Page 224 - Basic _ Clinical Pharmacology ( PDFDrive )

210 SECTION III Cardiovascular-Renal Drugs

Pharmacokinetics, Toxicities,
Subclass, Drug Mechanism of Action Effects Clinical Applications Interactions
BETA BLOCKERS
• Propranolol Nonselective competitive Decreased heart rate, Prophylaxis of angina • for Oral and parenteral, 4–6 h duration of
antagonist at β cardiac output, and blood other applications, see action • Toxicity: Asthma, atrioventricular
adrenoceptors pressure • decreases Chapters 10, 11, and 13 block, acute heart failure, sedation
myocardial oxygen demand • Interactions: Additive with all cardiac
depressants

• Atenolol, metoprolol, others: β 1 -selective blockers, less risk of bronchospasm, but still significant
• See Chapters 10 and 11 for other β blockers and their applications
CALCIUM CHANNEL BLOCKERS
• Verapamil, Nonselective block of Reduced vascular resistance, Prophylaxis of angina, Oral, IV, duration 4–8 h • Toxicity:
diltiazem L-type calcium channels in cardiac rate, and cardiac hypertension, others Atrioventricular block, acute heart failure;
vessels and heart force results in decreased constipation, edema • Interactions: Additive
oxygen demand with other cardiac depressants and
hypotensive drugs
• Nifedipine (a Block of vascular L-type Like verapamil and Prophylaxis of angina and Oral, duration 4–6 h • Toxicity: Excessive
dihydropyridine) calcium channels > cardiac diltiazem; less cardiac effect treatment of hypertension hypotension, baroreceptor reflex
channels but prompt release tachycardia • Interactions: Additive with
nifedipine is other vasodilators
contraindicated
• Amlodipine, felodipine, other dihydropyridines: Like nifedipine but slower onset and longer duration (up to 12 h or more)
MISCELLANEOUS
• Ranolazine Inhibits late sodium current Reduces cardiac oxygen Prophylaxis of angina Oral, duration 6–8 h • Toxicity: QT interval
in heart • also may modify demand • fatty acid prolongation (but no increase of torsades
fatty acid oxidation at oxidation modification de pointes), nausea, constipation, dizziness
much higher doses could improve efficiency of • Interactions: Inhibitors of CYP3A increase
cardiac oxygen utilization ranolazine concentration and duration of
action
• Ivabradine: Inhibitor of sinoatrial pacemaker; reduction of heart rate reduces oxygen demand
• Trimetazidine, allopurinol, perhexiline, fasudil: See text

REFERENCES Fihn SD et al: Guideline for the diagnosis and management of patients
with stable ischemic heart disease: Executive summary. Circulation
Amsterdam EA et al: 2014 AHA/ACC guideline for the management of patients 2012;126:3097.
with non-ST-elevation acute coronary syndromes: Executive summary: A
report of the American College of Cardiology/American Heart Association Fraker TD Jr, Fihn SD: 2007 Chronic angina focused update of the ACC/AHA
Task Force on Practice Guidelines. Circulation 2014;130:2354. 2002 guidelines for the management of patients with chronic stable angina.
Borer JS: Clinical effect of ‘pure’ heart rate slowing with a prototype If inhibitor: J Am Coll Cardiol 2007;50:2264.
Placebo-controlled experience with ivabradine. Adv Cardiol 2006;43:54. Goldman L et al: Comparative reproducibility and validity of systems for assessing
Burashnikov A et al: Ranolazine effectively suppresses atrial fibrillation in the cardiovascular functional class: Advantages of a new specific activity scale.
setting of heart failure. Circ Heart Fail 2014;7:627. Circulation 1981;64:1227.
Carmichael P, Lieben J: Sudden death in explosives workers. Arch Environ Health Husted SE, Ohman EM: Pharmacological and emerging therapies in the treatment
1963;7:50. of chronic angina. Lancet 2015;386:691.
Catterall WA, Swanson TM: Structural basis for pharmacology of voltage-gated Ignarro LJ et al: Mechanism of vascular smooth muscle relaxation by organic
sodium and calcium channels. Mol Pharmacol 2015;88:141. nitrates, nitrites, nitroprusside, and nitric oxide: Evidence for the involve-
Chaitman BR et al: Effects of ranolazine, with atenolol, amlodipine, or diltiazem ment of S-nitrosothiols as active intermediates. J Pharmacol Exp Ther
1981;218:739.
on exercise tolerance and angina frequency in patients with severe chronic
angina. A randomized controlled trial. JAMA 2004;291:309. Kannam JP, Aroesty JM, Gersh BJ: Overview of the management of stable angina
Chang C-R, Sallustio B, Horowitz JD: Drugs that affect cardiac metabolism: Focus pectoris. UpToDate, 2016. http://www.uptodate.com.
on perhexiline. Cardiovasc Drugs Ther 2016;30:399. Kast R et al: Cardiovascular effects of a novel potent and highly selective asaindole-
Chen JF, Eltschig HK, Fredholm BB: Adenosine receptors as targets—What are based inhibitor of Rho-kinase. Br J Pharmacol 2007;152:1070.
the challenges? Nat Rev Drug Discov 2013;12:265. Lacinova L: Voltage-dependent calcium channels. Gen Physiol Biophys
Chen Z, Zhang J, Stamler JS: Identification of the enzymatic mechanism of 2005;24(Suppl 1):1.
nitroglycerin bioactivation. Proc Natl Acad Sci 2002;99:8306. Li H, Föstermann U: Uncoupling of endothelial NO synthesis in atherosclerosis
Cooper-DeHoff RM, Chang S-W, Pepine CJ: Calcium antagonists in the treatment and vascular disease. Curr Opin Pharmacol 2013;13:161.
of coronary artery disease. Curr Opin Pharmacol 2013;13:301. Mayer B, Beretta M: The enigma of nitroglycerin bioactivation and nitrate
DeWitt CR, Waksman JC: Pharmacology, pathophysiology and manage- tolerance: News, views and troubles. Br J Pharmacol 2008;155:170.
ment of calcium channel blocker and beta-blocker toxicity. Toxicol Rev McGillian MM et al: Isosorbide mononitrate in heart failure with preserved
2004;23:223. ejection fraction. N Engl J Med 2015;373:2314.