Sedating And Non Sedating Antihistamines On Neuromuscular Control Biology Essay

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Objective. Antihistamines are often used to treat people with allergic rhinitis who suffer decreased levels of alertness, learning inattentiveness and drowsiness which can be further exacerbated by the sedating effects of first generation antihistamines. Second generation non-sedating antihistamines, such as Claratyne (Loratadine) were designed to combat the side effects, such as drowsiness and decreases attentiveness, that come with first generation sedating antihistamines such as Phenergan (Promethazine). The objective of this study is to assess the sedating effect of Phenergan (first generation antihistamine) and Claratyne (second generation antihistamine) compared with placebo using a series of tests to determine to what extent drowsiness and neuromuscular control are affected. Methods. Eight healthy subjects (five males and three females) between the ages of 20 to 22 who take antihistamines to treat allergies were enlisted in the study. The volunteer's level of drowsiness was measured using the Stanford Sleepiness Scale and visual analogue scales. Neuromuscular control was measured using a Simple Reaction Test and a Choice Reaction Test. After the initial series of tests, the participants were kept blinded and were randomly given either the placebo or an antihistamine; Phenergan (Promethazine) or Claratyne (Loratadine). The same tests for drowsiness and neuromuscular control were repeated one hour and two hours post ingestion and the following day. Results. Significant results were found in the simple reaction test between claratyne and phenergan, and between placebo and phenergan. Similar data was obtained during the choice reaction time, showing significant difference between claratyne and placebo, claratyne and phenergan and phenergan and placebo at differing times throughout the test. These results were consistent with the Stanford sleepiness scale and the visual analogue scales.

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Conclusion. First generation drugs may worsen the performance of patients with allergic rhinitis by impairing central nervous functions. Second-generation antihistamines, on the other hand, seem to improve performance in these patients, even if the degree of improvement does not quite bring performance levels to those of patients who do not suffer allergic rhinitis (placebo).

INTRODUCTION:

Histamine plays a key role in allergic inflammatory responses, which include sneezing, rashes, itchy eyes and watery rhinorrhoea. Histamine is also responsible for keeping us alert and attentive. Antihistamines cross the blood brain barrier to block histamine H1-receptors. 10%-25% of the population suffer allergies that require treatment with antihistamines (Verster and Volkerts, 2004). First generation antihistamines, such as Phenergan (Promethazine), bind non-selectively to H1-receptors as well as muscarinic-cholinergic, α-adrenergic and serotonergic neurons which may lead to common side effects such as sedation and reduced alertness (O'Donoghue and Tharp, 2005). Second generation antihistamines, such as Claratyne (Loratadine), were developed to combat the sedative and anti-cholinergic effects (e.g blurred vision) which are often associated with first generation antihistamines. Second generation antihistamines are more selective as they are composed of larger, more lipophobic molecules which are more difficult to pass through the blood brain barrier (Kay, 2000). (duration of 2 antihist in body- half life) 4-8hours half life- 30min onset of effect (pro) and 12-15hours half life, 1-3hr onset of effect (lor).

When taking antihistamines, several factors can lead to drowsiness. These include whether the antihistamines are sedating (first generation) or non-sedating (second generation), the dosage levels of the antihistamines, and the time the antihistamines are taken (circadian rhythm). A study by Kay (2000) found that when first generation sedating antihistamines (Diphenhydramine) were taken at night, they continued to effect sleep latency the following day and disrupted performance efficiency, compared to a second generation non-sedating drug (Loratadine), which did not have a clinically significant effect on central nervous system activity. Although most patients take antihistamines at the onset of symptoms, pharmacists generally recommend taking antihistamines in the morning before onset of symptoms. Evidence shows that continual use of second generation non-sedating antihistamines in patients with allergic conditions is more effective than occasional 'when required' usage.

Drowsiness is the brains perception of feeling tired during the day. It can be measured using both visual analogue scales and the Stanford Sleepiness Scale. Antihistamines affect on neuromuscular control can be measured by simple and choice reaction times. In simple reaction time, the emphasis is placed on initiating the movement as fast and accurately as possible. In choice reaction time, both temporal and event uncertainty are increased and initiation of the response requires selection of more than one stimuli. Sedating antihistamines are expected to increase drowsiness and therefore decrease reaction times.

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Current literature on the sedating effects of antihistamines has been shown to decrease the levels of alertness, affecting daily activities and learning processes. Research has found patients with allergic rhinitis consequently suffer learning inattentiveness. This problem is exacerbated by first generation sedating antihistamines which cause further decreases in decision-making and learning. In contrast, non-sedating agents do not impair performance and have even been found to increase learning attentiveness (Nolen, 1997). First generation antihistamine use has also been connected to increases in work-related injuries (Gilmore et al, 1996) and decreases in driving performance (Verster and Volkerts, 2004). The purpose of this study is to assess the sedating effect of Phenergan (first generation antihistamine) and Claratyne (second generation antihistamine) compared with placebo to determine if first generation antihistamines decrease attentiveness and reaction time, and to what degree.

METHOD:

Eight healthy volunteers (five males and three females) between the ages of 20 to 22 who take antihistamines to treat allergies were enlisted in the study. Participants were asked to avoid stimulants such as coffee, weight training and smoking before and during testing. Each subject completed a medical history questionnaire and informed consent.

Participant's levels of alertness were assessed by a series of tests. Drowsiness levels were measured using the Stanford Sleepiness Scale and visual analogue scales, where patients were asked to mark their level of alertness on a scale marked 'asleep' to 'wide awake'. Neuromuscular control was measured by simple reaction time and choice reaction time. Participants were asked to sit comfortably in a chair, their eyes on the screen and the index finger of their preferred hand resting gently on the pad (see figure 1). When a button on the screen lit up, the participant had to take their finger off the pad as quickly as possible and the single reaction time was recorded. The subject was given several trials to gain familiarisation with the program before 10 consecutive reaction times were recorded and averaged. Choice reaction time was measured by sitting the participant comfortably in a chair, both their left and right index fingers resting gently on pads (see figure 2). This time, one of two buttons (left and right) lit up on the screen and participants had to react by removing their respective hand from the pad as quickly as possible. Again, the subject was given several trials before 10 consecutive reaction times were recorded and averaged. In both simple and choice tests, the subjects were kept blinded of their reaction times to minimise bias.

After the initial series of tests, the participants were kept blinded and were randomly given either the placebo or an antihistamine; Phenergan (Promethazine) or Claratyne (Loratadine). The antihistamine (10mg dosage) or placebo was ingested at 2pm. The tests for drowsiness levels and neuromuscular control were repeated at 3pm and 4pm. The following day, subjects came in at 9am and drowsiness levels and neuromuscular performance were measured again.

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Figure 1: Photograph of Simple Reaction Time test.

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Figure 2: Photograph of Choice Reaction Time test.

RESULTS:

Figure 3: Stanford Sleepiness Scale change scores relative to the data obtained during the pre-ingestion testing sessions. Data represent the mean and error bars are the standard error of the mean. Positive change score indicates an increase in self-perceived drowsiness.

Figure 3 highlights significant differences between the data obtained for placebo and Phenergan during the 2 hour post test (p value= 0.020). There is also a significant result between placebo and Claratyne in the post 1 hour test (p value=0.039) and the placebo and claratyne post 2 hour test (p value= 0.039). The 'next day' test did not produce any significant results.

Figure 4: Visual analogue scale change scores relative to the data obtained during the pre-ingestion testing sessions. Data represent the mean and error bars are the standard error of the mean. Positive change score indicates an increase in self-perceived drowsiness.

Figure 4 illustrates statistically significant differences between the data obtained for placebo and Phenergan during the 1 hour post test (p value= 0.003) as well as the post 2 hour test (p value= 0.029). There is also a significant result between Phenergan and Claratyne in the post 2 hour test (p value=0.044). The 'next day' test did not produce any significant change in data.

Figure 5: Simple reaction time (ms) of antihistamines Claratyne, Phenergan and placebo. Simple reaction time was measured pre-ingestion, 1 hour post test, 2 hour post test and the next day. Data represent the mean and error bars are the standard error of the mean.

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Figure 5 shows all reaction times decrease one hour post ingestion of Claratyne, Phenergan and placebo tablets. However, the only statistically significant results were found using a paired t-test in the two hours post ingestion (post 2) between claratyne and phenergan (p value= 0.002) and between placebo and phenergan (p value= 0.015).

Figure 6: Choice reaction time (ms) of antihistamines Claratyne, Phenergan and placebo. Choice reaction time was measured pre-ingestion, 1 hour post test, 2 hour post test and the next day. Data represent the mean and error bars are the standard error of the mean.

Figure 6 also shows a decrease in reaction times one hour post ingestion of claratyne and phenergan, although these results were not statistically significant. Using a paired t-test, there was a significant result in the test conducted one hour post ingestion (post 1) between claratyne and placebo (p value= 0.005) and between placebo and phenergan (p value= 0.014). There was also a statistically significant difference in the post 2 test between claratyne and phenergan (p value= 0.003).

DISCUSSION:

Significant results were found in the simple reaction test between claratyne and phenergan, and between placebo and phenergan. Similar data was obtained during the choice reaction time, showing significant difference between claratyne and placebo, claratyne and phenergan and phenergan and placebo at differing times throughout the test.

Results may be interpreted in this section

• This is where arguments are presented indicating the relevance, usefulness, scope, importance, and limitations of the research.

Murison and Webb (1991) list several parts that can comprise the discussion section:

• Restatement of background of one or more results.

• Comments on whether the results are expected or unexpected, and why.

• Examples which support interpretations.

• Comparison of previous research.

• Claims about the generality of results.

• Comments on the support that the results provide for the hypothesis stated in the introduction.

• Recommendations and their justification.

Interestingly, claratyne didn't seem to improve reaction time as previous research suggests (ref). The subjects seemed to have the fastest reaction times and higher levels of attentiveness when the placebo pill was taken. However, phenergan slowed the reaction time in both the single and choice reaction tests, supporting the hypothesis that sedating drugs increase levels of drowsiness and decrease levels of attentiveness and alertness.

Since the tests were conducted at 1-3pm when the circadian rhythm leaves the body at its sleepiest state, this offers a confounding question; was it the antihistamines that decreased the reaction times and increased levels of drowsiness, or was it the circadian rhythm? Further studies could be done to examine this puzzling factor.

Another interesting fact to note was that the use of antihistamines did not continue to affect sleep latency the next day. Reaction times for the single and choice reaction time tests improved between the pre-ingestion of the antihistamine or placebo drug on day one and day two. Again, this presents the issue of the circadian rhythm.

Although first generation antihistamines are no longer recommended for the treatment of allergic rhinitis, they are still frequently used for this purpose. Phenergan packaging suggests the antihistamine should not be taken for more than ten days in a row as these drugs affect the central nervous system considerably (ref). Only non-sedating antihistamines, such as Claratyne, should be used as chronic relief for allergic rhinitis. Second generation antihistamines may improve lower airway symptoms in patients with allergic rhinitis and asthma (ref POTTER). Further research needs to be undertaken to determine whether these sedating antihistamines are really safe and if they should still be accessible as an over-the counter drug when there are safer second generation options available that do not cause drowsiness and decreased reaction times.

First generation drugs may worsen the performance of patients with allergic rhinitis by impairing central nervous functions. This leaves the patient with the prospect of enduring the symptoms of allergic rhinitis, or treating the condition and risking an even greater impairment of performance than is caused by the condition itself. Second-generation antihistamines, on the other hand, seem to improve performance in these patients, even if the degree of improvement does not quite bring performance levels to those of patients who do not suffer allergic rhinitis (placebo).

CONCLUSION:

Restates the aim of the research.

Restates the main findings.

• Outline the theoretical and practical implications of the findings.

• Make suggestions for further research.

First generation drugs may worsen the performance of patients with allergic rhinitis by impairing central nervous functions. This leaves the patient with the prospect of enduring the symptoms of allergic rhinitis, or treating the condition and risking an even greater impairment of performance than is caused by the condition itself. Second-generation antihistamines, on the other hand, seem to improve performance in these patients, even if the degree of improvement does not quite bring performance levels to those of patients who do not suffer allergic rhinitis (placebo).

liver affected (eg alcho) trouble breaking down antihistamines? Affect person? Adult vs children

breakdown of antihistamines. Children under 5yrs have been known to get schizo with ingestion of phenergan. Caution of backs of packaging!!

-mention first gen interaction with drugs? eg alcohol/antidepressants etc??? If need something else to discuss