This study investigated the intensity of stress, anxiety and depression in a sample of 141 migraineurs compared with a control group of 109 non-migraine workers matched for age and sex. Stress was measured using the Perceived Stress Questionnaire, and anxiety and depression using the Hospital Anxiety and Depression Scale. Results indicated that stress and anxiety were higher in the migraine group than in the control group and above the clinical level. Depression scores remained low in both groups, under clinical relevance. Stress is a primordial factor in the triggering and perpetuation of migraine attacks. The high score of the items 'morning fatigue', 'intrusive thoughts about work', 'feeling under pressure', 'impatience', and 'irritability' of the stress questionnaire in the migraineurs is particularly significant in the intensive stress response. It seems necessary to manage stress to improve the daily life of migraineurs and to study the link between stress, anxiety and migraine.

The pharmacokinetics of a single i.v. dose of dl-bisoprolol 0.16 mg.kg-1 ideal body weight has been studied in 8 obese women (mean weight 91 kg; 161% of ideal body weight) and 8 non-obese women (51 kg; 94% of ideal body weight). Compared to the controls, the obese subjects showed an increase in the total apparent volume of distribution (Vz) (182 vs 1351) and a decrease in Vz per kg body weight (2 vs 2.71.kg-1). There was a negative correlation between Vz l.kg-1 and the percentage of ideal body weight (r = -0.672). Total body clearance was increased, but t1/2 and renal clearance was unchanged. It is concluded that tissue diffusion of bisoprolol in obese subjects is limited, despite its lipophilicity, possibly because of alteration in the blood flow to adipose tissue produced by bisoprolol.

Abstract— Six obese subjects (mean ± s.d.: 145.1 ± 16.7% of ideal body weight) were randomly assigned to a single i.v. dose either of (±)‐propranolol base (0.108 mg kg−1 of ideal body weight) or of (±)‐sotalol base (1.06 mg kg−1 of ideal body weight). Each subject received the other drug 7 days later. Pharmacokinetic parameters were compared with those obtained previously in non‐obese control subjects. In obese subjects, the pharmacokinetic data calculated for sotalol were comparable with those measured in controls (total body clearance = 9.4 ± 2.9 L h−1; volume of distribution during the terminal phase = 79.8 ± 19.8 L or 0.9 ± 0.2 L kg−1; terminal half‐life = 6.2 ± 1.6 h). For propranolol, total clearance (44.3 ± 15.9 L h−1) and volume of distribution (230.5 ± 48.2 L or 2.7 ± 0.7 L kg−1) were significantly less than control values. The terminal half‐life (3.9 ± 1.1 h), was not significantly increased. These results could be explained by altered tissue blood flow and a decreased metabolic capacity of the liver in obese subjects.

All eye drops raise problems of local tolerance, but with variable frequencies. They can induce pain on instillation, allergic reactions, delayed healing, punctate keratitis, disturbances of lacrimal secretion, disturbances of accommodation (especially the parasympathomimetics) and local pigmentation after prolonged use. Corticosteroids are associated with 2 major risks: chronic glaucoma and cataract, initially reversible if treatment is stopped. There is still a major risk of corneal herpes with corticosteroids. It is important to be aware of these local problems as they are responsible for poor patient compliance. The systemic effects essentially concern the agonists and antagonists of the autonomic nervous system. beta-Blocker eye drops can cause bronchospasm, heart failure, syncope and psychiatric disorders, especially at high doses and with nonselective beta-blockers. These consequences are usually related to failure to comply with the prescribing precautions. alpha-Adrenergic agonists, which exert dose-dependent effects, can induce hypertensive crises or angina attacks. Apart from patients at risk (children under the age of 30 months and the elderly), parasympathomimetics cause few systemic adverse effects; anticholinesterases, which have curare-like properties, are contraindicated for 6 weeks before general anesthesia. In the very young and the very old, atropinic eye drops carry a risk of cardiovascular collapse and neuropsychiatric disturbances. Problems may also occur with other classes of drugs such as anti-infectives, antispectics, anti-inflammatories and contact lens products. Nevertheless, it is clear that this form of treatment is generally very well tolerated in relation to the volume of eye drops prescribed by ophthalmologists each day.

The beta 1- and beta 2-adrenoreceptor blockade by means of the systemic diffusion of three beta-blocker eyedrops--timolol, carteolol, and betaxolol--was evaluated in a randomized, single-blind, three-way crossover study in 18 volunteers. The blockade was evaluated by analyzing the variations of the beta 1- and beta 2-blockade effects of isoproterenol before and after instillation of one drop in each eye. The beta 1-blockade effect was judged on the variation of heart rate, and the beta 2-blockade effect was judged on the change in peripheral blood flow measured by veno-occlusive plethysmography. Comparison of the blockade by these drops showed that carteolol and timolol totally inhibited the beta 1 and beta 2 effects of a dose of isoproterenol able to increase heart rate by 50% (placebo eyedrops were used as a control). Betaxolol differ significantly because it allowed the same effects with the same dose of isoproterenol. Intensity of the blockade was measured by comparison of the effective doses of isoproterenol. Carteolol and timolol were shown to be four times more inhibitory.