Anticholinergics relative activities

B. Anticholinergic agents, such as procainamide and disopyramide, are relatively contraindicated in patients with glaucoma. Procainamide is hypotensive rather than hypertensive. The local anesthetic activity of procainamide would have no adverse interaction with the diabetes mellitus. 

These drugs are best avoided in patients with cerebrovascular, cardiovascular and hepatic disorders. Some sympathomimetic effects may occur, mainly mild tremor and occasionally cardiac arrhythmias. Apparent anticholinergic effects may also occur but these are the result of sympathetic potentiation in tissues with dual cholinergic/adrenergic innervation, e.g. pupil. Sympatholytic effects can also occur, principally postural hypotension, because of synthesis of relatively inactive false transmitters, e.g. octopamine, in nerve terminals following inhibition of MAO and activation of alternative metabolic pathways. 

There are some prophylactic treatments which are very individualized. Propanolol (p-blocker) has been used at 80-160 mg/day for up to 12 months. Methylsergide and dihydroergotamine(DHE), relatives of ergotamine, are used but have some serious side effects. Antihistamines such as cyproheptadine (Periactin ) have also been found to have tryptaminergic and anticholinergic activity in the CNS and can be used prophylactically. Calcium channel blockers have also been mentioned in an experimental vein. 

Anticholinergics. Antagonists at muscarinic cholinoceptors such as benztropine and bi-periden (p. 110) can be used to suppress the sequelae of the relative predominance of cholinergic activity in the striatum (in particular, tremor). Atropine-like peripheral side effects and impairment of cognitive function limit the tolerable dosage. Complete disappearance of symptoms cannot be achieved. 

Although it is claimed to be relatively free of effects usually attributed to anticholinergic activity, trazodone does cause complaints of dry mouth and blurred vision, which may be mediated through its actions on alpha-adrenoceptors. Urinary retention has been reported in a 69-year-old woman taking a combination of trazodone and an anticholinergic drug (isopropamide iodide) (15). Cholinergic overactivity has also been described in two patients after withdrawal (16). 

Inhibition of ejaculation was reported in a middle-aged man 1 week after he started taking trazodone 100 mg at night (27). The symptoms abated 3 days after withdrawal and did not return when treatment was changed to dox-epin 50 mg/day. Because trazodone has relatively more alpha-adrenoceptor blocking action and less anticholinergic activity than doxepin, the author speculated that this was the mechanism. 

The great avidity of mitochondria from rat brain for 3-qulnuclldlnyl benzllate has been mentioned previously (56). Lareson et al. (192) recorded the Infrared spectra of seven esters of benzllic acid, of ei t esters of 3-qulnuclidlnol, and of atropine and scopolamine and attempted to correlate the relative strengths of the intramolecular hydrogen bond with the threshold doses of the various compounds in producing psychotomimetic effects in dogs. The data of Albanus (42) on the psychotomimetic activities of anticholinergic compounds were used for the comparison. Of the esters of benzllic acid. 

It can be concluded from such structure-activity studies, which are based on extensive psychopharmacologlc stests in both animals and human volunteers, that BZ is the most representative of the most potent anticholinergics. However, atropine and methylatropine are the most representative of the relatively Inactive anticholinergics and could serve as control drugs, particularly because atropine is equlpotent, although of shorter duration, to BZ in peripheral anticholinergic effects. 

The second-generation antihistamines include acrivastine, astemizole, azelastine, carebastine, cetirizine, ebastine, loratadine, mizolastine, and terfenadine. They are used orally and some of them can be given by local application to the nose and eyes (2,16). They are relatively free from anticholinergic, antiserotonergic, and alpha-adrenergic activity. They cause markedly less sedation, perhaps because they penetrate the central nervous system less well than the first-generation antihistamines, being relatively hydrophilic (17-19). 

Thioridazine Hydrochloride, USP. Thioridazine hydrochloride. IO-[2-( I -mcthyl-2-piperidyl)elhyl -2-(methyl-thio)phenoihiazine monohydrochloride (Mellaril), is a member of the piperidine subgroup of the phenothiazines. The drug has a relatively low tendency to produce EPS. The drug has high anticholinergic activity, and this activity in the striatum, counterbalancing a suiatal DA block, may be responsible for the low EPS. It also has been suggested that there may be increased DA receptor selectivity, which may... 

TaWe 3.15 Relative Anticholinergic Activities of the Esters of Tropine and Pseudotropine... 

The mydriatic and cycloplegic activities of anticholinergics in humans are listed in Table 3.18. Atropine is recommended in situations requiring complete and prolonged relaxation of the sphincter of iris and the ciliary muscle. Mydriatics, like cyclopentolate, eucatropine, and homatropine bromide, with a shorter duration of action, are usually preferred for measuring refractive errors because of the relative rapidity with which their cycloplegic effects are terminated. 

The relative anticholinergic activities of the well-known therapeutic compounds are listed in Table 3.19. Although it is very difficult to justify collecting the results of a wide variety of experiments, it seems likely that the table gives some idea of their relative antisecretory. 

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