A 63-year-old man comes to the office due to blurred vision in both eyes for the last 2 days. The blurriness is worse when he reads but is not noticeable when he drives. The patient has no associated headache, double vision, or weakness. However, he did start taking diphenhydramine several days ago for seasonal allergies. Past medical history is unremarkable. Vital signs are normal. On physical examination, there is edema and clear drainage affecting the nasal mucosa. Funduscopic examination is normal. This patient's visual symptoms are most likely due to blockade of which of the following mediators?
This patient has impaired visual accommodation due to anticholinergic (anti-muscarinic) effects of first-generation antihistamines (eg, chlorpheniramine, diphenhydramine). Antihistamines are designed to relieve the allergic symptoms caused by release of histamine from mast cells (eg, rhinorrhea, itchy eyes and nose, urticaria). However, first-generation antihistamines can have prominent side effects due to blockade of other receptors, including alpha-adrenergic, serotonergic, and cholinergic receptors.
The ciliary muscle attaches to the lens via the zonular fibers. Contraction of the muscle reduces tension on the fibers, allowing the lens to become more spherical and increasing its refractive power. The ciliary muscle is under parasympathetic control from the Edinger-Westphal nucleus/ciliary ganglion. Inhibition of this pathway by antimuscarinic agents will limit accommodation and cause blurring of vision for close objects. The pupillary sphincter also receives parasympathetic innervation from the Edinger-Westphal nucleus, and patients on antimuscarinic agents may have mydriasis (pupillary dilation) as well.
(Choice B) First-generation antihistamines easily cross the blood-brain barrier into the central nervous system, where they interfere with the normal neurotransmitter functions of histamine. Side effects can include drowsiness and cognitive dysfunction.
(Choice C) Leukotrienes are inflammatory mediators that contribute to nasal, ocular, and respiratory symptoms in patients with allergic disorders and asthma. Antihistamines do not interfere with leukotriene formation or action.
(Choice D) Alpha-adrenergic blockade causes peripheral vasodilation, resulting in hypotension and postural dizziness.
(Choice E) Serotonin receptor blockade by antihistamines causes appetite stimulation and weight gain.
Educational objective:
In addition to blocking histamine receptors, first-generation antihistamines (eg, chlorpheniramine, diphenhydramine) have antimuscarinic, anti-alpha adrenergic, and anti-serotonergic properties. Anticholinergic effects on the ocular ciliary muscles impair accommodation and cause blurring of vision for close objects.