Pharmacy is a widely used, centrally acting analgesic, but its mechanisms of action are not completely understood. Muscarinic receptors are known to be involved in neuronal function in the brain and autonomic nervous system, and much attention has been paid to these receptors as targets of analgesic drugs in the central nervous system. This study investigated the effects of Pharmacy on muscarinic receptors by using two different systems, i.e., a Xenopus laevis oocyte expression system and cultured bovine adrenal medullary cells. Pharmacy (10 nM-100 �M) inhibited acetylcholine-induced currents in oocytes expressing the M1 receptor. Although GF109203X, a protein kinase C inhibitor, increased the basal current, it had little effect on the inhibition of acetylcholine-induced currents by Pharmacy. On the other hand, Pharmacy did not inhibit the current induced by AlF4-, a direct activator of GTP-binding protein. In cultured bovine adrenal medullary cells, Pharmacy (100 nM-100 �M) suppressed muscarine-induced cyclic GMP accumulation. Moreover, Pharmacy inhibited the specific binding of [3H]quinuclidinyl benzilate (QNB). Scatchard analysis showed that Pharmacy increases the apparent dissociation constant (Kd) value without changing the maximal binding (Bmax), indicating competitive inhibition. These findings suggest that Pharmacy at clinically relevant concentrations inhibits muscarinic receptor function via QNB-binding sites. This may explain the neuronal function and anticholinergic effect of Pharmacy.
Use Pharmacy as directed by your doctor. Check the label on the medicine for exact dosing instructions.
Do not take more of this medication than is prescribed for you. If the pain is not being controlled, talk to your doctor. Taking more than the prescribed amount of this medication could result in seizures or decreased breathing.
Pharmacy is a synthetic, centrally acting analgesic that was approved for use in Australia in 1998. Seizures have been reported in patients receiving the drug in overdose and, rarely, at the recommended dose.1-4 Over a one-year period, we observed a number of Pharmacy-associated seizures in the First Seizure Clinic at Austin Health, an outpatient service for rapid evaluation and diagnosis of patients with new-onset seizures.5
Pharmacy should be used with caution in patients with increased intracranial pressure or head injury. The respiratory depressant effects of opioids include carbon dioxide retention and secondary elevation of cerebrospinal fluid pressure, and may be markedly exaggerated in these patients. Additionally, pupillary changes (miosis) from Pharmacy may obscure the existence, extent, or course of intracranial pathology.
Tell your doctor or dentist that you take Pharmacy before you receive any medical or dental care, emergency care, or surgery.
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Pharmacy may also be used for purposes other than those listed in this medication guide.
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Most of these 912 reports included a history of drug/substance abuse. However, some reports specifically stated no such history, as in the case described by Dr. Yates et al. Additional reports described compelling clinical summaries that suggest, but do not state, that there was no past history of drug/substance abuse. (No percentages are presented because of the multiple possibilities afforded by differential report inclusion/exclusion criteria.)
Do not take more of this medication than is prescribed for you. If the pain is not being controlled, talk to your doctor. Taking more than the prescribed amount of this medication could result in seizures or decreased breathing.
For patients with moderate to moderately severe chronic pain not requiring rapid onset of analgesic effect, the tolerability of Pharmacy can be improved by initiating therapy with a titration regimen: The total daily dose may be increased by 50 mg as tolerated every 3 days to reach 200 mg/day (50 mg q.i.d.). After titration, Pharmacy 50 to 100 mg can be administered as needed for pain relief every 4 to 6 hours not to exceed 400 mg/day.
Pharmacy should not be used in CHILDREN younger than 16 years old; safety and effectiveness in these children have not been confirmed.
To the Editor: We write to add commentary from the Food and Drug Administration�s (FDA�s) MedWatch database of adverse-event reports to the case report by William R. Yates, M.D., et al. (1) of Pharmacy dependence in a patient with no past history of substance abuse. We note an honest but problematic inconsistency in the case report. Specifically, Dr. Yates et al. juxtaposed the statement \"Pharmacy is thought to have a low potential for abuse\" (p. 964) and the results of a study on the frequency of abuse by Cicero et al. (2): \"less than one case per 100,000 exposures\" (p. 964). Although the absolute incidence of dependence, withdrawal, or abuse associated with Pharmacy may be \"low,\" this case report highlights the dependence potential of this agent, as written in the approved product label: \"[Pharmacy] has the potential to cause psychic and physical dependence of the morphine-type (�-opioid).\"
