Erling Karlsson

Clinical pharmacokinetics of procainamide.

Procainamide is almost completely absorbed after oral administration and peak plasma concentrations are generally reached within 1 to 2 hours. Upon intravenous administration there is a rapid initial distribution phase, which is completed after about 30 minutes. The pharmacokinetics can be described by a 2-compartment open model. The plasma half-life during the β-phase averdges 3 hours. The apparent volume of distribution is about 2L/ kg body weight. At therapeutic plasma levels about 15 % is bound to plasma proteins.Approximately 50% of administered procainamide is eliminated as unchanged drug via the kidneys. N-Acetylprocainamide is the main metabolite and is pharmacologically active, with a recovery in urine of about 15% (range 7 to 34% in healthy subjects). The acetylation of procainamide seems to be under the same monogenic control as that of isoniazid. At least 2 more metabolites have been found but are not yet identified. The renal clearance of procainamide ranges from 179 to 660ml/ min. Glomerular filtration and active tubular secretion seem to be the most important mechanisms.In patients with low-output cardiac failure and / for renal impairment, the absorption, distribution and elimination of the drug may be significantly altered. Determination of plasma levels is of particular value in these cases and will contribute to more safe and effective therapy in the majority of patients. As N-acetylprocainamide seems to have pharmacological effects comparable with those of procainamide, both agents should be monitored simultaneously in order to optimise therapy.

Pericardiocentesis guided by 2‐D echocardiography: the method of choice for treatment of pericardial effusion

Abstract.  Lindenberger M, Kjellberg M, Karlsson E, Wranne B (Linköping University, Linköping, Sweden). Pericardiocentesis guided by 2‐D echocardiography: the method of choice for treatment of pericardial effusion. J Intern Med 2003; 253: 411–417.

Captopril and spironolactone therapy for refractory congestive heart failure

Short- and long-term clinical effects of the angiotensin-converting enzyme (ACE) inhibitor captopril in severe congestive heart failure (CHF) were evaluated during a 3-year open study of 124 inpatients with New York Heart Association (NYHA) functional class III or IV CHF refractory to treatment with cardiac glycosides and high doses of loop diuretics. Captopril was added to each patients regimen, which comprised combinations of furosemide (124 patients), digitalis (117 patients), and spironolactone (90 patients). By the end of the first month of captopril administration, improvement in NYHA functional class was seen in 89 patients (72%). During the first year of captopril treatment, the number of hospital admissions and hospital days declined significantly (p < 0.001) and functional class improved significantly (p < 0.001). Although most patients tolerated captopril well, 44% experienced hypotension, which in 10% of patients necessitated termination of captopril therapy. Although mean serum potassium levels tended to increase, serious hyperkalemia did not occur. After 1 year, a subset of 30 patients who had not initially received spironolactone deteriorated clinically and manifested increasing urinary aldosterone levels. Hypotension precluded increasing the captopril dose, but introduction of spironolactone improved clinical status in this cohort. The results suggest that rational therapy for severe CHF includes addition of the aldosterone antagonist spironolactone to low doses of captopril (or another ACE inhibitor) and high doses of loop diuretics, provided renal function is adequate.

Acetylation of procaine amide in man. A preliminary communication.

SummaryThe metabolism of procaine amide was studied in 41 cardiac patients who had achieved steady state plasma concentrations of the drug. Acetylated procaine amide accounted for 31±12% (range 16 – 63%) of the overall urinary recovery of the drug and is therefore a main metabolite in man. Plasma levels of the metabolite were usually lower but sometimes exceeded those of the parent compound with variations between 1 and 15 µg/ml. The metabolite had a weaker effect than procaine amide on the maximal electrical driving velocity of isolated atrial strips from guinea pig.

The circulating renin–angiotensin system during treatment with metoprolol or captopril in patients with heart failure due to non-ischaemic dilated cardiomyopathy

Abstract.  Jansson K, Dahlström U, Karlberg BE, Karlsson E, Nylander E, Nyquist O, Karlberg K‐E (Linköping University Hospital and Huddinge University Hospital, Sweden). The circulating renin–angiotensin system during treatment with metoprolol or captopril in patients with heart failure due to non‐ischaemic dilated cardiomyopathy. J Intern Med 1999; 245: 435–443.

The value of repeated echocardiographic evaluation in patients with idiopathic dilated cardiomyopathy during treatment with metoprolol or captopril

Serial echocardiographic investigations were carried out on patients with idiopathic dilated cardiomyopathy, to evaluate treatment effects on left ventricular (LV) performance during therapy with either metoprolol or captopril. Thirty-two patients (23 males and 9 females) with mild to moderate symptoms of heart failure (NYHA II-III) and a mean age of 49 years were included in the investigation. The patients were investigated with Doppler echocardiography before treatment, after 3 and 6 months of treatment (either metoprolol or captopril) and 1 month after withdrawal of treatment. Intra- and inter-investigator reproducibility was acceptable, with a coefficient of variation of less than 5% for LV dimensions. A reduction in LV dimensions was seen in both treatment groups. In the metoprolol group there was also an increase in LV stroke volume and fractional shortening. The non-invasive data were in accordance with invasive measurements of stroke volume and LV filling pressure. In patients with idiopathic dilated cardiomyopathy and mild to moderate symptoms of heart failure, echocardiography seemed to be sufficiently reproducible to be used for determination of treatment effects in a longitudinal heart failure study. Both metoprolol and captopril were well tolerated and had favourable effects on LV performance.