In Australia, Canada, New Zealand, Sweden, the United Kingdom, the United States and many other countries, codeine is regulated under various narcotic control laws. In some countries, it is available without a medical prescription in combination preparations from licensed pharmacists in doses up to 20 mg, or 30 mg when sold combined with 500 mg paracetamol. Of the European Union member states, 12 countries (Bulgaria, Cyprus, Denmark, Estonia, Ireland, Latvia, Lithuania, Malta, Poland, Romania, Slovenia) allow the sale of OTC codeine solid dosage forms. Australia
In Australia, since 1 February 2018, preparations containing codeine are not available without a prescription.Preparations containing pure codeine (e.g., codeine phosphate tablets or codeine phosphate linctus) are available on prescription and are considered S8 (Schedule 8, or "Controlled Drug Possession without authority illegal"). Schedule 8 preparations are subject to the strictest regulation of all medications available to consumers. Prior to 1 February 2018, Codeine was available over-the-counter (OTC). Canada
In Canada, codeine is regulated under the Narcotic Control Regulations (NCR), which falls under the Controlled Drugs and Substances Act (CDSA). Regulations state the pharmacists may, without a prescription, sell low-dose codeine products (containing up to 8 mg of codeine per tablet or up to 20 mg per 30 ml in liquid preparation) if the preparation contains at least two
additional medicinal ingredients other than a narcotic (S.36.1 NCR).In Canada tablets containing 8 mg of codeine combined with 15 mg of caffeine and 300 mg of acetaminophen are sold as T1s (Tylenol Number 1) without a prescription.
It may lead to an increased risk of a sensitization to corneal antigens and an autoimmune reaction against antigens expressed in corneal tissues. HLA association
Like most autoimmune diseases, Moorens ulcer is thought to be associated with specific HLA haplotypes. In some studies, HLA-DR17 and HLA-DQ2 have been found in increased frequencies in affected patients compared to healthy controls. These results propose a possible association between HLA and Moorens ulcer. Pathology
The precise pathophysiological mechanism of Moorens ulcer remains unclear, but most data suggest that both cell-mediated immunity and humoral immunity are involved in the pathogenesis of the disease.Reduces numbers of suppressor T cells have been found in peripheral blood from patients with Moorens ulcer. This deficit in systematic immunoregulatory mechanism may lead to loss of a control over autoreactive T and B cells and contributes to disease pathogenesis.Immunohistochemical studies in patients suffered from Moorens ulcer showed massive infiltration of multiple types of inflammatory cells in the conjunctival tissue. The cell types in the inflammatory lesion includes CD4+ and CD8+ T-lymphocytes, B-lymphocytes, macrophages, a small amount of neutrophils was also observed in the conjunctiva from patients with Moorens ulcer.In addition, circulating IgG antibodies with specificity for corneal and conjunctival antigens have been isolated from patients with Mooren’s ulcer. Gottsch and colleagues have suggested that calgranulin C, a protein expressed in the corneal stroma, may be a possible main target for autoimmune response causing Mooren’s ulcer.Also, significantly increased expression levels of adhesion and co-stimulatory molecules have been found in ocular tissues affected by Moorens ulcer compared to healthy eyes.