A Rare Case of Domperidone-Induced Acute Dystonia in a Young Adult Due to Consumption of Combination Drug (Proton Pump Inhibitors With Domperidone) and Its Possible Pathomechanism

Abstract

Globally, a substantial number of people are tormented by dystonia. Domperidone, a D-2 receptor antagonist acts outside the blood-brain barrier in the brain stem as well as on the gastrointestinal tract. In India, domperidone is conveniently obtainable over the counter as a combination drug with proton pump inhibitors (PPIs) for dyspepsia and gastro-esophageal reflux disease. We present a rare case of domperidone-induced acute dystonia in a young adult presented within 72 hours after consuming two oral doses of this combination drug (PPIs with domperidone) for dyspepsia. Drug-induced extra pyramidal symptoms (EPS) are often misdiagnosed as some psychiatric condition and undoubtedly its expeditious diagnosis staves off unnecessary investigations and ameliorates prognosis. Our case ignites alertness amongst practitioners in India over the judicious use of PPIs with domperidone as the latter may trigger EPS. Such combination drugs can be prescribed if absolutely mandatory by the treating physician. The possible pathomechanism of this hyperkinetic motor phenomenon, perturbing the equilibrium of the cortical-subcortical circuit and resulting in an overflow of muscular activity, is attempted to be explained here, although the explicit mechanism is still blurry.

Keywords: acute dystonia; d2 receptor antagonist; domperidone; dopamine receptor super sensitivity; drug induced dystonia (did); extra pyramidal syndrome; proton pump inhibitors (ppis).

Figure 1. Striato-pallidal circuit is regulated by the amount of dopamine and other neurotransmitters along with its receptors. A simplified flowchart is illustrated here for drug-induced EPS. The direct pathway (direct-SPNs on right side) is inhibited and the indirect pathway (indirect-SPNs on left side) is activated. A combination of akinesia/severe bradykinesia and rigidity could be the end result of right and left side of flowchart respectively climaxing with dystonia.

STN: subthalamic nuclei; GPi: globus pallidus internus; GPe: globus pallidus externa; SNr: substantia nigra pars reticularis; GABA: gamma amino butyric acid (neurotransmitter); EPS: extrapyramidal symptom; SPN: spiny projection neurons Source: Original illustration

Figure 2. A simplified representation of different projections and interrelation of neuronal network in striatum. Cortical fibers project to direct SPNs, indirect SPNs, and cholinergic interneuron through glutamate neurotransmitter. In the direct path, the axons of SPNs converge on GPi relays back to cortex through thalamus. The indirect pathway maintains the antagonist portion of a voluntary movement via GPe through gabanergic projections. It finally converges on GPi through STN from where commences the common pathway to cortex via thalamus. Nigrostriatal projections have connections to direct, indirect, and cholinergic interneuron (large aspiny neurons) through a complex network of receptors and neurotransmitters (details not shown). The neuronal projections are illustrated in colorful curved lines.

SPN: spiny projection neurons; GPi: globus pallidus interna; GPe: globus pallidus externa; M4R: mucarinic 4 receptors; STN: subthalamic nucleus; AChR: nicotine acetylcholine receptors; D1R: dopamine 1 receptor; D2R: dopamine 2 receptor; SPN: spiny projection neurons; SNc: substancia nigra compacta; SNr: substancia nigra reticularis; Chls: Cholinergic interneurons; GABA: gamma amino butyric acid (neurotransmitter) Source: Original illustration