Gingival overgrowth (GO) includes gingival enlargement and hyperplasia and may be induced by certain drugs, including calcium channel blockers (CCBs), particularly first-generation CCBs. However, to date, only few cases of GO induced by second- or third-generation CCBs have been reported. The present study reports on a case of a 48-year-old diabetic male who was admitted to the First Hospital of Jilin University (Changchun, China) due to poor blood glucose control. This patient was diagnosed with GO. Review of the patient\'s medical history revealed diagnoses of type 2 diabetes and hypertension, as well as the use of felodipine, a second-generation CCB, to control hypertension. The hypertensive drugs were replaced and the new drugs helped the patient control his blood glucose levels. Additionally, the patient was instructed on methods he could use to improve his oral hygiene, including rinsing of the teeth following each meal and increasing the frequency of tooth brushing per day. After 3 months, the clinical symptoms of GO were relieved. The relevant literature was also reviewed to gain an improved understanding of the correlation between GO and CCBs, as well as diabetes and poor oral hygiene.

Because of health benefits that are manifested across various disease areas, the consumption of herbal products and/or health supplements containing different kinds of flavonoids has been on the rise. While the drug-drug interaction potential between flavonoids and co-ingested drugs still remain an issue, opportunities exist for the combination of flavonoids with suitable anti-cancer drugs to enhance the bioavailability of anti-cancer drugs and thereby reduce the dose size of the anti-cancer drugs and improve its therapeutic index. In recent years, scores of flavonoids have undergone preclinical investigation with variety of drugs encompassing therapeutic areas such as oncology (etoposide, doxorubicin, paclitaxel, tamoxifen etc.), immunosuppression (cyclosporine) and hypertension (losartan, felodipine, nitrendipine etc.). The review provides examples of the recent trends in the preclinical investigation of 14 flavonoids (morin, quercetin, silibinin, kaempferol etc.) with various co-administered drugs. The relevance of combination of flavonoids with anti-cancer drugs and a framework to help design the in vitro and in vivo preclinical studies to gain better mechanistic insights are discussed. Also, concise discussions on the various physiological factors that contribute for the reduced bioavailability of flavonoids along with the significant challenges in the data interpretation are provided.

The objective of this study was to investigate the pharmacokinetics of felodipine (CAS 72509-76-3) in healthy male Taiwanese subjects. This is a retrospective review of five felodipine pharmacokinetic studies completed in Taiwan. A total of 100 evaluable healthy Taiwanese males were enrolled in these studies. The subjects received 5 mg (n = 80) or 10 mg (n = 20) of Plendil (felodipine extended-release tablets; felodipine ER) once daily for 6 days. The mean +/- SD t(max,ss,) CG(max,ss) and AUG(tau) of dose normalized to 10 mg felodipine was 3.32 +/- 1.33 h, 13.12 +/- 5.34 nmol/L and 136.33 +/- 63.18 nmol x h/L, respectively. By using Kolmogorov-Smirnov\'s test and probit plots, the results indicated that the frequency distribution of AUC/dose, C(min)/dose and CL/F was bimodal. Compared to data from the literature, the mean C(max,ss) and AUG(tau) of 5 mg felodipine in healthy young Taiwanese subjects were similar to or slightly lower than data from Swedish, Danish, Turkish and Canadian studies in healthy young subjects who received 10 mg felodipine. Comparable C(max) values and approximately 30% lower AUC values were observed when comparing the 5 mg Taiwanese data to data in healthy elderly German subjects who also received 5 mg felodipine. Taiwanese subjects might have lower CYP3A4 activity to metabolize felodipine, which is similar to the phenomenon observed with nifedipine.

All children aged > or = 3 years should have an annual blood pressure (BP) measurement taken during a routine physical examination. Physicians should become familiar with recommended pediatric normative BP tables. BP above the 95th percentile may require drug therapy. There are several categories of antihypertensives available to the clinician. Calcium channel antagonists (CCAs) are a class of drugs that exert their antihypertensive effect by inhibiting the influx of calcium ions across the cell membranes. This results in dilatation of peripheral arterioles. When given orally, CCAs are metabolised in the liver by cytochrome P450 (CYP) enzyme CYP3A4; hence, some CCAs will affect the half-life of drugs that share this enzyme system for their metabolism. CCAs can be safely used in children with renal insufficiency or failure and as a general rule there is no need to modify drug dosage in this population. CCAs are generally well tolerated; most adverse effects appear to be dose related. Headache, flushing, gastrointestinal upset, and edema of the lower extremities are the most common symptoms reported with the use of CCAs. Pediatric data regarding safety and efficacy of CCAs have mostly been obtained from retrospective analyses. Extended-release nifedipine and amlodipine are the two most commonly used oral CCAs in the management of pediatric hypertension. These drugs can be given once a day, although many children require twice-daily administration. Extended-release nifedipine has to be swallowed whole; hence, its use in younger children who cannot swallow pills is limited. Amlodipine can be made into a solution without compromising its long duration of action; therefore, it is the CCA of choice for very young children. Oral short-acting nifedipine and intravenous nicardipine are safe and effective CCAs for the management of hypertensive crisis in children. Short-acting nifedipine can cause unpredictable changes in BP; hence, it should be used cautiously and in low doses. Intravenous nicardipine has a rapid onset of action and a short half-life. Intravenous infusion of nicardipine can be titrated for effective control of BP. Intravenous nicardipine has been used safely in hospitalized children and newborns for the management of hypertensive crisis, and for controlled hypotension during surgery. CCAs are a class of antihypertensives that are safe and effective in pediatric patients. They have relatively few adverse effects and are well tolerated by children. This article reviews CCAs as antihypertensives in the management of pediatric hypertension.

\"Gingival enlargement\" is the term now used to describe medication-related gingival overgrowth or gingival hyperplasia (AAP, 2004), a condition commonly induced by three main classes of drugs: anticonvulsants, antihypertensive calcium antagonists and the immunosuppressant cyclosporin. It is important that the health practitioner is aware of the potential aetiologic agents and characteristic features in order to be able to accurately diagnose and successfully manage patients who present with a condition such as outlined in the following case presentation.

Ramipril/felodipine extended release (ER) [Triapin and Triapin Mite, Unimax] is a once-daily fixed-dose combination of the ACE inhibitor ramipril and the ER formulation of the dihydropyridine calcium channel antagonist felodipine. It is indicated in adult patients with essential hypertension whose blood pressure (BP) is inadequately controlled with ramipril or felodipine monotherapy. In this patient population, commercially available fixed-dose combinations (i.e. 2.5 mg/2.5 mg and 5 mg/5 mg) of ramipril and felodipine ER are more effective at controlling hypertension than the individual components used as monotherapy at the same dosages. Likewise, the 5 mg/5 mg combination is as effective as felodipine ER 10 mg, and more effective than ramipril 10 mg administered as monotherapy. The addition of low-dose ramipril plus felodipine ER (fixed-dose or combination of individual components) to the existing antihypertensive regimen also appears to provide adequate BP control and renal protection in hypertensive patients with non-diabetic chronic renal disease. In these patients, the low-dose combination of ramipril and felodipine ER was as effective as standard-dose felodipine ER, but more effective than standard-dose ramipril, in providing diastolic BP (DBP) control, and as effective as standard-dose ramipril, but more effective than standard-dose felodipine ER, in slowing the rate of regression of glomerular filtration. The ramipril/felodipine ER combination is as well tolerated as ramipril or felodipine ER monotherapy administered at the same dosages, and is better tolerated than felodipine ER monotherapy given at twice the dosage used in the combination. Overall, ramipril/felodipine ER appears to be an effective option for the treatment of adults with essential hypertension that is poorly controlled with monotherapy. In addition, a fixed, low-dose combination of ramipril/felodipine ER is a potential alternative to monotherapy for the initial management of essential hypertension.

The main objective of fixed dose combination therapy for hypertension is to improve blood pressure (BP) control with lower, better tolerated dosages of 2 antihypertensives rather than higher dosages of a single agent. Felodipine and metoprolol lower BP via different, but complementary, mechanisms and controlled release formulations of these 2 drugs are available as a fixed dose combination, felodipine/metoprolol. In clinical trials in patients with hypertension, felodipine/metoprolol was significantly more effective than placebo and the respective monotherapies administered at the same dosages. Mean BP was reduced to < 155/90 mm Hg in patients treated with combination therapy and controlled in approximately 70% of patients. In one study that titrated dosages to effect, fewer felodipine/metoprolol than felodipine or metoprolol monotherapy recipients required dosage increases to achieve BP control (45 vs 60 and 67%, respectively). Data from double blind comparative studies show that the antihypertensive efficacy of felodipine/metoprolol 5 to 10/50 to 100 mg/day is significantly greater than that of enalapril monotherapy or captopril plus hydrochlorothiazide and equivalent to nifedipine/atenolol and amlodipine. In comparisons with enalapril, fewer felodipine/metoprolol than enalapril recipients required dosage titration to achieve BP control. Compared with amlodipine, felodipine/metoprolol significantly reduced mean 24-hour average BP (8.9/5.5 vs 14.4/9.5 mm Hg after 6 weeks; p < 0.001). Both treatments preserved diurnal rhythm. Long term follow-up studies show that the antihypertensive effect of felodipine/metoprolol occurs mostly during the first month of treatment with small additional decreases in BP being observed in the second and third months, and a relatively constant effect thereafter. According to a validated questionnaire, quality of life was relatively similar during 12 weeks treatment with felodipine/metoprolol, enalapril or placebo. In a retrospective pharmacoeconomic analysis conducted in Sweden, felodipine/metoprolol was more cost effective than enalapril as initial treatment for hypertension. Peripheral oedema, headache and flushing were the most commonly reported adverse events with felodipine/metoprolol and felodipine monotherapy, whereas dizziness, fatigue, headache and respiratory infection were more frequent with metoprolol monotherapy. Dose-dependent adverse events such as oedema may occur less often in patients taking lower dosages in combination than in those taking higher dosages of felodipine monotherapy. Thus, patients with hypertension treated with felodipine/metoprolol experience greater control of BP, with less need for dosage titration, than those treated with felodipine, metoprolol or enalapril monotherapy. Importantly this greater efficacy does not appear to be associated with a higher incidence of adverse events relative to monotherapy. Additionally, in short term studies felodipine/metoprolol had a similar (minimal) effect on QOL to enalapril monotherapy but was more cost effective.

Hypertension is due to disturbance of the complex interplay between numerous known and unknown mechanisms that normally control blood pressure. Antihypertensive agents may, therefore, reduce blood pressure through widely different actions and, at the same time, elicit counterregulatory responses. This is a review of the long-term hemodynamic effects at rest as well as during exercise of nine relatively new antihypertensive compounds: a beta-blocker (epanolol), an alpha-receptor blocker (doxazosin), two double-acting compounds (dilevalol and carvedilol), three calcium antagonists (amlodipine, felodipine, and diltiazem), an angiotensin-converting enzyme inhibitor (lisinopril), a serotonin antagonist (ketanserin), and low-salt diet as a nonpharmacological treatment in 171 patients with mild to moderate essential hypertension. The results in the treatment groups are compared to the hemodynamic changes seen in 28 hypertensive patients left untreated for 10 years. The patient populations of the different groups were comparable. The invasive hemodynamic technique, including intraarterial blood pressure recording and measurements of cardiac output by Cardigreen, was the same in all studies. While blood pressure remained nearly unchanged in the untreated group, all antihypertensive compounds induced significant and sustained blood pressure reduction both at rest and during exercise. The modest reduction (3-5%) in blood pressure during a low-salt diet was also statistically significant. This review shows the multiplicity of the long-term hemodynamic changes, ranging from a reduction in cardiac output to peripheral vasodilatation, during chronic antihypertensive therapy. In untreated hypertensives, the cardiac output is reduced by 1-2% per year and total peripheral resistance is increased by 2-3% per year. The review also focuses on counterregulatory responses and modify the initial reduction in blood pressure after drug treatment for hypertension. It is concluded that proper understanding of the hemodynamic effects of antihypertensive agents is useful in the selection of the right treatment for specific groups of hypertensive patients.

Felodipine is a dihydropyridine calcium antagonist which selectively relaxes vascular smooth muscle. By acting at peripheral arterioles, it lowers systemic vascular resistance and thereby produces substantial decreases in blood pressure and increases in cardiac output. Felodipine is indicated for the management of hypertension, and in patients with mild to moderate disease felodipine monotherapy markedly lowers blood pressure. It proved as effective as atenolol, and equivalent to hydrochlorothiazide, either with or without amiloride, in terms of antihypertensive activity. Comparative studies also demonstrated that once daily administration with an extended-release formulation provides equivalent antihypertensive efficacy to the same amount of drug administered twice daily as the standard tablets. As a second- or third-line treatment for patients with moderate to severe hypertension refractory to standard drug combinations, felodipine produced considerable reductions in blood pressure when added to beta-blockers and diuretics, either alone or in combination, in studies lasting up to 48 weeks. In comparative studies of multiple-drug treatments felodipine was found to have superior efficacy to hydralazine and prazosin, and was at least as effective as nifedipine, minoxidil and propranolol, when used with diuretics and/or beta-blockers. As an alternative to hydrochlorothiazide, in combination with beta-blockers, felodipine consistently controlled blood pressure in a greater percentage of patients and usually provided greater decreases in blood pressure. The main side effects with felodipine are ankle oedema, headache and flushing. Although the overall incidence of effects is quite high, they are usually mild in nature. Nevertheless, withdrawal due to side effects has been necessary in about 7% of patients overall. Thus, the efficacy of felodipine has been demonstrated in mild, moderate and severe hypertension. At the present time it seems particularly suitable as a second- or third-line treatment in refractory hypertension, but it also can be used as monotherapy for mild to moderate disease.

Felodipine lowers blood pressure by reducing peripheral vascular resistance through a highly selective action on smooth muscle in arteriolar resistance vessels. The selective action may be considered a safeguard against untoward effects on cardiac contractility and conduction. Felodipine does not cause orthostatic hypotension since it has no effect in clinical doses on venous smooth muscle. Felodipine has a natriuretic/diuretic effect, which counteracts the salt and water retention that is often seen during treatment with other potent vasodilators. In clinical studies, felodipine has proved more effective than several established antihypertensive drugs. The combination of felodipine and a beta-adrenergic blocker appears to be a good alternative to standard triple treatment, and felodipine is often effective in patients with previously \"refractory\" hypertension. The antihypertensive effect of felodipine is dose related. In patients with moderate hypertension, a dose regimen of 5 mg twice a day is usually sufficient, and doses greater than 10 mg twice a day are not often required. Felodipine is generally well tolerated. The most common adverse effects are those expected from a potent arteriolar dilator: ankle swelling, headache, dizziness, flushing, etc. Adverse effects are usually transient or diminish in intensity with continued treatment. The overall frequency of adverse effects with felodipine appears to be similar to that for the established antihypertensive drugs, although the adverse effects differ. Felodipine is a potent arteriolar dilator with therapeutic advantages, especially for patients with moderate to severe hypertension.