Gastric Emptying Effect by 4-Aminopyridine in Patients with Chronic Spinal Cord Injury

Grijalva, Israel; Guı́zar-Sahagún, Gabriel; Rodríguez-Pacheco, Delia; Francisco-Argüelles, Carlos; Castañeda‐Hernández, Gilberto; Palma-Aguirre, José Antonio

doi:10.1016/j.arcmed.2006.11.007

Cited by 5 publications

(5 citation statements)

References 36 publications

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“…The present results, as well as those reported elsewhere by our group 4,[12][13][14][15] and other researchers, [5][6][7][8][9][10] clearly indicate that pharmacokinetics of a given drug can exhibit important differences in patients with SCI compared with able-bodied individuals. An adequate understanding of these phenomena is warranted, and therefore further research is still required.…”

Section: Discussionsupporting

confidence: 89%

“…On the other hand, there is also evidence that SCI diminishes gastrointestinal motility, 4,19,20 leading to a slow gastric emptying that has been suggested to result in a reduced drug absorption at the duodenum. 4,[7][8][9][10]12 It is notable that the effect of SCI on absorption is of such magnitude that it not only compensates for reduced clearance, but also overrides it. Therefore, the net result is a reduction of bioavailability after oral diclofenac in SCI rats, despite a prolonged half-life.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4] These changes are known to modify drug availability. Significant changes in volume of distribution and clearance have been reported in patients after cord lesion for various drugs, including aminoglycosides 5 and methylprednisolone.…”

Section: Introductionmentioning

confidence: 99%

“…10 There is evidence suggesting that the magnitude of the pharmacokinetic changes will depend on variables related to the injury itself: site of injury, intensity and the time elapsed after lesion. 4,7,10 It then appears that it is not possible to generalize on the impact of SCI on drug disposition and thus systematic research is required to fully elucidate this issue. Therefore, animal models, where the lesion can be standardized, are useful to understand these phenomena.…”

Section: Introductionmentioning

confidence: 99%

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Contrasting effects of cord injury on intravenous and oral pharmacokinetics of diclofenac: a drug with intermediate hepatic extraction

et al. 2012

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Study design: Laboratory investigation in rats submitted to experimental spinal cord injury (SCI). Objective: To determine the effect of acute SCI on the pharmacokinetics of diclofenac, a marker drug of intermediate hepatic extraction, administered by the intravenous and the oral routes. Methods: Female Wistar rats were submitted to complete section of the spinal cord at the T8 level. SCI and sham-injured rats received 3.2 mg kg À1 of diclofenac sodium either intravenously or orally, diclofenac concentration was measured in whole blood samples and pharmacokinetic parameters were estimated. Diclofenac was not selected as test drug because of its therapeutic properties, but because to its biopharmaceutical properties, that is, intermediate hepatic extraction. Results: Diclofenac bioavailability after intravenous administration was increased in injured rats compared with controls due to a reduced clearance. In contrast, oral diclofenac bioavailability was diminished in SCI animals due to a reduction in drug absorption, which overrides the effect on clearance. Conclusion: Acute SCI induces significant pharmacokinetic changes for diclofenac, a marker drug with intermediate hepatic extraction. SCI-induced pharmacokinetic changes are not only determined by injury characteristics, but also by the route of administration and the biopharmaceutical properties of the studied drug.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Contrasting effects of cord injury on intravenous and oral pharmacokinetics of diclofenac: a drug with intermediate hepatic extraction

et al. 2012

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“…Second, the detrusor muscle is innervated by autonomic parasympathetic nerves via acetylcholine [ 9 ]. Aminopyridines are known to increase the release of different neurotransmitters, including acetylcholine, noradrenaline, dopamine, and serotonin; all closely related to the autonomic nervous system [ 10 ]. Furthermore, in animal models, the increasing effect of 4-AP on sympathetic preganglionic neurons was shown to be possibly due to an increase in transmitter release by the presynaptic terminal [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

4-Aminopyridine Improves Lower Urinary Tract Symptoms in a Patient With Benign Prostatic Hyperplasia and Downbeat Nystagmus Syndrome

et al. 2014

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Aminopyridines are potassium channel blockers that increase the excitability of nerve cells and axons; therefore, they are widely used to treat different neurological disorders. Here we present a patient with idiopathic downbeat nystagmus and lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia who was treated with the sustained-release form of 4-aminopyridine (4-AP). During treatment with 4-AP, the LUTS improved. This improvement was monitored by using uroflowmetry and the International Prostate Symptom Score. A significant improvement of symptoms was observed in relation to the voided volume. This included an improved emptying of the bladder without an increase in residual urine. In animal studies, both nonselective K+ channel blockade and selective voltage-sensitive potassium blockade by 4-AP resulted in increased contraction on rat detrusor strips. To our knowledge, this is the first clinical observation of the mode of action of 4-AP in urological symptoms in humans.

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Alkylpyridines and Miscellaneous Organic Nitrogen Compounds

Peterson

2023

Patty's Toxicology

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This chapter provides a broad overview of topics related to the occupational use and exposure to a variety of miscellaneous nitrogen‐containing compounds. Topics addressed include chemical/physical properties, uses, exposure assessment, and toxic effects, as well as standards, regulations, and guidelines for exposure. Some of the chemicals and classes represented in this chapter include pyridine, alkylpyridines, vinylpyridines, aminopyridines, aminopicolines, pyridinethione compounds (pyrithiones), nicotine, the substituted uracils, quaternary herbicides, s ‐triazine herbicides, propazine, cyanazine, ametryn, prometryn, simazine, hexazinone, azides, and hydrazine and its derivatives.

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Gastric Emptying Effect by 4-Aminopyridine in Patients with Chronic Spinal Cord Injury

Cited by 5 publications

References 36 publications

Contrasting effects of cord injury on intravenous and oral pharmacokinetics of diclofenac: a drug with intermediate hepatic extraction

Contrasting effects of cord injury on intravenous and oral pharmacokinetics of diclofenac: a drug with intermediate hepatic extraction

4-Aminopyridine Improves Lower Urinary Tract Symptoms in a Patient With Benign Prostatic Hyperplasia and Downbeat Nystagmus Syndrome

Alkylpyridines and Miscellaneous Organic Nitrogen Compounds

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