Saw this being shared around quite a lot recently and thought it'd be fun to see the variety of responses :) pretty simple game, spell out all the medications you know from A-Z and let us guess which specialty you hail from. (Of course this is fairly difficult to have everything under the same subspecialty but just a general gist, since we do tend to name things we are most familiar with)
E.g. Atenolol, Bisoprolol, Clopidogrel, Digoxin screams cardio...
I'll start!
Amikacin Bortezomib Cyclophosphamide Dexamethasone Ethambutol Furosemide Gentamicin Hydrocortisone Isoniazid Jardiance Ketoconazole Levofloxacin Meropenem Omeprazole Pentamidine Quinine Rituximab Sorafenib Tacrolimus Unfractioned heparin Vancomycin Warfarin Xeloda Y-90 Zidovudine
My father is due to have elective surgery soon, he's having a PCNL to remove a single stone in his left kidney that proved too awkward for ureteroscopy. He takes 75mg aspirin daily following a heart valve replacement and double bypass a decade ago. He also routinely takes warfarin but is currently bridging with enoxaparin.
I've been told to administer a final dose of enoxaparin no later than 8am the day before his surgery but have not been told to stop the aspirin. Is this normal for someone with his history?
Relevant info:
81M
UK
White British
79Kg
5'11"
Non smoker, no drugs or alcohol
History - Alzheimer's, type 2 diabetes, mechanical valve replacement and double bypass in 2011, diagnosed with kidney stone in late 2021
Meds - enoxaparin sodium 80mg twice a day, aspirin 75mg once a day, metformin 500mg two twice a day, gliclazide 80mg two twice a day, oxybutynin 2.5mg twice a day, linagliptin 5mg once a day, tamsulosin 400 micrograms once a day, donepezil hydrochloride 5mg once a day, colcalciferol 1,000 units once a day, bisoprolol 1.25mg once a day, atorvastatin 40mg once a day
I’m a 27F who’s on a few medications, listed below: 150mg Bupropion 5mg Bisoprolol 200mg Hydroxychloroquine 200mg Lamotrigine 1000mg Glumetza 30mg Lansoprazole 875/125 Amoxi Clav 9mg Warfarin.
Last night I was having a massive panic attack, so I took 2 of my .5mg lorazepam tabs (1mg). As I was instructed, I took 2 more (2mg total) when the first dose didn’t help. The issues is that I was told to take until it helped, but I’d never had it not work past 2mg. So I took another two pills and then another two later. So I was up to 4mg. I had also had a glass of rum and Coke earlier in the night.
I woke up this morning at 4:30 stumbling around like a drunk person when I got up to use the toilet. I woke up again at nine, same stumbling around. Was up for about an hour where my boyfriend because increasingly concerned that I couldn’t walk straight and was stumbling around like a drunk person and then he sent me back to bed. I slept another three hours, got up, around 2, he made me breakfast (I guess lunch at that point), we watched a show on the couch, and then he suggested I go back to bed again, as I was still super out of it. He says the whole time I was talking slow, slurring my words, and didn’t seem to be making sense. I woke up around 6 and we ordered takeout. I did manage to get dressed and get to the car, but I stayed in the car and he went in and got the food. I did manage to eat a burger and a half a thing of fries, and am not feeling any nausea. I’m still dizzy and stumbling, but my boyfriend says my speech has improved. My heart rate tracker hasn’t caught anything dangerously low or high. And I haven’t noticed any issues breathing. Should I go to the hospital? Or is the worst past? Is there even anything they would DO at the hospital? Thanks!
From the day I was put on the beta blocker Bisoprolol for a few weeks two years ago, I have become very ill and not recovered.
A recent DNA report from Promethease has listed a few bad genes I have regarding the slow metabolising of certain medicines. Whilst the most common is Wayfarin, three genes mention being a slow metaboliser due to NAT2 enzymes, further research seems to show a link with NAT2 and the slow metabolising of a similar beta blocker.
Here is the list of my bad genes, their actions, and some quotes I have found from online research. Wondering if their might be a more definite link between my adverse effects to beta blockers and these genes of mine?
One of the syptokms I have been left with is Neurophty, especially peripheral.
rs1799807(A;G) Heterozygous for 'atypical' BuChE 3.5Magnitude gs162CYP2C9 Poor Metabolizers CYP2C9 poor Drug Metabolisms3.3 magnitude gs191 Impaired NSAID drug metabolism impaired NSAID drug metabolism,3.1 magnitude rs10509680(G;T) probably impaired Warfarin metabolism. 3 magnitude rs1057911(A;T) carrier of one CYP2C9_50298A>T allele possibly influences Warfarin dosing, 3. magnitude
rs1057910(A;C) CYP2C9*3 carrier; average 40% reduction in warfarin metabolism 2.5 magnitude gs140 NAT2 slow metabolizer gs154 NAT2 Slow metabolizer rs1495741(A;A) NAT2 slow metabolizer (predicted) Predicted to be a NAT2 slow metabolizer. rs9923231(C;T) reduced warfarin dose rs776746(A;G) carrier of 1 nonfunctional CYP3A5 allele; drug metabolism affects rs1799853(C;T) ~20% reduction in warfarin metabolism; some NSAID risk
Metabolic Fate of Pharmaceuticals: A Focus on Slow Metabolizers A substantial portion of the population may have altered drug metabolism due to genetic factors that substantially affects their ability to metabolize specific drugs. These individuals are identified as slow metabolizers. Such individuals tend to accumulate substantially higher drug concentrations than normal metabolizers, which increases their risk for drug adverse events.
- Drug Metabolism – Slow Metabolizers When the parent drug is an active agent and most of its metabolism and clearance from the system are affected by a polymorphic enzyme, the affected individual is considered a slow metabolizer.
The reduction in,or lack of, a functional enzyme in such an individual results in decreased metabolism and accumulation of the active drug. This results in increased bioavailability of the active drug and prolongation of its half life. Slow acetylators are also more likely to develop peripheral neuropathy than rapid acetylators
Drugs That Undergo Polymorphic N-Acetylation It has been shown that a wide variety of drugs may undergo polymorphic acetylation, including acebutolol,(Beta Blocker). Two distinct enzymes found in the liver are N-acetylators, called N-acetyltransferase 1 and 2.
The enzyme NAT2 is involved in the genetic polymorphism associated with N-acetylation. In slow acetylators, NAT2 levels are reduced.
The slow acetylator phenotype has a 10% to 20% reduction in the quantity of NAT2 in the liver, resulting in accumulation of the parent drug.
Drug Interactions in Slow Metabolizers The mephenytoin polymorphism effects a variety of drugs that are metabolized by CYP2C19.
The metabolism of propranolol, (beta blocker), is affected by altered mephenytoin metabolism.
Summary
Adverse drug reactions are a serious clinical problem
Genetic polymorphism in metabolism may result in drug responses that are outside the therapeutic range
Slow metabolizers may be at increased risk for drug -related adverse events
When confronted with an agent known to be subject to polymorphic metabolism, physicians should consider whether additional monitoring for efficacy and safety is appropriate
Pharmacological drugs of metabolic and cytoprotective action applied to correction of a functional condition of a myocardium designate the term "cardioprotectors" which appeared in the nineties 20th century when ideas of the most important role of biochemical changes in a pathogenesis of coronary heart disease were formulated.
Myocardium constantly needs delivery of the oxygen providing process of oxidizing phosphorylation. The ischemia/hypoxia can be treated as an imbalance between delivery of an oxygenic blood to a myocardium and its need for oxygen. If delivery of oxygen doesn't correspond to requirements of cardiomyocytes as at patients with the chronic coronary heart disease (CCHD), and healthy people in the conditions of excessive exercise and emotional stresses, the functional condition of cells of a cardiac muscle worsens and there are clinical symptoms of stenocardia.
Universal mechanism of adaptation of a cell to the changing living conditions is reorganization of a metabolism and energy. At the present stage of development of pharmacology the whole arsenal of the cardioprotectors possessing a broad spectrum of activity, promoting synthesis and mobilization of energy and plastic resources, optimization of activity of physiological systems, acceleration of processes of restoration including in a cardiac muscle is developed and tested.
Main directions of correction by pharmacological agents of metabolic action: improvement of energy balance (intensifying of synthesis of macroergs, expansion of their reserve pool, more economical and effective use in various biochemical processes; depression of degree of a fatigue); correction of plastic metabolism (acceleration of formation of structural "trace" of adaptation, prophylaxis of dystrophic processes, acceleration of processes of aftertreatment); protection of cellular structures and free radical oxidation; optimization of neuroendocrinal regulation.
Mechanisms of action of cardioprotectors are various and multidimensional. In the absence of a hypoxia cardiomyocytes "receive" ATP due to splitting atsetil-KOA in Krebs's cycle, and the glucose and the free fatty acids (FFA) act as the main sources of energy. At adequate blood supply of a myocardium of 60 — 90% atsetil-KOA it is formed due to oxidation of free fatty acids, and other 10 — 40% — due to decarboxylation of pyruvic acid (PVK). About a half of PVK in a cell is formed at the expense of a glycolysis, and the second half — of Sodium lactatum coming to a cell from a blood. SZhK catabolism in comparison with a glycolysis demands larger amount of oxygen for synthesis of equivalent number of ATP. At sufficient entering of oxygen in a cell glucosic and fat and acid systems of power supply are in a condition of dynamic equilibrium. In the conditions of a hypoxia the amount of the arriving oxygen isn't enough for oxidation of fatty acids. Thereof in mitochondrions there is an accumulation of the activated forms of fatty acids (an acylcarnitine, atsil-KOA) which are capable to block that is followed by suppression of transport of the ATP produced in mitochondrions in cytosol and damage of a membrane of cells.
It is possible to improve the energy status of a cage with the help:
- increases in efficiency of use by mitochondrions of scarce oxygen owing to the prevention of dissociation of oxidation and phosphorylation, stabilization of membranes of mitochondrions;
- weakening of inhibition of reactions of a cycle of Krebs, especially maintenance of activity of a suktsinatoksidazny link;
- compensations of the lost components of a respiratory chain;
- forming of the artificial redoks-systems shunting the respiratory chain overloaded with electrons;
- ekonomization of use of oxygen and decrease in an oxygen request of fabrics weakening of respiratory control in mitochondrions or inhibition of the ways of its consumption which aren't necessary for the emergency maintenance of activity in critical conditions (nefosforiliruyushchy enzymatic oxidation — thermoregulatory, mikrosomalny, etc., non-enzymatic oxidation of lipids);
- increases in formation of ATP during glycolysis without increase in products of a lactate;
- decrease in an expenditure of ATP a cage on the processes which aren't determining the emergency maintenance of activity in critical situations (various synthetic recovery reactions, functioning of volatile transport systems, etc.);
- introductions from the outside of high-energy connections.
With respect thereto cardioprotectors can be divided conditionally on direct and indirect. Action of direct cardioprotectors is caused as local (stabilization of membranes, influence on a metabolism is direct in the kardiomiotsitakh, vasodilating effect), and the central impacts (regulation of a vascular tone through influence on structures of TsNS). Cardioprotectors of indirect action reduce load of a myocardium and therefore reduce or prevent violations of functioning of a cardiac muscle.
Classification of cardioprotectors of direct action - The drugs regulating a metabolism in a myocardium
1.1. Drugs with primary impact on power processes — триметазидин, ritmokor, meksikor, reatine phosphate (neotone), a taurine (dibikor), kratat, ATF-LONG, sodium adenosine triphosphate, to asparka (Pananginum), etc.
1.2. Anabolic agents of steroid and nonsteroid structure — metandienon, Retabolilum, potassium orotat, magnerot, Riboxinum, etc.
1.3. Antioxidatic agents — a tocopherol an acetate, Quercetinum, corvitin lipoflavon, lipin, tiotriazolin, Niacinum, ritmokor, corargin, ascorbic acid, hepatocuprein, etc.
1.4. Elektronoaktseptora — ubikhinon, cytochrome C, Riboflavinum, energosty, etc.
- The drugs influencing electrolytic balance in a cardiac muscle
2.1. Selective blockers of slow calcium channels — verapamil, diltiazem, amlodipin, felodipin, latsidipin, etc.
2.2. Na+/N inhibitors + - channels — amiloride, cariposid, etc.
2.3. — nikorandit the agents opening ATP-dependent K-channels, etc.
- The drugs stabilizing a membrane of cells of a myocardium
3.1. Antiarrhythmic agents - Amiodaronum, соталол, Gilurytmalum, neogilurytmalum, Disopyramidum, Lidocainum a hydrochloride, meksiletin, etatsizin, propafenon, fleksainid, etc.
- The agents reducing the need of a myocardium for oxygen
4.1. Organic Sodium nitritums — - Nitroglycerinum, Nitrongum, Isosorbidum dinitrate, koronarolitik of the similar mechanism of action — Molsidominum.
4.2. beta Adrenoblockers — anaprilin, atenolol, metoprolol, bisoprolol, betacsolol, nebivolol, tseliprolol, esmolol, etc., and, (3 adrenoblockers — carvedilol, labetolol, etc.
4.3. Drug of a natriuretic peptide – niseretid
Classification of cardioprotectors of indirect action - Anti-hypertensive agents of various mechanism of action
1.1. Diuretics — Hydrochlorthiazidum, Clopamidum, indapamid, Furosemidum, Spironolactonum, eplerenon, etc.
1.2. APF inhibitors — captopril, enalapril, berliprit, lizinoprit, fozinoprit, ramiprit, perindoprit, etc.
1.3. Blockers of receptors of an antotenzin of II — losartan, irbesartan, eprosartan, candesartan, telmisartan, valsartan, etc.
1.4. Antagonists of endothelin (bosentan), (kandoksatrit) blockers of a neutral endopeptidase, the drugs having also properties of inhibitors of APF — omanatrilat.
- The agents influencing rheological properties of a blood
2.1. Inhibiting aggregation of thrombocytes — acetylsalicylic acid, atselizin, tiklopidin, clopidogrel, tirofiban, eptifibatid, etc.
2.2. Anticoagulants — a heparin, the low-molecular fractioned heparins (fraksiparin, enoksiparin, deltaparin, fondaparinus, warfarin), Syncumarum, Phenilinum, etc.
- The medicines influencing lipide exchange
3.1. Gipolipidemichesky agents — statines (lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin, rozuvastatin, etc.), fibrata (fenofibrat, bezafibrat, etofibrat, etc.).
3.2. Drugs of unsaturated fatty acids — thecomas, Linaetholum, Essentiale, эпадол, the omakor, lipostabit, an omega-3 and others.
In sports medicine special attention is paid to medicines which regulate a metabolism in a myocardium, especially in the conditions of a hypoxia. Other medicines are appointed during the recovery period, in case of business disruptions of cardiovascular system owing to excessive overloads, the wrong mode and other reasons.
Application in sports preparation of cardio action is determined not only by ideas of an orientation of the main effect of such medicines, but also availability to practical doctors of information which is created by results of scientific developments and advertizing of producers of such medicines. At the same time it is necessary to consider that purpose of medicines depends on type of the performed work and a training cycle. In particular, application o f cardio protectors and plastic regulators of exchange processes more reasonably during the competitive period. Regulatory antigipoksant are shown, generally against the background of the basic loadings developing adaptation opportunities of cardio respiratory system at the athletes specializing in cyclic sports.
The leading place on urgency of impact against the background of the developed picture of a fabric hypoxia is taken by substring antigipoksant. The first of them can be considered glutamic, asparaginovy and amber acids, and also their salts. Though the potential of protective action of these cure for a hypoxia of a myocardium is rather limited, numerous researches proved activation of processes of oxidizing phosphorylation by them. Apparently, it is connected with the fact that glutamic and amber acids recover substring fund of a cycle of Krebs due to education and acids that brings to NADN to recovery of fumarat.
The central place among antigipoksant, by our experience, is occupied by substances which main point of application activation of anaerobic products of makroerg against the background of deficit of oxygen shall be. These substances can be united in two groups, first of which is to some extent available to each sports doctor.
These are regular substrata of glycolysis — glucose and fosforilirovanny derivatives of hexoses — glyukozo-6-phosphate and fruktozo-1,6-diphosphate (in the form of ezafosfina medicine). The possibility of anti-hypoxemic effect of substrata of glycolysis was connected, first of all, with economy own the makroergicheskikh of phosphates of the cages spent for preliminary phosphorylation of hexoses. Unfortunately, hopes for protective effect the fosforilirovannykh of hydrocarbons in case of a hypoxia weren't equaled. In case of various forms of a hypoxia only moderate favorable changes are received from use of glyukozo-6-phosphate, fruktozo-1,6-phosphate and their mix — geksozofosfat. It is established that on anti-hypoxemic activity various fosforilirovanny carbohydrates differ from each other a little. It is considered, that membranes of cages practically not of pronitsayema for all intermediate products of glycolysis that reduces the value of these means as antigipoksant and explains their approximately identical efficiency in the conditions of a hypoxia.
We believe that in the conditions of need of application of these means for each athlete decision making about specific medicines for achievement of necessary anti-hypoxemic effect shall go on the way of intravenous injection the glyukozirovannykh of solutions with the maximum doses of insulin. Use in such circumstances, as well as in case of other forms of miokardialny weakness, the concentrated glucose solutions with insulin in the doses reaching 1 ME on 0,5 — 1 g of hexose promotes prevention of injury of a myocardium which substantially can be connected with an organ hypoxia.
Widely known use of the so-called polarizing mix offered N. by Laborit is based on the same effect — on switching of metabolism of the myocardium to some extent injured by a lack of oxygen from uneconomical oxidation of free fatty acids on the glucose energetically more profitable as a substratum in the conditions of a hypoxia. The Gipoksichny myocardium is an optimum object for such therapeutic impact as even in usual conditions in it only 25 — 30% 02 are spent for glucose oxidation, other quantity 02 goes for oxidation of fatty acids and a lactate. It is shown that use of the polarizing mix in case of a sharp myocardial infarction almost for 100% slows down oxidation of free fatty acids and by 2 — 3 times increases absorption by the injured glucose heart.
For glycolysis strengthening, including it is reasonable to apply the ritmokor which is a stimulator of the shunt of oxidation of glucose to efficiency strengthening of "the polarizing mix". Oxidation of glucose in shunt has the advantages for the reason that functioning of the shunt is almost autonomous, i.e. doesn't depend on oxygen availability: on each 1 mol of the oxidized glucose 1 mol of glyukozofosfat, a glitseralyaldegida and ribozofosfata going to reactions of glycolysis at stages below limiting is formed that promotes its prolongation. Use of medicine is shown as during a base period, and is direct during the competitions. Intravenous administration of medicine stimulates oxygen - the transport function of erythrocytes mediated by accumulating of glitseralyaldegid and 2,3-phosphoglyceric acid that is followed by return strengthening hemoglobin of oxygen and elimination of a circulator hypoxia. Medicine is applied orally to increase in adaptation opportunities of cardio respiratory system during a base period of preparation by rates on 21 days (on 2 capsules 2 times a day). In case of need increases in oxygen reservoir of work perhaps intravenous administration of 10% - го solution on 10 ml on isotonic solution of sodium of chloride for 2 — 3 h to loadings.
Attempts of broad use of medicines exogenous were ATP enzymes, insolvent owing to its fast destruction. Use of ATP in the form of a coordination complex in medicines ATF-LONG and ethane was more effective because their molecules are less subject to hydrolytic splitting by enzymes. On resistance of ATF-LONG and ethane by 2,5 times exceed actually ATP. The mechanism of action of ATF-LONG and ethane is connected first of all with influence on receptors of heart that limits a "calcic" overload and promotes prolongation and power education. ATF-LONG has the expressed activity in case of loadings during which endurance is developed.
Medicine ATF-LONG promotes increase in endurance at the athletes specializing in game cyclic and sports. Results of researches showed that course acceptance of ATF-LONG promotes the best shipping athletes of training loads, increases endurance and improves indicators. Single application of ATF-LONG promotes increase at athletes of critical capacity during performance of work of the testing loading against the background of more economic work which is shown in smaller accumulating of lactic acid in case of bigger amount of work. At the same time resistance of an organism to physical activities increases. Medicines accept sublingual on 0,02 — 0,01 g for 2 — 3 h to loading.
Eton differs from drug ATF-LONG in the fact that contains in the structure not Histidinum, and acid which is the regulator of shunt.
The known breakthrough in treatment of organ hypoxemic lesions began after introduction in clinical practice of drugs of an exogenous phosphocreatine. It is known that physiological function of the last providing intracellular transport of energy in cardio myocytes and cells of sceletal musculation, brain and some specific cells, such as cells of a retina of an eye and spermatozoons is considered. The phosphocreatine which contains in normal cardiomyocytes in high concentration should be considered as one of natural factors of stabilization of cellular membranes. Its disappearance from cardiomyocytes at an ischemia can be one of the reasons of destabilization and damage of their membranes. On the basis of appreciable on volume and versatile pilot studies it was shown that the exogenous phosphocreatine entered into a blood in high doses has significant effect on power, structural integrity of membranes of ischemic cardiomyocytes and their sokratitelny function. It is considered that the mechanism of protective action of an exogenous phosphocreatine is difficult and consists, at least, of three-cellular components and one extracellular, including:
- penetration of phosphocreatine in a cell and immediate participation in maintenance of local cellular pools of ATP which, according to Saint-Dyerdi, is "a power change";
- inhibition of degradation of myocardial adenilnukleotid at a stage 5 '-nucleotidases of a sarkolemma of cardiomyocytes;
- inhibition of accumulation of lizofosfoglitserid in an ischemic myocardium and conservation of an intaktnost of sarkolemma;
- inhibition of aggregation of thrombocytes at the first stage by excision of ADF in extracellular creatin reaction and augmentations of plasticity of membranes of the circulating erythrocytes.
Thus, against the background of action of an exogenous phosphocreatine there is a decrease of functional implications of an ischemia of a myocardium, aritmogenny activity of the ischemic center, excess activation is HOLLOW. Industrial drug of a phosphocreatinine — neotone (Alfa Schipparelli Wassermann) is applied in an urgent cardiology in the earliest terms after emergence of the first symptoms of an acute myocardial infarction. Usually bolyusno 2 g of drug with the subsequent drop infusion during 2 h with rate of 3 — 4 g an hour are entered. The maintenance therapy for the next 5 days makes 4 — 8 g of neotone a day. At the same time protection against hypoxemic damage of myocytes of a sceletal musculation or cells of other ischemic organ is observed as distinct stability of the central hemodynamics after including of a zone of an ischemia owing to protection of cardiomyocytes against toxic reperfusion metabolites, and.
In sports practice neotone found application as drug of the mobilizing action. The full scheme consists in purpose of 2 — 4 g of drug in 24 — 48 hours prior to competitions.
Inconvenience of use of drug is bound to use of intravenous infusions that is forbidden to WADA without special prescriptions. In this regard emergence in the pharmaceutical market of the first domestic drug of a phosphocreatine for oral administration — a reaton ("Farkos", Ukraine) draws attention. Each tablet contains 0,5 g of coordination hydrophylic stabilized phosphocreatine complex with ions of a magnesium and ATP. Drug is approved in schemes of pharmacological maintenance of work on endurance, on improvement of high-speed and power characteristics, and just as the activator of recovery processes. Reaton accept 2 tablets with an interval of 1 — 2 p 2 — 3 times a day.
Some time ago abroad, and then and we, had works on use as substratny antigipoksant of salts of succinic acid under the influence of which considerably decreases or the post-hypoxemic metabolic acidosis of various parentage is completely compensated. Such effect is bound, first of all, to the power giving succinate influence. The ATP synthesis augmentation, inhibition of a glycolysis and intensifying of a gluconeogenesis is result.
Succinate oxidation — a necessary condition of catalytic influence of any of carboxylic acids as endogenic substrates, for example mA - lat or a fumarat, on assimilation by oxygen tissues. This phenomenon was explained with Krebs who showed that the sequence of reaction of oxidation of a series di - and tricarboxylic acids is closed in the cycle later called by his name at - than for maintenance of normal tissue respiration there is theoretically enough entering only of the activated acetic acid (atsetil-KOA), and other substrates can not be spent.
Succinate is a stimulator of synthesis of recovery factors in a cell. The phenomenon of bystry oxidation of succinate in a cellular cytoplasma with the participation of suktsinatdegi-drogenaza enzyme which is followed by restoration of a pool of dinucleotides is taped. The phenomenon noted when entering into internal medium of excess of succinic acid received the name of monopolization by succinate of a respiratory chain of oxidation. Biological value of this phenomenon consists in a bystry resynthesis by cells of ATP and rising of their antioxidatic activity.
The most appreciable group of substances which could be carried to regulatory antigipoksant long time was made by nonspecific activators ferment and the kofermentnykh of systems. They were considered as only clinically available medicines of this plan; treat them:
- group B vitamins — Nicotinamidum, a cocarboxylase, a pyridoxine, pangamovy and folic acids (a calcium a folate), to a lesser extent — cyancobalamine;
- tiolovy derivatives — Unithiolum, acetyl - Cysteinum;
- pyrimidine derivatives.
Their efficiency in clinical medicine was very moderate, and often and the sports working capacity which isn't proved in bench tests for rising. So, a series of reactions of the referred synthesis which are inhibited by an oxygen disadvantage is necessary for transformation of Nicotinamidum in OVER, and therefore the final anti-hypoxemic effect of Nicotinamidum is small and unstable. Thiaminum and a coenzyme, derivative of it — a cocarboxylase are a part of many cellular dehydrogenases catalyzing oxidizing decarboxylation of ketoacids (pyrogrape and and-ketoglyutarovoy). But even high doses of a coenzyme, without speaking about initial Thiaminum, can hardly get into a cell without dephosphorylization, undoubtedly, volatile. Anti-hypoxemic action often applied in combination with cocarboxylase of ascorbic acid and Riboflavinum is small.
Efficiency of a cocarboxylase as reducer deserves attention for the reason that it regulates rate of formation of Sodium lactatum in the conditions of deficiency of insulin (gipoinsulinemiya) which develops in 6 — 8 hours after the competitions or other intensive exercise and psychoemotional stresses and is bound as believe, to emission the kontrinsulyarnykh of hormones in response to a stressful phase of exercise stresses. In this regard intensifying of transketolazny reaction of the pentozny shunt under the influence of a cocarboxylase enlarges formation of a pyruvate from Sodium lactatum and its utilization in Cory's cycle.
Use of a cocarboxylase is presented in the form of a coordination complex with glycine and a betaine as a part of drug алактон perspective. Due to intensifying in a liver of reactions of a transmethylation under the influence of aetaine and intensifying of formation of NADFN, the main source of energy for a neutralization test of xenobiotics, алактон accelerates recovery processes in the conditions of exercise stresses, has aktoprotektorny effect, increases detoksikatsionny function of a liver.
The substances found among derivatives — gutimin and its derivatives which possess very much a broad spectrum of activity on the practical level are of appreciable interest. Drugs of a gutiminovy series of the second generation (амтизол, Treminum) not only activate glycolysis, but also reduce Sodium lactatum level in a cytoplasma, extracellular liquid, a blood and tissues (except for a liver), normalizing thus the acid and main equilibrium broken as a result of a hypoxia. Resynthesis of a glucose at the same time happens not due to switching of a cycle of Krebs to primary oxidation and in glyukozo-laktatny cycle of Cory or in glyukozo-alaninovy cycle.
It is shown that the thiourea derivative — amtizol-succinate as cyclic derivative a gutimina is most active in the prevention of an oxygen failure after a post-operational and posttransfusion hypoxia, acute falling of cordial activity against the background of a myocardial infarction and after open heart operations (septic shock). The dosage of an amtizol indirectly confirms its regulatory character as antigipoksant: bolyusny — 2 — 3 mg-kg "1, daily — 5 — 8 mg-kg-1 of body weight against the background of the greatest expression of a hypoxia.
The accurate positive inotropic effect, and also ability to interfere with hypercoagulation and development of a postoperative thrombophilia against the background of deficiency of oxygen and substrates is found in an amtizol. It possesses the expressed membrane stabilizing action what ability to reduce intensity the FLOOR testifies to.
Influence of a trimetazidin on physical working capacity in the absence of pathology is known that preliminary (in 30 min. prior to physical activity in the form of swimming) inside-bryushinnoye introduction to rats of medicine in a dose of 50 mg-kg "1 didn't show any aktoprotektorny action (Moroz et al., 2002). In scientific and scientific and methodical literature there are no data concerning efficiency of application of a trimetazidin in practice of sports preparation. In too time of G. A. Makarov, based on results of own observations (триметазидин in connection with magneroty appointed to 2 — 3 weeks in daily doses 40 and 1000 mg to members of national teams on rowing on kayaks and to a canoe and cycle road cycling respectively on an all-preparatory and spetsialnopodgotovitelny stage of the preparatory period of one macrocycle), assumes that medicine deserves attention first of all as means which allows to prevent the negative changes revealed on the electrocardiogram against the background of large volumes of loadings of an aerobic and aerobic and anaerobic orientation.
Mildronate synthesized in the early eighties the last century at Institute of organic synthesis of Latvia is one of the strongest inhibitors at - butyrobetainehydroxylases, reduces intensity of r-oxidation of free fatty acids by means of prevention of receipt them in a mitochondrion. It occurs owing to the fact that medicine slows down receipt in a cage of a L-carnitine which, in turn, provides transfer of fatty acids through a membrane. Mildronat reversibly limits the speed of biosynthesis of a L-carnitine from his predecessor — at - a butyrobetaine. Thereof the carnitine - the mediated transport the dlinnotsepochechnykh of fatty acids through membranes of mitochondrions without impact on metabolism the korotkotsepochechnykh of fatty acids is broken. Blockade of oxidation of fatty acids includes an alternative production system of energy — oxidation of glucose which considerably (for 12%) uses oxygen for ATP synthesis more effectively. However the positive effect of a mildronat as structural antagonist of a carnitine is still unclear, and the L-carnitine has the expressed cytocardioprotective effect, including in case of a sharp myocardial infarction, reducing expressiveness of diastolic dysfunction (Colonna, Iliceto, 1999).
Carnitine (W vitamin) is endogenous connection and is formed of a lysine and methionine in a liver and kidneys, fatty acids through an internal membrane of mitochondrions while activation and penetration of the lowest fatty acids happens without it plays an important role in transfer. Besides, the L-carnitine plays a key role in education and regulation of level atsetil-KOA. Physiological concentration correlate with increase in level which provides oxidation of limits lactate products. Thus, its anti-hypoxemic action is connected with transport of fatty acids in a mitochondrion, is shown in case of purpose of high doses of medicine while low doses possess only specific vitamin action.
The mechanism of influence of a mildronat on physical (including sports) working capacity in the absence of clinical pathology is studied insufficiently. It is known that preliminary (in 30 min. before physical activity in the form of swimming) introduction to rats of a mildronat in a dose of 100 mg-kg "1 didn't reveal action, as well as in a case with trimetazidiny. As for a possibility of effective use of a mildronat in practice of sports medicine, serious researches in this direction are almost absent. Only results of scientific research known to us given in N. I. Volkov (1990) work demonstrate that one-time oral administration of a mildronat by cyclists racers in a dose of 1,0 g for 3 h to loading promotes bigger use of carbohydrate inventories in the working muscles, to some increase in the maximum consumption of oxygen and improvement of indicators of aerobic efficiency. However these data can hardly be considered rather convincing because in principle it is impossible to expect from similar medicine in case of oral administration of immediate effect, especially, when there is a speech about changes of the main criterion of aerobic capacity — MT To. Other authors (Kulinenkov, 2002) recommend to accept mildronat in the period of intensive loadings (the preparatory period) on 1 — 2 capsule in 30 min. after food 2 — 3 times a day within 10 — 14 days whereas at the beginning of a special preparatory stage and just before start the dosage doesn't exceed half of the specified dose.
Tiotriazolin possesses antioxidatic, anti-radical action, improves blood supply of tissues of a brain, heart, eye; fibrinolytic, radio tire-tread influence of this drug is taped.
Realization of a cardiopatronage by means of use of antioxidants — Quercetinum and its soluble form of a korvitin which show properties of the modulator of activity of various enzymes which are taking part in degradation of phospholipids deserves attention. Drugs promote formation of nitrogen oxide, 5 lipoxygenases and synthesis of leucio-Tryenums brake activity, prevent rising of concentration of a calcium in thrombocytes.
Quercetinum represents агликон a flavo-noidny glycoside of Rutinum. This bioflavonoid which is released in granules, tablets and solution for injections is capable to prevent or liquidate implications of an oxidative stress. It expressed antioxidatic, anti-radical, membrane stabilizing properties thanks to a primary ingibition of activity of a lipoxygenase, and also, to a lesser extent, phospholipases, cyclooxygenases. Quercetinum prevents rising of level of a potassium in a cell, possesses the vazoprotektorny action bound to ability to release nitrogen oxide and to inhibit a protein kinase. Drug in a peroral form (Quercetinum) is included in a complex of actions for treatment of stenocardia, and in an injection (korvitin) applied in an urgent cardiology at an acute myocardial infarction. It is established that drug is capable to reduce a necrosis zone (according to serial definition of a cardiospecific isoenzyme).
Inside Quercetinum is prescribed in granules on 1 g by 3 — 4 times a day, at the same time 0.5 teaspoons of granules of Quercetinum (1 g) dissolve in half of glass of water and accept in 30 min. prior to food.
Good cardiotyre-tread effect gives Quercetinum combination with lipiny — lipoflavon which is an antioxidant, and, besides, has ability to restore the level of macroergs, though itself lipiny has sufficient cardiotyre-tread effect. Efficiency of lipoflavon in complex treatment of patients with coronary heart disease is established. However influence of Quercetinum and corvitin on physical working capacity isn't studied.
Cardioprotectors of a plant origin which possess antioxidatic and membrane stabilizing action improve a coronary circulation activity of a myocardium, hawthorn drugs — tincture, liquid extract, cardioplant are. They are included in a complex pharmacotherapy of coronary heart disease and a heart failure.
Drug possesses the expressed cardiotonic, anti-anginal, anti-hypoxemic, antiagregantny action, containing in one tablet of taurine 0.867 g, extract of fetuses of a hawthorn of prickly dense — 0,043 g, extract of a motherwort dense — 0.0867 g. Drug exerts the inhibiting impact on systems, improves blood supply and pump function of heart, reduces arterial pressure, normalizes heart rate.
Taurine reduces displays of intoxication warm glycosides, and also exponentiates the normalizing action of warm glycosides on energy inventories.
Medicine the cardiotone containing except hawthorn extract, ions of magnesium, potassium and acid folic has the expressed cardiotyre-tread effect. In addition to direct influence of extract of cardiotracks-nogo of a hawthorn medicine normalizes the level of the specified minerals, reducing the myocardium dystrophy phenomena.
Further pharmacological properties of some medicines of this group which took the worthy place in sports medicine are given.
Mildronate after intake is quickly soaked up, bioavailability makes it 78%, the maximum concentration in plasma of blood is reached in 1 — 2 h after acceptance. Medicine in an organism with formation of two main metabolites which are removed by kidneys is metabolized; elimination half-life in case of intake constitutes 3 — 6 h.
Quickly inosine (inosine), a ritmokor, a dibikor (taurine), ATP — LONG, ethane and other medicines of metabolic type are soaked up and join in exchange processes.
Medicines of a creatinfosfat — neotone and ritmokor — work the same though are entered in the different ways. Neotone is entered only parenterally intravenously by drop infusion. In case of single intravenous infusion its maximum concentration in blood is determined on 1 — the 3rd minute, and elimination half-life in a slow phase constitutes several hours. Neotone is distinguished with kidneys, the greatest number accumulates in skeletal muscles, a myocardium and a brain, in a liver and lungs accumulating of medicine is insignificant.
Reaton, unlike neotone, is applied sublingual or inside. After sublingual acceptance it is found in blood in 10 — 12 min., quickly diffundirut in fabric.
Meksikor, derivative amber acid, at parenteral introduction passes into bodies and fabrics, is metabolized by brought with urine. Trimetazidin after intake is quickly absorbed, the maximum concentration in plasma of blood is reached less than in 2 h. At repeated reception stable concentration in serum of blood is defined by 24 — 36 h and is maintained throughout all course of treatment. Medicine well gets into all bodies and fabrics, mainly with urine in not changed look, elimination half-life makes about 6 h. At oral introduction stable concentration in plasma of blood is reached no later than 60 h from an initiation of treatment.
Retabolil is gradually soaked up from the place of intramuscular introduction, his action develops slowly, reaches a maximum for the 7th day and not less than 3 weeks last. It is metabolized in a liver with formation of various forms of cetosteroids, about 90% from them are removed with urine.
Metandiyenon is quickly and completely soaked up from the digestive channel, its low bioavailability is caused by effect of the first passing through a liver. In blood he for 90% contacts specific globulins — carriers. In a liver is exposed to biotransformation with formation of inactive metabolites, it ekskretirutsya with urine. Duration of action of a metandiyenon makes to 14 h.
The maximum concentration at intravenous administration is noted through 50 with, elimination half-life makes 0.73 — 0.85 min.
Use of cardioprotectors as activators practically of all types of exchange is shown in sports medicine both in preparatory, and during the recovery period. Drugs promote adaptation of organs and tissues to the raised loads (to a hypoxia, an ischemia), and during the recovery period thanks to combined effect on a metabolism normalize function of vitals. Besides, they are included in complex treatment of cardiovascular diseases, hepatitises. The drugs containing a potassium and a magnesium are used at a hypopotassemia and a hypomagnesiemia, intoxication by cardiac glycosides.
Side effects are insignificant, quickly pass after cancellation of drugs. Interchangeability of drugs is caused by their purposeful influence on these or those processes of exchange in vitals and systems of an organism.
Pharmacology of the specified agents testifies to expediency of new approach to including the metabolitaykh of drugs in an arsenal of sports doctors taking into account of medicines of cardiotyre-tread action, individual approach in complex schemes of pharmacological providing the preparatory and recovery period, during the competitions.
Use in sports medicine and in practice of sports preparation In sports practice belongs to cardiotyre-tread drugs the important place as cardiovascular system is the main part of the kislorodtransportny system of an organism directly bound to physical working capacity, especially in the sports bound to endurance implication. This fact gives the grounds to consider use of the cardioprotectors increasing functionality of heart as one of the leading factors determining the level of physical working capacity.
Use of cardio protectors in sports medicine is caused by the aspiration to increase resistance of a myocardium and other vitals to physical activity. During the recovery period medicines restore processes of a metabolism, activity of immune system, reparations promote.
As for negative impact of cardio protectors on the athlete's organism, it can be shown at the wrong reception, namely at excess of the recommended doses, reception duration, and also against the background of existence of contraindications.
Forms of production of medicines - Mildronate — capsules on 0,25 g
- Trimetazidin — tablets on 0,02 g; tablets with the modified release on 0,035 g
- Mexicor — capsules on 0,1 g; ampoules on 1 ml of 5% - го solution
- ATP-LONG — ampoules on 1 and 2 ml of 2% - го solution; tablets on 0,01; 0,02 g
- Natrii adenosintriphosphas — ampoules on 1 ml of 1% - го solution
- Tiotriazolin — tablets on 0,1 g; ampoules on 2 ml of 1% - го and 2,5% - го solution; suppositories rectal 0,2 g; drops eye 5 ml of 1% - го solution
- Riboxin — tablets on 0,2; 0,4 g; kmpula on 5; 10 ml of 2% - го solution
- Kalii orotas — tablets on 0,2 g
- Magnerot — tablets on 0,5 g
- Retabolil — ampoules on 1 ml of 5% - го solution
- Methandienon — tablets on 0,005 g
- Asparkam (Panangin) - tablets; ampoules on 5; 10; 20 ml
- Dibicor — tablets on 0,5; 0,25 g
- Cratal — tablets
http://drdoping.com/blog/cardioprotectors Hi, first time posting, but I need some assistance/assurance on how to come put to family, you see i've alfrady cone out to ym therapist and my GP, i've had a referral sent to charing cross in london to get the ball irreversibly rolling (because this is something I NEED, and I regret not doing this eaflier in life), I have kept this under wraps since I was 7, no one in my family knows, no one even has a hint that this is what I need, I don't trust that they have the best opinion on trans topics amd I second guess any hints or assurances that they are LGBT friendly.
I have SEVERE trust issues, I got bullied in senior school to the point of suicidal depression (not on account of being trans), I can't go outside without looking over my shoulder constantly or having a defensive reaction to people getting too close (ie. Almost walking into someone as we each go around ghe same corner from opposite directions) I have a very unsupportive brotger who loves to troll and essentially shit all over my life so I can confirm he cannot be trusted.
How would you reccomend I tell my mum, the most likely person to accept me, should I tell her when i go to the doctors so I can ensure sge won't blow her top? I have no social life or friends, my therapist sessions ended pre-christmas so that's kinda out....
I go into a panic when I think about telling, regardless of of how much I work myself up to it, i've has the nightmare of family unexpectedly finding out and then outing me to the rest, i've had the GOOD dream where you envisage yourself in your ideal body.
I have serious anxiety, social anxiety, fear of the result, self-worth issues and body-image issues (most likely dismorphia, officially undiagnosed as of yet), kinda new to accepting myself, it's always been kind of a forgotten dream, left to the side to deal with depression.
I've always wanted it, but my medical health isn't the best, I have a pacemaker and a mechancial heart valve so i assume that will factor in to if they let me go ahead with this. I take anti-depressants for obvious reasons, warfarin and bisoprolol for heart issues
No exposure to hormones, just the freedom to practice being the me i want to be (on the down low for now), kinda lost with next steps..
Any ideas???? Thanks! Kinda scared to reach out beforehand, I just feel like i've already waited far too long for this....