SLE, systemic lupus erythematosus.
Table 1.12 Drugs safe for breastfeeding mothers.
| Penicillins, cephalosporins |
| Theophylline, salbutamol by inhaler, prednisolone |
| Valproate, carbamazepine, phenytoin |
| Beta‐blockers, methyldopa, hydralazine |
| Warfarin, heparin |
| Haloperidol, chlorpromazine |
| Tricyclic antidepressants |
Drugs that can safely be given to breastfeeding mothers are listed in Table 1.12. Certain drugs achieve sufficient concentration in breast milk, and they are sufficiently potent that their use in breastfeeding mothers should be avoided. They are listed in Table 1.13.
Table 1.13 Commonly used drugs that should be avoided in women who are breastfeeding.
| Drug | Effect of drug |
|---|---|
| Amiodarone | Iodine content may cause neonatal hypothyroidism |
| Aspirin | Theoretical risk of Reye's syndrome |
| Barbiturates | Drowsiness |
| Benzodiazepines | Lethargy |
| Carbimazole | Hypothyroidism at higher doses |
| Contraceptives (combined oral) | May diminish milk supply and reduce nitrogen and protein content |
| Cytotoxic drugs | Potential problems include immune suppression and neutropenia |
| Ephedrine | Irritability |
| Tetracyclines | Theoretical risk of tooth discoloration |
2 Clinical trials and drug development
A chemist in a major pharmaceutical company has been performing research into a compound that appears to provide neuronal protection from ischaemia in in vitro models. This discovery has caused some excitement – if it is shown to have efficacy in humans then it might be a useful treatment for patients with acute stroke. What are the various stages that this compound has to go through in development before it can be licenced as a drug to be used in patients?
Many compounds are screened as potential drugs but few make it through to being used in patients
Drug development is a lengthy process with high costs, particularly in the later stages
Rigorous regulatory requirements have to be met before a drug can be tested in humans
To get a licence, a drug has to be shown to be safe and efficacious
Introduction
The process of drug development, approval, manufacturing and marketing is regulated by international agreement and/or by regulatory authorities such as the European Medicines Agency (EMA), the United States Food and Drug Administration (FDA) and the Japanese Pharmaceutical and Medical Devices Agency. Drug regulation in the UK and elsewhere arose following the use of thalidomide in the late 1950s and early 1960s. In 1961, it became clear that thalidomide use in early pregnancy as a treatment for morning sickness resulted in the congenital defect phocomelia, where the long bones of the foetus fail to develop properly. In the UK, this resulted in the formation of the Committee on Safety of Drugs (CSD) in 1963 and the passing of the Medicines Act in 1968, providing a system of licencing to regulate the manufacture, sale, supply and importation of medicinal products into the UK. Other European countries implemented similar systems and as early as 1965 there was a European directive to try and harmonise the processes within Europe. Currently, the EMA is responsible for the evaluation and supervision of medicines within the European Union and the UK Medicines and Healthcare products Regulatory Agency (MHRA) contributes to this work, while in the USA, the FDA fulfils a similar role to the EMA. New drugs can be reviewed and licenced across all members states simultaneously, i.e. in partnership, or the drug can get a licence from one member state first, and undergo a shortened ‘mutual recognition’ review and approval in the other member states. Developing a drug is a long and expensive process with many stages to go through before approval.
Drug discovery
It has been acknowledged that traditional approaches to drug discovery based on serendipity and screening of a large number of compounds are limited by inefficiency and there has since been a move towards more focused approaches.
Models of drug development
Research was traditionally divided into basic and applied clinical research studies, with basic research involving in‐vitro or animal studies and clinical research involving patients. This model was limited by a lack of integration that contributed to delays in applying basic research into meaningful treatments for patients. More recently, the research community has moved towards an integrated and translational approach where studies involve basic and
