Biomedical subjects
D Faulds
Publications and source records attributed to D Faulds.
Felodipine. A review of the pharmacology and therapeutic use of the extended release formulation in older patients.
Felodipine is a dihydropyridine calcium antagonist which may be administered once daily in an extended release (ER) formulation. As monotherapy in older patients with mild to moderate essential hypertension, felodipine ER once daily provides effective control of blood pressure (BP). The drug has also been effective, either as monotherapy or in combination with other antihypertensive medications, in comparisons with other antihypertensive agents, and does not adversely affect lipid profiles or, in patients with diabetes mellitus, glycaemic control. Results in patients with angina pectoris and congestive heart failure indicate a potential role for felodipine ER in these indications and data also suggest the drug reduces left ventricular hypertrophy. In addition, felodipine ER appears suitable for use in patients with concomitant respiratory disease, renal or hepatic dysfunction, cerebrovascular or peripheral ischaemic disease, or gout, making it particularly useful in the elderly who often have more than one significant clinical condition. Felodipine ER has generally been well tolerated by older patients in clinical trials, although further confirmation in the long term is desirable. Thus, felodipine ER effectively lowers BP in older patients with essential hypertension with the added convenience of once daily administration. It may be used as monotherapy or in combination with other antihypertensive agents and is a practical advance in the treatment of hypertension in the elderly.
Nilutamide. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in prostate cancer.
Nilutamide is a nonsteroidal antiandrogen with affinity for androgen receptors but not for progestogen, estrogen, or glucocorticoid receptors. Consequently, nilutamide blocks the action of androgens of adrenal and testicular origin which stimulate the growth of normal and cancerous prostatic tissue. Nilutamide has a long half-life which permits once-daily administration. Nilutamide is usually given in combination with surgical or chemical castration using gonadotrophin-releasing hormone (GnRH) [luteinising hormone-releasing hormone (LHRH)] agonists. In castrated patients the addition of nilutamide improves objective response rates, bone pain, urinary symptoms, tumour markers and time to disease progression. The tolerance of nilutamide is generally acceptable. Adverse effects are usually mild and reversible and consistent with androgen depletion. Unexpected but reversible adverse effects of nilutamide include delayed adaption to dark after exposure to bright light, transient increases in transaminases, and more severe but rare interstitial pneumonitis. Thus, nilutamide is a welcome treatment option that may be particularly useful in patients to whom the convenience of once-daily administration is seen as a worthwhile benefit.
Nicardipine. A review of its pharmacology and therapeutic efficacy in older patients.
Nicardipine is a second generation dihydropyridine calcium antagonist which selectively inhibits vascular smooth muscle contraction. In elderly patients, the drug has demonstrated clinical efficacy in the management of hypertension, angina pectoris and ischaemia-related cerebrovascular disease. In particular, nicardipine effectively controls blood pressure in elderly hypertensive patients with or without coexistent disease. In noncomparative trials, a regimen containing nicardipine has been associated with an improvement of symptoms in hypertensive patients with concurrent coronary artery, cerebrovascular or peripheral vascular disease, while in essentially 'healthy' elderly hypertensive patients, nicardipine monotherapy has resulted in improved indices of mobility and cognitive function. As yet, however, there is no evidence that nicardipine (and/or other calcium channel antagonists) decreases cardiovascular morbidity and mortality in elderly patients, as has been demonstrated for more established antihypertensive therapies, namely diuretics and/or beta-blockers. The pharmacokinetic properties of nicardipine in elderly hypertensive patients appear to be similar to those in younger patients. The main adverse events associated with nicardipine in the elderly are related to the vasodilator properties of the drug and include pedal oedema, headache and flushing. However, the drug does not exacerbate spontaneous postural hypotension in the elderly, nor does it adversely affect the coronary artery disease risk profile, even in patients with type II diabetes mellitus. In summary, widespread clinical experience in the elderly indicates that nicardipine monotherapy or a regimen containing nicardipine is useful for the treatment of hypertension, particularly in patients with coexistent coronary artery, cerebrovascular or peripheral vascular disease. Nicardipine monotherapy has also demonstrated efficacy in angina pectoris and shown promise in the management of ischaemia-related cerebrovascular diseases, notably subarachnoid haemorrhage.
Tiapride. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in geriatric agitation.
Tiapride is a substituted benzamide derivative with selective dopamine D2-receptor antagonist properties which appears to have preferential affinity for extrastriatal dopamine receptors. Animal and clinical studies show that tiapride has anxiolytic properties but the mechanism of action is uncertain. Results from limited studies indicate that the clinical efficacy of tiapride in the treatment of agitation, aggressiveness, anxiety and sleep disorders in the elderly appears superior to that of placebo, chlorpromazine, lorazepam and meprobamate. Tiapride also exerts a beneficial effect on vigilance and alertness in elderly patients and causes less sedation than chlorpromazine. Tiapride is well tolerated at the dosages recommended for elderly patients. Further well designed comparative studies with newer drugs are needed to determine the relative place of tiapride in the treatment of geriatric agitation, and such studies should also address the quality-of-life benefits for the patient. Additional clinical experience to determine the efficacy of tiapride in elderly patients with more than one disease condition, receiving concomitant medications, and/or with renal impairment is also required. However, despite these current limitations, tiapride may have potentially important applications in this difficult area of clinical medicine.
Epalrestat. A review of its pharmacology, and therapeutic potential in late-onset complications of diabetes mellitus.
Epalrestat is a carboxylic acid derivative which inhibits aldose reductase, an enzyme of the sorbitol (polyol) pathway. Under hyperglycaemic conditions epalrestat reduces intracellular sorbitol accumulation, which has been implicated in the pathogenesis of late-onset complications of diabetes mellitus. Epalrestat 150 mg/day for 12 weeks improved motor and sensory nerve conduction velocity, and vibration threshold compared with baseline and placebo in patients with diabetic neuropathy. Subjective symptoms including pain, numbness, hyperaesthesia, coldness in the extremities, muscular weakness, dizziness, and orthostatic fainting were also improved. Similar benefits were seen in a comparison with historical controls. Epalrestat 300 mg/day for 1 or 3 years was also significantly superior to placebo or no treatment in improving electroretinogram parameters and photo stress recovery time in patients with diabetic retinopathy. Improvements were also documented by funduscopy and fluorescein angiography. Epalrestat appeared most effective in patients with less severe diabetes mellitus and more recent development of late-onset complications. Epalrestat is apparently well tolerated with predominantly minor adverse events reported in clinical trials. Liver enzyme elevations were most commonly reported but generally resolved spontaneously on dose reduction or discontinuation. The effects of age and renal impairment on the efficacy and tolerability of epalrestat require clarification, and data on its use in other late-onset complications of diabetes such as nephropathy are also lacking. Comparisons with other aldose reductase inhibitors are also required to fully determine the role of epalrestat. The suggested ability of epalrestat to prevent the onset of diabetic complications should also be investigated. Thus, available data suggest epalrestat produces some improvement in the late-onset neuropathy and retinopathy associated with diabetes mellitus, although additional trials are required to determine whether ongoing therapy is necessary to maintain the improvements achieved and to confirm tolerability in the long term. Nevertheless, preliminary results suggest that epalrestat may be a useful drug in an area where there is a need for effective therapy.
Ibopamine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in congestive heart failure.
Ibopamine is an orally administered dopamine agonist which is rapidly converted to its active metabolite epinine by esterase hydrolysis. Ibopamine acts predominantly as a vasodilator and inhibitor of neuroendocrine activation in congestive heart failure, but also has mild positive inotropic effects at higher doses. The beneficial effects on cardiac and systemic haemodynamic parameters seen in short term studies have been maintained in predominantly noncomparative trials for up to 1 year, and improvements in New York Heart Association (NYHA) functional class and clinical symptoms have been observed in patients with congestive heart failure of varying severity. In double-blind studies conducted in small numbers of patients, the efficacy of ibopamine was comparable to that of digoxin, captopril, enalapril and hydrochlorothiazide. Ibopamine can successfully replace treatment with intravenous dopamine in patients with severe heart failure, and is effective and well tolerated when administered in combination with digoxin, diuretics and/or angiotensin converting enzyme (ACE) inhibitors. Ibopamine has shown no detrimental effects on renal function, few adverse effects on neurohormonal parameters and has demonstrated no significant proarrhythmic properties at therapeutic doses in patients with congestive heart failure. No adverse metabolic effects were observed during ibopamine therapy in patients with diabetes mellitus, nor did ibopamine have detrimental effects in patients with chronic obstructive pulmonary disease. While reliable evidence is required concerning effects on mortality before the role of ibopamine can be clearly defined, the drug appears to be a useful agent for combination with conventional therapies in treating patients with mild to severe congestive heart failure.
Salmeterol xinafoate: a review of its pharmacological properties and therapeutic potential in reversible obstructive airways disease.
Salmeterol xinafoate, like salbutamol (albuterol), is a saligenin derivative, and a selective beta 2-adrenoceptor agonist. It produces bronchodilation for at least 12 hours following inhalation of a single 50 micrograms dose. Salmeterol is intended for regular twice-daily treatment of reversible airways obstruction and not for immediate symptomatic relief, and when used in this manner. 50 micrograms twice daily is more effective than salbutamol 200 micrograms or terbutaline 500 micrograms administered 4 times daily, or individually titrated oral doses of theophylline in improving objective and subjective criteria of efficacy in patients with mild to moderate asthma. Salmeterol 100 micrograms inhaled twice daily may provide better control than the lower dose in patients with severe asthma. The long duration of effect of salmeterol makes it particularly suitable for treating patients with nocturnal asthma in whom it improves sleep quality. The place of salmeterol, like that of other beta 2-adrenoceptor agonists used regularly in the treatment of asthma, is being debated. Patients in need of regular beta 2-agonist therapy should also be regarded as candidates for inhaled corticosteroids to counteract underlying inflammation. Thus, salmeterol may be particularly useful in patients requiring regular treatment with beta 2-agonists for nocturnal asthma and results of trials in progress involving large numbers of patients are awaited with interest.