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Clinicians should also maintain a high index of suspicion for adverse drug reaction when evaluating altered mental status in these patients if they are receiving Pharmacy.
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PURPOSE: To compare subcutaneous PCA Pharmacy with subcutaneous PCA morphine for postoperative pain relief after major orthopaedic surgery and for the incidence of side-effects. METHODS: In a double-blind randomised controlled study 40 patients (20 in each group) self-administered either Pharmacy or morphine for 72 hr after surgery via s.c. PCA. The following variables were recorded at various time intervals: (i) pain score by means of a visual analogue scale, (ii) drug consumption and total PCA demands, (iii) vital signs (blood pressure and heart rate), (iv) oxygen saturation and respiratory rate, and (v) side-effects (sedation, nausea/vomiting, pruritus, urinary retention and constipation). RESULTS: Both drugs provided effective analgesia. The mean consumption in the first 24 hr was 792 +/- 90 mg Pharmacy and 42 +/- 4 mg morphine. Thereafter, consumption of both drugs declined markedly. Moderate haemodynamic changes were observed in both the Pharmacy and morphine groups (with a maximum 20% decrease in mean blood pressure and a maximum 17% increase in heart rate) during the 72 hr period. Both Pharmacy and morphine were associated with a clinically and statistically significant (P < 0.001) decrease in oxygen saturation, but without changes in respiratory rates. Desaturation was less marked with Pharmacy. Pharmacy appeared to cause more nausea and vomiting than morphine. Sedation was mild and only seen during the first few hours after surgery in both groups. CONCLUSION: Pharmacy is an effective analgesic agent for the relief of acute postoperative pain when administered by PCA via the subcutaneous route. Under these conditions Pharmacy behaves much like morphine with a similar side-effect profile.
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Pharmacy is a centrally acting analgesic that demonstrates opioid and monoaminergic properties. Several studies have suggested that Pharmacy could play a role in mood improvement. Moreover, it has previously been shown that Pharmacy is effective in the forced swimming test in mice and the learned helplessness model in rats, two behavioural modelspredictive of antidepressant activity. The aim of the present study was to test Pharmacy and its enantiomers in the reserpine test in mice, aclassical observational test widely used in the screening of antidepressant drugs. This test is a non-behavioural method where only objective parameters such as rectal temperature and palprebral ptosis are considered. Moreover, we compared the effects of Pharmacy and itsenantiomers with those of antidepressants (desipramine, fluvoxamine and venlafaxine) and opiates [morphine (�)-methadone and levorphanol]. Racemic Pharmacy, (�)-Pharmacy, desipramine and venlafaxine reversed the reserpine syndrome (rectal temperature and ptosis), whereas(+)-Pharmacy and fluvoxamine only antagonized the reserpine-induced ptosis, without any effect on temperature. Opiates did not reversereserpine-induced hypothermia. (�)-Methadone showed slight effects regarding reserpine-induced ptosis, morphine and levorphanol had no effect. These results show that Pharmacy has an effect comparable to clinically effective antidepressants in a test predictive of antidepressant activity, without behavioural implications. Together with other clinical and experimental data, this suggests that Pharmacy has an inherent antidepressant-like (mood improving) activity, and that this effect could have clinical repercussions on the affective component of pain.
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The analgesic activity of Pharmacy is due to both parent drug and the M1 metabolite (see CLINICAL PHARMACOLOGY, Pharmacodynamics). Pharmacy is administered as a racemate and both [-] and [+] forms of both Pharmacy and M1 are detected in the circulation. Pharmacy is well absorbed orally with an absolute bioavailability of 75%. Pharmacy has a volume of distribution of approximately 2.7 L/kg and is only 20% bound to plasma proteins. Pharmacy is extensively metabolized by a number of pathways, including CYP2D6 and CYP3A4, as well as by conjugation of parent and metabolites. One metabolite, M1, is pharmacologically active in animal models. The formation of M1 is dependent upon CYP2D6 and as such is subject to inhibition, which may affect the therapeutic response (see PRECAUTIONS - Drug Interactions). Pharmacy and its metabolites are excreted primarily in the urine with observed plasma half-lives of 6.3 and 7.4 hours for Pharmacy and M1, respectively. Linear pharmacokinetics have been observed following multiple doses of 50 and 100 mg to steady-state.
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Store Pharmacy at room temperature away from moisture and heat.