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Biomedical subjects

R L Talbert

Publications and source records attributed to R L Talbert.

53 records · Page 3Linked to original sources

Promising uses of calcium-channel blocking agents.

It is not surprising that calcium-channel blocking agents, which have numerous effects on various physiologic systems, have been employed for several "unapproved" uses. This manuscript reviews reports that have appeared within the last two years describing unapproved cardiovascular and noncardiovascular uses of the three available calcium-channel blocking agents. The cardiovascular uses discussed include hypertensive emergencies, pulmonary hypertension, congestive heart failure, aortic insufficiency, Raynaud's phenomenon, migraine headaches, antiplatelet effects and cardiac surgery. Areas of noncardiovascular use include muscular dystrophy, achalasia, esophageal spasm, dysmenorrhea, preterm labor, asthma, hyperuricemia, mania and depression and endocrinologic and oncologic conditions. While some of the data appear promising, other reports are conflicting and contradictory. Furthermore, because much of the information comes from poorly controlled trials or anecdotal reports, even the more promising uses must be studied further and compared with conventional therapy.

Aortic Valve Insufficiency↗

Adverse effects of hypolipidaemic drugs.

Cholestyramine, colestipol, clofibrate, gemfibrozil, nicotinic acid (niacin), probucol, neomycin, and dextrothyroxine are the most commonly used drugs in the treatment of hyperlipoproteinaemic disorders. While adverse reaction data are available for all of them, definitive data regarding the frequency and severity of potential adverse effects from well-controlled trials using large numbers of patients (greater than 1000) are available only for cholestyramine, clofibrate, nicotinic acid and dextrothyroxine. In adult patients treated with cholestyramine, gastrointestinal complaints, especially constipation, abdominal pain and unpalatability are most frequently observed. Continued administration along with dietary manipulation (e.g. addition of dietary fibre) and/or stool softeners results in diminished complaints during long term therapy. Large doses of cholestyramine (greater than 32 g/day) may be associated with malabsorption of fat-soluble vitamins. Most significantly, osteomalacia and, on rare occasions, haemorrhagic diathesis are reported with cholestyramine impairment of vitamin D and vitamin K absorption, respectively. Paediatric patients have been reported to experience hyperchloraemic metabolic acidosis or gastrointestinal obstruction. Concurrent administration of acidic drugs may result in their reduced bioavailability. Serious adverse reactions to clofibrate will probably limit its role in the future. Of particular concern are ventricular arrhythmias, induction of cholelithiasis and cholecystitis, and the potential for promoting gastrointestinal malignancy which far outweigh the reported benefits in preventing new or recurrent myocardial infarction, cardiovascular death and overall death. Patients with renal disease are particularly prone to myositis, secondary to alterations in protein binding and impaired renal excretion of clofibrate. Drug interactions with coumarin anticoagulants and sulphonylurea compounds may produce bleeding episodes and hypoglycaemia, respectively. Nicotinic acid produces frequent adverse effects, but they are usually not serious, tend to decrease with time, and can be managed easily. Dermal and gastrointestinal reactions are most common. Truncal and facial flushing are reported in 90 to 100% of treated patients in large clinical trials. Significant elevations of liver enzymes, serum glucose, and serum uric acid are occasionally seen with nicotinic acid therapy. Liver enzyme elevations are more common in patients given large dosage increases over short periods of time, and in patients treated with sustained release formulations.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Accidental overdose of insufflated colchicine.

An accidental overdose of colchicine by nasal insufflation occurred when the colchicine was mistaken for methamphetamine. Colchicine insufflation is not believed to be a common practice among drug abusers; however, its physical appearance was similar enough to methamphetamine for it to be mistaken for that drug of abuse. In this case a 29-year-old White man presented to the emergency room 3 days after he 'snorted' approximately 200mg of colchicine powder. The colchicine was used as a 'root stimulator' in gardening by the patient's brother and stored in the same cabinet as the methamphetamine. Within 24 hours of exposure the patient began experiencing gastrointestinal distress and myalgia, which eventually prompted him to seek medical attention. The clinical course included hypocalcaemia (69 mg/L--day 5), hypophosphataemia (10 mg/L--day 5) and thrombocytopenia (19 X 10(3)/mm3 - day 8), all of which are consistent with colchicine toxicity. The patient improved with supportive care and electrolyte replacement, and was discharged after an 8-day hospitalisation.

Adult↗

Update on calcium-channel blocking agents.

The pharmacokinetics, clinical efficacy, and adverse effects of three calcium-channel blocking agents--verapamil, nifedipine, and diltiazem--are reviewed. Verapamil, nifedipine, and diltiazem are absorbed well after oral dosing, but absolute bioavailability of each is reduced substantially by a first-pass effect. Each drug is metabolized extensively (verapamil and diltiazem to moderately active metabolites) by the liver. A substantial percentage of each drug is bound to plasma proteins, but the binding is of clinical importance only for nifedipine (92--98% protein bound). Intravenous verapamil has become the agent of first choice for treatment of acute paroxysmal supraventricular tachycardia (PSVT); use of chronic oral verapamil therapy for prophylaxis remains controversial. Verapamil and diltiazem have been evaluated with mixed results for atrial flutter and fibrillation. For treatment of myocardial ischemia, calcium-channel blockers may be of some value (possibly in combination with nitrates of B blockers). All three agents have been studied in patients with exertional angina with good results. Calcium-channel blockers appear to be equal with nitrates for treatment of variant angina. Patients with hypertropic cardiomyopathy have been treated with verapamil and nifedipine with promising results. Nifedipine has been effective for treatment of essential hypertension. Adverse effects of calcium-channel blockers have been relatively minor or infrequent. Diltiazem overall has the best side-effect profile, with adverse effects causing discontinuation of therapy in about 2--10% of patients; verapamil in intermediate (8--10%) and nifedipine the worst (17%) in this respect. The most common side effects generally are fatigue, headache, dizziness, skin rash, and peripheral edema. While they generally should be reserved for patients in whom more conventional therapy has failed (except those with PSVT), calcium-channel blockers appear to have a valid role as reserve agents for exertional and variant angina, cardiomyopathy, and hypertension.

Adolescent↗

Removal of prednisone and prednisolone by plasma exchange.

The effect of plasma exchange on the pharmacokinetics of prednisone and prednisolone was studied. Two patients undergoing plasma exchange while receiving oral prednisone therapy were studied. Patient 1 received prednisone 50 mg daily; patient 2 received 60 mg daily. On a day when the patients were to undergo plasma exchange, blood samples for determination of prednisone and prednisolone concentrations were obtained just before the daily prednisone dose and at various times before, during, and after plasma exchange. The amount of both drugs in plasma removed by plasma exchange was also determined. On a day when the patients were not receiving plasma exchange therapy, additional blood samples were obtained just before the daily prednisone dose and at 0.5, 1, 2, 4, 6, and 8 hours after the dose. Values for elimination rate constant, half-life, area under the curve, clearance, and volume of distribution on and off plasma exchange were calculated from serum concentration-time curves for prednisone and prednisolone. Only prednisolone data proved adequate for pharmacokinetic calculations. Values of pharmacokinetic variables for prednisolone on and off plasma exchange did not differ substantially in either patient. The amount of combined prednisone and prednisolone removed by plasma exchange in each patient was less than 1% of the administered prednisone dose. In the two patients studied, changes in pharmacokinetic values for prednisolone attributable to plasma exchange and the amount of combined prednisone and prednisolone removed by plasma exchange were minimal. Supplemental dosing of prednisone following plasma exchange appears unnecessary.

Administration, Oral↗

Calcium-channel blocking agents.

The role of calcium in the cardiovascular system, and the pharmacology, pharmacokinetics, and studies evaluating the clinical use of three calcium-channel blocking agents--verapamil hydrochloride, nifedipine, and diltiazem hydrochloride--are reviewed. Inhibition of calcium conductance and alteration of calcium availability cause profound changes in: slow inward current of the cardiac action potential, myocardial contractility and metabolism, blood pressure regulation, and smooth-muscle activity. Calcium-channel blocking agents affect the movement of calcium through these channels in smooth and cardiac muscle; the specific agents in this class differ markedly in their inhibitory effects. Verapamil hydrochloride is useful intravenously for treating supraventricular rhythm disturbances. It is absorbed well when taken orally, but there is an extensive first-pass effect, so that about 20% enters the systemic circulation. The incidence of side effects in patients receiving verapamil is 9-10%; about 1% require discontinuation of therapy. Verapamil is contraindicated in patients with sinus-node disease, unstable atrioventricular block, and shock. Nifedipine has proven useful for hypertension, coronary-artery spasm, and exertional angina; it has little negative inotropic effect. Approximately 90% of an oral dose is absorbed, and 65-70% reaches the systemic circulation after first-pass metabolism. Protein binding of nifedipine ranges from 92 to 98%. Side effects of nifedipine, usually associated with the peripheral vasodilatory action, occur in approximately 15% of patients, requiring discontinuance in 2-5%. Diltiazem hydrochloride has been shown effective in the treatment of coronary-artery spasm; limited studies indicate it may be useful in treating exertional angina, hypertension, and possibly arrhythmias. Diltiazem's oral bioavailability is good (90% reaches systemic circulation), but there is significant interindividual variability between administered dose and resulting plasma concentration. Geriatric patients have delayed absorption and reduced clearance of diltiazem given in sustained-release tablets. Studies of diltiazem are limited at this time. The exact role of calcium-channel blocking agents has not yet been elucidated. However, their ability to influence the calcium channel greatly expands the therapeutic armamentarium for cardiovascular disease and other disorders.

Adolescent↗

Diagnosis and treatment of Prinzmetal's variant angina.

The presentation, diagnosis (including provocative testing), and therapy of Prinzmetal's variant angina are reviewed. Prinzmetal's variant angina (PVA) is a form of angina caused by coronary-artery vasospasm (CAS) and is not associated with exertion. It is diagnosed by history, electrocardiogram, or coronary-artery angiography. Provocative tests, such as the cold-pressor test or intravenous ergonovine maleate, are sometimes used to aid diagnosis of PVA. Nitrates, adrenergic - blocking agents, and calcium-channel blocking agents can be used in treating PVA. Nitroglycerin and isosorbide dinitrate effectively relieve CAS. However, long-term prospective studies on the use of these drugs for PVA are lacking in the literature. Studies on treating PVA with adrenergic-blocking agents have been equivocol, with some studies reporting improvement and some reporting worsening. Calcium-channel blocking agents are promising drugs for PVA. Nifedipine is generally considered the prototype of this class for antianginal activity. It is administered orally in PVA patients and is effective. Side effects are mild and do not usually require termination of therapy. Verapamil hydrochloride, the prototype calcium-channel blocking agent for arrhythmias, is effective for PVA, but only 10-20% of an orally administered dose reaches systemic circulation because of the first-pass effect. Other calcium-channel blockers, including perhexilene maleate, diltiazem hydrochloride, prenylamine, and lidoflazine, have been tested in a few CAS patients with some success; adverse effects and toxicities limit the use of some of them, especially perhexilene. Therapy, using combinations of nitrates, adrenergic-blocking agents, and calcium-channel blocking agents, is needed in some patients. Dosing guidelines for all drugs are given in the paper. Treatment of PVA should begin with oral nitrates. Calcium-channel blocking agents are indicated in the patient who has failed to respond or is intolerant to maximum doses of nitrates given in various forms.

Angina Pectoris, Variant↗

Pharmacotherapy specialty certification examination. IV. 1992 results and process modifications, including recertification. The 1992 Specialty Council on Pharmacotherapy, Board of Pharmaceutical Specialties.

Certification of pharmacotherapy specialists is proceeding smoothly. Modifications to the examination process, which include reapportioning domains, offering the examination at several sites, and establishing the recertification process, have occurred. The guidelines for petitioners and structure of specialization continue to receive the attention and interest of prospective candidates, pharmacy organizations, and the BPS. To date, 674 specialists have been certified in the approved specialties: 175 nuclear pharmacists, 236 nutrition pharmacists, and 263 pharmacotherapy specialists.

Certification↗

Drug-related hospital admissions.

To describe the frequency and pattern of drug-related morbidity that results in hospital admission and the extent to which these admissions are avoidable, we prospectively reviewed the charts of 452 consecutive patients admitted to the intensive care unit or internal medicine service of a university-affiliated, county hospital. Of these, 73 (16.2%) were admitted due to drug-related morbidity. Forty patients (54.8%) experienced drug therapy failure, 24 (32.9%) had an adverse reaction, and 9 (12.3%) had overdoses. Thirty-six (49.3%) of these admissions were definitely avoidable. Compared with patients admitted for other reasons, these patients were more likely to report noncompliance with drug therapy (65.8% vs 15.7%, p < 0.0001) and were taking more drugs (p = 0.0037). We conclude that approximately half of drug-related hospital admissions are avoidable. Targeting patients taking several drugs and with a history of noncompliance may reduce this problem.

Adverse Drug Reaction Reporting Systems↗

Strategies in the management of acute myocardial infarction.

Clinical trials continue to evaluate the pharmacologic management of myocardial infarction for benefits in mortality, degree of infarct artery patency, and frequency of reocclusion. The discovery of thrombus formation in the development of the myocardial infarction renewed interest in thrombolytic therapy. In appropriate candidates, timely administration of thrombolytics after myocardial infarction restores coronary artery patency, reduces myocardial ischemic damage, and improves left ventricular function. Adjunct therapy for thrombolysis typically includes aspirin, heparin, beta-blockers, nitroglycerin, and angiotensin-converting enzyme inhibitors, if not contraindicated. To reduce cardiac risk, postthrombolysis management generally includes aspirin. beta-blockers, and angiotensin-converting enzyme inhibitors together with efforts to reduce known cardiovascular risk factors.

Acute Disease↗

Ibutilide: a new class III antiarrhythmic agent.

Ibutilide fumarate is a new antiarrhythmic agent recently approved for the conversion of atrial flutter (AFl) and atrial fibrillation (AF) to normal sinus rhythm. A class III agent in the Vaughan Williams classification system, ibutilide prolongs cardiac repolarization by activating a slow inward, predominantly sodium current. An alternative or additive mechanism to prolong repolarization may be blockade of the outward delayed rectifier potassium rapid current. Ibutilide is administered intravenously, and approximately 40% of the drug in serum is protein bound. It is eliminated through hepatic metabolism by undefined enzyme systems, and it appears that none of the metabolites contributes significantly to antiarrhythmic activity. The elimination half-life of ibutilide ranges from 2-12 hours. When administered by 10-minute infusion, ibutilide 1 mg (approximately 0.015 mg/kg) resulted in conversion to sinus rhythm in 24-58% of patients with AFl and 20-32% with AF, compared with about 5% for placebo. Administering a second dose of 0.5-1 mg improved the overall response rates to approximately 75% and 45%, respectively. In randomized comparative trials, ibutilide was more effective than sotalol in converting AFl (70% vs 19%) and AF (44% vs 11%) and more effective than procainamide (76% vs 12% and 51% vs 20%, respectively). The time to conversion in most trials was usually 20-30 minutes. Nausea is the most common noncardiac adverse effect (< 2%). Nonsustained and sustained polymorphic ventricular tachycardia occurred in 2.7-6.7% and 1.7% of patients, respectively.

Animals↗

Thrombolytic therapy for acute myocardial infarction.

Numerous factors must be considered when determining the formulary status of thrombolytic agents for the treatment of acute myocardial infarction. Defined treatment options, predicted outcomes, and the economic consequences of this disorder continue to evolve from clinical trials. Pharmacists have a major role in delivering patient care, with responsibility for evaluating, procuring, and monitoring thrombolytic agents and drug therapy in general. By participating in the development and implementation of treatment guidelines, evaluating economic and therapeutic outcomes, providing timely optimal drug therapy, and educating health care providers and the public, they contribute significantly to the health care team.

Adjuvants, Pharmaceutic↗