Anticholinergic-speak is endemic in psychiatry. Since it’s 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 SLUD-C, drugs that are anti-cholinergic – 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.
It’s a little more complicated, because there are actually two different ACh receptor types: muscarinic receptors, which mediate the SLUD part of SLUD-C, and nicotinic, which mediate the pro-cognitive, or “C” part of the mnemonic. We hear a bit about nicotinic receptors in promotional talks for Razadyne (galantamine), a cholinesterase inhibitor which has the added property of modulating nicotinic receptors. We’ll also hear a whole lot more about these receptors with the recent FDA approval of Pfizer’s Chantix (varenicline), a nicotinic receptor partial agonist that appears to be twice as good 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 Parkinson’s Disease, which is a condition caused by depletion of dopamine from specific brain regions. The fact that drugs such as Cogentin ease parkinsonian symptoms led to theory that there is a reciprocal relationship between ACh and dopamine (DA); what causes this reciprocity isn’t clear, but ACh may act to block DA reuptake in certain areas (J Neurosci 1999; 19(2):630-636).
At any rate, this balance between DA and ACh helps to explain why the most inherently anticholinergic of the conventional antipsychotics, such as Thorazine (chlorpromazine) and Mellaril (thioridizine), cause very little EPS. The potent antipsychotics, on the other hand, such as Haldol (haloperidol) are not inherently anticholinergic, and therefore require co-treatment with exogenous anticholinergics, such as Cogentin or Artane, in order to prevent EPS.
Finally, what about anticholinergics and the heart? While 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 anti-norepinephrine alpha blockade, and the cardiac conduction problems are caused by inherently toxic effects of the drug on the heart. So, please, don’t blame everything on anticholinergic effects!