Narcissus and Daffodil

346 D. Brown
Galanthamine causes bradycardia and might be expected to have a negative
effect on blood pressure. However, when the drug has been tested in animals at
larger doses than those used therapeutically in man, species-specific differences
have been observed. A significant fall in blood pressure was noted in anaesthetised
dogs (Irwin and Smith, 1960a,b), but a significant rise was noted in anaesthetised
rats (Chrusciel and Varagic, 1966). In the latter experiment, physostigmine but
not neostigmine produced a similar effect, suggesting a central mechanism, but
the effect was not blocked by autonomic ganglion blocking drugs such as hexamethonium.
Galanthamine-induced hypertension was attenuated by drugs capable
of blocking the central action of the drug, such as adrenoreceptor antagonists,
nicotine and atropine. Galanthamine produced no hypertensive response in
pithed rats. With the exception of the lack of effect of the sympathetic ganglion
blockers, the evidence points toward a central stimulant action, at least in anaesthetised
rats.
Mild bradycardia was noted as a side effect in a trial of galanthamine in 14
surgical patients. A dose of 20mg produced a reduction in mean pulse rate to 69
from 72 beats per minute (Cozanitis et al., 1973a), but this had no appreciable
effect on blood pressure. Six patients had more marked bradycardia, down to 55
beats per minute, associated with minor arrhythmias. When the drug was administered
with atropine, mild bradycardia persisted, but only two patients showed
anything like the more dramatic falls in pulse rate described above. In a trial by
Khmelevsky and Gadalov (1980), galanthamine without atropine produced significant
bradycardia in just two of 40 surgical patients. As with other cholinergic
drugs, one should be alert to the possibility of cardiac complications in patients
with pre-existing disease and in those suffering from Parkinson’s disease (often
co-morbid with AD) where other treatments may interact. Very limited evidence
suggests that galanthamine may be administered with selegiline or muscarinic
receptor blockers with appropriate caution (Losev and Kamenetski, 1985;
Rainer, 1997) but there is no evidence to suggest that co-administration is safe
with other drug classes that are likely to interact. The effects of galanthamine are
likely to be additive with other anticholinesterases and cholinergics (including
those with cholinergic side effects such as the non-selective mono-amine oxidase
inhibitors) and the drug would be expected to antagonise and be opposed by anticholinergic
drugs such as the antiparkinsonian agents. Thus, it is feasible that a
centrally-acting anticholinergic drug might oppose the efficacy of galanthamine in
AD, while one which acts peripherally might reduce unwanted side effects.
As with other drugs used in anaesthesia, it is important to know if galanthamine
affects respiration. Cozanitis et al. (1972) used cine-bronchography to research the
effect of galanthamine on the bronchial tree in five asthmatic volunteers. Parenteral
doses of 20 mg produced no suspicious changes and blood gas composition
was not altered.
The ability of galanthamine, in common with some other cholinergic drugs, to
stimulate raised serum levels of cortisol was noted quite early on in the use of the
drug in anaesthesiology (Cozanitis et al., 1973b; Cozanitis, 1974). Typically, a
single 20 mg dose of galanthamine produced a 48% increase in plasma cortisol
from 0.54 to 0.8 µM/litre. No effect was observed with neostigmine, leading the
authors to suggest that galanthamine was working centrally. A later study by the
same group (Cozanitis et al., 1980) demonstrated that galanthamine was capable of