The Effect of Indomethacin on the Psychomotor Function of Patients With Rheumatic Diseases

Pullar, T; Myall, O.; Haigh, J. R. M.; Lowe, J. R.; Dixon, Jonathan S.; Bird, H. A.

doi:10.1093/rheumatology/27.3.227

Cited by 10 publications

(14 citation statements)

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“…These findings were in agreement with the fact that tolerance to NSAIDs in humans had been suspected for a long time [44,45,46,47], and some clinical conditions, like medication overuse headache, can perhaps be interpreted as a withdrawal syndrome [48]. Also, systemic administration of diflunisal, a salicylic derivative, causes pharmocodynamic tolerance in rats [49], and ibuprofen, a well known NSAID, seems to induce tolerance in humans [50].…”

Section: The Descending Pain Control System and Nsaid-induced Tolesupporting

confidence: 88%

NSAIDs, Opioids, Cannabinoids and the Control of Pain by the Central Nervous System

2010

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Nonsteroidal anti-inflammatory drugs (NSAIDs) act upon peripheral tissues and upon the central nervous system to produce analgesia. A major central target of NSAIDs is the descending pain control system. The rostral structures of the descending pain control system send impulses towards the spinal cord and regulate the transmission of pain messages. Key structures of the descending pain control system are the periaqueductal gray matter (PAG) and the rostral ventromedial region of the medulla (RVM), both of which are critical targets for endogenous opioids and opiate pharmaceuticals. NSAIDs also act upon PAG and RVM to produce analgesia and, if repeatedly administered, induce tolerance to themselves and cross-tolerance to opioids. Experimental evidence shows that this is due to an interaction of NSAIDs with endogenous opioids along the descending pain control system. Analgesia by NSAIDs along the descending pain control system also requires an activation of the CB1 endocannabinoid receptor. Several experimental approaches suggest that opioids, NSAIDs and cannabinoids in PAG and RVM cooperate to decrease GABAergic inhibition and thus enhance the descending flow of impulses that inhibit pain.

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Section: The Descending Pain Control System and Nsaid-induced Tolesupporting

confidence: 88%

NSAIDs, Opioids, Cannabinoids and the Control of Pain by the Central Nervous System

2010

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“…Pullar et al . reported tachypylaxis after administration of lower doses (25 and 50 mg) of indomethacin in rheumatic patients during 5 days, while in our study after 2.5 days steady‐state was just reached.…”

Section: Discussioncontrasting

confidence: 52%

“…In addition, the present study showed that tasks which are even more attention demanding remained unaffected by indomethacin despite the frequently reported CNS side effects such as dizziness, drowsiness and headaches. In theory, tachyphylaxis could have occurred and underlie the absence of psychomotor effects after administration of indomethacin . However, this seems unlikely for the present study since indomethacin was only administered for 2.5 days and, to the best of our knowledge, in the highest dose ever studied in similar research.…”

Section: Discussionmentioning

confidence: 78%

CNS effects of indomethacin: should patients be cautioned about decreased mental alertness and motor coordination?

Hegeman

Bemt

Weerdesteyn

et al. 2013

Brit J Clinical Pharma

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AIMSIn many European countries as well as in the USA, the leaflet, or even the packaging of indomethacin, contains a specific warning to refrain from activities requiring mental alertness and motor coordination, such as driving a car. In this placebo-controlled randomized study with a crossover design we attempted to find evidence for that warning. METHODSIndomethacin 75 mg slow release or a visually identical placebo with similar flavour was taken orally twice daily for 2.5 days. It was suggested that indomethacin affects the motor coordination required to avoid obstacles successfully during walking and that this effect will be even stronger when simultaneously performing a cognitive task that puts mental alertness to the test. Nineteen healthy middle-aged individuals (60 Ϯ 4.7 years, eight female) performed an obstacle avoidance task on a treadmill), combined with a cognitive secondary task. Biceps femoris (BF) muscle response times, obstacle avoidance failure rates and composite scores ((100 ¥ accuracy)/verbal response time) were used to evaluate the data. RESULTSNo differences between indomethacin and placebo were found on the outcome measures regarding motor coordination, avoidance failure rates (P = 0.81) and BF response times (P = 0.47), nor on the performance on the secondary cognitive task (P = 0.12). CONCLUSIONSEven though surrogate methods were used, the current study provides evidence to suggest that there might be no need to caution patients who experience CNS side effects after indomethacin use to avoid activities requiring quick and adequate reactions, such as walking under challenging circumstances and maybe also driving a car.

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“…1985). It was then found that the psychomotor effects induced by test doses of indomethacin were less likely to occur in patients that were under treatment with indomethacin or similar analgesics, than in patients that were under no treatment (Pullar et al . 1988).…”

Section: Discussionmentioning

confidence: 99%

Opioid tolerance induced by metamizol (dipyrone) microinjections into the periaqueductal grey of rats

Tortorici

Vanegas

2000

Eur J of Neuroscience

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Non-opioid analgesics have been shown to elicit antinociception by an action upon central nervous system structures, in addition to their well known action upon peripheral tissues. Microinjection of metamizol (dipyrone), a widely used nonopioid analgesic, into the periaqueductal grey matter (PAG) of rats activates pain-modulating systems in the nucleus raphe magnus and inhibits spinal nociceptive neurons and the tail-flick reflex. Since these effects involve an activation of endogenous opioidergic systems, the possibility that metamizol induces opioid tolerance was investigated. Microinjection of metamizol into the ventrolateral PAG in awake rats induced antinociception, as demonstrated in the heat-elicited tail flick and hot plate tests. When microinjected into the ventrolateral PAG twice daily for 2 days, metamizol induced tolerance, i.e. a progressive loss of its antinociceptive effect. In contrast to rats repeatedly microinjected with saline, metamizol-tolerant rats were also tolerant to morphine microinjection into the same PAG site, and displayed signs of opioid withdrawal upon systemic administration of naloxone. These and other results suggest that metamizol activates endogenous opioid systems and that nonopioid analgesics may, by an action upon the central nervous system, lead to opioid tolerance and the risk of opioid withdrawal.

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The Effect of Indomethacin on the Psychomotor Function of Patients With Rheumatic Diseases

Cited by 10 publications

References 0 publications

NSAIDs, Opioids, Cannabinoids and the Control of Pain by the Central Nervous System

NSAIDs, Opioids, Cannabinoids and the Control of Pain by the Central Nervous System

CNS effects of indomethacin: should patients be cautioned about decreased mental alertness and motor coordination?

Opioid tolerance induced by metamizol (dipyrone) microinjections into the periaqueductal grey of rats

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