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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Organic nitrates are available in a remarkably diverse variety of formulations, including sublingual, buccal and oral tablets, capsules, topical creams, ointments, patches, tapes, inhalable sprays and intravenous solutions. Although not all of these formulations are available in the United States, the array of drugs and dosages approved for use is extensive. It is only by weighing the pharmacologic properties of these agents against the patient's clinical status and needs that a concise and appropriate treatment regimen may be derived. Numerous recent studies have confirmed the protracted efficacy of the organic nitrates in the treatment of patients with angina pectoris and congestive heart failure (CHF) as evidenced by improvements in cardiac hemodynamics and desired clinical parameters. It is appropriate that the patient's dosage of nitrates be administered with a formulation most likely to be both clinically effective and well tolerated. The use of nitroglycerin and isosorbide dinitrate in the acute and chronic treatment of CHF will be discussed in the context of their unique pharmacologic and pharmacokinetic properties. A rationale for the most efficacious use of these agents will be presented. Tolerance phenomena and adverse effects (i.e., headache) will also be discussed from the perspective of their significance in chronic nitrate therapy.
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PMID:Pharmacology of nitroglycerin and long-acting nitrates. 392 50

A hypertensive urgency should be distinguished from a hypertensive emergency. Although the distinction may not always be obvious, certain guidelines may help the clinician determine which therapeutic approaches are most appropriate for each patient. Hypertensive emergencies include those conditions in which new or progressive severe end-organ damage is present and a delay in appropriate therapy might result in permanent damage, progression of complications, and a poor prognosis. Hypertensive urgencies include those conditions with minimal to no obvious end-organ damage in which blood pressure should be lowered expeditiously. The risk of immediate complications or organ damage is less likely to occur, and thus the immediate prognosis is better, although the ultimate prognosis, if untreated, is poor. There is a marked individual, racial, sexual, and age difference in the ability to tolerate high intraarterial pressure, as evidenced by patients' symptoms and signs of end-organ damage. Patients may have no symptoms of elevated blood pressure until significant intraarterial levels are reached. If symptoms are present, they may include headache, dizziness, blurred vision, shortness of breath (especially with exertion), chest pain, rapid pulse, palpitations, malaise and fatigue, nocturia, or pedal edema. Signs of hypertensive disease vary and depend not only on the level of blood pressure but also include funduscopic changes with arteriolar narrowing, atrioventricular nicking, hemorrhages, exudates or papilledema, central nervous system changes and neurologic abnormalities, cardiac changes with gallop rhythm, cardiomegaly, tachycardia, ectopic ventricular beats, left ventricular hypertrophy or signs of congestive heart failure, pulmonary edema, and signs of renal insufficiency.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hypertensive emergencies and urgencies: pathophysiology and clinical aspects. 394 53

Using a double-blind, crossover design, the comparative efficacy and safety of nifedipine and isosorbide dinitrate in the treatment of stable angina were studied in 34 patients. The study included a 2-week placebo washout period and two 6-week periods during which patients were randomized to either nifedipine or isosorbide dinitrate. The doses were titrated for each patient, and mean doses of the 2 drugs were comparable. A time-limited thallium treadmill test was performed at the end of each phase. Ischemic zone count rates were normalized to those of the nonischemic zone, and the change in this ratio with redistribution was calculated as reversible thallium defect. Two patients were discontinued from the study within 1 week after initiation of isosorbide dinitrate because of severe, intolerable headache. Two patients were withdrawn while receiving nifedipine: one had new congestive heart failure and the other had increasing angina. Of the remaining 30 patients who tolerated both drugs for at least 1 week, 4 patients from the isosorbide dinitrate group were either prematurely crossed over or discontinued from the study because of headache. One patient suffered headache from both drugs and was discontinued from the study. In the 30 patients, only nifedipine significantly reduced resting arterial pressure compared with baseline. Further, only nifedipine therapy resulted in significant decreases in the rate-pressure product and systolic pressure at a given workload. However, significant decreases in angina frequency, nitroglycerin consumption and exercise-induced maximum ST-segment depression and reversible thallium perfusion defect were produced by both nifedipine and isosorbide dinitrate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of antianginal efficacy of nifedipine and isosorbide dinitrate in chronic stable angina: a long-term, randomized, double-blind, crossover study. 400 86

To assess the effects of nitroglycerin ointment (NTG) on hemodynamics and autonomic nervous activity, 17 normal subjects and 13 patients with severe congestive heart failure (CHF) were studied. In 12 normal subjects, NTG significantly increased the plasma norepinephrine concentration in association with a slight reduction in systolic blood pressure and a slight increase in heart rate, plasma cyclic adenosine monophosphate (cyclic AMP) concentration, and renin activity at 1 hr. All normal subjects complained of headache or felt heavy-headed after NTG administration. In the 13 patients with CHF, NTG significantly decreased plasma norepinephrine and cyclic AMP concentrations in association with a significant increase in the cardiac index and a significant reduction in pulmonary arterial diastolic pressure, systemic vascular resistance, systolic blood pressure, and heart rate. The effects occurred at 30 min after NTG administration and continued for 3 hr. Relief from dyspnea or orthopnea in patients with CHF was observed. NTG did not change the plasma cyclic GMP concentration in normal subjects and patients with CHF. We conclude that in patients with CHF, NTG decreases the enhanced sympathetic nervous activity, with concomitant beneficial effects on hemodynamics and improvement of clinical symptoms. In contrast, NTG increases sympathetic nervous activity in normal subjects.
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PMID:Effects of nitroglycerin ointment on plasma norepinephrine and cyclic nucleotides in congestive heart failure. 616 16

A new topical dosage form of nitroglycerin has been developed in which nitroglycerin and its vehicle are incorporated in a polymer gel matrix of fixed dimension. Venous plasma nitroglycerin concentrations were measured for 24 h after application of nitroglycerin polymer gel systems measuring 10 cm and containing 2% nitroglycerin (wt/wt) to 10 normal male volunteers. Five of these subjects were subsequently tested with 20-cm2 gel systems of similar composition. With the 10-cm2 nitroglycerin polymer gel system, venous plasma nitroglycerin concentrations were 0.83 +/- 0.26 ng/ml ast 4 h and 0.89 +/- 0.23 ng/ml at 24 h. For the 20-cm2 system, venous plasma nitroglycerin concentrations were 1.83 +/- 0.55 ng/ml at 8 h and 1.81 +/- 0.13 ng/ml at 24 h. The only adverse effect noted was headache, which affected all the subjects tested with the 20-cm2 appliance. The plasma nitroglycerin concentrations obtained with the polymer gel system appear to be in a clinically useful range; thus this new form of topical nitroglycerin should be of benefit to patients in whom sustained plasma nitroglycerin concentrations are desirable, e.g., those patients with chronic congestive heart failure and angina on awakening.
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PMID:The nitroglycerin polymer gel matrix system: a new method for administering nitroglycerin evaluated with plasma nitroglycerin levels. 617 52

Nitrates are potent relaxers of vascular smooth muscle and act by dilating veins, arteries, and arterioles (especially at high doses). Their clinical effects have been considered to be dominantly related to peripheral actions: systemic venodilatation and a decrease in systemic vascular resistance, reducing the preload and afterload of the heart. Considerable experimental work confirms potent salutary effects on the coronary circulation. These drugs are readily absorbed across mucosal surfaces; they are available in multiple formulations, including sublingual, buccal, oral, and topical delivery systems. Nitrate administration should begin with low doses and increased to doses that are often higher than previously recommended until a specific clinical end point or limiting side effects occur. Organic nitrate esters are effective in the treatment of stable angina pectoris, unstable angina, coronary vasospastic syndromes, and in vasodilator therapy in severe congestive heart failure. The pathophysiology of these syndromes is reviewed with respect to the clinical actions of nitrates on the central and peripheral circulations. The side effects of nitrates include headache, dizziness, and nausea. Nitrate tolerance, a controversial subject, does not appear to be an important clinical problem. Using the guidelines presented in this review, nitrate therapy provides effective, inexpensive, well-tolerated therapy for many patients with cardiovascular disease.
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PMID:Nitroglycerin and long-acting nitrates in clinical practice. 640 16

The recently introduced preparation of intravenous glyceryl trinitrate (nitroglycerin) provides a rapid steady therapeutic blood concentration of nitrates during continuous infusion. Intravenous glyceryl trinitrate causes venodilation at low doses, but at higher doses dilates both arteries and veins. Its principal haemodynamic effects at therapeutic dosages include a decrease in blood pressure in preload (left ventricular filling pressure) and in determinants of afterload, and a decrease in myocardial oxygen demand. Human pharmacokinetic data are few and difficult to interpret due to wide interstudy and interindividual variation. There is no close correlation between infusion rate, blood concentration and haemodynamic effects. The nature of the patient population treated with intravenous glyceryl trinitrate has largely precluded the use of a placebo, but in open trials the drug has been used successfully in the treatment of unstable angina, left ventricular failure accompanying acute myocardial infarction and in the control of hypertension associated with cardiac surgery at dosages titrated to achieve a specific end-point. Favourable haemodynamic responses have been achieved in very short term studies in congestive heart failure, and preliminary studies suggest that institution of intravenous glyceryl trinitrate early after acute myocardial infarction may limit ischaemic damage. However, use of the drug in acute myocardial infarction remains controversial. Intravenous glyceryl trinitrate is generally well tolerated, although hypotension and headache occur occasionally, and sinus tachycardia and bradycardia less frequently. Careful titration of dosage is required (beginning at 5 micrograms/min), and if the infusion sets contain polyvinylchloride, the delivered dose is lower than that calculated, because of adsorption of glyceryl trinitrate onto the plastic tubing.
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PMID:Intravenous glyceryl trinitrate (nitroglycerin). A review of its pharmacological properties and therapeutic efficacy. 642 Jan 39

Amrinone, 100 mg orally every 8 hours, was administered to 13 patients with moderate-to-severe congestive heart failure (CHF) for 1 month on an outpatient basis to determine the beneficial and undesirable effects of this new cardioactive agent in this clinical setting. These subjects received conventional CHF medications during the course of study. Ten patients who received conventional CHF medications alone served as a control group. Changes in functional classification were not significantly different between the 2 treatment groups. Amrinone augmented exercise capacity 37% above baseline compared with a 12% improvement for the control group. Noninvasive indexes of resting left ventricular function (echocardiography and systolic time intervals) did not change significantly for either group, nor was there a significant change in the exercise ejection fraction. All patients treated with amrinone had greater than or equal to 1 symptom-related or laboratory-detected adverse effect. An increase in the frequency of ventricular ectopic beats was noted at rest in 4 and with exercise in 6 patients (salvos of nonsustained ventricular tachycardia in 2). Six subjects treated with amrinone had gastrointestinal symptoms and 8 developed a viral-like illness. Other adverse effects noted in the amrinone-treated group included near-syncope, headaches, marked anxiety, chest pain, palpitations, maculopapular rash, hypokalemia, and elevation of serum transaminase levels. The control patients had significantly fewer adverse effects. Although individual patients with CHF may benefit from long-term amrinone therapy, the low benefit-to-risk-adverse effect ratio does not warrant widespread application of this drug in the outpatient management of CHF and requires caution when prescribing.
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PMID:Amrinone therapy for congestive heart failure in outpatients with idiopathic dilated cardiomyopathy. 668 63

Tolerance and cross-tolerance to nitrates has been known since 1900 but the actual clinical importance of this phenomenon is unclear. Vasodilator treatment of congestive heart failure has provided an important new role for long-acting nitrates. The advent of high-dose nitrate regimens for both angina and heart failure raises the possibility that nitrate tolerance could be a potential detriment to therapy. A number of older studies have documented the development of tolerance and cross-tolerance to blood pressure and heart rate responses to nitrates as well as the rapid onset of tolerance to nitrate headaches in subjects given nitrates on a regular basis. Animal experiments also confirm the ready appearance of nitrate tachyphylaxis. Needleman has proposed a cellular mechanism for nitrate tolerance based on a chemical alteration of nitrate receptors in the vascular wall. In spite of these studies, there is considerable evidence that clinically relevant tolerance to nitrates is rare. Several recent investigations designed to look at this problem using high-dose isosorbide dinitrate (ISD) failed to demonstrate tachyphylaxis to the anti-anginal or hemodynamic effect of ISD. However, very recent work in patients with angina suggests that tolerance to high dose ISD does occur and may reduce the duration of action of long-acting nitrates. Overall, the bulk of current evidence does not support tolerance to be a major problem in nitrate treatment of cardiac diseases, although attenuated vasodilator responses may occur after several weeks of nitrate therapy.
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PMID:Nitrate tolerance and dependence. A critical assessment. 677 5

Sublingual glyceryl trinitrate (nitroglycerin) is the most widely used drug in the treatment of angina pectoris, but its use is limited due to its short acting effect. Recent investigations have shown that some longer acting nitrates administered orally or topically have a long acting antianginal effect. The mechanism of the antianginal effect of nitrates is multifactorial. Nitrates increase oxygen supply to the myocardium by causing redistribution of coronary blood flow. In addition, nitrates decrease myocardial oxygen demand by reducing left ventricular volume, intramyocardial tension, and left ventricular afterload. The use of nitrates for the treatment of congestive heart failure has also been established in recent years. Nitrates have a predominant venodilatory effect resulting in peripheral blood pooling and decreased venous return to the heart, thereby decreasing left ventricular filling pressure. The effect of nitrates on the arteriolar circulation is small, and there is usually little or no change in cardiac output. Some reduction in systemic blood pressure can be seen, while there is usually no change in heart rate. In a small number of patients with myocardial infarction complicated by congestive heart failure, the use of long acting nitrates has resulted in haemodynamic and symptomatic improvement. Nitrates has also bee shown to improve variant angina. Nitrates are usually well tolerated in most patients. However, some troublesome side effects can occur, including headache, postural hypotension, and methaemoglobinaemia.
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PMID:Glyceryl trinitrate (nitroglycerin) ointment and isosorbide dinitrate: a review of their pharmacological properties and therapeutic use. 680 2


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