Anticholinergic-speak is endemic in psychiatry. Since its unlikely to go away, we invite you to buff up your knowledge of acetylcholine (ACh) and to review the many ways in which it makes an appearance in clinical practice.

In medical school pharmacology courses, many of us were taught about cholinergic effects with the mnemonic SLUD: Salivation, Lacrimation, Urination, Defecation. I suggest augmenting this with a C standing for Cognition. If ACh facilitates SLUDC, drugs that are anticholinergic for example, the tricyclics, Paxil (paroxetine), Cogentin (benztropine), Artane (trihexyphenydil), and Benadryl (diphenhydramine) are Anti-SLUD-C. This means that they cause dry mouth, dry eyes (and blurry vision), urinary retention, constipation, and confusion.

Its a little more complicated, because there are actually two different ACh receptor types: muscarinic receptors, which mediate the SLUD part of SLUDC, and nicotinic, which mediate the procognitive, or C, part of the mnemonic. We hear a bit about nicotinic receptors in promotional talks for Razadyne (galantamine), a cholinesterase inhibitor that has the added property of modulating nicotinic receptors. Well also hear a whole lot more about these receptors due to the recent FDA approval of Pfizers Chantix (varenicline), a nicotinic receptor partial agonist that appears to be twice as effective as Zyban (bupropion) for smoking cessation.

How does ACh relate to antipsychotic medications? We need to take a step back and recall that anticholinergics were once a common treatment for Parkinsons disease, a condition caused by depletion of dopamine (DA) from specific brain regions. The fact that drugs such as Cogentin ease parkinsonian symptoms (presumably by increasing DA) led to the theory that there is a reciprocal relationship between ACh and DA. What causes this reciprocity isnt clear, but ACh may block DA reuptake in certain areas (J Neurosci 1999;19(2):630-636).

This balance between DA and ACh helps to explain why the most inherently anticholinergic of the conventional antipsychotics, such as Thorazine (chlorpromazine) and Mellaril (thioridazine), cause very limited extrapyramidal symptoms (EPS) (which, like Parkinsons disease, stem from a deficiency in DA). The highpotency antipsychotics such as Haldol (haloperidol), on the other hand, are not inherently anticholinergic and therefore require cotreatment with exogenous anticholinergics such as Cogentin or Artane in order to avoid causing EPS.

Finally, what about anticholinergics and the heart? Although an anticholinergic effect can cause some increase in the heart rate, the cardiac problems caused by tricyclics and antipsychotics are not mediated by their anticholinergic properties. The orthostatic hypotension common with these agents is caused by antinorepinephrine alpha blockade, and the cardiac conduction problems are caused by inherently toxic effects of the drug on the heart. So please, dont blame everything on anticholinergic effects!