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Hypertensive patients, particularly the elderly, may often suffer from other diseases. Therefore, antihypertensive compounds should not negatively affect such disorders. Felodipine is a calcium antagonist that has potentially beneficial effects in angina pectoris and congestive heart failure. Further, it does not adversely affect lung function in asthmatic patients or glucose tolerance in patients with diabetes. Preliminary investigations also indicate that felodipine has no negative influence on plasma lipid levels. Although felodipine seems to be safe in most patients, treatment with felodipine should at present be avoided in pregnant women, since digital anomalies have been observed in rabbit fetuses. The adverse effects seen during treatment with felodipine are usually mild and transient and generally related to the vasodilatory action of the drug, the most common being ankle edema, headache, flushing, dizziness, and palpitations. The only significant drug interactions with felodipine occur with inducers and inhibitors of the cytochrome P-450 system, which is responsible for the metabolism of felodipine.
J Cardiovasc Pharmacol 1990
PMID:The safety of felodipine. 169 36

The antihypertensive efficacy and tolerability of the new calcium antagonist isradipine was assessed in 86 hypertensive patients who had pretreatment diastolic blood pressures (DBP) greater than or equal to 105 mm Hg and who were randomly allocated to a double-blind comparison of three different dosage regimens: 1.25 mg, 2.5 mg, and 5 mg b.i.d., and placebo. A 2-week run-in period was followed by a 4-week course of treatment. Isradipine reduced systolic and diastolic blood pressures dose-dependently; the normalization rate (DBP less than or equal to 90 mm Hg) was 5% with placebo and 29, 55, and 64% with isradipine 1.25, 2.5, and 5 mg b.i.d., respectively. The proportion of patients experiencing at least a 10 mm Hg reduction in sitting DBP was 29, 67, 86, and 91%, respectively. All three dosages proved to be significantly effective compared to placebo. Neither heart rate nor blood pressure regulation in orthostasis were influenced. The main side effects were headache, dizziness, and flushing; isradipine 1.25 and 2.5 mg b.i.d. were well tolerated (not significantly different from placebo). In conclusion, isradipine 2.5 mg b.i.d. appears to be the potential dose of first choice, exhibiting a favorable benefit-risk profile.
J Cardiovasc Pharmacol 1990
PMID:Efficacy and tolerability of the new calcium antagonist isradipine in essential hypertension. 169 4

The new calcium antagonist isradipine was compared with nifedipine retard in a multicenter, double-blind, placebo-controlled, randomized study involving 159 patients with mild hypertension. A 2-week run-in period was followed by a 6-week course of treatment with the possibility of dose doubling after 3 weeks, depending on blood pressure (BP) response (target diastolic BP less than 90 mm Hg). Systolic and diastolic BPs were reduced by isradipine (mean dose of 3.6 mg daily) from 151/101 to 136/89 mm Hg, by nifedipine (mean dose of 50 mg daily) from 155/101 to 144/90 mm Hg, and by placebo from 155/101 to 154/99 mm Hg. Normalization rates were 64% with isradipine, 56% with nifedipine, and 16% with placebo. Adverse events consisted mainly of flushing, headache, edema, and dizziness. Altogether, 8 patients receiving isradipine experienced adverse events in comparison to 21 taking nifedipine and 4 taking placebo. The superior tolerability of isradipine was paralleled by a significant improvement in the subjective well-being of the patients as assessed by the von Zerssen questionnaire (List of Complaints). With nifedipine and placebo, no statistically significant improvement was observed.
J Cardiovasc Pharmacol 1990
PMID:Calcium antagonists as first-line antihypertensive agents: a placebo-controlled, comparative trial of isradipine and nifedipine. 169 8

The pharmacokinetic and clinical characteristics of a once-daily formulation of diltiazem are described. In a 20 subject, 5 day, steady-state pharmacokinetic study, 120 and 240 mg of once-daily diltiazem were bioequivalent on a dose-adjusted basis and were bioequivalent to a conventional reference product administered four times daily. The conventional formulation showed marked diurnal variation in its pharmacokinetics. Plasma concentrations following its administration at 2100 and 0300 h were significantly lower than following administration at 0900 and 1500 h. One hundred forty-four hypertensive patients completed a 16 week placebo-controlled, dose-titrated study examining the effects of once-daily diltiazem at doses of 120, 240, and 360 mg. Blood pressure was measured manually and (in 121 patients) by ambulatory evaluation. Following dose titration, diltiazem given once daily reduced blood pressure with significant effects present at 24 h following drug administration. Ambulatory blood pressures were lower than those measured manually and data from the manual measurements demonstrated a placebo effect suggested to result primarily from investigator bias. The placebo-adjusted reduction in blood pressure 24 h following a dose of diltiazem was approximately 5 mm Hg and was comparable for manual (supine and standing) and ambulatory measurements. Diltiazem was well tolerated. The only significant findings were of tiredness/dizziness (9 patients of 144) or oedema (also 9 of 144). The incidence of headache was not different than placebo. On both pharmacokinetic and pharmacodynamic grounds, the results indicate that diltiazem can be formulated in a manner suitable for once-daily antihypertensive use.
J Cardiovasc Pharmacol 1991 Jun
PMID:Pharmacokinetic properties and antihypertensive efficacy of once-daily diltiazem. 171 21

In this study of the efficacy and safety of isradipine as first-line therapy in hypertension, 1,647 patients enrolled; 1,472 completed the 4-week placebo run-in period and began treatment with isradipine at 2.5 mg twice daily for 4 weeks. During placebo, 11% (n = 175) of the 1,647 patients withdrew because of normalization of blood pressure, side effects, noncompliance, violation of the study protocol, side effects from concomitant therapy, or other reasons. During isradipine therapy (n = 1,376), blood pressure decreased from 168 +/- 18/102 +/- 8 mm Hg at the end of the placebo period to 155 +/- 17/94 +/- 9 mm Hg after 2 weeks (p less than 0.001) and 151 +/- 16/92 +/- 9 mm Hg after 4 weeks (p less than 0.001). During active treatment, 6.4% (n = 94) were withdrawn because of flushing, headache, edema, palpitations, gastrointestinal side effects, skin rashes, or other side effects, and two patients because of lack of efficacy. The side effect score in the remaining patients worsened for flushing, remained unchanged for edema, but significantly improved for palpitations, fatigue, dizziness, headache, and nervousness. After 4 weeks, 60% of patients had diastolic blood pressures of less than or equal to 90 mm Hg. Thus, isradipine is effective and safe as first-line therapy in patients with primary hypertension as seen in general practice.
J Cardiovasc Pharmacol 1991
PMID:Calcium antagonists as first-line therapy in hypertension: results of the Swiss Isradipine Study. Swiss Hypertension Society. 172 Apr 76

A total of 555 hypertensive patients took part in a 2-year multicenter, open-label study to determine the efficacy, tolerance, and safety of long-term therapy with ramipril. In the beginning, all patients were to receive 5 mg of ramipril/day. The dosage was then adjusted in accordance with response to treatment and ranged from 1.25-20 mg of ramipril daily. Of these patients, 129 also received 25 mg of hydrochlorothiazide daily at some point during the trial. To evaluate whether tolerance to ramipril developed during long-term treatment, a subgroup of 202 patients was analyzed for efficacy maintenance. Prior to enrolling in the 2-year study, these patients had received ramipril monotherapy in a short-term, double-blind study and had been classified as responders, i.e., their diastolic blood pressure had been maintained at less than or equal to 90 mm Hg. At the end of 104 weeks of treatment, 45.9% of patients were on 2.5 mg of ramipril alone and 43.6% were on 5 mg of ramipril alone. Only four patients required the addition of 25 mg of hydrochlorothiazide. No clinically important changes occurred, and kidney function was well maintained. The most frequently reported adverse events excluding intercurrent illnesses were dizziness/vertigo (6%), asthenia (4%), nausea (3%), headache (2%), and abdominal pain, gastrointestinal disorder, rash, and increased cough (1% each). Ramipril was safe, effective, and well tolerated in the long-term treatment of patients with mild-to-moderate essential hypertension.
J Cardiovasc Pharmacol 1991
PMID:Antihypertensive efficacy, tolerance, and safety of long-term treatment with ramipril in patients with mild-to-moderate essential hypertension. 172 24

In this study, the tolerability and safety of ramipril, as monotherapy and in combination with a low dose of furosemide, were assessed in patients with mild-to-moderate hypertension in general practice. After a placebo run-in phase, patients received ramipril as monotherapy in a dose of 2.5 to 5 mg daily for 6 weeks. Nonresponders (diastolic blood pressure greater than 90 mm Hg) entered a double-blind treatment period, and received either 10 mg of ramipril daily, or 5 mg of ramipril in combination with 20 mg of furosemide daily. The tolerability of the study medication was assessed by reported adverse events, and by monitoring blood cell count, electrolytes, serum creatinine, fasting blood glucose, and apolipoproteins AI and B. Of a total of 770 patients who entered the placebo run-in phase, 661 patients were enrolled in the first active treatment period. The most commonly reported adverse events were headache, cough, dizziness, asthenia, cramps, diarrhea, and nausea, but not all of these events were related to ramipril treatment. A total of 38 patients discontinued active treatment due to nonserious adverse events, mainly cough, dizziness, or diarrhea. There appeared to be a relationship between the prevalence of cough and ramipril dosage; however, an increased incidence of cough was also observed during outbreaks of influenza in France. There were no significant changes in laboratory variables during the study.
J Cardiovasc Pharmacol 1991
PMID:Tolerability of ramipril in a multicenter study of mild-to-moderate hypertension in general practice. 172 26

We describe a case of coronary-subclavian steal syndrome treated with percutaneous transluminal angioplasty. A 58-year-old female who had her first coronary bypass operation 6 years previously and a second operation 3 years previously involving the left internal mammary artery and right gastroepiploic artery, developed unusual angina on effort characterized by left precordial pain, pain in the left shoulder and arm, tinnitus and dizziness. Angiography revealed retrograde flow to the left subclavian artery via the left vertebral artery and left internal mammary artery. Severe stenosis of the left subclavian artery was demonstrated at its ostium. Restoration of antegrade flow to the vertebral artery and left internal mammary artery by transluminal angioplasty resulted in complete resolution of these symptoms.
J Cardiovasc Surg (Torino)
PMID:Coronary-subclavian steal corrected with percutaneous transluminal angioplasty. 201 35

We present our experience on the efficacy of propafenone in ten symptomatic patients with Wolff-Parkinson-White syndrome. The symptoms were dizziness in seven patients and syncope in three patients. While experiencing the symptoms, three of them presented an episode of atrial fibrillation, the shortest preexcited RR intervals being 140, 190, and 200 ms. In the other seven patients, the ECG was not recorded during the symptoms, but an episode of atrial fibrillation was subsequently induced by transesophageal pacing. The shortest preexcited RR intervals during induced atrial fibrillation were 180, 200, 270, 240, 230, 250, and 200 ms. Seven patients had both atrial fibrillation and supraventricular tachycardia. Propafenone (1-2 mg/kg) administered IV in only the patients with sustained atrial fibrillation (spontaneous in two and induced in one patient) prolonged the shortest preexcited RR intervals from 190, 200, and 180 ms to 340, 335, and 340 ms. In the other seven patients, propafenone was not given IV because atrial fibrillation rapidly deteriorated into ventricular fibrillation (one patient) or spontaneously reverted within 1-2 minutes to sinus rhythm (six patients). After oral propafenone, serial trans-esophageal pacing studies reinduced atrial fibrillation in 4 of 6 patients (the shortest preexcited RR intervals increased from 190, 180, 200, and 270 ms to 420, 320, 340, and 380 ms); only in one patient was it possible after propafenone to induce an atrial flutter without preexcitation. After propafenone therapy in 4 of 7 patients, supraventricular tachycardia was not inducible.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiovasc Drugs Ther 1990 Jun
PMID:Propafenone in Wolff-Parkinson-White syndrome at risk. 207 78

Isradipine is a dihydropyridine calcium-entry blocking agent with pronounced vasodilator activity and no significant cardiac effects at clinical doses, a desirable profile for an antihypertensive drug. Prazosin, a post-junctional alpha-adrenoceptor blocking agent, may produce a similar hemodynamic pattern. Therefore, we compared the effects of isradipine (2.5-10 mg bid) with those of prazosin (2-8 mg bid) in 83 patients with established essential hypertension, using a randomized, double-blind, parallel-group design. Patients received a placebo for 3-5 weeks, then either isradipine or prazosin over a 6-week titration period, followed by a 4-week plateau phase. During the plateau period, isradipine therapy lowered sitting blood pressure more effectively than did the administration of prazosin: Mean systolic BP fell 16.7 versus 8.1 mmHg (p less than 0.001) and mean diastolic BP was reduced 15.6 versus 12.6 mmHg (p less than 0.01). In the dosing range used (while also noting that prazosin is occasionally titrated up to doses of 30 mg qd), 83% of isradipine-treated patients had at least a 10 mmHg reduction in diastolic BP, compared with 64% of prazosin-treated patients (p = 0.05, FET). Tachyphylaxis did not occur with either drug. The rate of occurrence of side effects was similar in both treatment groups; the most common adverse event seen with isradipine was headache (20%) and with prazosin, dizziness (19%).
Cardiovasc Drugs Ther 1990 Apr
PMID:A multicenter comparison of isradipine and prazosin for treatment of essential hypertension. 214 12


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