Headache derivatives

Among the indole derivatives which have found use as drugs are indo-methacin, one of the first non-steroidal anti-inflammatory agentsfll], sumatriptan, which is used in the treatment of migraine headaches[12] and pindolol[13], one of the p-adrenergic blockers. 

Common side effects of theophylline therapy include headache, dyspepsia, and nausea. More serious side effects such as lethal seizures or cardiac arrythmias can occur if blood levels are too high. Many derivatives of theophylline have been prepared in an effort to discover an analogue without these limitations (60,61). However, the most universal solution has resulted from the development of reHable sustained release formulations. This technology limits the peaks and valleys in semm blood levels that occur with frequent dosing of immediate release formulations. ControUed release addresses the problems inherent in a dmg which is rapidly metabolized but which is toxic at levels ( >20 7g/mL) that are only slightly higher than the therapeutically efficacious ones (10—20 p.g/mL). Furthermore, such once-a-day formulations taken just before bedtime have proven especially beneficial in the control of nocturnal asthma (27,50,62). 

Venlafaxine (48) is a stmcturaHy novel phenylethylamine derivative that strongly inhibits both noradrenaline and serotonin reuptake. It lacks anticholinergic, antihistaminergic, and antiadrenergic side effects. As compared to placebo, most common adverse events are nausea, somnolence, dizziness, dry mouth, and sweating. Venlafaxine-treated patients also experienced more headaches and nausea, but less dry mouth, dizziness, and tremor than patients treated with comparator antidepressants. 

The compounds of Se, Te and Po should all be treated as potentially toxic. Volatile compounds such as H2Se, H2Te and organo derivatives are particularly dangerous and maxirnum permissible limits for air-bome concentrations are 0.1 mg m (cf. lOmgm for HCN). The elements are taken up by the kidneys, spleen and liver, and even in minute concentrations cause headache, nausea and irritation of mucous membrane. 

This drug is quite frequently found in headache remedies in com-liination with aspirin and caffeine (APC , PAG ). Although the iniline derivatives show analgetic potency comparable to aspirin,... 

Adverse reactions associated wiHi administraHon of the xanHiine derivatives include nausea, vomiting, restiess-ness, nervousness, tachycardia, tremors, headache, palpitations, increased respirations, fever, hyperglycemia, and electrocardiographic changes. 

Opioids and derivatives (e.g., meperidine, butorphanol, oxycodone, hydromorphone) provide effective relief of intractable migraine but should be reserved for patients with moderate to severe infrequent headaches in whom conventional therapies are contraindicated or as rescue medication after failure to respond to conventional therapies. Opioid therapy should be closely supervised. 

The AEGL-1 values were based on concentrations at 0.5 ppm and 0.1 ppm, which were the thresholds for mild headaches in healthy individuals at exposure durations of 1 and 6 h, respectively (Stewart et al. 1974). This effect can be considered the threshold for mild discomfort (only one subject was affected at each exposure), which falls within the definition of an AEGL-1. The 0.5-ppm concentration was used to derive the 30-min and 1-h AEGL-1 values, and the 0.1-ppm concentration was used for the 4- and 8-h values. Because the time and concentration values were based on the most susceptible subject, these concentrations were adjusted by an uncertainty factor (UF) of 3 to account for potential differences in human sensitivity and scaled to the appropriate time periods using the C xt=k relationship. A UF of 3 was considered sufficient as no susceptible populations were identified (the headache effect is the same as that experienced by patients medicated with nitro... 

The study by Stewart et al. (1974) with human volunteers is relevant to the derivation of AEGL-1 values. Within the definition of an AEGL-1, both healthy and susceptible individuals could experience mild discomfort. A mild headache can be considered mild discomfort and the threshold concentration-time at which one or more subjects first developed a mild headache was used to derive the AEGL-1 values. No subjects (other than the one that developed a headache during the control sessions) developed headaches during an 8-h exposure at 0.03 ppm. The highest concentrations and exposure durations that did not result in headache and the lowest concentrations and exposure durations that resulted in mild headaches are as follows ... 

The severe headache accompanied by slight loss of equilibrium in one of several sensitive equilibrium tests after a 6.25-h (rounded down to 6 h) exposure at 0.5 ppm was considered the threshold for inability to escape and was used to derive the AEGL-2 values. A UF of 3 was used to adjust the value as no susceptible populations were identified and the threshold for narcosis for most anesthetics does not differ among individuals by more than a factor of 2 (Kennedy and Longnecker 1996 Marshall and Longnecker 1996). The intraspecies UF of 3 is supported by the steep dose-response curve for the induction of headaches namely, a 2-fold difference in the threshold concentration of PGDN and the concentration that induces headache in the majority of healthy individuals (Stewart et al. 1974). The 6-h 0.5-ppm concentration was... 

Data adequacy The preponderance of data from the key studies support an 8-h noeffect concentration of 1 ppm. The Leeser et al. (1990) study encompassed subjective symptoms as well as extensive medical examinations. The occupational monitoring study of El Ghawabi et al. (1975), in which it is believed that workers inhaling a mean concentration of 8 ppm may suffer mild headaches, supports the safety of the derived values. The values are also supported by a NIOSH (1976) report in which 5 ppm was identified as a no-effect concentration in the Grabois et al. (1954) occupational study. Additional monitoring studies support the values. ... 

Sodium - the atomic number is 11 and the chemical symbol is Na. The name derives from the English soda and Latin sodanum for headache remedy . The chemical symbol Na derives from the Latin natrium for natron (soda in english) . It was discovered in 1807 by the English chemist Humphry Davy from electrolyosis of caustic soda (NaOH). 

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