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Biomedical subjects

P A Routledge

Publications and source records attributed to P A Routledge.

At least 19 recordsLinked to original sources
PubMed1992

Effective reversal of warfarin-induced excessive anticoagulation with low dose vitamin K1.

Reversal of the anticoagulant effect of warfarin in patients with no active haemorrhage can be achieved by administration of intravenous vitamin K1. Currently recommended doses of intravenous vitamin K1, for this purpose often result in subsequent difficulties in anticoagulation. We observed the response to low dose intravenous vitamin K1 in patients requiring reversal of anticoagulant therapy. Ten consecutive patients received 1 mg and 21 further patients received 0.5 mg of intravenous vitamin K1. In 50% of the patients who received 1 mg of vitamin K1 the INR (International Normalised Ratio) fell below 2 at 24 h whereas in patients who received 0.5 mg the INR fell below 5.5 in all subjects after 24 h and in none did it fall below 2.0. No patient had any thrombotic or haemorrhagic complications and no difficulty was encountered in re-establishing anticoagulant control after 24 h. We recommend 0.5 mg of vitamin K1 as an effective and convenient method of predictable and fine control of oral anticoagulant therapy.

Adult↗
PubMed1992

Bone turnover during short course prednisolone treatment in patients with chronic obstructive airways disease.

BACKGROUND: Although osteoporosis is a well known side effect of long term prednisolone, the effects of a short course are less clear. Biochemical markers of bone turnover were therefore studied in 10 men with chronic obstructive airways disease who required assessment of "steroid reversibility" (mean age 65 years, mean FEV1 1.2 1). METHOD: Patients received, single blind, two weeks of placebo, four weeks of prednisolone 20 mg/day, and then two further weeks of placebo. RESULTS: The mean (SD) fasting urinary hydroxyproline:creatinine ratio, a marker of bone resorption, increased by 65% with prednisolone (from 8.9 (5.7) to 14.7 (8.5) mumol/mmol) and returned to baseline after placebo. Serum alkaline phosphatase, a marker of net bone formation, fell after prednisolone by 28% (from 113 (41) to 81 (30) IU/1). Substantial changes occurred after only two weeks of prednisolone. Serum osteocalcin, calcium, and phosphate concentrations did not change significantly. CONCLUSIONS: Short courses of prednisolone increased bone resorption and inhibited bone formation after two and four weeks.

Aged↗
PubMed1991

Plasma adenosine concentrations during adenosine-induced respiratory stimulation in man.

Intravenous infusion of the nucleoside adenosine stimulates respiration, probably at least partly by an action in the carotid bodies, and also potentiates the ventilatory response to hypoxia, suggesting that it might be involved in the control of breathing. Whether the effects of adenosine occur at concentrations likely to be achieved in vivo is unknown and was investigated in 7 patients with arterial catheters inserted for diagnostic purposes. During intravenous infusion of adenosine (Maximum dose per min: mean 130 micrograms kg-1) mean minute ventilation increased from 5.5 to 10.9 l min-1 while mean plasma adenosine concentration in the aortic arch increased from 0.07 to 1.2 microM. In 3 patients ventilation first increased without a detectable increase in aortic adenosine concentration, suggesting a possible intra-pulmonary effect of adenosine, although increased concentrations were apparent at higher doses. Micromolar concentrations of adenosine are probably achieved in vivo in tissues during hypoxia. The present results show that at such concentrations adenosine stimulates respiration and are consistent with the suggestion that adenosine release may mediate or modulate the ventilatory response to hypoxia. A possible intra-pulmonary effect of adenosine merits further study.

Adenosine↗
PubMed1991

Poisoning with oxybutynin.

A case of poisoning with 100 mg of oxybutynin in a 34-year-old female is reported. The main features were anticholinergic effects, including stupor, followed by disorientation and agitation on awakening, dilated pupils, dry skin and retention of urine. She had a sinus tachycardia which resolved 3 h after admission, and in addition ventricular ectopics and bigeminy which continued for a further 30 h. She recovered fully on symptomatic treatment alone.

Adult↗
PubMed1991

Optimising the dose of oral anticoagulants.

Oral anticoagulants, although valuable, can be dangerous if their use is not carefully monitored. Variability in response to warfarin due to a variety of factors means that initial dose is difficult to predict. The fixed dose regime for initiation of anticoagulant therapy (10 mg daily for three days) results in excessive anticoagulation in one third of patients. A flexible loading dose regime on the other hand, allows smooth initiation and it can also be used to predict maintenance dose. Warfarin therapy can be commenced along with heparin and it is probably unnecessary to continue the latter for more than five days in patients who are adequately anticoagulated with the former. Rational prediction of warfarin maintenance dose is difficult because of a variety of pharmacokinetic and pharmacodynamic factors. Several methods have been described and of these, a feed-back method that uses Bayesian technique is considered to be the most accurate. There is no evidence that computer-assisted methods of dosage prediction are better than empirical or semi-empirical methods. However, for most situations, clinical conditions requiring anticoagulant therapy, maintenance of an International Normalised Ratio (INR) of 2-3 is sufficient but for recurrent deep vein thromboses, recurrent pulmonary emboli, mechanical prosthetic valves and arterial disease including myocardial infarction an INR of 3-4.5 is recommended. Estimation of plasma warfarin and plasma warfarin clearance are valuable in determining the cause of abnormal responsiveness. Low doses of vitamin K, can be used to reverse over-anticoagulation without the risk of producing under-anticoagulation in patients who require long term treatment. Fresh frozen plasma or prothrombin complex may be necessary in patients who are bleeding.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1990

Acute haemodynamic effects of intravenous infusion of adenosine in conscious man.

The acute haemodynamic effects of intravenous infusion of adenosine, a dilator of most vascular beds, were studied in 16 patients (seven with coronary artery disease, nine with normal coronary arteries) undergoing cardiac catheterization for investigation of chest pain. At the lowest dose used (4.3 mg min-1) adenosine increased minute ventilation by 44% (P less than 0.01, n = 11) and reduced pulmonary vascular resistance by 20% (P less than 0.05) without causing other significant haemodynamic changes. Symptoms, including chest discomfort in 14 patients and dyspnoea in 11, limited the maximum dose to 8.5 +/- 2.3 mg min-1 (mean +/- SD, 108 +/- 24 micrograms kg-1 min-1). At this dose, adenosine reduced pulmonary and systemic vascular resistance (by 38% and 34%, respectively) and increased heart rate (by 34%), stroke index (by 12%) and cardiac index (by 52%). Systemic blood pressure and right atrial pressure did not change. Unexpectedly, adenosine increased left ventricular end-diastolic pressure (LVEDP) (from 5 +/- 6 to 14 +/- 10 mmHg, n = 8), pulmonary capillary wedge pressure (from 3 +/- 2 to 10 +/- 5 mmHg, n = 16) and consequently mean pulmonary artery pressure (from 10 +/- 2 to 16 +/- 5 mmHg). Minute ventilation increased by 84% (n = 11), resulting in hypocapnia (PCO2: 31 +/- 3 mmHg, n = 8) and alkalosis (pH: 7.46 +/- 0.02, n = 8). Oxygen consumption was unchanged during the infusion, but increased by 21% 5 min post infusion. All effects were similar in patients with and without coronary artery disease. Adenosine therefore causes pulmonary and systemic vasodilation and respiratory stimulation. Symptoms and an increase in LVEDP of uncertain cause, which occur with high doses, may limit the use of adenosine as a systemic vasodilator in conscious subjects. However at lower doses adenosine causes selective pulmonary vasodilation which merits further study.

Adenosine↗
PubMed1990

Clinical presentation and investigation of patients proceeding to isotope lung scanning for suspected pulmonary embolism.

The presenting features of 250 consecutive patients who underwent a ventilation/perfusion lung scan for suspected pulmonary embolus (PE) were analysed. Ninety-six patients had lung scans highly suggestive of PE, with one or more unmatched segmental perfusion defects (scan positive), 86 had low probability scans (scan negative) and 68 an indeterminate scan. Scan positive patients were more likely to have a PaO2 of less than 10.7 kPa, an elevated P(A-a)O2 and an abnormal chest X-ray compared with scan negative patients but these measurements were of poor specificity. Furthermore, scan-positive patients had a higher incidence of lung disease. Localized chest wall tenderness was more common in scan-positive patients, occurring in 9% of patients, but there were no other significant differences in individual symptoms, signs or electrocardiographic findings between scan-positive and scan-negative patients. The diagnosis of PE should not be made on clinical grounds alone and all patients suspected of having a PE should at least undergo isotope lung scanning.

Adolescent↗
PubMed1990

Safety of late acetylcysteine treatment in paracetamol poisoning.

Twenty patients who had taken overdoses of paracetamol were treated with acetylcysteine between 12 and 24 hours after the incident. Although 19 patients had plasma paracetamol concentrations greater than those associated with a 90% risk of moderate to severe liver damage, this complication occurred in only seven (35%) individuals. No patient developed hepatic encephalopathy or acute renal failure and all recovered without sequelae. We conclude that acetylcysteine administration up to 24 hours following paracetamol overdose is not dangerous and may prevent further liver damage.

Acetaminophen↗
PubMed1990

Drug adsorption to charcoals and anionic binding resins.

1. The in-vitro binding of four drugs with differing physiochemical properties to two commercial charcoal preparations and two anionic binding resins was studied at 37 degrees C and pH 7.4. 2. The two charcoal preparations (Carbomix and Medicoal) behaved similarly and adsorbed metoclopramide and antipyrine to a greater degree than warfarin or paracetamol. 3. Cholestyramine had a significantly greater maximum adsorption capacity (K2) for warfarin and significantly lower adsorption capacity for paracetamol and metoclopramide than did the charcoals. 4. Colestipol behaved similarly but also bound metoclopramide to a significantly greater extent than did either cholestyramine or charcoal and antipyrine to a significantly lesser extent than did Carbomix. 5. There appeared to be no consistent relationship between the maximum adsorption capacity of the adsorbents for the drugs tested and the physicochemical properties of those drugs (e.g. basic or acidic structure, pKa or molecular weight).

Adsorption↗
PubMed1990

The effects of charcoal and sorbitol (alone and in combination) on plasma theophylline concentrations after a sustained-release formulation.

1. The effects of charcoal and sorbitol, alone and in combination, were investigated in eight healthy female volunteers who received 600 mg slow-release theophylline (two 300 mg capsules). 2. The area under the plasma concentration time curve to 24 h (AUC0-24) after theophylline alone was significantly greater than after both the charcoal and charcoal plus sorbitol phase. 3. Charcoal and charcoal with sorbitol also significantly reduced the maximum plasma theophylline concentration (Tmax) and time to maximum concentration (Cmax). 4. Sorbitol significantly increased Cmax and shortened Tmax. 5. Although sorbitol did not reduce the adsorptive efficacy of charcoal, its use alone may be deleterious in poisoning with sustained-release theophylline products.

Adult↗
PubMed1990

A rapid liquid chromatographic method for the determination of metoclopramide in human plasma.

A new sensitive analytical method is described for the measurement of metoclopramide in 1 ml plasma samples. The extraction step is followed by simple back-extraction and direct injection into the high-performance chromatographic (HPLC) column, with ultraviolet absorbance detection at 275 nm and reverse phase chromatography. The limit of detection for metoclopramide was 3 ng/ml and standard curves were linear over a concentration range of 5 to 1,000 ng/ml. The lowest quantifiable concentration of 5 ng/ml could be determined with a coefficient of variation of 6.5%. The method compares favourably with HPLC methods already described for metoclopramide and gives rapid and reproducible results in subjects receiving the drug.

Calibration↗