This medication is one of the most widely spread and popular drugs all over the world. The main proof is that it may be bought without a doctor’s prescription in any pharmacy online as well as in ordinary drugstore. Even in places where it is a very serious question, Paracetamol is freely sold and more than that without any limitations. This, on one hand, says about effectiveness of the medication and on the other hand, about its safety.

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Buspirone, marketed as Buspar, a nonbenzodiazepine and generally nonsedating anxiolytic, was the first prominent anxiolytic introduced after the benzodiazepines. Its antianxiety effects are believed to be secondary to its acting as a partial agonist of the 5-HT1A receptor. Buspirone is as effective as diazepam and superior to placebo in double-blind trials involving anxious outpatients (Schatzberg et al. 2003). The parent drug is metabolized by CYP3A4 while its metabolite is metabolized by CYP2D6. Important drug

Investigations into the use of noradrenergic agents as anxiolytics were first directed toward their use in anxious musical performers. B-Blockers such as propranolol were found to be useful in alleviating symptoms of anxiety (e.g., palpitations, sweating). Years later, clonidine was shown by Gold et al. (1978) to be effective in blocking physiological symptoms associated with opioid withdrawal. Although not found to be effective in blocking panic, agents such as propranolol, atenolol, and nadolol have been found to be useful when used adjunctively with other agents in reducing symptoms of autonomic arousal associated with panic and social anxiety (Rosenbaum et al. 1998). Importantly, propranolol is metabolized primarily by CYP2D6 and should probably be used in lower dosages in Asians who are slower metabolizers of CYP2D6 substrates.

In addition to pharmacokinetics, differences in receptor sensitivity between Asians and Caucasians also have been demonstrated, rendering the former even more susceptible to the side effects of propranolol (Zhou et al. 1992).

Handbook of Experimental Pharmacology, Vol. 169
Anxiety and Anxiolytic Drugs (2004)

Monoamine oxidase inhibitors (MAOIs) have been shown to be effective in the treatment of anxiety disorders such as social anxiety and panic disorder. In a 12-week, placebo-controlled trial of patients with panic disorder, Sheehan and colleagues reported that phenelzine (45 mg/day) was better than placebo; however, higher doses of the MAOI (e.g., 60

Several SSRIs have been FDA approved for one or more specific anxiety diagnoses [e.g., paroxetine for social anxiety, generalized anxiety disorder (GAD) and posttraumatic stress disorder (PTSD); sertraline for obsessive

Imipramine, a TCA, was the first pharmacological agent noted to treat panic disorder (Klein 1964). Other TCAs, notably clomipramine, have also been found to have significant anxiolytic properties (den Boer et al. 1990; Modigh 1992). Studies of ethnic differences in the pharmacokinetics of the TCAs in Asian Americans have led to inconclusive results. Of six studies comparing Asians with Caucasians, three revealed that Asians metabolize TCAs significantly slower than their Caucasian counterparts; however, the differences observed in the other three studies did not reach statistical significance, particularly after controlling for body weight (Kishimoto 1984; Rudorfer 1984; Schneider 1991). Other studies also did not find significant differences in the pharmacokinetics of nortriptyline between Mexican Americans and Caucasians. Pharmacodynamically, results from two clinical studies in Asia indicated that severely depressed hospitalized Asian patients responded clinically to lower combined concentrations of imipramine and desipramine (130 ng/ml) than studies previously reported on North American and European patients (180

Benzodiazepines comprise the most frequently prescribed subclass of antianxiety agents. These agents, first introduced in the early 1960s, quickly replaced the use of barbiturates as the pharmacological approach to anxiety. The popularity of these agents can be attributed to their generally quick onset of action and wider safety margin in overdose compared to the barbiturates. However, the potential of these agents to elicit physical dependence also quickly became apparent. In addition to the frequent use of these agents as anxiolytics, benzodiazepines are also commonly used for muscle tension, insomnia, status epilepticus (diazepam), myoclonic epilepsy (clonazepam), preoperative anesthesia, and alcohol withdrawal. Importantly, Ativan (lorazepam) is often used in the emergency room and inpatient setting to manage acute agitation in patients. Controlled studies involving Asians and Caucasians demonstrated significant pharmacokinetic differences involving use of the benzodiazepines (Ghoneim et al. 1981; Kumana et al. 1987). The volume of distribution of diazepam in these studies was found to be lower, and both serum diazepam and desmethyldiazepam levels were higher in Asian than in white physically and psychiatrically healthy volunteers. These differences became statistically insignificant, however, after controlling for ethnic differences in skinfold thickness and the ratio of actual to ideal body weight, suggesting that ethnic differences may be secondary to differences in the percentage of body fat.

Lin et al. (1988) studied plasma alprazolam concentrations in 14 American-born Asian, 14 foreign-born Asian, and 14 Caucasian healthy male volunteers. Both Asian groups had greater AUCs and peak plasma concentrations and lower total plasma clearance than did the Caucasian group, after both oral and intravenous administration of alprazolam. Pharmacodynamically, the onlysignificant difference was that foreign-born Asians experienced more sedation compared with both Caucasian and American-born Asian subjects. In a more recent study, Ajir et al. (1997) also reported that Asians had higher maximum serum concentrations, larger AUCs, and lower clearance of both adinazolam and its major active metabolite than did their Caucasian and African American counterparts. Together, the findings support the concept that Asian patients require smaller doses of adinazolam than do Caucasian patients to achieve similar levels of the parent drug and its metabolite.

Similar to Asians, African Americans have been found to have slower clearance of the benzodiazepines. Furthermore, many studies have reported that African Americans have greater cognitive effects and more anxiety reduction from the benzodiazepines when compared to Caucasians on the same dose of medications. In a study by Ajir et al. (1997), African Americans were found to have increased clearance of adinazolam. However, the AUC of its metabolite N-desmethyladinazolam was found to be higher in African Americans and may be responsible for the larger drug effects on African Americans in terms of adverse effects such as slower psychomotor performance, despite the higher metabolic capacity for adinazolam in this ethnic group.

In terms of the ethnic response to benzodiazepines in Hispanics, studies have implicated the important role of dietary effect. When Mexican subjects were fed a corn-rich diet, the metabolism of nifedipine by 3A4 appears to be reduced (Palma-Aguirre et al. 1994). Many studies suggest that the flavonoid quercetin is effective at inhibiting the intestinal agglomeration of CYP3A4. Corn is rich in quercetin and is a dietary staple for Hispanics. Importantly, many benzodiazepines such as alprazolam, midazolam, and triazolam are all metabolized by CYP3A4, and their use in Hispanics should be downwardly adjusted with caution to take into account the dietary effect on CYP3A4 activity. Similar considerations may apply for citrus-loving Hispanics, since flavonoid naringin found in grapefruit juice is a powerful inhibitor of CYP3A4.

Handbook of Experimental Pharmacology, Vol. 169
Anxiety and Anxiolytic Drugs (2004)

The focus of pharmacogenetic studies has largely been on those genes that encode enzymes responsible for the metabolism of medications. However, ethnic differences may also be affected by genes controlling the function and response of therapeutic targets. A well-established example of the difference that exists between different ethnic groups is the metabolism of alcohol. One of the enzymes responsible for the metabolism of alcohol is acetaldehyde dehydrogenase (ALDH), and 40%

Research on anxiety and anxiety disorders is undergoing a paradigmatic transformation as disparate areas of psychiatric nosology, epidemiology, pharmacology and cognitive neuroscience converge towards an integrated understanding of the pathophysiology of these disorders.

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