6 hr
Type AT1 blocker (ARB), as per ACEI but no cough
direct renin inhibitor →  angiotensin I, no cough
ISA = Intrinsic sympathetic activity (partial agonist), LA = Local anesthetic action (membrane-stable)
(Inderal) Hypertension, angina, arrhythmias, tremor,  non-selective, LA-action, no ISA; v. useful group,
migraine, hyperthyroidism, panic stress
depression, insomnia CI: HF, asthma, diabetes
(Visken) Angina, hypertension, arrhythmia
 LA-action, ISA, angina commonly
(Blocadren)
, no LA-action, no ISA, glaucoma ( secretion)
Glaucoma, HT, angina, arrhythmia
(Lopressor) Hypertension, arrhythmia, HF, angina, MI 1, LA-action, no ISA, arrhythmia, common agent
Metoprolol
Atenolol
(Tenormin) Hypertension, angina (common), HF, MI
1, no LA-action, no ISA, CI: pregnancy
Sotalol
(Betapace) Arrhythmia
, no LA-action, no ISA, block K+ (class III), QT
Esmolol
(Brevablock)
1, no LA-action, no ISA, very short acting (10 min)
Arrhythmia, angina
 / , some -agonist action (Labetalol)
DHP = Dihydropyridine class
CG = Cardiac glycoside
Labetalol (Normadyne), Carvedilol (Coreg) HT, HF (carvedilol), hypertensive crisis
Calcium Channel Blockers (CCBs)
Verapamil
(Isoptin, Calan) Hypertension, angina, arrhythmia
Diltiazem
(Cardizem)
Nifedipine
(Adalat)
Amlodipine
(3A4) Mainly cardiac, ↓HR, edema, constip. I: CG CI: HF
Hypertension, angina, arrhythmia
Both cardiac & arterioles,  SNS, ↓HR, CI: HF 
Hypertension, Raynaud D., PAD
Mainly arterioles, HR, edema, gingival hp. CI: HF
(Besylate, Maleate) Hypertension, angina, Raynaud D., PAD
Drugs Acting on the Sympathetic NS
Mainly arterioles, HR, edema, long acting, DHP
italic = less important agent
NE = Norepinephrine
Alpha-Adrenoceptor Antagonists
Hypertension, opioid & nicotine withdraw
[ADHD],
(-methyl-dopa → +Coombs test)
A& C = Acute & Chronic
2,  cns sympathetic outflow,  NE release,
rebound HT; S: dry mouth, sedation, impotence.
-methyl-dopa → -methyl-NE (2- agonist, preg)
PHT = Postural hypotension
Phenoxybenzamine
Pheochromocytoma (a & c), HT (a & c)
1, irreversible, S: PHT, reflex tachycardia, long act.
Pheochromocytoma, acute HT
, competitive, non-selective, S: PHT, reflex HR
Benign prostate hypertrophy (BPH),
hypertension (A & C)
1, competitive; no reflex tachycardia, first pass
effect S: PHT, nausea, drowsiness
Clonidine
(Catapres)
-Methyl-dopa
Phentolamine
Prazosin
[-azosin]
Terazosin
(Aldomet)
(Dibenzyline)
Tolazoline
Tamsulosin
Doxazosin
Miscellaneous Agents
Dopamine
Fenoldopam
[ ] = Questionable therapeutic value
(Intropin) Shock to BP (renal vasodil.?, D,), HF
(Corlopam)
Acute hypertension (BP), renal failure
TCA = Tricyclic antidepressants
1 / 1 / D receptors, precursor to NE, I: MAOI
D,A -receptor agonist, SE: HR, ocular P.,  K+
Rarely used  Trimethapan, Mecamylamine: BP, HT, Nn-ganglia blockers Reserpine (deplete NE), Guanethidine (NE release); HT
Vasodilators
Trade Name = (Italics)
Hydralazine
Nitroprusside
Minoxidil
(Apresoline)
Hypertension, HF (Bidil: hydralazine +
isosorbide dinitrate, Afro-Amercian)
(Nipride) Acute Hypertension crisis & HF
(Rogaine, Loniten) Hypertension, HF, baldness
Direct vasodilate, mainly arterioles TPR, combo Rx
S: reflex  SNS, flushing, palpitations, Lupus
 NO, cGMP, veins & arterioles TPR, iv only,
toxic oral S: cyanide toxicity, methhemoglobinemia
Open K+ channel, hypertrichosis, mainly arterioles,
Diazoxide
(Hyperstat)
Hypertensive crisis
TPR S: reflex SNS, fluid retention, hyperglycemia
(CO, EDP, ejection volume <40%)
HEART FAILURE (HF, ‘Hormonal storm’)
Cardiac Glycosides
TI = Therapeutic index, CA = Catecholamines
Digoxin
(Lanoxicaps, Lanoxin) HF, SVT (arrhythmia), Important Rx
(use for HF, caution in women
interactions: Toxicity; : Ca++ blockers ie
verapamil; diuretics, quinidine, CAs, Amiod
ACEI/ARBs Lisinopril, Losartan (ARB)
Hypertension, HF
Inhibit Na/K ATPase, [Ca++]i, [Na+]i, CO, vagus
activity, low TI; kidney T1/2 35hr, S: tachycardia,
visual halo, nausea, vomiting T: VT/VF; AV block
pre/afterload, use HF, break neurohumoral cycle
Positive Inotropic Agents
PDE = Phosphodiesterase
Dobutamine
(Dobutrex) HF (acute), cardiac stimulant
Milrinone, Amrinone
(Primacor, Inocor)
β-Blockers
Metoprolol, Carvedilol,
Bisoprolol (EBM)
Vasodilators: Hydralazine, Bidil et al
1, iv, CO, tolerance, may cause angina
HF (chronic & acute)
Inh. PDE3, pre/afterloadcAMP, [mortality, oral]
Hypertension, HF (FDA approved 2002),
angina, arrhythmias etc
Hypertension, HF (see earlier notes)
afterload, use HF, CI: for HF if bronchospasm,
unstable HF, significant bradycardia (low reserve)
 preload,  afterload,  mortality, not primary Rx
Nesiritide; -naturiuretic peptide (Natrecor) Severe decomp HF (Class IV, acute, iv)
Diuretics
Thiazides, Furosemide et al Hypertension, HF (see earlier notes)
cGMP  vasodilation,  pre- & afterload, 20 min
 pre- & afterload, congestion (furosemide) I: CG
ANGINA PECTORIS
CCBs=Calcium blockers, NO=Nitric oxide
(Nitrong, Nitrogard) Angina
CI: Sildendafil (Viagra)
Bioavailability
(10-20%),
Amyl & butyl
Isosorbide dinitrate & mononitrate
nitrites: Volatile, recreational abuse
β-blockers Propranolol etc (see earlier) Angina, HT, arrhythmia & others
NO, cGMP  vasodilation, preload coronary
flow, oral long duration, sublingual (fast), tolerance
(drug free time) S: headache, flushing, hypotension
 O2 demand CI: non-select. (HF), asthma, diabetes
CCBs Verapamil, Diltiazem, Nifedipne etc Angina, HT, arrhythmia
O2 demand, dilate coronary v O2 supply; CI: HF
Nitroglycerin
Peripheral Vascular Disease (PVD, PAD)
Aspirin
PAD, Prevent thrombosis
Warfarin
(Coumadin)
Heparin
DI = Drug Interactions
Inh. COX, Irrev. acetylation TXA2, platelet ag 
Pulmonary E, DVT, AF, MI Prevent thromb Inh. Vit. K.   II, VII, IX, X, CYP2C9, many DI
DVT, Pulmonary E, Prevent thrombosis
PAD, Prevent thrombosis
Act. antithrombin III, thrombocytopenia (HIT), T
1hr
nh. ADP receptor, platelet ag., cyp2C19, prodrug
Pentoxifylline (PDE4), Cilostazol (PDE3)
Intermittent claudication
Inh. PDE, cAMP, platelet ag., Inh. TNFa (Pento)
Dipyridamole
(Persantin)
PAD, Stroke, Prevent thrombosis
nh. TXA synthase, TXA2, platelet ag.,
Abciximab
(Reopro)
Adjunct angioplasty, prevent thrombosis
MABnh. Platelet IIB/IIA receptors, platelet ag.,
Erectile dysfunction
Inh. PDE5, cGMP, need arousal, CI: nitrates,  B
Acute MI, Pulmonary E. (clot-busters)
Activate plasminogendissolve clot, best < 2hr
SVT Supraventricular tachycardia
Clopidogrel (Plavix),
Ticlopidine
Sildendafil, Vardenafil,
Streptokinase,
Tadalafil
Alteplase,
Reteplase
ANTIARRHYTHMIC AGENTS
Phase 0:Fast upstroke Phase 1:Partial repolarization
Phase 2:Plateau
Phase 3:Repolarization
Phase 4:Forward current
Nai+ open,
Na+ close, K+ open/close
Cai++ open, Ko+ leak
Ca++ close, Ko+ open
K+ close, Na+ Ca++ leak in
Sodium Channel blockers
APD = Action potential duration, CV = conduction velocity, RP = Refractory period
Quinidine
Disopyrimide
Procainamide
Lidocaine
(Xylocaine) VT, VF (old DOC), iv, im
Phenytoin
Flecainide
β-Blockers
Atrial arrhythmias, SVT
(Proneotyl) Ventricular arrhythmias; NAPA (Class III)
(Dilantin) Arrhythmia, oral anticonvulsant
(Tambocor)
Ventricular arrhythmia
Metoprolol etc, see earlier
Angina, HT, arrhythmia (SVT) & others
Esmolol (10min), Sotalol (also Class III) Sotalol (also VT/VF)
Potassium Channel Blockers
Class IA, Moderate block Phase 0, CV, QT, APD
S: M-, -receptor (TPR) block, diarrhea, nausea,
cardiac dep., Lupus (Proca) I: Quinidine-CG, tinnitus
Class IB, Minimal block Phase 0, shorten Phase 3,
CV (least), phenytoin-gingival H. T: least toxicity
Class IC, Marked block Phase 0, CV (marked), no
chg APD T:  mortality, last resort agents
Class II, suppress Ph 4, SNS action on heart, CV,
 VG SVT not VT, LA-action better, ISA not good
Damaged tissue usually depolarized (CV), effects of antiarrhythmics more pronounced (all classes)
Amiodarone
(Cardarone) Arrhythmia, VT (new DOC, multiple class Class III, Ph 3, APD, RP; QT, Pulmon F, >25d,
(Dronedarone new agent, less SE)
actions: I, II, III, IV, corneal D, thyroid dys) cardiac dep, CYP3A4 sub/inh, I: CG, warfarin others
Ibutilide
Bretylium (save ET)
Atrial Fib/Flutter
Class III, VG SVT, QT, low TdP 2%
CCBs
Verapamil, Diltiazem (not
Arrhythmia (SVT, acute + chronic),
Class IV, CV, RP, increasing use, not for VT/VF,
Nifedipine) (see earlier notes) hypertension, angina
constipation, rash, edema, gingival H CI: HF
Adenosine
(Adenocard) Acute SVT (acts on adenosine-R)
A-R→ AC→ Open K+ channel; RP, CV; 15 secs
Digoxin
(Lanoxicaps, Lanoxin) Atrial arrhythmia (stimulate Vagus N)
RP myocardium,RP purkinje fibers, AV CV
Potassium ions
Arrhythmia
Depress ectopic pacemakers, suppress Phase 4
Autonomic agents (EPI, atropine)
Arrhythmia (AV block)
Increase CV in AV node
DYSLIPIDEMIA (Lipid Lowering Agents)
Statins: HMG-CoA reductase inhibition
Atorvastatin, Simvastatin, Lovastatin
Resins:: Bile acid reabsorption
Cholestyramine, Colestipol
Niacin: Inhibit VLDL release, Lipolysis
(also called Nicotinic A. or Vit B3)
Fibrates : :Stimul. Lipoprotein Lipase, ↑PPARα
Gemfibrozil, Fenofibrate, Clofibrate,
Inh. Cholesterol absorption: Ezetimibe
LDL, HDL, TGs
[-vastatin]
LDL, HDL, TGs
 Use, Liver toxicity, myopathy, rhabdomyolsis,  mylination CI:
pregnancy, children (? < 12 yrs).  LDL-rec→LDL uptake
Hate it, gritty taste, GI discomfort, constipation.  VLDL,  TGs,
 LDL-Rec., absp fat sol Vits (A, D, E, K), digoxin, warf absp
LDL, HDL, TGs Flushed face (aspirin), GI discomfort, glucose intolerance, gout,
liver toxicity, peptic ulcer, diabetes
LDL, HDL, TGs Nausea, skin rash, headache,  statin myopathy.
LDL synthesis (turnover), gallstones. CI: Gemfibrozil + statin
+ Statin combo (?) No major E, diarrhea, headache, ↑cancer (?)
LDL, HDL
Omega-3 FA: ↓VLDL/TG synthesis. Lovaza
LDL, HDL, TGs
↑bleeding, fishy odor, diabetes, thrombocytopenia, GI disorders