Side Effects of Anticholinergic Drugs

Considering the diverse uses of the previously named anticholinergics, these drugs can obviously affect a number of different tissues. A systemically adminis- 

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Dryness of mucous membranes is a common side effect of anticholinergic drug use and is due to dose-dependent inhibition of glandular secretion. In one study, oral administration of atropine caused tear secretion to fall from 15 to 3 mcl/min.A similar dose of atropine given subcutaneously gave a nearly 50% reduction in lacrimal secretion. Scopolamine at a dose of 1 to 2 mg orally reduced tear secretion from 5 to 0.8 mcl/min. Atropine combined with diphenoxylate (Lomotil) has been reported to cause severe keratoconjimctivitis sicca in susceptible individuals. 

Tertiary-amine muscarinic receptor antagonists gain access to the central nervous system and are therefore the anticholinergic drugs used to treat parkinsonism and the extrapyramidal side effects of antipsychotic drugs. Specific agents used primarily for these conditions include benztropine mesylate (Cogentin) and trihexyphenidyl hydrochloride (Artane, others). 

The actions of neuroleptics on histamine, muscarinic and alpha] adrenergic receptors explain the side effects of these drugs, i.e. sedation, anticholinergic effects and hypotensive effects, respectively, which are generally considered to be undesirable and can lead to poor patient compliance. Table 11.9 summarises the main side effects of the typical neuroleptics. 

Benztropine Mesylate, USP. Benztropine mesylate. 3o-(diphenylmethoxy)-1 otH.SatH-ttopane methane.sulfonaic (Cogentin), has anticholinergic, antihistaminic. and local anesthetic properties. Its anticholineigic effect makes it applicable as an antiparkinsonian agent. It is about as potent an anticholinergic as atropine and shares some of the side effects of this drug, such as mydriasis and dryness of mouth. Importantly, however, it does not produce central stimulation but instead exerts the characteristic. sedative effect of the antihistamine.s. 

Kerkut I am not clear on the behavioural side about the link between the effects of anticholinergic drugs on learning and on cutting out extraneous noise. If the animals learn more quickly, you would expect them to pay attention to what is going on. I wonder whether an explanation of the failure of your cats to respond when they are conditioned under atropine is because they are not paying attention to the signal. 

Compounds 13-15 are tertiary aminoalcohol ethers, a type of structure typically associated with the early antihistamines such as diphenhydramine. It is known that one of the most prominent and annoying side effects of such drugs (dryness of the mouth) are effects associated with anticholinergic mechanisms. In fact, this property has led to its use in Parkinsonism and particularly for drug-induced extrapyramidal movement disorders. The o-methyl analog, orphenadrine, was introduced because of its lower antihistaminic activity and higher anticholinergic action. Because it also reduces spasticity in voluntary muscles it is marketed as a skeletal muscle relaxant as well (under a different trade name). 

The side effects of these drugs are well known and have been summarized earlier (SED VIII, p. 313). Drugs with selective activity may be classified as antidepressants, antipsychotics, antihistamines, antispasmod-ics or antiparkinsonism agents and yet have anticholinergic actions as side effects. When two or more are given together the unwanted effects are more likely to arise. 

Renal/Hepatic function impairment Use with caution and in reduced doses in patients with hepatic impairment metabolism may be impaired, leading to drug accumulation. Use with caution in patients with significantly impaired renal function. Elderly Be cautious in dose selection for an elderly patient, usually starting at the low end of the dosing range. Elderly patients may be sensitive to the anticholinergic side effects of TCAs. 

Insomnia, hypotension, agitation, headache, and rhinitis are the most common side effects of risperidone. These tend to lessen with time. Overall, the drug tends to be well tolerated. Average weight gain associated with risperidone after 10 weeks of treatment is 2.10 kg (AUison et al. 1999). Risperidone does not have significant anticholinergic side effects. Hyperprolactinemia is common. 

FIGURE 11-8. Side effects of the conventional antipsychotics (part 1). In this diagram, the icon of a conventional antipsychotic drug is shown with its Ml anticholinergic-antimuscarinic portion inserted into acetylcholine receptors, causing the side effects of constipation, blurred mouth, dry mouth, and drowsiness. 

Physostigmine, given intravenously, counteracts both the peripheral and central side effects of atropine and other anticholinergic drugs such as thioridazine (neuroleptic), imipramine (antidepressant), and benztropine (antiparkinsonian medication). 

The efficacy of imipramine has been repeatedly demonstrated in controlled trials about 85% of children treated within a week of the start of medication, but tolerance frequently develops after a number of weeks and relapse is high after discontinuation of the treatment. Relatively low doses of imipramine only are needed, but the typical side effects of tricyclic antidepressants limit the prolonged use of the drug. The mechanism of action of imipramine in the treatment of nocturnal enuresis is unclear but one possible action is through a direct anticholinergic action on the bladder wall. 

In SUMMARY, it can be seen that the types of psychotropic drug medication that may be used in the elderly are essentially similar to those used in the younger adult patient. The main difference lies in the reduction in distribution, metabolism and elimination of the drugs, which necessitates their administration in lower doses initially followed by a slower escalation of the dose until optimal benefit is obtained. Side effects, particularly anticholinergic effects, are more pronounced in the elderly and can... 

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