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Ephedrine


Pharmaceutical Name: Ephedrine
Drug Classification: Sympathomimetic/Alpha and Beta Adrenergenic Agonist
Active Life: four to seven hours


Ephedrine is a sympathomimetic alkaloid derived from the herb ma huang, also known as ephedra, and is considered to be the so-called active ingredient of the herb along with pseudo ephedrine (1). Ephedra, and now ephedrine itself, is primarily used for its ability to increase the activity of the central nervous system of the user while also stimulating various target cells in the body via its mechanism as an alpha and beta adrenergenic agonist. These abilities of ephedrine offer numerous advantages for both bodybuilders and strength athletes.

The stimulatory effect that ephedrine has on the central nervous system offers several benefits to athletes. For example, this enhanced stimulation should allow for an increase in the force able to be generated in skeletal muscle contractions. Obviously this could result in increased strength that a user could generate and/or more explosive actions or movements during athletic endeavors. Other such possible beneficial results of this increased activity in the central nervous system include such things as improved lung function, anaerobic capacity, hand-eye coordination and cardio-respiratory endurance, among others. These listed potential benefits should not be looked upon as absolutes however due to some contradictory research that indicates no such benefits were seen with ephedrine supplementation (2, 3). Despite these contradictory findings however, the vast majority of research does indeed indicate a direct correlation between ephedrine use, an increase in central nervous system activity and an improvement in numerous athletic performance measures.

A second, related benefit of ephedrine administration is the increase in metabolism and lipolytic effects in the body. For the most part this is accomplished by the thermogenic effect that the compound produces. In much the same way that a drug such as clenbuterol does, although clenbuterol is a selective beta-2 agonist while ephedrine is an alpha and beta adrenergenic agonist, ephedrine raises the body temperature of the user which creates the increase in metabolism.

A third benefit of ephedrine, at least for some, is a reduction in appetite. Like many other stimulants this effect varies from user to user with some experiencing this effect much more severely then others. If one has problems ingesting their target number of calories per day when using ephedrine they may want to discontinue administering it.

When taken alone ephedrine should deliver these benefits for the user quite adequately. Among users and producers of products containing ephedrine however, other compounds are often administered along with the ephedrine to increase the effect of the supplement. The most popular compound to include with ephedrine is caffeine. It is thought by many that this is due to the thermogenic nature of caffeine and that it would be of added benefit in this regard. This is not true however. The actual effect that is trying to be produced by using caffeine with ephedrine is to attempt to prolong and intensify the effects of the ephedrine. This is accomplished because ephedrine produces its thermogenic effect by way of catecholamine release, catecholamines being chemicals that are produced and released via the amino acid tyrosine (4). Examples of catecholamines are norepinephrine and epinephrine. When increased levels of catecholamines are released due to ephedrine use a negative feedback loop is triggered and the release of catecholamines is reduced and the thermogenic effect of ephedrine is stunted. Caffeine interferes with this negative feedback loop mechanism and thus ephedrine can continue to produce its effects to a greater degree then if no caffeine had been supplemented. Aspirin has a similar effect on this negative feedback loop and is also included by some users and ephedrine product producers when using or manufacturing ephedrine supplements. It does appear however that the action of aspirin in this regard is not as effective as caffeine and therefore if a user were already supplementing with caffeine no further benefit is likely to be achieved with the inclusion of aspirin.


Use/Dosing

Due to the action of ephedrine as a central nervous system stimulant, users will want to begin administering relatively small amounts of the compound so that they are able to gage how well they tolerate it. Dosages in the range of four to eight milligrams would be appropriate for most. Once a user becomes familiar with how they react to ephedrine doses anywhere from four to fifty milligrams at a time are normal for users to administer. Due to receptor downgrade, which will be discussed in depth below, dosages far in excess of this range are used by some individuals. However dosages that begin to climb higher and higher soon become impractical for a user to continue and cessation of use of the compound should take place. Despite this receptor downgrade however users have administered ephedrine for several months consecutively or even for years on end with little detectable negative side effects, while acknowledging that regular markers of general health should be consistently monitored to help and avoid serious complications. In studies conducted assessing the effects of long term use of ephedrine there has been little evidence of increased risk to the users in terms of toxicity or the general health of the heart (5).

The active life of ephedrine is relatively short, approximately four to seven hours, so multiple dosing per day can be used depending on the tolerance of the user. A single dose per day to as many as three evenly spread out throughout the day is the norm for the majority of users. The synthetic version of ephedrine reaches its peak plasma level approximately one hour after ingestion (6), with the herbal version taking slightly longer then this to reach its maximum level.

Due to the fact that ephedrine is an alpha and beta agonist the downregulation of the cardiac, pulmonary and central nervous system beta-adrenergic receptors is an issue that users must combat when using this compound. A proven method to help alleviate this effect and ensure that the ephedrine remains effective throughout its use is via the administration of ketotifen. Ketotifen is a prescription anti-histimines that acts to reduce beta-2 receptor activity. By reducing this activity the receptor function is restored to nearly its original capability and the potency of the ephedrine remains in effect. Doses of two to ten milligrams of ketotifen have been used by users of ephedrine, but most would be well served to start at lower doses. It is unlikely that many will need doses higher then 5 milligrams per day. Taking ketotifen for seven days every two to three weeks should be enough to maintain well functioning beta-2 receptors and ensure that the ephedrine maintains its effectiveness.

An alternative to ketotifen may be diphenhydramine, commonly referred to as Benedryl. Benadryl is a cationic ampiphylic drug, with this fact being significant because cationic ampiphylic drugs have the ability to inhibit phospholipase A2 and therefore upgrade beta-2 receptors (7). The inhibition of the enzyme phospholipase A2 is key due to it being responsible for methylated phospholipids. It is thought that by reducing and/or ending this action allows the phospholipid membrane to remain relatively intact and the beta-adrenoreceptors will be able to remain functioning at their full capacity, or near to it, for much longer. For most an effective dose would be 50-100mgs per day for seven days every three weeks while running ephedrine. Users would be well served to take this dosage just prior to going to sleep as it will likely cause drowsiness.

Having said this, there is much more anecdotal feedback in regards to the effectiveness of ketotifen in relation to ephedrine then there is Benedryl simply because ketotifen has been used much longer by strength athletes and bodybuilders for this purpose. As well, there is seemingly more direct research that indicates that ketotifen is effective while only a few studies suggest the same of Benedryl. That is not to say that Benedryl is ineffective, just that there is less �real world� feedback as to its use with ephedrine.


Risks/Side Effects

The action of ephedrine as a central nervous system stimulant obviously suggests that an increase in heart rate and/or blood pressure is likely. This is not as irrefutable as one would be led to believe however. It appears as though that while ephedrine does indeed produce a noticeable increase in heart rate in many users, it alone does not produce a dramatic rise in the blood pressure of some users in specific circumstances (8, 9). When combined with caffeine however both heart rate and blood pressure seemingly almost always rise to significantly elevated levels (10). Related to this, there is little evidence that suggests ephedrine poses serious risks to users in terms of cardiac health in healthy individuals. Of course as would be assumed by most, use of ephedrine by users suffering from prior conditions such as hypertension, cardiac arrhythmia, or other circulatory conditions should not be attempted without first consulting with a doctor.

In a small number of healthy individuals however ephedrine can sometimes cause heart arrhythmias. One explanation of why this could occur would be due to the tendency of ephedrine use to decrease serum potassium levels in users (11). When a person is significantly deficient in potassium this can result in the development of heart arrhythmias. For this reason ephedrine users will want to ensure that they are getting sufficient amounts of potassium in their diets to compensate for this effect of the compound or else use a potassium supplement.

A relatively small number of cases have shown that some individuals have died while using a supplement containing ephedrine (12, 13). For the most part there were circumstances outside of simply using ephedrine that led to these deaths. Factors such as gross overdosing of the compound, temperature and humidity, as mentioned earlier prior medical conditions, and severe dehydration are all potential contributing factors that may be exasperated by improper use of ephedrine. However when used correctly by healthy individuals ephedrine is a safe compound for use by most adults.

Other less serious side effects of ephedrine use can include such things as excessive sweating, tremors, sleeplessness, anxiety, rapid speech, and other common side effects associated with stimulant use. For the most part these can be controlled by reducing the dosages used. However for some users these side effects may be inevitable.

As mentioned, anxiety is a possible side effect of ephedrine use (14). Other psychological side effects can include rapid thought processes, euphoria (15), and increased alertness. For the most part physical addiction is not a concern however a very small number of users may find that some withdrawal symptoms do occur although these should not be severe (16). Mental addiction may occur is some users however especially when using ephedrine as a pre-workout or pre-competition stimulant. For this reason frequent breaks from use of ephedrine are recommend so that one does not become dependent upon it for the physical sensations that it produces.



References

1. White LM, Gardner SF, Gurley BJ, Marx MA, Wang PL, Estes M. Pharmacokinetics and cardiovascular effects of ma-huang (Ephedra sinica) in normotensive adults. J Clin Pharmacol. 1997;37:116�122.

2. Gillies H, Derman WE, Noakes TD, Smith P, Evans A, Gabriels G. Pseudoephedrine is without ergogenic effects during exercise. J Appl Physiol. 1996;81:2611�2617.

3. Sidney KH, Lefcoe NM. The effects of ephedrine on the physiological and psychological responses to submaximal and maximal exercise in man. Med Sci Sport. 1977;9:95�99.

4. Powers, ME. Ephedra and Its Application to Sport Performance: Another Concern for the Athletic Trainer? J Athl Train. 2001 Oct;36(4):420-424.

5. Greenway FL, De Jonge L, Blanchard D, Frisard M, Smith SR. Effect of a dietary herbal supplement containing caffeine and ephedra on weight, metabolic rate, and body composition. Obes Res. 2004 Jul;12(7):1152-7.

6. Backer R, Tautman D, Lowry S, Harvey C, Poklis A. Fatal ephedrine intoxication. J Forensic Sci. 1997;42:157�159.

7. Hirata F, Tallman JF, Henneberry RC, Mallorga P, Strittmatter WJ, Axelrod J. Phospholipid methylation: a possible mechanism of signal transduction across biomembranes. Prog Clin Biol Res. 1981;63:383-8.

8. Dulloo AG. Ephedrine, xanthines and prostaglandin-inhibitors: actions and interactions in the stimulation of thermogenesis. Int J Obes Relat Metab Disord. 1993;17(suppl 1):35�40.

9. Gurley BJ, Wang P, Gardner SF. Ephedrine-type alkaloid content of nutritional supplements containing Ephedra sinica (Ma-huang) as determined by high performance liquid chromatography. J Pharm Sci. 1998;87:1547�1553.

10. Gurley BJ, Gardner SF, White LM, Wang PL. Ephedrine pharmacokinetics after ingestion of nutritional supplements containing Ephedra sinica (ma huang). Ther Drug Monit. 1998;20:439�445.

11. Martin WR, Sloan JW, Sapira JD, Jasinski DR. Physiologic, subjective, and behavioral effects of amphetamine, metamphetamine, ephedrine, phenmetrazine, and methylphenidate in man. Clin Pharmacol Ther. 1971;12:245�258.

12. Naik SD, Freudenberger RS. Ephedra-associated cardiomyopathy. Ann Pharmacother. 2004 Mar;38(3):400-3. Epub 2004 Jan 23.

13. Samenuk D, Link MS, Homoud MK, Contreras R, Theoharides TC, Wang PJ, Estes NA 3rd. Adverse cardiovascular events temporally associated with ma huang, an herbal source of ephedrine. Mayo Clin Proc. 2002 Jan;77(1):12-6.

14. Chait LD. Factors influencing the reinforcing and subjective effects of ephedrine in humans. Psychopharmacology (Berl). 1994 Jan;113(3-4):381-7.

15. Powell T, Hsu FF, Turk J, Hruska K. Ma-huang strikes again: ephedrine nephrolithiasis. Am J Kidney Dis. 1998 Jul;32(1):153-9.

16. Gruber AJ, Pope HG Jr. Ephedrine abuse among 36 female weightlifters. Am J Addict. 1998 Fall;7(4):256-61.






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