Acetylcholine-Related Side Effects

When all else fails, the patient may need to switch to another medication. Serotonin-boosting antidepressants are a reasonable alternative to benzodiazepines for patients with anxiety disorders. Likewise, there are several options for the bipolar patient who cannot tolerate GABAergic medications. 

The only medication that blocks GABA activity is flumazenil (Mazicon). Flumaze-nil is used only in the emergency room or in an inpatient hospital setting to treat benzodiazepine overdose. It quickly and reliably reverses the toxic effects when a patient has accidentally or purposefully taken an overdose. Restricted to emergency situations, flumazenil is never used on a routine basis. 

Flumazenil s one problematic side effect is that it can trigger benzodiazepine withdrawal including increased pulse, increased blood pressure, shakiness, anxiety, and seizures. Because it is only used in the hospital, supportive medical care is, by definition, available if this occurs. 

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All the aminoglycosides produce cochlear and vestibular damage (ototoxicity) which is a dose and duration of treatment related side effect. Another serious side effect is nephrotoxicity. Aminoglycosides also reduce the acetylcholine release from the motor nerve endings and cause neuromuscular blockade. 

Epibatidine was shown to be a very potent and selective agonistic ligand of nicotinic acetylcholine receptors. This natural product is effective in various animal models of pain through a pronounced nAChR agonistic mechanism (Ki <100 pm) which is accompanied by severe and nACh-related side-effects (Corey et al. 1993 Rupniak et al., 1994 Boyce et al., 2000). A clear differentiation between antinociceptive activity in animal models of pain and toxic side-effects cannot be determined. Nevertheless there is some activity directed towards the development of epibatidine as an analgesic (Bai et al., 1997). 

Neuromuscular blockade is a rare side-effect of the aminoglycosides, related to blockade of acetylcholine at the nicotinic cholinergic receptor. This is most often seen as respiratory depression and apnea when anesthetic agents are administered... 

The side effects and toxicity of local anesthetics seem to be related to their actions on other excitable membrane proteins, such as in the sodium and potassium channels in the heart, the nicotinic acetylcholine receptors in the neuromuscular junctions, and the nerve cells in the CNS. In general, neuromuscular junctions and the CNS are more susceptible than the cardiovascular system to the toxic effects of local anesthetics. 

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