PROCEEDINGS OF THE B.P.S., 3rd-5th JANUARY, 1979
We therefore confirm the results of Tuomisto & Tukiainen (1976) and Coppen et al. (1978) which showed a decreased accumulation of 5-HT in platelets from depressed patients, and, in addition, we present results of a decreased accumulation of DA in these patients, suggesting an involvement of both amines in depression. We thank the Lawson Tait Medical and Scientific Research Trust and Geigy Pharmaceuticals Ltd for their financial support.
References COPPEN, A., PRANGE, Jr., A.J., WHYBROW, P.C. & NOGUERA, R. (1972). Abnormalities of indoleamines in
affectivedisorders.Arch. Gen. Psychiat. 26,474-478. COPPEN, A., SWADE, C. & WOOD, K. (1978). Platelet 5-
435P
hydroxytryptamine accumulation in depressive illness. Clinica Chim. Acta, 87, 165-168. EHSANULLAH, R.S.B., GHOSE, K., KIRBY, MJ., TURNER, P. WITTS, D. (1977). Clinical pharmacological studies of
tandamine, a potential antidepressive drug. Psychopharmacology, 53, 73-77. SNEDDON, J. M. (1973). Blood platelets as a model for monoamine-containing neurones. In Progress in Neurobiology, 1, 151-198. STAHL, S.M. & MELTZER, H.Y. (1978a). A kinetic and pharmacologic analysis of 5-hydroxytryptamine transport by human platelets and platelet storage granules: Comparison with central serotonergic neurons. J. Pharmac. exp. Ther., 205, 118-132. STAHL, S.M. & MELTZER, H.Y.(1978b). The human platelet as a model for the dopaminergic neuron: kinetic and pharmacologic properties and the role of amine storage granules. Exp. Neurol, 59, 1-15. TUOMISTO, J. & TUKIAINEN, E. (1976). Decreased uptake of 5-hydroxytryptamine in blood platelets from depressed patients. Nature, Lond., 262, 596-598.
Decreased sensitivity to propranolol with ageing in hyperthyroid patients J. FEELY,J. CROOKS, T.E. ISLES& I.H. STEVENSON Department of Pharmacology and Therapeutics and Biochemical Medicine, University of Dundee Ninewells HospitalandMedicalSchool, DundeeDD 1 9SY
Digoxin dosage regimens-A comparison of intuitive and predicted digoxin prescribing G.D. JOHNSTON & D.G. McDEVITT Department of Therapeutics and Pharmacology, The Queen's University of Beffast and The Beffast City Hospital
Thirty-seven patients on maintenance digoxin therapy were observed in hospital over an 8 day period, during which plasma digoxin and serum creatinine concentrations were monitored. From day 1 to day 8 these measurements indicated that the patients were in the equilibrium state with regard to digoxin therapy and renal function according to previously defined
criteria (Johnston & McDevitt, 1978). Therefore, 'steady-state' plasma digoxin and serum creatinine concentrations were taken as the mean of those obtained on day 1 and day 8. The daily digoxin doses prescribed by their physicians (intuitive) were noted. Assuming a linear relationship between digoxin dose and plasma dogoxin concentration (Redfors, 1972), these data were used to calculate the digoxin doses which could have produced plasma digoxin concentrations both of 1.5 ng/ml and at the limits of the usual therapeutic range, 0.8 and 2.0 ng/ml (Whiting, Sumner& Goldberg, 1973)from the formula: Calculated dose = Prescribed dose xx Measured plasma digoxin concentration (ng/ml)
whereX = required plasma digoxin concentration
436P PROCEEDINGS OF THE B.P.S., 3rd-Sth JANUARY, 1979 Table 1
Digoxin doses estimated by prescribing aid and prescribed intuitively in 37 patients
Nomogram Digoxin dose
(Mawer, 1976)
Too low* Correctt Too high:
Nomogram (Jeliffe & Brooker,
Computer programme
Equation
Equation
Score
1974)
(Mawer, 1976)
6 18
4 20
6 19
3 14
2 11
7 21
11 21
13
13
12
20
24
9
5
(Sumner et al., (Dobbs et al., (Dobbs et al., Intuitive 1976) 1976) 1978)
< 0.8 ng/ml 0.8-2.0 ng/ml >2.0 ng/ml
* producing plasma digoxin concer t producing plasma digoxin concen
t producing plasma digoxin concer
For this group of patients digoxin doses were also determined by 6 prescribing aids based on age, weight and measures of renal function (Jeliffe & Brooker, 1974; Mawer, 1976; Sumner et al. 1976; Dobbs et al., 1976; Dobbs et al., 1978). These doses and those prescribed intuitively by the physician were compared with the doses calculated to be correct as described above. It was possible to determine the number of patients in whom the dose prescribed (by aid or by intuition) would have resulted in plasma digoxin concentrations between 0.8 and 2.0 ng/ml (correct), below 0.8 ng/ml (too low) and greater than 2.0 ng/ml (too high). The results are summarised in Table 1. None of the prescribing aids studied appeared to be more effective than the physicians' intuitive choice in determining satisfactory digoxin dosage. Indeed a majority of the prescribing aid methods seemed to be more likely to overestimate the dose and this could result in toxicity in compliant patients.
Evaluation of some non-invasive indices of cardiovascularfunction C.D. BURGESS,JANEWADSWORTH & S.J. WARRINGTON (introduced by N.A.J. HAMER) Departments of Clinical Pharmacology and Medical Electronics, St Bartholomew's Hospital, London ECIA 7BE
Measurement of the peak normalised first derivative (dA/dt/At max) of the apex cardiogram (ACG) might
References DOBBS, S.M., NICHOLSON, P.W., RODGERS, E.M.,
WOODCOCK, B.G. & LUCAS, S.B. (1976). Can maintenance digoxin dose requirements be predicted? Br. J. clin. Pharmac., 3, 231-237. DOBBS, S.M., NICHOLSON, P.W., GODGERS, E.M.,
MAWER, G.E. & KENYON, W.I. (1978). Digoxin prescribing: an evaluation of clinical judgement. Br. med. J., 2, 668-669. JELIFFE, R.W. & BROOKER, G. (1974). A nomogram for digoxin therapy. Am. J. Med., 57, 63-68. JOHNSTON, G.D. & McDEVITT, D.G. (1978). Variations of plasma digoxin concentrations in the equilibrium state after multiple dosing. Br. J. clin. Pharmac., 5, 92-93. MAWER, G.E. (1976). Computer assisted prescribing of drugs. Clin. Pharmacokin., 1, 67-78. REDFORS, A. (1972). Plasma digoxin concentrations - its relation to digoxin dosage and clinical effects in patients with atrial fibrillation. Br. Heart J., 34, 383-391. SUMNER, DJ., RUSSEL, AJ. & WHITING, B. (1976). Digoxin pharmacokinetics: Multicompartmental analysis and its clinical implications. Br. J. clin. Pharmac., 3, 221-229. WHITING, B., SUMNER, D.J. & GOLDBERG, A. (1973). An assessment of digoxin radioimmunoassay. Scot. med. J., 18, 68-74.
be of value in clinical pharmacology, but the effect of changes in heart rate on this variable is unknown. Systolic time intervals (STI) are already widely used, but there is not universal agreement as to how they should be corrected for changes in heart rate (Cokkinos, Heimonas, Demopoulos, Haralambakis, Tsartsalis & Gardikas, 1976; Weissler, Harris & Schoenfeld 1968). We have examined the effect of changes in heart rate induced by atropine on both dA/dt/At max and the STI. We have also studied the variability of these measurements within subjects, between subjects, within days and between days. In a further experiment, we have compared the variation
We therefore confirm the results of Tuomisto & Tukiainen (1976) and Coppen et al. (1978) which showed a decreased accumulation of 5-HT in platelets from depressed patients, and, in addition, we present results of a decreased accumulation of DA in these patients, suggesting an involvement of both amines in depression. We thank the Lawson Tait Medical and Scientific Research Trust and Geigy Pharmaceuticals Ltd for their financial support.
References COPPEN, A., PRANGE, Jr., A.J., WHYBROW, P.C. & NOGUERA, R. (1972). Abnormalities of indoleamines in
affectivedisorders.Arch. Gen. Psychiat. 26,474-478. COPPEN, A., SWADE, C. & WOOD, K. (1978). Platelet 5-
435P
hydroxytryptamine accumulation in depressive illness. Clinica Chim. Acta, 87, 165-168. EHSANULLAH, R.S.B., GHOSE, K., KIRBY, MJ., TURNER, P. WITTS, D. (1977). Clinical pharmacological studies of
tandamine, a potential antidepressive drug. Psychopharmacology, 53, 73-77. SNEDDON, J. M. (1973). Blood platelets as a model for monoamine-containing neurones. In Progress in Neurobiology, 1, 151-198. STAHL, S.M. & MELTZER, H.Y. (1978a). A kinetic and pharmacologic analysis of 5-hydroxytryptamine transport by human platelets and platelet storage granules: Comparison with central serotonergic neurons. J. Pharmac. exp. Ther., 205, 118-132. STAHL, S.M. & MELTZER, H.Y.(1978b). The human platelet as a model for the dopaminergic neuron: kinetic and pharmacologic properties and the role of amine storage granules. Exp. Neurol, 59, 1-15. TUOMISTO, J. & TUKIAINEN, E. (1976). Decreased uptake of 5-hydroxytryptamine in blood platelets from depressed patients. Nature, Lond., 262, 596-598.
Decreased sensitivity to propranolol with ageing in hyperthyroid patients J. FEELY,J. CROOKS, T.E. ISLES& I.H. STEVENSON Department of Pharmacology and Therapeutics and Biochemical Medicine, University of Dundee Ninewells HospitalandMedicalSchool, DundeeDD 1 9SY
Digoxin dosage regimens-A comparison of intuitive and predicted digoxin prescribing G.D. JOHNSTON & D.G. McDEVITT Department of Therapeutics and Pharmacology, The Queen's University of Beffast and The Beffast City Hospital
Thirty-seven patients on maintenance digoxin therapy were observed in hospital over an 8 day period, during which plasma digoxin and serum creatinine concentrations were monitored. From day 1 to day 8 these measurements indicated that the patients were in the equilibrium state with regard to digoxin therapy and renal function according to previously defined
criteria (Johnston & McDevitt, 1978). Therefore, 'steady-state' plasma digoxin and serum creatinine concentrations were taken as the mean of those obtained on day 1 and day 8. The daily digoxin doses prescribed by their physicians (intuitive) were noted. Assuming a linear relationship between digoxin dose and plasma dogoxin concentration (Redfors, 1972), these data were used to calculate the digoxin doses which could have produced plasma digoxin concentrations both of 1.5 ng/ml and at the limits of the usual therapeutic range, 0.8 and 2.0 ng/ml (Whiting, Sumner& Goldberg, 1973)from the formula: Calculated dose = Prescribed dose xx Measured plasma digoxin concentration (ng/ml)
whereX = required plasma digoxin concentration
436P PROCEEDINGS OF THE B.P.S., 3rd-Sth JANUARY, 1979 Table 1
Digoxin doses estimated by prescribing aid and prescribed intuitively in 37 patients
Nomogram Digoxin dose
(Mawer, 1976)
Too low* Correctt Too high:
Nomogram (Jeliffe & Brooker,
Computer programme
Equation
Equation
Score
1974)
(Mawer, 1976)
6 18
4 20
6 19
3 14
2 11
7 21
11 21
13
13
12
20
24
9
5
(Sumner et al., (Dobbs et al., (Dobbs et al., Intuitive 1976) 1976) 1978)
< 0.8 ng/ml 0.8-2.0 ng/ml >2.0 ng/ml
* producing plasma digoxin concer t producing plasma digoxin concen
t producing plasma digoxin concer
For this group of patients digoxin doses were also determined by 6 prescribing aids based on age, weight and measures of renal function (Jeliffe & Brooker, 1974; Mawer, 1976; Sumner et al. 1976; Dobbs et al., 1976; Dobbs et al., 1978). These doses and those prescribed intuitively by the physician were compared with the doses calculated to be correct as described above. It was possible to determine the number of patients in whom the dose prescribed (by aid or by intuition) would have resulted in plasma digoxin concentrations between 0.8 and 2.0 ng/ml (correct), below 0.8 ng/ml (too low) and greater than 2.0 ng/ml (too high). The results are summarised in Table 1. None of the prescribing aids studied appeared to be more effective than the physicians' intuitive choice in determining satisfactory digoxin dosage. Indeed a majority of the prescribing aid methods seemed to be more likely to overestimate the dose and this could result in toxicity in compliant patients.
Evaluation of some non-invasive indices of cardiovascularfunction C.D. BURGESS,JANEWADSWORTH & S.J. WARRINGTON (introduced by N.A.J. HAMER) Departments of Clinical Pharmacology and Medical Electronics, St Bartholomew's Hospital, London ECIA 7BE
Measurement of the peak normalised first derivative (dA/dt/At max) of the apex cardiogram (ACG) might
References DOBBS, S.M., NICHOLSON, P.W., RODGERS, E.M.,
WOODCOCK, B.G. & LUCAS, S.B. (1976). Can maintenance digoxin dose requirements be predicted? Br. J. clin. Pharmac., 3, 231-237. DOBBS, S.M., NICHOLSON, P.W., GODGERS, E.M.,
MAWER, G.E. & KENYON, W.I. (1978). Digoxin prescribing: an evaluation of clinical judgement. Br. med. J., 2, 668-669. JELIFFE, R.W. & BROOKER, G. (1974). A nomogram for digoxin therapy. Am. J. Med., 57, 63-68. JOHNSTON, G.D. & McDEVITT, D.G. (1978). Variations of plasma digoxin concentrations in the equilibrium state after multiple dosing. Br. J. clin. Pharmac., 5, 92-93. MAWER, G.E. (1976). Computer assisted prescribing of drugs. Clin. Pharmacokin., 1, 67-78. REDFORS, A. (1972). Plasma digoxin concentrations - its relation to digoxin dosage and clinical effects in patients with atrial fibrillation. Br. Heart J., 34, 383-391. SUMNER, DJ., RUSSEL, AJ. & WHITING, B. (1976). Digoxin pharmacokinetics: Multicompartmental analysis and its clinical implications. Br. J. clin. Pharmac., 3, 221-229. WHITING, B., SUMNER, D.J. & GOLDBERG, A. (1973). An assessment of digoxin radioimmunoassay. Scot. med. J., 18, 68-74.
be of value in clinical pharmacology, but the effect of changes in heart rate on this variable is unknown. Systolic time intervals (STI) are already widely used, but there is not universal agreement as to how they should be corrected for changes in heart rate (Cokkinos, Heimonas, Demopoulos, Haralambakis, Tsartsalis & Gardikas, 1976; Weissler, Harris & Schoenfeld 1968). We have examined the effect of changes in heart rate induced by atropine on both dA/dt/At max and the STI. We have also studied the variability of these measurements within subjects, between subjects, within days and between days. In a further experiment, we have compared the variation
