Oral Amantadine Versus Gabapentin to Attenuate the Response to Laryngoscopy and Tracheal Intubation

Study Overview
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Brief Summary
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To evaluate the effect of oral amantadine versus gabapentin premedication on the hemodynamic response to laryngoscopy and tracheal intubation and their effect on β-endorphins.

Detailed Description
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Direct laryngoscopy and passage of endotracheal tube through the larynx is a noxious stimulus, which can provoke untoward response in the cardiovascular, respiratory and other physiological systems. Gabapentin, is 1-aminomethyl cyclohexane acetic acid.Gabapentin is structurally related to the neurotransmitter gamma-aminobutyric acid (GABA). Gabapentin act in central nervous system CNS), it acts by decreasing the synthesis of neurotransmitter glutamate and by binding to the alpha 2 delta subunits of voltage dependent calcium channels. Amantadine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, and compared to ketamine, it is well tolerated with fewer side effects (mainly dizziness, sedation, and dry mouth). Amantadine's formulation permits the oral route for drug delivery, as well as the IV route. The side-effects profile of amantadine via all routes seems not to be harmful in appropriate dosages.. Amantadine has been clinically used as an antiviral drug, for dementia, and in the treatment of Parkinson's disease and spasticity. It is a non-competitive NMDA receptor antagonist, and compared to ketamine, it is well tolerated with fewer side effects (mainly dizziness, sedation, and dry mouth). Amantadine's formulation permits the oral route for drug delivery, as well as the IV route. The side-effects profile of amantadine via all routes seems not to be harmful in appropriate dosages. In the central nervous system, beta-endorphins bind mu-opioid receptors and exert their primary action at presynaptic nerve terminals. However, instead of inhibiting substance P, they exert their analgesic effect by inhibiting the release of GABA, an inhibitory neurotransmitter, resulting in excess production of dopamine. The investigators designed this study to prove the efficacy of oral amantadine versus gabapentin premedication on the hemodynamic response to laryngoscopy and tracheal intubation and their effect on β-endorphins.

Official Title
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Oral Amantadine Versus Gabapentin to Attenuate the Hemodynamic Response to Laryngoscopy and Tracheal Intubation and Their Effect on β-endorphin

Conditions
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Effect of Laryngoscopy and Tracheal Intubation

Intervention / Treatment
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* Other: oral amantadine sulfate
* Drug: oral gabapentin
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ASA I&II scheduled for elective spine surgery Exclusion Criteria: Patient refusal Patients with ASA score III (with chronic kidney, lungs, Gastrointestinal tract, liver, or cardiovascular diseases) Pregnant or breastfeeding women. Allergy to any of the study medications and taking medications that could significantly interact with amantadine (tramadol, atropine, antipsychotic medications) diabetes mellitus, thyroid disease any endocrine disease Suspected difficult intubation or intubation time more than 30 second.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: amantadine group (Group A)<br>the patients will receive oral amantadine sulfate using the dose 100 mg 120 minutes prior to the surgery, 5 ml saline IV 5 minutes before intubation. | Other: oral amantadine sulfate<br>* In amantadine group:the patients will receive100 mg oral amantadine sulfate 90 minute prior to the surgery<br>* Other names: infex;|
| Active Comparator: gabapentin group(Group B)<br>the patients will receive oral gabapentin using the dose 800 mg 120 minutes prior to surgery,5 ml saline IV 5 minutes before intubation. | Drug: oral gabapentin<br>* In gabapentin group: the patients will receive oral 800 mg gabapentin 90 minute prior to the surgery<br>* Other names: gabapentin;|
| Placebo Comparator: control group (group C)<br>the patients will receive placebo oral tablet 120 minutes prior to surgery, IV fentanyl 2µ/kg in 5 ml saline 5 minutes before intubation. | Drug: Placebo Oral Tablet<br>* in control group : the patients will receive Placebo Oral Tablet 90 minute prior to the surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| effect of oral amantadine versus gabapentin premedication on laryngoscopy and tracheal intubation on β-endorphins. | analysis of change of β-endorphins in blood sample | baseline blood sample taken before drug administration and after 15 minutes after intubation and before skin incision | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| effect of oral amantadine versus gabapentin premedication on the Mean arterial blood pressure due to laryngoscopy and tracheal intubation | change of Mean arterial blood pressure | baselineMAP before drug administration and after 15 minutes after intubation and before skin incision | 
| effect of oral amantadine versus gabapentin premedication on the heart rate due to laryngoscopy and tracheal intubation | change of heart rate | baseline heart rate before drug administration and after 15 minutes after intubation and before skin incision | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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β-endorphins,laryngoscopy and tracheal intubation