Video explaining the science behind Clopidogrel
Clopidogrel sold into the name plavix is a second generation and see platelet truck belonging to the fire no paradeen family clopidogrel works which used the risk of stroke and other cardiovascular diseases quite diverting platelet clot formation drop adobo is an all formulation often taking loans like aspirin for maximum efficiency typical club adobe formulation
Contains 75 milligrams of the drug itself the drug has a long onset zone around two hours when the desired effects can last for three to five days globule was designed in 1977 he patented in 1982 in a joint venture by sanofi and bristol-myers squibb code the drug was fda approved and released onto the market in 1998 where it was very successful before his patent
Expire in 2012 it was the second best-selling drug globally and in 2010 grossed over nine billion us dollars club the double works by inhibiting the pt wide swell receptor which are combined into his adp agonist induces platelet aggregation a fundamental step in atherosclerosis atherosclerosis is where plaque develops this can be very dangerous because it causes
An increase in blood pressure subsequently increasing the risk of stroke aneurysms at ischemic heart disease atherosclerosis develops on low-density lipoproteins known as ldls and deposited in the blood vessels ldls will eventually become oxidized and this initiator chronic inflammatory response including leukocytes macrophages and lymphocytes it also activates
A platelet adhesion a critical step in the form of the plaque the platelets aggregated by the binding of adp into the p2 wide 12 receptor which in turn activates gpa and gpa iv receptors that cause cross links with religion the adhesion of the platelets acts to direct the inflammatory cells to impact the platelets also carry a significant amount of stromal derive
Factor one known as sdf one sdf is a potent chemo crime for the cells recruited in the inflammatory response recruited macrophages try to remove the ldl but cannot effectively remove it resulting in the formation of foam cells increasing the mass of the ldl before will apply this plaque is known as after sclerosis drugs such as takapa dean and clopidogrel covalently
Bind to the pt y 12 receptor and stop the platelets from aggravated by oh no pyridine drugs our family irreversible p2 white swirled receptor inhibitors whose structure contains a five-pin ring fused with tetra hydro pyridine ring the first thyroid paradeen drug introduced was de property discovered by sanofi in 1972 while screening for novel anti inflammatory
Molecules its mechanism of action with unknown until after the development of the second generation of drug two coupling was released globally in 1991 but upon its release research started with the development of a novel analog as patients experienced many healers illogical adverse effects some patients experienced huge piña the deficiency in neutrophil cells the
Most prevalent leukocyte in the bloodstream meaning the body’s ability to fight infection is greatly reduced there were also some reported cases of robotic from both sides of a medical error also known as ttp the disorder leading to the formation of small blood clots forming in the smaller blood vessels all over the body these clots result in reduced platelet and
Red blood cell count but ultimately leads to failure of major organs such as the brain along with these serious adverse effects typical side effects including treatment include diarrhea nausea dyspepsia and abdominal pain the novel analyte was developed in the form of cobra dogma which began preclinical trials in 1987 and was released onto the market eleven years
Later the major notice will change the analog was the replacement of a hydrogen with an ester group through changing this group the incidence of ttp jobs for per million patients treated the synthesis of clopidogrel can be completed by many different reactions the one that is shown is generally considered to be the most effective method as determined by sanofi the
Company introduced the double first step in this mechanism with the formation of methyl ester continued refluxing with chlorinated mandalay acid with methyl or in the presence of hydrochloric acid produced methyl ventilate the product forward was chlorinated using thionyl chloride which leads to the formation of alpha chloro acetate the latter was then displaced
With phi e no pyridine through an sn2 reaction which finally leaves the formation of the drugs final structure the problem found in these methods was that their produced racemic mixtures this was problematic because only the dexstar rotary epidural variant was the active compound and a lever rafi papa doble was the inactive compound and had no binding interactions
With the p12 receptor this problem was overcome by treating the racemic mixture with level rotary panful tense of folic acid in acetone for salt 90 this was recrystallized from acetone to graduation and aunt american dexter rotary this is the current where synthesis large something clapping dog is actually approached number and his only active water has undergone
Two sequential oxidations by cytochrome p450 enzymes known as simple types to form as active metabolites firstly copper dogma is transported into the liver via the action of the abc b1 transporter this is where the two sequential oxidation steps occur the first oxidation converts clopidogrel into two oxide copper dr. via the action is sit one a to sip to c19 and
Sit to be six the first step involves the addition of a ketone through the pop side formation the major enzyme responsible is sit 180 the second oxidative step converts to officer clopidogrel into the active metabolite by the action of sip three a four sip to c9 sip three a five sit to v6 a sip to see one line as well as the two upper station steps there is also
An enzyme called ces one who can deactivate clopidogrel two octave epidural and the active metabolite ces one is the major hydrolytic enzyme in the liver and performs approximately 95% of the total hydrolytic activity in the ces one hydrolyzes clever governor two octave and the active metabolite when adp activates obtain aggregation it binds to the p2 y 12 assembly
And p2 y 1 percent both receptors possibly act aggregation to come once activated the gi-protein is bound to the p 2 y 12 assembler is liberated into the g alpha and g beta gamma subunits the g alpha subunit inhibits the dental cyclase reducing the production of cyclic adenosine monophosphate this in turn inhibits protein kinase a and activates vasodilators
Stimulating phosphate protein known as vas vas causes platelet degranulation and from bacchus own production activated gpib and gpio a causing the release of religion this ultimately causes platelet aggregation clopidogrel binds to the p2 wide 12 receptor probaly forming a disulfide bond to the thigh area of the active metabolite and the cysteine residue in the
Binding pocket the adp cannot activate both necessary centers to cause aggravation this means the playlist cannot aggregated for the rest of their life cycle stopping the formation of atherosclerosis kluber dog food is introduced as a safer alternative to the proper dean reducing the serious adverse effects and to improve antiplatelet action but it’s not free
With own adverse effects along with some incidents of ttp patients may experience a hemorrhage which is a blood loss from the circulatory system this can occur either internally or externally through openings such as the north and moe’s incidence of hemorrhage she was aggravated upon jewel administration with aspirin although co-administration increases the
Drugs antiplatelet ability this can explain the adverse effects application of both drugs as an additive effect further inhibiting the ability of platelets to induce platz both those necessary and atherosclerosis this leads to increased bleeding this excessive bleeding to least other common side effects such as easily bruising caused by internal bleeding to the
Interstitial tissues associated with blunt trauma other common side effects include nausea inches there is potential for club with operates interact with other drugs using treatment alternative conditions in cellular models proper doctor was found to inhibit sick to c19 and so may increase plasma concentrations of drugs that metabolizes for example potassium
Channel blocker table you to mind which can lead to adverse systemic side effects in 2009 the fda restricted to put the double administration with proton pump inhibitors and met basalt and isa members own due to its detrimental interactions clapping document is metabolized was active formed by sip to c19 however variety and genotyping leaves the inactivity of the
Drug due to variation in the enzyme it is suggested as much as 14% of patients my cytochrome p450 poor metabolizers seeing minimal benefit from popular pretreatment and oh it’s an almost four times greater risk of cardiovascular related disease in order to combat this inherited clopidogrel resistance the third generation firebird in drug for surgery was brought to
Mark in 2009 the company’s daiichi sankey and eli lilly along with its lion-o coding predecessors subbu is a proton becomes metabolized in a different means due to two significant changes at the general final grading structure observed and papa doug firstly the ester group found in papadopoulou was switched to a ketone group attached to a tri cycle as the parking
Structure making it more metabolically stable secondly the hydrogen at the 2 position 5 union is replaced with an ester group this ester group addition shifted the metabolic process to be conducted per ester as enzymes conquering the issue of sip to c19 variation at this point the sudras metabolism converges with clopidogrel and to property as the non active fire
Elector and undergoes real opening function the sip enzymes
Transcribed from video
Clopidogrel WITHOUT REFERENCES By Ellie Hyde
