Methods for monitoring and documenting adverse drug reactions.
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Biomedical subjects
Publications and source records attributed to M ten Ham.
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The Dutch Board for the Evaluation of Medicines approves applications for a marketing authorization if on the basis of pharmaceutical, pharmacological--toxicological, and clinical data the benefit--risk balance is considered positive. In the Netherlands, almost 4000 drugs have a marketing authorization, 145 of these belonging to the psychotropic drugs. During the Board's existence the number of applications and the number of approvals for antipsychotics and antidepressants decreased, while an increasing amount of anxiolytics was applied for and approved. This phenomenon may reflect the prescribing behavior of doctors. The Board has on several occasions actively influenced the market situation of certain drugs, e.g., amphetamines have almost totally disappeared from the market since a strong restriction of the indications was imposed. A certain shift in the evaluation policy of the Board can be noticed in some respects, for instance, data on chronic use are no longer required for registration of hypnotics. The requirements for registration of antidepressants are less strict than in the past. The Board tries by its registration policy to be an objective interface between the drug-producing companies and the consumer, the patient, and seeks the highest standards possible in the drug market.
The waterloading test in rabbits, using 100 ml of waterloads per kg body weight, without general anaesthesia and with applanation tonometry to measure intraocular pressure (IOP), deserves a place in glaucoma research. Using this model we found adrenaline not to have an effect on the IOP with or without waterloading. Isoprenaline and to a lesser physostigmine reduced the pressure in the normal eye markedly, but these drugs did not have any effect on the pressure after waterloading. delta 9-THC (Tetrahydrocannabinol) and pilocarpine increased the IOP in the normal rabbit eye. After waterloading delta 9-THC decreased the pressure, but its value was still significantly higher than the control pressure. Pilocarpine did not reduce the pressure after waterloading. Acetazolamide and timolol did not reduce the pressure in the normal eye, but after waterloading a significant reduction was observed.
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Two groups of rats were trained in a shuttle-box and received delta9-tetrahydrocannabinol (delta9-THC), either before or after being tested. The drug-before group showed tolerance--within 3-6 sessions--to the response-inhibiting effect of THC. The drug-after animals appeared also to be tolerant when they received delta9-THC before being tested. It is concluded that the tolerance to this effect probably is not learned, but has a physiological base. This is corroborated by the finding that during the same study all the animals developed tolerance to the hypothermic effect of delta9-THC.
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