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R M Procyshyn

Publications and source records attributed to R M Procyshyn.

11 recordsLinked to original sources
PubMed2004

Patterns of antipsychotic utilization in a tertiary care psychiatric institution.

OBJECTIVE: To perform a retrospective survey of discharge medications at a tertiary care psychiatric facility in an attempt to gain insight into, and perhaps an understanding of, the most recent pattern of antipsychotic utilization in patients with a diagnosis not restricted to schizophrenia. METHODS: This is a retrospective survey that used the Department of Pharmacy's computer database to obtain relevant discharge information on all non-geriatric patients discharged from Riverview Hospital between 1 January and 31 December 2000. The records of 372 patients met the inclusion criteria and formed the database for the survey. RESULTS: The results of this survey revealed a relatively high prevalence of antipsychotic polypharmacy (the use of two antipsychotics). Perhaps surprisingly, the highest rate of antipsychotic polypharmacy was found in individuals diagnosed with schizoaffective disorder (49.3%), followed by schizophrenia (44.7%), bipolar disorder (29.9%), and psychosis not otherwise specified (22.5%). CONCLUSION: Although antipsychotic polypharmacy is not a new phenomenon in schizophrenia, this study is the first to document its employment among other diagnoses.

Adult↗
PubMed2002

Do triglycerides modulate the effectiveness of clozapine?

We describe a case in which a patient's clinical response to clozapine appears to correlate positively with his serum triglyceride concentrations. We propose that the observed clinical response may partly be the result of the physical interaction of clozapine with the very low-density lipoproteins. We base this supposition on our previous in-vitro study showing that the plasma distribution of clozapine is significantly altered by increases in plasma triglyceride concentrations. Although this case only represents one patient, it highlights the possibility that serum lipids may be potential contributors to the clinical effectiveness of clozapine.

Adult↗
PubMed2001

A comparison of smoking behaviours between patients treated with clozapine and depot neuroleptics.

The high prevalence of smoking among individuals diagnosed with schizophrenia is well recognized and documented. Many explanations have been put forth to explain this phenomenon including the effects of antipsychotic medication. We sought to determine if there is a difference in smoking behaviour between patients treated with clozapine and depot neuroleptics. This cross-sectional study recruited patients with schizophrenia from the Forensic Psychiatric Institute of British Columbia. Eligibility for the study required that patients be on either clozapine or depot neuroleptic for at least 2 months. The patient's smoking behaviour was evaluated using expired carbon monoxide (CO) measurements, the Fagerstrom Test for Nicotine Dependence (FTND), and a semi-structured interview. Our results showed that patients treated with clozapine had significantly lower expired CO values than patients treated with depot neuroleptics (11.8 +/- 9.2 versus 21.2 +/- 7.1 p.p.m., respectively, P < 0.01). This finding was further supported by the noted trend in which patients receiving clozapine self-reported smoking less than patients treated with depot neuroleptics (13.7 +/- 11.3 versus 26.8 +/- 18.3 cigarettes per day, respectively, P = 0.08). Thus, according to measurements of expired CO levels, patients treated with clozapine smoke less than patients treated with depot neuroleptics.

Adult↗
PubMed2001

Plasma protein and lipoprotein distribution of clozapine.

OBJECTIVE: The authors' goal was to determine what effect dyslipidemia has on clozapine's plasma distribution. METHOD: [(3)H]Clozapine plus cold clozapine (335 ng/ml) were incubated in plasma samples with varying total cholesterol, lipoprotein cholesterol, and triglyceride concentrations. Following incubation, the plasma was separated into its lipoprotein and lipoprotein-deficient fractions by density gradient ultracentrifugation and clozapine distribution was determined. RESULTS: Compared with the plasma standard, significantly more clozapine was recovered in the very-low-density lipoprotein fraction, which contained elevated total cholesterol and triglycerides. Correlation analysis revealed a positive correlation between total plasma triglyceride concentration and clozapine recovery in this fraction. CONCLUSIONS: In plasma samples with elevated triglycerides, clozapine shifts from the lipoprotein-deficient fraction to the very-low-density lipoprotein fraction. This redistribution of clozapine may affect the pharmacological activity of clozapine.

Antipsychotic Agents↗
PubMed2001

Antipsychotic polypharmacy: a survey of discharge prescriptions from a tertiary care psychiatric institution.

OBJECTIVE: To perform a retrospective survey of discharge medications at a tertiary care psychiatric facility and to assess the incidence of antipsychotic polypharmacy. METHOD: This is a retrospective survey that used the Department of Pharmacy's computer database to obtain relevant discharge information on all nongeriatric patients with schizophrenia discharged from Riverview Hospital between November 1, 1996 and October 31, 1998. From a total of 492 eligible patients, 229 met the inclusion criteria and formed the database for the survey. RESULTS: The main finding of the survey was that 27.5% of our discharged patients diagnosed with schizophrenia left our facility on an antipsychotic polypharmacy regimen. Compared with patients discharged on a single antipsychotic, the pooled data revealed a significantly greater use of anticholinergic agents in those patients prescribed an antipsychotic polypharmacy regimen. Further, of the atypical agents, only risperidone showed a statistically significant reduction in dosage when coprescribed with a second antipsychotic. CONCLUSION: Although antipsychotic polypharmacy persists today, as it has over the past 30 years, evidence-based data to support this controversial treatment strategy is lacking. As a result clinicians are relying on their clinical experience, and perhaps intuition, to design antipsychotic polypharmacy treatment protocols. Efforts should be made to replace subjective clinical impression with a more rational approach to antipsychotic polypharmacy--one that is based on pharmacodynamic and pharmacokinetic understanding of drug action.

Adult↗
PubMed2000

Rational antipsychotic polypharmacy.

The use of two antipsychotics for the treatment of individuals with psychiatric disorders is not uncommon in clinical practice but is rarely documented in the literature. The present article suggests an alternative method of treating individuals who show a partial but inadequate response to antipsychotic monotherapy. A rational strategy for augmenting one antipsychotic with a second, based on pharmacodynamic and pharmacokinetic principles, is provided. The present approach considers the 5-hydroxytryptamine2 to dopamine2 ratio, other complementary receptor affinities and drug-drug interactions involving the cytochrome P450 isoenzymes. The present article presents a rationale for augmenting haloperidol in patients who are partially responsive to clozapine.

Antipsychotic Agents↗
PubMed1995

Engineering magnesium selectivity in the helix-loop-helix calcium-binding motif.

Engineering magnesium selectivity into the helix-loop-helix (hlh) cation binding site is relatively unstudied in the calmodulin superfamily of calcium-regulated proteins, which include parvalbumin, oncomodulin, troponin C, calbindin, and calmodulin. Studies using a 33-residue synthetic peptide model of the hlh cation binding motif have indicated that magnesium will induce structural change in those peptide motifs containing three or four acid residues in chelating positions with a single-acid-pair on the Z-axis. Decreasing the cation binding cavity size in Z-axis acid-paired motifs through replacement of chelating residues in the +Z or -X metal ion coordinating positions in the loop region by glutamic acid has been successful in decreasing the calcium ion affinity. The same changes did not create or enhance magnesium binding in the 33-residue model hlh cation binding motif.

Amino Acid Sequence↗
PubMed1994

A structure/activity study of calcium affinity and selectivity using a synthetic peptide model of the helix-loop-helix calcium-binding motif.

The acid pair hypothesis predicts the calcium affinity of the helix-loop-helix calcium-binding motif based on the number and location of acidic amino acid residues in chelating positions of the calcium-binding loop region. This study investigates the effects of the number and position of acidic residues in the loop region on calcium affinity and selectivity using 33-residue synthetic models of single helix-loop-helix calcium-binding motifs. Increasing the number of acidic residues in the octahedrally arranged chelating positions of the loop region from 3 to 4 by replacing an asparagine in the +y position with an aspartic acid increases the calcium affinity of the models between 2- and 38-fold. Differences in affinities are more pronounced in the models containing an x axis acid pair. The calcium affinities of peptide models containing 3 or 4 acidic residues in chelating positions of the loop region and an x axis acid pair are reduced when the residue in the +z position is changed from asparagine to serine. A similar reduction in calcium affinity occurs in the z axis acid paired peptides when the -x chelating residue is changed from serine to asparagine. Models with 3 acidic residues in chelating positions containing a z axis acid pair have greater calcium affinity than comparable peptide models with an x axis acid pair. The presence of x or z axis acid pairs in comparable peptides containing 4 acidic residues in chelating positions does not greatly alter calcium affinity. Calcium selectivity resides in x axis acid paired peptides, whereas z axis acid paired peptides exhibit both magnesium- and calcium-induced structural changes. This ion selectivity may be explained by postulating that the z axis residue side chains produce the initial, rate-limiting interactions with the cation, causing hydration shell destabilization and initiating the subsequent ligand interactions.

Amino Acid Sequence↗
PubMed1994

An examination of glutamic acid in the -X chelating position of the helix-loop-helix calcium binding motif.

Poor calcium affinity was exhibited in helix-loop-helix calcium binding motifs with X-axis acid pairs containing aspartic acid in the -X chelating position. In order to increase interaction of the -X chelating residue with the cation, helix-loop-helix calcium binding motifs were synthesized containing three and four acid residues in chelating positions, with a glutamic acid replacing aspartic acid in the -X chelating position. The glutamate-containing motif gave an unexpected 6-fold decrease in cation affinity for the three-acid residue loop motif (KCa = 524 microM vs KCa = 3140 microM) and a 46-fold decrease for the four-acid residue loop motif (KCa = 42.1 microM vs KCa 1950 microM). To improve calcium binding of the glutamate-containing motifs, peptides were synthesized keeping glutamate in the -X position and inserting serine in the +Z position to provide a hydrogen-bonded system stabilizing the glutamate interaction with the cation. The serine residue further reduced calcium affinity in both the three-acid residue loop (KCa = 19.6 mM) and the four-acid residue loop (KCa = 2806 microM). These results indicate that glutamate and serine residues in the -X and +Z positions, respectively, can be detrimental to calcium binding. However, in natural calcium binding proteins, glutamate in the -X chelating position can confer high affinity for calcium in helix-loop-helix calcium binding motifs, but this may be dependent on the environment created by as yet undetermined factors.

Amino Acid Sequence↗
PubMedDate not supplied

Drug utilization patterns and outcomes associated with in-hospital treatment with risperidone or olanzapine.

This study compared the drug-utilization costs and indicators of clinical outcomes associated with the use of risperidone and olanzapine in a hospital setting. We conducted a nonrandomized, retrospective chart review of consecutive patients identified as presenting with psychotic symptoms on inpatient wards at Riverview Hospital in British Columbia and given either risperidone or olanzapine as their first new drug after reassessment (n = 30 per treatment group). Data were collected for up to 120 days. No significant differences were observed between groups in terms of sex, age, duration of illness, or diagnosis. The mean dosage of risperidone for responders was 4.89 +/- 2.56 mg/d, whereas that for olanzapine was 17.19 +/- 3.88 mg/d. The associated daily drug-acquisition costs were significantly different, at CA$4.69 for risperidone and CA$11.52 for olanzapine. Notes in patient charts indicated that a significantly greater proportion of risperidone-treated patients (60.0%) than olanzapine-treated patients (26.7%) responded to therapy, as indicated by improvement in at least one target symptom (P < 0.01). Forty percent of patients initially treated with risperidone were discharged on their original therapy, compared with 13.3% of patients treated with olanzapine (P < 0.05). These results were not substantially affected by correction for markers of illness severity or treatment resistance. Overall, no significant differences in side effects were recorded in the patient records of the two groups. Within this cohort of patients, risperidone treatment was associated with lower drug-acquisition cost and better treatment outcomes than olanzapine.

Adolescent↗