CAPÍTULO II: Descripción de la Oferta y Demanda Turística de los
2.1.1 Recursos
2.1.2.1 Servicios de Alojamiento
2.1.2.1.2 Caracterización de Hostal Familiar según categoría
Angina pectoris is characterized by transient episodes of chest dis- comfort precipitated by myocardial ischemia, which usually occurs as the result of atherosclerotic narrowing of one or more coronary arteries, as described on page 103. Typically, angina develops when an atherosclerotic plaque obstructs at least 70% of the arte- rial lumen and is triggered by physical activity or emotional distur- bance. In addition, the presence of atherosclerotic lesions can cause vasomotor dysfunction so that vasospasm is superimposed on the preexisting lesion, further restricting blood flow to the myo- cardium. Most patients have a least some episodes of asymptom- atic myocardial ischemia (silent ischemia).
Medications for angina aim to provide symptomatic and pro- phylactic treatment by correcting and maintaining the balance between myocardial oxygen supply and demand (see Figure 4-14, page 104). These are listed in Table 5-12 and consist of organic nitrates,b-adrenergic receptor antagonists, calcium chan- nel blockers, ACEIs, ranolazine, antiplatelet agents, and the sta- tins, which may play a role in stabilizing vulnerable plaques.
• Drugs that reduce myocardial work, and thus the demand for oxygen, include theb-adrenergic receptor antagonists, CCBs, and nitrates, and those that increase oxygen delivery (i.e., cor- onary blood flow [CBF]) to the myocardium through vasodila- tion are the nitrates and CCBs.
• Combination therapy may be required for effective prophylaxis of angina and typically consists of ab-blocker and a dihydropyr- idine CCB, although a CCB and a long-acting nitrate may also be used.
• Standard treatment for chronic stable angina also includes med- ications that provide vascular protection through attenuation of the progression of atherosclerosis and potential stabilization of coronary plaques: aspirin, clopidogrel, ACEIs, HMG-CoA reduc- tase inhibitors (statins), and dipyrimadole. The antiplatelet drugs and statins are presented in later sections.
• Research has revealed that myocardial ischemia alters the nor- mal handling of sodium within the myocytes, leading to increased levels of intracellular sodium and calcium. The calcium overload causes increased actin–myosin filament inter- action and impairs myocardial relaxation. This diastolic dys- function reduces myocardial perfusion (as described on page 103) and increases oxygen demand.6,106Thus, a positive feed- back loop is created, wherein ischemia perpetuates further ischemia. Newer antianginal agents (e.g., ranolazine) target these derangements in sodium and calcium.
• The hemodynamic effects of various antianginal medications at rest and during exercise are also described later in this chapter (see Table 5-22 on page 216).
b-Adrenergic Blocking Agents
b-Blockers reduce myocardial oxygen demand by inhibiting SNS stimulation of the heart through competitive blockade of the b- adrenergic receptors (see Table 5-12). b-Blockers are the most effective therapy for reducing myocardial ischemia both at rest and during exercise. However, there is a wide variety of activity and selectivity within theb-blocking drugs, as described on page 174 and shown in Table 5-10. Not all agents are effective in treat- ing angina. Cardioselective b1-blockers are frequently prescribed as they are often tolerated better.
• b-Blockers reduce myocardial ischemia by:
4 Reducing cardiac contractility, which lowers wall stress and thus myocardial oxygen demand
4 Slowing the HR, which reduces myocardial work and increases the diastolic period, which allows greater CBF 4 Reducing BP, which decreases afterload and eases myocar-
dial effort both at rest and during exercise
• Thus, b-blockers curtail the number of angina attacks and improve exercise tolerance.
• In addition, patients who have stable angina along with certain comorbidities derive additional benefits from b-adrenergic blockade:
4 Patients with symptoms of congestive heart failure due to systolic left ventricular (LV) dysfunction show a reduc- tion in HF-related mortality of about 35% with b-blocker therapy.102
4 Patients who take b-blockers post-MI experience significant reductions in subsequent myocardial ischemia, reinfarction, HF, and sudden death.4,34
• The side effects associated with these drugs are listed in Table 5-10.
Calcium Channel Blockers
CCBs are also valuable in the treatment of stable and unstable angina, as well as Prinzmetal’s angina (i.e., coronary spasm). These drugs (see Table 5-7) act by dilating the coronary and peripheral arteries, thus increasing CBF and reducing PVR (see Table 5-12).
• The decrement in afterload that results from reduced PVR low- ers myocardial oxygen demand.
• In addition, inhibition of the sinoatrial (SA) and atrioventricular (AV) nodes produced by the nondihydropyridine CCBs reduces HR, which further decreases the work of the heart.
• The various drugs differ in the type of effects they produce. Nicardipine and nifedipine produce the greatest systemic TABLE 5-11: Combination Antihypertensive Agents
Combination Product Brand Name(s)
Diuretic/Diuretic Combinations
Triamterene/HCTZ Dyazide, Maxzide
Spironolactone/HCTZ Aldactone Amiloride/HCTZ Moduretic b1-Blocker/Diuretic Combinations Propranolol/HCTZ Inderide Metoprolol/HCTZ Lopressor/HCT Atenolol/chlorthalidone Tenoretic Nadolol/bendroflumethiazide Corzide Timolol/HCTZ Timolide
Propranolol LA/HCTZ Inderide LA
Bisoprolol/HCTZ Ziac
Centrally Acting Drug/Diuretic Combinations
Guanethidine/HCTZ Esimil Methyldopa/HCTZ Aldoril Methyldopa/CTZ Aldoclor Reserpine/CTX Diupres Reserpine/chlorthalidone Demi-Regroton Reserpine/HCTZ Hydropres Clonidine/chlorthalidone Combipres ACE Inhibitor/Diuretic Combinations
Captopril/HCTZ Capozide
Enalapril/HCTZ Vaseretic
Lisinopril/HCTZ Prinzide, Zestoretic
Fosinopril/HCTZ Monopril/HCT Quinapril/HCTZ Accuretic Benazepril/HCTZ Lotensin/HCT Moexipril/HCTZ Uniretic ARB/Diuretic Combinations Losartan/HCTZ Hyzaar Valsartan/HCTZ Diovan/HCT Irbesartan/HCTZ Avalide Candesartan/HCTZ Atacand/HCT Telmisartan/HCTZ Micardis/HCT Eprosartan/HCTZ Teveten/HCT Olmesartan/HCTZ Benicar/HCT
Calcium Channel Blocker/ACE Inhibitor Combinations Amlodipine/Benazepril Lotrel
Diltiazem/Enalapril Teczem
Verapamil (ER)/Trandolapril Tarka Felodipine (ER)/Enalapril Lexxel Vasodilator/Diuretic Combinations
Hydralazine/HCTZ Apresazide
Prazosin/polythiazide Minizide Triple Combination
Reserpine/hydralazine/HCTZ Ser-Ap-Es
ACE, Angiotensin-converting enzyme; ARB, angiotensin II receptor blocker; CTZ, chlorothiazide; ER, extended release; HCTZ, hydrochlorothiazide; LA, long-acting.
TABLE 5-12: Antianginal Agents
Drug BrandName
Indications
Mechanisms
of Action Adverse Reactions Acute ImmediateProphylaxis
Long- acting
Prophylaxis Other
b-Blockers* ü HTN, CHF,
tachyarrhythmias # HR and " diastolicperiod ! " CBF # contractility # BP at rest þ during exercise (# afterload) # myocardial O2demand Per Table 5-10 Calcium channel
blockers{ ü HTN, CHF,arrhythmias Coronary and collateralvessel vasodilation
Peripheral vasodilation Verapamil, diltiazem: # HR
and myocardial contractility Some drugs # BP and
thus afterload
Per Table 5-7
Ranolazine Ranexa ü Selective inhibition of late sodium channels altered by myocardial ischemia so calcium excess is inhibited Attenuation of electrical
dysfunction due to excessive sodium
Dizziness, headache, constipation, nausea, asthenia, syncope, palpitations, tinnitus, vertigo, abdominal pain, dry mouth, peripheral edema, dyspnea
Organic Nitrates Nitroglycerin Intravenous{ Sublingual Lingual spray Buccal tablets}
Oral and ER/SR tabs Transdermal patch} Nitrostat Nitrolingual Nitroglyn, Nitro-Bid ü ü ü ü ü ü ü ü HTN, CHF ü ü ü
All organic nitrates: Vasodilation of CAs, collaterals, þ stenotic sites to " CBF Prevention of CA spasm Venodilation ! # preload
In large doses, systemic vasodilation ! # afterload
" Exercise tolerance, # ST segment depression
General: GI disturbances, headache, which may be severe and persistent, apprehension, vertigo, tachycardia, hypotension, arthralgia
Adverse reactions are usually dose related and secondary to vasodilation
Continued CHAP TER 5 44 Pha rmaco logy 179
TABLE 5-12: Antianginal Agents—Cont’d
Drug BrandName
Indications
Mechanisms
of Action Adverse Reactions Acute ImmediateProphylaxis
Long- acting
Prophylaxis Other Topical ointment Nitro-Bid,
Nitrol ü ü
Isosorbide
dinitrate} Dilatrate,Isochron,
Isordil, Sorbitrate
ü ü CHF, PAH, PortH
Isosorbide
mononitrate** Imdur,Ismo, Monoket
ü PortH Erythrityl
tetranitrate{{ Cardilate ü
Pentaerythritol
tetranitrate{{ PeritrateSA,
Duotrate
ü Amyl nitrate
(inhalant)} Aspirols,Vaporole ü
BP, Blood pressure; CA, coronary artery; CBF, coronary blood flow; CHF, congestive heart failure; ER, extended-release; GI, gastrointestinal; HR, heart rate; HTN, hypertension; PAH, pulmonary hypertension; PortH, portal hypertension; SR, sustained release.
*See Table 5-10.
{See Table 5-7.
{Intravenous nitroglycerin: Tridil, NitroBid.
}Buccal tablets (Nitrogard) are placed under the upper lip or between the teeth and gums and allowed to dissolve slowly.
}Transdermal patch: Nitro-Dur, Transderm-Nitro, Nitrodisc, Minitran, Deponit.
}Isosorbide dinitrate (Isordil, Sorbitrate, Dilatrate) comes in sublingual and chewable tablets and controlled-release capsules.
**Available in immediate release and extended release tablets.
{{Available in sublingual and oral tablets.
{{Available in oral tablets and long-acting capsules and tablets.
}}Comes in a protective cloth-covered glass capsule, which is broken and inhale one to six times while seated.
180 CAR DIOV ASCUL AR AND PULMON ARY PHYSIC AL THERAP Y
vasodilation, whereas verapamil has the greatest negative ino- tropic effect. Nicardipine appears to produce the greatest increase in coronary blood flow.
• Refer to page 178 for a description of the CCBs and to Table 5-7 for a list of these agents and their indications, as well as their adverse effects.
Organic Nitrates
Organic nitrates produce potent vasodilation, including both the coronary and peripheral arteries as well as the venous system. They exert their effects by reducing myocardial oxygen demand due to reductions in preload and, at high does, afterload. They are often the first-line therapy for angina. Nitrates also produce vasodilation of stenotic segments of the coronary arteries and increase collateral blood flow, so perfusion of ischemic myocar- dium is enhanced.
• The effects of nitroglycerin (NTG) are almost immediate in terms of pain relief and favorable alterations in the electrocar- diographic patterns, but are short in duration (less than 30 minutes). NTG can be used prophylactically in situations of increased demand, when chest discomfort is likely (e.g., before exercise or physical therapy).
4 Immediate-acting agents are available in intravenous, sublin- gual, spray, and buccal forms, as shown in Table 5-12. 4 Patients who have angina should have their short-acting emer-
gency medication on their persons at all times. Therapists should be aware of the medication each patient uses and have access to it in case of emergency. The patient’s medication can be easily administered by a third party in case of emergency. • Various longer acting nitrates are also available to provide pro-
phylaxis against angina.
4 The primary drug is isosorbide dinitrate, which is available in several forms, including sublingual, chewable, and oral cap- sules. The sublingual tablets are shorter acting than the chewable tablets, which are shorter acting than the con- trolled-release capsules.
4 Nitrates also come in the form of a topical ointment and as a more aesthetically pleasing patch.
• The main problem with nitrates is that tolerance often devel- ops with continuous or intermittent around-the-clock use of these drugs, so they lose their effectiveness. Tolerance can be prevented by intermittent dosing, during which treatment is interrupted at night. However, this regimen leaves patients unprotected at night and early in the morning, when 7% to 10% of patients experience angina.
• The major adverse effects associated with NTG and other nitrates include headache, dizziness, weakness, palpitations, and severe hypotension and occasionally syncope. Hypotension and reflex tachycardia may aggravate angina.
Ranolazine
Ranolazine (Ranexa) is a novel antianginal agent that is used in the treatment of chronic stable angina that is refractory to more stan- dard antianginal drugs (see Table 5-12).6By inhibiting the derange- ments in sodium and calcium that lead to intracellular calcium overload, ranolazine addresses the consequences of myocardial ischemia that act to perpetuate the ischemia.
• Ranolazine causes selective inhibition of the late sodium chan- nels, which are altered by myocardial ischemia, and so pre- vents the resultant intracellular excesses of sodium and calcium.6,106
• Ranolazine improves diastolic ventricular relaxation, increasing peak filling rate and myocardial wall lengthening during isovo- lumic relaxation of ischemic regions of the LV.6
• It has demonstrated effectiveness in decreasing the frequency of angina attacks and increasing exercise tolerance in patients with CAD who are taking concomitant atenolol, amlodipine, or diltiazem.106
• Side effects of ranolazine include dizziness, headache, con- stipation, nausea, and asthenia. Less common are syncope, palpitations, tinnitus, vertigo, abdominal pain, dry mouth, peripheral edema, and dyspnea.
• Prolongation of the Q–T interval may occur but is not asso- ciated with increased arrhythmias; in fact, ranolazine appears to have an antiarrhythmic effect, resulting in significantly lower incidence of ventricular tachycardia, supraventricular tachycardia, and significant ventricular pauses.100
ACE Inhibitors
A number of studies have observed the value of ACEIs in reducing MIs and death in patients with heart failure. Subse- quently, two major studies using ramipril and perindopril have confirmed the same findings in patients with chronic CAD with preserved LV function. Unfortunately, these findings are not universal; however, methodologic differences (ACEI agent used, dosage, and patient population) may account for the discrepancies.106