Lithium and pregnancy.
Explore the source record for details and available documents.
Abnormalities, Drug-Induced↗
Biomedical subjects
R E Ferner
Publications and source records attributed to R E Ferner.
Drug-induced diabetes.
The only drugs which commonly cause diabetes during therapeutic use are the anti-hypertensive vasodilator diazoxide, and corticosteroids in high doses such as those used to palliate intracranial tumours. Thiazide diuretics have in the past been used in higher doses than necessary to treat hypertension, and the lower doses now used probably carry only a slight risk of inducing diabetes. The risk from beta-blockers is also quite small, but there is some evidence that thiazides combined with beta-blockers may be more likely to cause diabetes than either drug alone. The combination is probably best avoided in patients with a family history of non-insulin-dependent diabetes. The effect of the low-oestrogen combined oral contraceptive pill seems to be slight, and it presents a risk only to women who have had gestational diabetes. Bodybuilders who take enormous doses of anabolic-androgens can develop impaired glucose tolerance. Several drugs, including theophylline, aspirin, isoniazid and nalidixic acid can cause transient hyperglycaemia in overdosage, but only streptozotocin, alloxan and the rodenticide Vacor are likely to cause permanent diabetes.
Diabetes Mellitus↗
Acute non-oliguric renal failure secondary to sulphinpyrazone overdose.
Explore the source record for details and available documents.
Acute Kidney Injury↗
Rhabdomyolysis and acute renal failure following carbon monoxide poisoning: two case reports with muscle histopathology and enzyme activities.
Two patients with carbon monoxide poisoning are presented, both of whom suffered rhabdomyolysis complicated by acute renal failure. One patient, an attempted suicide, developed a compartment syndrome of the right thigh that required fasciotomy and recovered after a period of hemofiltration and hemodialysis. Muscle biopsy appearances were consistent with partial muscle infarction. The other patient, rescued from a smoke filled room, exhibited raised creatine kinase but no evidence of muscle swelling. He developed anuric renal failure and adult respiratory distress syndrome and died despite maximum intensive care. Muscle biopsy showed early evidence of muscle necrosis. In both cases there was a marked reduction of enzyme activities in the muscle biopsy consistent with metabolic derangement. Although there was a clinical compartment syndrome in the first case, there was no muscle swelling at the time of biopsy or subsequently in the second case. A direct toxic effect of carbon monoxide may thus have been an important mechanism contributing to the muscle necrosis in the second case, although local ischemia may have been an exacerbating factor in the first case.
Acute Kidney Injury↗
Liver transplantation after paracetamol overdose.
Explore the source record for details and available documents.
Acetaminophen↗
The relationships between dose and concentration of tolbutamide and insulin and glucose responses in patients with non-insulin-dependent diabetes.
It is uncertain how the hypoglycaemic effect of sulphonylureas varies with drug concentration in patients with non-insulin-dependent diabetes mellitus. The inter-relationship of tolbutamide dosage and concentration, and glucose and insulin concentrations were therefore examined in 54 out-patients (the observational group) and in 20 patients studied under controlled conditions (the experimental group). In the observational group, tolbutamide concentration depended significantly on the daily dose, time from dose to sampling, body weight, and age. Blood glucose and insulin concentration were related, but were independent of tolbutamide concentration. In the experimental group, peak, but not pre-dose, tolbutamide concentration, depended on dose and on body mass index. Fasting and maximum post-prandial blood glucose concentration were positively correlated with maximum tolbutamide concentration, probably because tolbutamide dosage was highest in those with the poorest response. In the subset with a fasting blood glucose concentration of less than 8 mmol.l-1, neither glucose nor insulin concentrations depended significantly on tolbutamide concentrations. Tolbutamide concentration does not directly determine hypoglycaemic response in outpatients, and therapeutic monitoring of drug concentrations would not improve the management of such patients.
Aged↗
The effects of enalapril and sulindac on the dermal response to substance P and neurokinin A.
The effects of pretreatment with enalapril, and sulindac, on the weal response to intradermal injections of substance P and neurokinin A were assessed in a randomised, double-blind, placebo-controlled study. Weal responses to both substance P and neurokinin A depended significantly on dose. Neither enalapril nor sulindac, nor the combination of these agents influenced the responses to either tachykinin. These results do not suggest any role for substance P or neurokinin A in the clinical effects of angiotensin converting enzyme inhibitors.
Adult↗
The metabolic effects of aspirin in fasting and fed subjects: relevance to the aetiology of Reye's syndrome.
As a possible model for the mechanism of precipitation of Reye's Syndrome in children the metabolic effects of oral aspirin were studied in normal subjects in the fasted and fed states, to determine whether aspirin altered fatty acid oxidation. Starvation increased blood 3-hydroxybutyrate concentrations, but aspirin had no effect on this or other metabolite concentrations in either the fasted or fed states.
3-Hydroxybutyric Acid↗
The effect of sulindac on dermal responses to bradykinin in normal subjects given an angiotensin converting enzyme inhibitor.
The ability of sulindac to modify the weal response to four doses of intradermal bradykinin in subjects given enalapril was tested in a double-blind cross-over study in normal volunteers. The dose-dependent increase in skin thickness after bradykinin was significantly reduced by prior administration of sulindac. Certain of the actions and adverse effects of angiotensin converting enzyme inhibitors may be due to the interaction of prostaglandins and bradykinin.
Adult↗
Lack of effect of co-trimoxazole on the pharmacokinetics and pharmacodynamics of nifedipine.
The pharmacokinetics of nifedipine and its primary oxidised metabolite, M-I were studied in nine healthy volunteers following a single oral dose of 20 mg nifedipine alone or after pretreatment with oral co-trimoxazole. Following pretreatment with co-trimoxazole, no significant effect was detected on maximum plasma concentration, elimination half-life, or area under the plasma concentration-time curve of either nifedipine or M-I, nor on the blood pressure response to nifedipine.
Adult↗
Pharmacokinetics and toxic effects of nifedipine in massive overdose.
A 57-year-old man took 30 x 20 mg nifedipine retarded release tablets. He developed hypotension, tachycardia and flushing, but remained in sinus rhythm. The concentration of nifedipine 10 h after overdose was 604 micrograms 1-1, and of the M-I metabolite 110 micrograms 1-1. Log concentration time curves were linear from 10-72 h for nifedipine, with a half-life of 7.5 h; and for M-I with a half-life of 8.2 h. On this evidence, oral absorption of nifedipine retarded release is complete by 10 h. There was no evidence of saturation of nifedipine or M-I metabolism, even at concentrations ten times above the therapeutic concentration.
Drug Overdose↗
Drugs in donated blood.
Blood from donors who are or who have been on drug treatment may be hazardous to the recipient. Guidelines are proposed to increase the safety of donated blood without needless rejection of donors, based on the time that should elapse between the last dose and safe blood donation for a range of commonly used drugs.
Blood Banks↗
The effects of intradermal bradykinin are potentiated by angiotensin converting enzyme inhibitors in hypertensive patients.
1. To test the hypothesis that angiotensin converting enzyme (ACE) inhibitors potentiate the tissue effects of bradykinin, the thickness of weals produced by intradermal injections of bradykinin was measured in 17 hypertensive subjects whose antihypertensive regimen included an ACE inhibitor, and in 12 whose treatment did not. 2. Weal thickness increased linearly with the logarithm of the bradykinin dose in both groups (P less than 0.0001). 3. The patients receiving ACE inhibitors showed a mean response of 1.18 +/- 0.08 mm (mean +/- s.e. mean), compared with a mean response of 0.75 +/- 0.08 mm for patients not receiving an ACE inhibitor (P = 0.002). Mean weal response (1.08 +/- 0.9 mm) was not significantly different in patients taking captopril (n = 11) compared with that (1.29 +/- 0.12 mm) in patients taking enalapril (n = 9). 4. Facial flushing during the experiment occurred in six patients taking ACE inhibitors but none who were not. 5. Dermal responses to bradykinin are enhanced in patients taking ACE inhibitors as routine antihypertensive therapy. This study supports the hypothesis that bradykinin may be responsible for some of the adverse effects of these drugs.
Adult↗
Plasma exchange for Guillain-Barré syndrome.
The impact of plasma exchange (PE) on the treatment of severe Guillain-Barré syndrome (GBS) was studied by comparing all the 16 patients treated with PE in a London teaching hospital between January 1985 and August 1987, with 64 historical controls drawn from a series of patients observed during a prospective study in South East England in 1983 and 1984. There were no GBS-related deaths in the PE treated group but seven in the historical controls (2P = 0.39). The median duration of ventilation was only 20 days (range 7-64) in the PE group compared with 36 days (range 14-365) in the surviving patients in the control group (2P = 0.06, 95% confidence interval of difference in medians -36 to 0 days). The PE group walked earlier without aid (median 55.5 compared with 86 days, 2P = 0.04, 95% confidence interval of difference in medians -88 to -2 days). Three months after the onset of neuropathy all PE treated patients were able to walk with support or better, whereas 19 of the surviving historical controls were unable to walk even with support (2P = 0.009). The costs of PE were offset by savings in intensive care unit and hospital expenditure.
Adult↗
Pharmacokinetics and toxic effects of diltiazem in massive overdose.
A 50-year-old man with ischaemic heart disease took 98 tablets of diltiazem 60 mg with alcohol. He developed a junctional bradycardia, hypotension and reduced cardiac function refractory to intravenous calcium gluconate. He survived with temporary cardiac pacing and infusion of dopamine. As much as half the dose was vomited back, but nonetheless the plasma diltiazem concentration reached 6090 micrograms/l before falling mono-exponentially with a half-life of 8.6 h. Sinus rhythm returned when the plasma concentration of diltiazem was around 750 micrograms/l. Standard resuscitative procedures sufficed to treat massive diltiazem overdosage.
Adult↗
Spinal neurofibroma presenting as atlanto-axial subluxation in von Recklinghausen neurofibromatosis.
A patient with von Recklinghausen neurofibromatosis (NF-1) developed spinal cord compression from atlanto-axial subluxation caused by a neurofibroma involving the odontoid peg. His case is discussed and the relevant literature reviewed.
Aged↗