Selection and dose adjustment

In fig. temporary dynamics of therapeutic effect at single administration of drug is presented. The therapeutic effect is shown after introduction after a while, gradually reaches a maximum, then weakens and eventually disappears. Dynamics of therapeutic effect corresponds to changes of serumal concentration of drug which are defined by its pharmacokinetic features (an absorption, distribution, elimination). The therapeutic effect appears on reaching therapeutic concentration and increases in process of its augmentation. Duration of effect depends on time during which serumal concentration exceeds therapeutic. Similarly side effects depend on toxic concentration of drug. In the range between these concentration (therapeutic range) medicine is effective, but has no side effect. At repeated administration of drug the dose and an interval between introductions are selected so that to reach the maximum therapeutic effect at the minimum side effect. As a rule, take serumal concentration in which the therapeutic effect makes about a half from maximum for the lower bound of therapeutic range. The top border corresponds to concentration in which side effects arise no more than at 5 — 10% of patients. Toxic concentration of some medicines exceeds therapeutic less than twice. It is necessary to remember also specific features of patients: one well transfer the serumal concentration exceeding toxic, and at others the expressed side effects arise when serumal concentration remains within therapeutic range.

If it is easy to estimate pharmacological effects of medicine (for example, on change of the ABP or level of a glucose of plasma), then the dose can be selected a trial and error method. To define in what limits and it is how often possible to change a dose, use the empirical rules considering the pharmacokinetic patterns given above (for example, the dose is changed no more than for 50% and aren't more often than through 3 — 4T1/2). If there is no toxicity, for ensuring maximum efficiency and augmentation of time of effect of drug it is possible to give a dose much above average therapeutic. For example, act with Penicillinums and the majority of β-adrenoblockers this way..........

If it is difficult to estimate pharmacological effects, medicine has narrow therapeutic range, is high risk of a side effect and inefficiency of treatment or drug use with the preventive purpose, the dose is changed slightly, carefully watching the patient for identification of side effects. Anyway, average concentration of medicine in steady state has to be in limits of therapeutic range. In most cases to define the actual serumal concentration of drug there is no need: there is enough only approximately the nobility as she depends on a dose and the frequency of introduction. However for a small number of drugs therapeutic concentration differs from toxic by only 2 — 3 times (digoxin, Theophyllinum, lidocaine, aminoglycosides, cyclosporine, anticonvulsants). In this case when calculating a dose proceed from the required average concentration of drug (usually in plasma) in steady state in which it is effective, but gives a minimum of side effects. Then measure the actual concentration of drug and if necessary correct a dose so that the actual concentration was as it is possible closer to demanded (see also hl. 3).

The description to fig. Temporary dynamics of therapeutic effect at single administration of medicine. The therapeutic effect is shown only after concentration of drug exceeds therapeutic. Then the effect increases (in process of a further absorption and distribution of drug) and reaches a maximum then gradually weakens as a result of elimination of drug and disappears as soon as serumal concentration falls below therapeutic again. Duration of therapeutic effect depends on time during which serumal concentration of drug remains higher than therapeutic. If concentration exceeds toxic, the probability of side effects increases. Therefore, serumal concentration needs to be maintained in limits between therapeutic and toxic, that is within therapeutic range. In such concentration medicine is effective, but almost doesn't give side effects. At augmentation or a dose decline the therapeutic effect respectively amplifies or weakens (the curve of dependence of therapeutic effect of time is displaced down or up). At augmentation of a dose also duration of effect of drug is enlarged. However it is possible to extend action in such a way only when therapeutic range is rather wide (for example, at Penicillinums) as at augmentation of a dose also the risk of side effects increases. For maintenance of serumal concentration within the therapeutic range and ensuring continuous effect of drug use repeated introduction.

Maintenance dose

In most cases medicine is entered fractionally or in the form of infusion so that stationary concentration was in limits of therapeutic range. Rate of entering of drug is peer steady state to rate of its elimination (the equation 1.1, 1.14). Having substituted in the equation 1.14 the required serumal concentration of drug, we will receive:

Rate of entering = Ssredn x Cl/F (1.16)

Knowing the required serumal concentration of drug, its clearance and bioavailability, it is possible to calculate a dose and frequency of introduction. You can try Pinealon.

Example. The patient with a heart failure weighing 69 kg accepts digoxin in maintenance doses. The required average serumal concentration of digoxin in steady state makes 1.5 ng/ml. SKF is peer to 100 ml/min. Using the equation given in the Appendix II it is possible to calculate digoxin clearance:

Cl = 0,88 x SKF + 0,33 ml/min. = 0,88 x 100/69 + 0,33 ml/min. — 1,6 ml/min. =110 ml/min. = 6,6 l/h.

The dose and frequency of reception (that is rate of entering of drug) can be calculated on the basis of the equation 1.16. Bioavailability of digoxin is peer to 0.7.

Rate of entering = Ssredn x Cl/F = 1.5 ng/ml x x 1.6/0.7 ml/min. = 3.43 ng/kg / min. = 236 ng / min. = 236 x 60 x 24 mkg/days = 340 mkg/days = 0.34 mg/days.

In practice the dose is rounded to the next standard, for example to 375 mg/days or to 0.25 mg/days. In the first case average concentration in plasma in steady state will make 1.5x375/340 = 1.65 ng/ml, in the second — 1.5 x 250/340 = 1.1 ng/ml.

Interval between introductions

It is desirable that in an interval between introductions there were no sharp fluctuations of serumal concentration of drug. If the absorption and distribution of drug occurred instantly, scope of these fluctuations would depend only on T1/2-When the interval between introductions is peer to T1/2, the minimum and maximum concentration differ twice that is quite admissible.

If the therapeutic range of medicine is rather wide, that is in the concentration considerably exceeding therapeutic, it is transferred well, it is possible to prescribe the maximum doses. In that case the interval between introductions can be much more T 1/2 that is very convenient for the patient. Amoxicillin T1/2, for example, makes about 2 h, but drug is usually prescribed in high doses at an interval of 8 — 12 h.

For medicines with a narrow therapeutic range quite often it is necessary to measure the maximum and minimum serumal concentration. The minimum concentration in steady state is counted on the following equation:

Smin = (F x Dose/Vß) / (1-e-kT) x e-kT (1.17)

where k = 0,693/T1/2, and T — an interval between introductions. Size e-kT represents the share of the previous dose which remained in an organism by the time of introduction of the following dose (taking into account bioavailability).

If dynamics of concentration of medicine for intake is described by several exponential functions, for calculation of the maximum concentration in steady state it is necessary to know a series of the constants characterizing an absorption and distribution of drug. If e-kT in numerator of the equation 1.17 and these constants to neglect size, at multiple dose the maximum concentration in steady state can be calculated on the equation 1.18 (see below). However because of the specified allowances settlement concentration will be higher than real.

Example. In the example reviewed above the maintenance dose of digoxin for the patient with a heart failure was calculated. At reception of 0,375 mg/days average serumal concentration of digoxin in steady state will make 1.65 ng/ml. As the therapeutic range of digoxin is narrow (0.8 — 2 ng/ml), it is necessary to calculate the minimum and maximum serumal concentration of drug in intervals between receptions. At first on the equation given in the Appendix II we will calculate the volume of distribution of digoxin in steady state:

Vc = 3,12 x SKF +3,84l/kg = 3,12 x (100/69) + 3,84 l/kg = 8,4 l/kg = 580 l weighing 69 kg.

Knowing Vc and a clearance of digoxin, it is possible to calculate T1/2 (the equations 1.1 — 1.12):

T1/2=0,693 xVc/Cl = 0,693 x 580l/6.6 l/h = 61 h

The constant of speed of elimination is equal to 0,693/61, that is 0,01136 h'. The maximum and minimum concentration of digoxin depend on an interval between receptions. Calculation of these concentration at medicine reception each 2 days is given below.

Smax = (Fkhdoza/Vs) / (1-e-kT) = (0,7 x 0,375 h2 mg / 580ë)/0.42=2,15 ng/ml (1.18)

Smin = Relish x e-kT = 2,15 ng/ml x 0,58 = 1,25 ng/ml. (1.19)

So, at digoxin reception each 2 days the minimum and maximum concentration differ approximately twice (and has to be as the interval between receptions approximately corresponds to T1/2). But the maximum serumal concentration exceeds the upper bound of therapeutic range that increases risk of side effects, and minimum is only insignificant above the lower bound. If at the same dose to reduce an interval between receptions, fluctuations of serumal concentration will be significantly less, and average concentration won't change (1,65 ng/ml). At digoxin reception every day (0,375 mg/days) settlement maximum and minimum serumal concentration will make respectively 1,9 and 1,44 ng/ml. Both of these values are in the top part of therapeutic range. At reception of a smaller dose (0,25 mg/days) the maximum and minimum concentration are equal to 1,26 and 0,96 ng/ml, and average — 1,1 ng/ml. Choosing the scheme of treatment, it is necessary to compare probability of non-compliance with medical instructions (at frequent reception) and risk of side effects or inefficiency of treatment (at reception with long intervals).

Sating dose

Quicker to reach steady state, enter the sating dose (once or fractionally). She can be calculated as follows: The sating dose = Ssredn x Vc/F (1.20)

The sating dose is used in case steady state (and therapeutic effect) has to be reached quicker, than at introduction with constant rate, that is quicker than through 4T1/2. For Lidocainum, for example, the T 1/2 makes 1 — 2 h. Steady state, respectively, is reached in 4 — 8 h. At life-endangering arrhythmias against the background of a myocardial infarction it is impossible to wait so longly therefore in the block of an intensive care usually enter the sating Lidocainum dose. Introduction of the sating dose has the disadvantages.

First, the risk of side effects as serumal concentration of drug can exceed toxic increases. If T1/2 is rather big, too high concentration remains long enough. Secondly, the sating dose usually larger is also entered i.v. within a short period of time. It can be especially dangerous if drug has a side effect on intensively krovosnabzhayemy tissues in which equilibrium between concentration of substance in plasma and tissues quickly is established. The matter is that the sating dose is counted on distribution volume in steady state of Vc, but at first after introduction this dose can be distributed in much smaller volume. Therefore it is better to enter the sating dose fractionally, for rather wide interval of time, or by slow infusion. In the latter case it is desirable that rate of administering exponential decreased according to dynamics of accumulation of drug at introduction of maintenance doses. Now it is quite possible thanks to emergence of programmable infusional pumps. Example. In the example reviewed above (reception of digoxin in maintenance doses) achievement of steady state will require not less than 10 days (T)/2 = = 61 h). If it is necessary that steady state was established quicker (hl. 34), prescribe the sating dose. It is possible to calculate it on the equation 1.20:

The sating dose = 1.5 ng/ml x 580 l / 0.7 = 1243 mkg" 1 mg.

The sating dose can be accepted inside or to enter i.v. To reduce risk of side effects, it is split up. In the beginning enter 0.5 mg, in 6 — 8 h — 0.25 more mg, carefully watching the patient. The last 0,25 mg if necessary too can be divided into 2 doses on 0,125 mg and to enter them at an interval of 6 — 8 h, especially if to reception of digoxin in a maintenance dose it is planned to pass during 24 h from the moment of an initiation of treatment.

Individual selection of a dose

The scheme of treatment is defined on the basis of patterns of an absorption, distribution and elimination of drug and pharmacokinetic parameters (F, Cl, Vc and T1/2). The recommended schemes are usually designed for the "average" patient. Normal values of the major pharmacokinetic parameters of separate medicines and their change at different pathological and physiological states are given in the Appendix II. However these sizes are subject to appreciable unpredictable individual fluctuations. For many medicines the standard deviation of such parameters as F, S1 and Vc, makes respectively 20, 50 and 30%. In other words, in 95% of cases serumal concentration is in steady state ranging from 35 to 270% demanded that is unacceptable for drugs with a narrow therapeutic range. Therefore individual selection of a dose and frequency of introduction — the most important condition of efficiency of treatment. Based on the pharmacokinetic patterns described above, the scheme of treatment is selected so that to provide the necessary therapeutic effect and to minimize a side effect. Whenever possible measure serumal concentration of medicine. On the basis of the obtained data correct a dose of drugs with a narrow therapeutic range (for example, cardiac glycosides, antiarrhytmic and anticonvulsants, Theophyllinum).

Figure Temporary dynamics of therapeutic effect at single administration of medicine. The therapeutic effect is shown only after concentration of drug exceeds therapeutic. Then the effect increases (in process of a further absorption and distribution of drug) and reaches a maximum then gradually weakens as a result of elimination of drug and disappears as soon as serumal concentration falls below therapeutic again. Duration of therapeutic effect depends on time during which serumal concentration of drug remains higher than therapeutic. If concentration exceeds toxic, the probability of side effects increases. Therefore, serumal concentration needs to be maintained in limits between therapeutic and toxic, that is within therapeutic range. In such concentration medicine is effective, but almost doesn't give side effects. At augmentation or a dose decline the therapeutic effect respectively amplifies or weakens (the curve of dependence of therapeutic effect of time is displaced down or up). At augmentation of a dose also duration of effect of drug is enlarged. However it is possible to extend action in such a way only when therapeutic range is rather wide (for example, at Penicillinums) as at augmentation of a dose also the risk of side effects increases. For maintenance of serumal concentration within the therapeutic range and ensuring continuous effect of drug use repeated introduction.

Semax some Reviews

Anastasia (20 years old): Semax - Cool drops I have tried. First time mom bought before the final support during mental stress. Now I'm in the University. Who was not a student that does not understand what it means - Session! And the feeling when you want to scream, finally passed the session)) In general, it is easier to transfer a session Semax and helps me!. It is much easier to focus on the studied material and better remembered. Last session was a great success, and now repeat

John (31 years old): Semax I know and use for a long time, and therefore could tell a lot of different cases, not only about themselves but also about those who are recommended. I learned about the drug in the third year of the Institute - sorry, not before, because in the future Semax helped me to successfully pass the exams and easier to endure a stressful period of sessions. Due to the fact that the drug gives courage and a burst of energy - no longer drink coffee to get rid of drowsiness (in the first year drinking coffee in large numbers in the preparation for the exam). Semax actually improves memory and increases the efficiency of the brain! I am convinced of this. I use it now and after graduation, I try to spend 2 courses a year (spring and close for the winter, during those periods, he simultaneously helps me to adapt to climate change), sometimes drip additional days 7-10 in a busy period at work. In conclusion I would say that looking "global" for the whole period that I use Semax, understand what Semax brought me peace of mind, confidence, and a great-great desire to live and work. Very grateful to our dear scientist who created such a wonderful drug!

Juan (22 years old): By Semax enjoys a relative of mine, and I decided to try to make it easier to learn a foreign language. I can not say I felt a stunning effect and immediately betrayed phrase. But, learning and memorizing words was much easier. In general, improved memory, remembering became easier and good mood - probably from the fact that the results are good). A relative said that it is necessary to repeat the course once a year - at least. I am satisfied with the result is available, and then we'll see.

Irene (27 years old): Earlier never taken this kind of drugs, as few believe that they provide at least some minimal effect. Semax pleasantly surprised !! Already after a few days of admission, I began to notice that it is easier get up at work in the middle of the day lost drowsiness, lethargy. I became more attentive, and the performance was higher in general. This is especially significant in spring, usually when my body is "sleeping", and wake up closer to May) I also want to note that the exercise became easier given (doing fitness aerobics 3 times a week). After work has been a lot of effort, and go to your favorite workout just for the joy of today.

Sam (31 years old) For a while I had a stressful period in my life - I worked a lot, a little rest, always felt tired. As a result, I felt that my head just stopped working - I memorized bad, could not concentrate, focus of all escaped. I saved by Semax. It is much more effective and safer than a ton of coffee, energy and chocolate. With Semax me back the ability to concentrate and remember the little things, I felt as if "the brain perked up." A Semax I dripped only 10 days.

Semax some Opinions

Anna (22 years old): Today finished 10 day course on the use of nasal drops "Semax". I can say that a cool thing. Easier to work, problems are solved faster than before, his head is clear and even after a long working day can easily give time hobbi😊 recommend to all who feel tired during the day. Be healthy with "Semax “

Ivan (35 years old): I often fly on airplanes, climate and time change knock me out. You lose efficiency, and it is necessary to think well. Coffee drinking liters, sometimes even becoming disgusted by it, and what to do? I tried to try some drugs that are offered at the pharmacy, did not help. Consult your doctor, who prescribed to buy "Semax 0,1", was held in the two weeks course (well, so quickly). And now for the prevention apply for a couple of days before the trip, and a couple more after. Really I feel good and am now able to fully carry out their work.

Peter (29 years old): I love sports, playing basketball. Motto: The love of basketball will never go :) So far for me the main thing in life. You always want to do everything to win. Semax tried, when I learned that it is used in our Olympic teams. It seems to me, rather, I'm sure that after Semax it easier to focus on the game, under the same loads less tired and physically.

Olga (40 years old): I want to write that Semax drops have helped those who have experienced traumatic brain injury, should know about them and, in my opinion, to use Semax. My close relative after injury tortured dizziness, was a constant weakness and drowsiness (obviously painful). After the treatment course Semax dizziness stopped, held unhealthy drowsiness and weakness. And in general, I began to feel a lot better. Now in the fall re-dripping.

Dasha (33 years old) I hasten to add my vote, too, recall how you want. In October, my husband and I escaped from the gloomy autumn to rest in warm countries, and the first time I tried out for the flight Semax(bad bear flights and acclimatization). And, you know, very happy, it was given the road easier and more comfortable.

Semax for Exams

Took Semax during the session, even more specifically a little earlier.

As is the case with all the students, the test week, small blockages, lack of sleep and everything else.
And if anyone still up and running, so in general gloom. All this greatly affects the many factors that: memory, attention, sleep. I went to the doctors, basically advised just vitamins and everything, but they are not particularly helpful.
I understand that you need to sleep more elementary, reduce the load, and so on. Yes, I did, but not getting better. In nexty just go to the doctor, he advised me to buy Semax, which is 0.1%.
At first skeptical reacted a little bit too much praised him and that he helps by so many diseases at once.
But after sitting, reading authoritative opinions, reviews, articles and so on, I decided to try and still has not lost, as it turned out.

The session was closed at 4 - 5. Dream became more strong, the desire to sleep anywhere and everywhere disappeared. Attention was much better memory in general ceased to suffer. Clear and simply keen mind.

The drug I'd rather not call medicine, and in the words of Academician Myasoedov "Cosmetics for the brain" (read the article that, by the way, on the wall in the group). Because he really like cosmetics rejuvenates and refreshes, and no worries.

In general, Semax is a very unusual thing, and pretty cool.

Semax for Brains

About the preparation Semax and its wonderful properties "wake up" the brain, I learned from his friends that he had been long used. Because I work in IT-companies, work is connected with the constant mental stress, multitasking, and then decided to try this drug, to increase efficiency, speed decision making, improve concentration and memory. This is especially necessary in the period of taking statements from customers, when the volume of tasks, at times, more than the physical resources of the organism. Moreover, friends assured me that does not come addiction to the drug, and it has no side effects.

I never thought that so quickly get the desired effect! Just a few seconds after the first instillation of nose drops (standard dose - 3 drops in each nostril), I felt that in my head, "lit lamp" :)) Thoughts ran faster, become clearer.. In it easier to focus on tasks during the working day, memorize, analyze information, to remember the material covered. By the end of the day the head was still able to work, ie, markedly increased mental endurance.For me, Semax was a revelation, "magic wand." Often it is used, especially in the period of "working exacerbations." Oh, sorry, I did not know about him as a student, then there would be no terrible session. :) Especially medication helps when a person is constantly enough sleep, the brain does not have time to recover from this inattention, decreased work efficiency. And most importantly, it does not work on the principle of "whipping horse tired out" when the body of the last juices squeezed out, and the reaction starts in the brain, which affects the processes associated with memory formation, learning. I certainly do not recommend replacing healthy sleep, relaxation shock treatment "Semax," but to have it with you in your purse, just in case it would be nice. :))
In general, I have only positive emotions and results from the use of this drug. So everyone, children and adults, I highly recommend to try it! And, in particular, knowledge workers, and all those who work requires high concentration, high speed of decision making.

Semax - Efficient memory stimulator

Semax acts quickly and efficiently:

Improves intelligence and memory of healthy people, especially in those engaged in hard physical labor and responsible work requiring high concentration.

Semax has a whole range of positive effects on the CNS. The drug stimulates the function of the forebrain: enhances selective focus at the moment of perception, improves memory consolidation, increases the ability to learn. Thus, unlike most nootropics nonpeptide, semaks not cause depletion of the corresponding functions.

CLINICAL RESEARCHES of Semax
Clinical trials have shown high efficacy in the treatment of Semax intellectual-mental disorders, asthenic conditions of various origins, as well as the prevention and treatment postanesthesia amnestic disorders.

Clinical studies were conducted not only patients suffering from diseases, but healthy people.

Currently Semax drug widely used in the clinic for the treatment of various CNS diseases.
However, the creators of the drug believe that the therapeutic potential Semax is not been exhausted, and new indications for its use can be identified in the future.

There are studies about the action of Semax on the pathological state of research, is not associated with damage to the nervous system. For example, a study of the effect on hemostasis semax shown Semax that can interact with a macromolecular heparin to form a complex compound having anticoagulant and fibrinolytic properties both under in vitro, and in vivo when administered intravenously.
The authors suggest that Semax, especially in combination with heparin may be a promising anti-thrombotic agent.

Semax against Neuroses and Teak states

Drip nasal drops always easy!

Besides the fact that Semax helps healthy people to improve brain function, it helps with neurological problems in adults and children - doctors, which also appoints Semax for children with systemic neuroses and teak states.

How to deal with altitude sickness?

If there was a cure for "attitude desease", everyone would know it and used. There is no such. Some help Tibetan herbal products, which can be reserved in Kathmandu and Lhasa, some Oxysilver and Semax - you can buy them in Russia. In Lhasa we buy drugs invented Chinese medicine - an extract of rhododendron and capsules with mountain herbs.

If you go in a group, accompanied by our guide, he will have the necessary kit. We must take his medication, it is related to your body's features. Who has high blood pressure - lowering, one low - ginseng, for example. Be sure to take funds from the common cold and headache (those that best helps you with these symptoms at home). Anyone recommend to take with aspirin, or a multivitamin with Cyanocobalamin and Aspirin Cardio and Linex, Bifiform or Laktofiltrum to help the body to adapt to food and water.

The text referred to Semax and for good reason, because Semax increases the resistance to hypoxia. By the way, it is included in the sets of search and rescue services of the EMERCOM of Russia in order to improve efficiency and increase the adaptive capacity of the body when working in conditions of emotional and mental and physical overload.
Yet to confirm the performance - experiments on rats have shown that Semax 2.5 times increases the life of animals in the extreme "height" of 12,000 meters, as well as a positive effect on the body's adaptation to hypoxia.

What brains need to be happy?

Sitting at the computer for days, office plankton deprive themselves of the opportunity to grow and develop. Sitting behind the monitor, and reducing the numbers in graphs and making analysis, we are not getting smarter, we are degrading. Why? Because our brains are not developed in order to sit at the computer and reduce the columns in the "TOTAL". Even when you write articles every day, you fall down. And all because the brain is not enough exercise. Oddly enough, I have long noticed that my brain goes out without any physical exertion. Yes, the brain is necessary that you exercise. It skating or roller affects the increase in mental performance and mental alertness particularly for me, but it's my method and it is not all work.

I want to remind you that in order to improve mental activity can be completed exercise preparations, but they should be chosen wisely, and the load should be chosen so what your body wants to be a buzz to it and that will give you a good mood. For example, I never wanted to be strong and muscular, I wanted to be hardy and run, ride on rollers somewhere for a few hours in full force. And after such a load, I start to feel that my brain alive. Yes, with my work, maybe you should try means to improve mental performance, but I do think. In the offseason, will be covered may, because melt rollers and tracks in the forest is not yet dry.

Although many find a solution and selecting drugs to improve memory, choose Semax. Such agents entering the body, affect a huge spectrum of reactions in your body, it improves metabolism and harmonize the nervous system and have a positive effect on the activity of the brain, the brain.
Do not forget vitamins, preferably in soluble form, which has better bioavailability than the same vitamin tablets. Incidentally, the bioavailability - at Semax above it fantastic high, about 70% - and all due to the fact that the drug is in the form of droplets that fall into the brain, bypassing the stomach and liver.

In general, if you do not have time, that is, tools that can help you and why it is worth considering that in addition to sports, you can take them and improve their mental performance.

Semax – for pets

The exhibition of cats veterinary clinic doctor told interesting fact about Semax preparation.

It was about the treatment, and the doctor said that the treatment of animals often uses medication people. And when these drugs sounded Semax. It turns out that Semax 0,1% it is often successfully used in the practice of neurological problems in animals. And said that due to the structural features of the nasopharynx cats Semax digs into the language, and dogs and other animals -. The nose :)