Page 223 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 12 Vasodilators & the Treatment of Angina Pectoris 209

TABLE 12–7 Effects of nitrates alone and with a blockers or calcium channel blockers in angina pectoris.

Beta Blockers or Calcium Combined Nitrates with Beta Blockers
Nitrates Alone Channel Blockers or Calcium Channel Blockers
1
Heart rate Reflex increase Decrease Decrease
Arterial pressure Decrease Decrease Decrease
End-diastolic volume Decrease Increase None or decrease
1
Contractility Reflex increase Decrease None
Ejection time Decrease 1 Increase None
1
Baroreceptor reflex.
Note: Undesirable effects are shown in italics.

with stenting), glycoprotein IIb/IIIa inhibitors such as abciximab at reversal or control of atherosclerosis requires measurement and
should be added. In addition, therapy with nitroglycerin and β control of hyperlipidemia (see Chapter 35), hypertension (see
blockers should be considered; calcium channel blockers should be Chapter 11), and obesity; cessation of smoking; and control of
added in refractory cases for relief of myocardial ischemia. Primary diabetes, if present. Physical therapy and exercise training are
lipid-lowering and ACE-inhibitor therapy should also be initiated. of proven benefit. Conventional vasodilators are of no benefit
because vessels distal to the obstructive lesions are usually already
dilated at rest. Antiplatelet drugs such as aspirin or clopidogrel
TREATMENT OF PERIPHERAL (see Chapter 34) are often used to prevent clotting in the region
ARTERY DISEASE & INTERMITTENT of plaques and have documented benefit in reducing the risk of
CLAUDICATION myocardial infarction, stroke, and vascular death even though
they have little or no effect on claudication. Two drugs are used
Atherosclerosis can result in ischemia of peripheral muscles just almost exclusively for PAD. Cilostazol, a phosphodiesterase type
as coronary artery disease causes cardiac ischemia. Pain (claudi- 3 (PDE3) inhibitor, may have selective antiplatelet and vaso-
cation) occurs in skeletal muscles, especially in the legs, during dilating effects. This drug has been shown to increase exercise
exercise and disappears with rest. Although claudication is not tolerance in patients with severe claudication. Pentoxifylline, a
immediately life-threatening, peripheral artery disease (PAD) is xanthine derivative, is widely promoted for use in this condition
associated with increased mortality, can severely limit exercise but is not recommended. It is thought to act by reducing the
tolerance, and may be associated with chronic ischemic ulcers, viscosity of blood and perhaps increasing the deformability of red
susceptibility to infection, and the need for amputation. blood cells, allowing blood to flow more easily through partially
Intermittent claudication results from obstruction of blood obstructed areas. Naftidrofuryl, a 5-HT 2 antagonist, is available
flow by atheromas in large and medium arteries. Insertion of outside the USA and appears to have benefits similar to those of
stents in the obstructed vessels is becoming more common. Super- cilostazol. Percutaneous angioplasty with stenting may be effec-
vised exercise therapy is of benefit in reducing claudication and tive in patients with medically intractable signs and symptoms of
increasing pain-free walking distance. Medical treatment directed lower limb ischemia.

SUMMARY Drugs Used in Angina Pectoris

Pharmacokinetics, Toxicities,
Subclass, Drug Mechanism of Action Effects Clinical Applications Interactions

NITRATES
• Nitroglycerin Releases nitric oxide in Smooth muscle relaxation, Angina: Sublingual form for High first-pass effect, so sublingual dose
smooth muscle, which especially in vessels • other acute episodes • oral and is much smaller than oral • high lipid
activates guanylyl cyclase smooth muscle is relaxed transdermal forms for solubility ensures rapid absorption
and increases cGMP but not as markedly prophylaxis • IV form for • Toxicity: Orthostatic hypotension,
• vasodilation decreases acute coronary syndrome tachycardia, headache • Interactions:
venous return and heart size Synergistic hypotension with
• may increase coronary flow phosphodiesterase type 5 inhibitors
in some areas and in variant (sildenafil, etc)
angina
• Isosorbide dinitrate: Very similar to nitroglycerin, slightly longer duration of action; no transdermal form
• Isosorbide mononitrate: Active metabolite of the dinitrate; used orally for prophylaxis

(continued)