Mercaptopurine is an antimetabolite that shows drug interaction with Allopurinol, the later is used as prophylactic in case of gout. How this interaction is possible?
Hi everyone today in this video let us discuss about the dragon traction between mercaptopurine and yellow purinol what is illopiranol yellowpenel is one of the antigoutaisent and this drug can be used in the treatment of primary gout where there is an increased levels of uric acid resulting in the hyperuricemia and these razor levels of uric acid can form
The crystals within the joints producing the gouty arthritis so primary gravity is a metabolic disorder where there is an increased production of the uric acid in such case a low pnl can inhibit the sense of the uric acid thereby it can decrease the uric acid levels similarly this drug can also be used in the treatment of secondary gout where there is again
Increased levels of uric acid within the plasma but this may be due to any other disorders diseases and any other conditions like the drug uses which may increase uric acid levels for example the patients having the diabetes as well as the renal failure there may be a chance of increased levels of uric acid within the body in such case again yellow panel can
Be used to control the uric acid levels but interestingly here this yellow piano is not used for the aq treatment of gout it is used as a prophylactic because this drug is going to inhibit the sense of the uric acid which takes some reasonable time to control the uric acid levels to the normal level and this drug is not increasing the excretion of the uric acid
But it is going to inhibit the sins of the uric acid similarly this yellow penile can also be used as a mouthwash when this cellophase is going to be used this die can control the mucositis produced by excessive production of the purines and many of the times yellow penal can be combined with the anti-cancer agents in order to control the mucositis for example
5-fluorouracil is one of the drag which acts as an anti-metabolite and it can produce a mucositis as one of the important side effect so in such conditions elephant or mouthwash can be given in order to control the mucositis so these are the various indications of the yellow pyranol now let us see the structure of aleppyranol so this is the structure of the yellow
Pyranol and what is the ring system it is having even it is having some structural similarity but it is not having the pure rendering system for example this is one of the structure of purine which is nothing but the hypoxanthine and if we compare the yellow penile and purine the purine is having the nitrogen at first and third portion whereas yellow penile is
Having the nitrous at first and second position so there is a small change in the relative position of the nitrogens that’s why la penal is not a purine but it is a pyrozolo pyrimidine the pyrazole ring is attached with the pyrimidine ring so it is a pyrazolopyridine but even with a small difference in the structure still it’s having some structural similarity
With the purines so it can inhibit the metabolism of the purines so one of the important purine is the hypoxanthine this hypoxanthine is going to count to one of the metabolite xanthine by oxidation process so here you can observe an extra keto group is present so it is an oxidation reaction so the enzyme is nothing but the xanthane oxidase so xanthan oxidizes
Response for the oxidation of the hypoxanthin to the oxanthine and then this xanthan is going to be converted into uric acid which is the end product of the metabolism of the purines within the mammalians and again here you can observe an extra keto group is going to be introduced so this is again an oxidation reaction mediated by same enzyme xanthine oxidase
Enzyme in this way xanthine oxidase can convert the hypoxanthin to the uric acid by two-step process and here the silicone can inhibit the xanthine oxidase activity at these two steps thereby can control the formation of uric acid from the hypoxanthine in this way elopino can reduce the uric acid levels by inhibition of the xanthan oxidizing joint now let us see
How the cellophanol interacts with the second drag mercaptopurine what is mercaptopurine mercaptopurine within the name we can observe a purine is there so it is a purine analog and this drug acts as an antimetabolite so mercaptopurine can act as a false purine analog which can inhibit the denom versions of the purines thereby it can interfere with the nucleic
Acid senses so this drug acts as an anti-cancer agent because it acts as an antimetabolite and this drug is used particularly in the treatment of acute lymphatic leukemia so in the lymphocytic leukemia mercaptopurine can be given along with the other drugs and another related drug is the agile thioprin this agitator is one of the pro rag which can be converted
Into mercaptopurine so azathioprine is a product of the six mercaptopurine so this is a structure of six mercaptopurine which can exist as this form so here the sulfur may be present as a thial group or thio group so since the thyroid group is present at the sixth position it is called as six mercaptopurine now let us see how this six mercaptopurin acts as an
Antimetabolite and how it can interact with the illoperinol so six mercafter purine can be converted into one of the false intermediate this drug is having only nucleic acid base which can be attached with the sugar moiety so it can undergo one of the reactions such that it is going to form a intermediate like this what is the name of this intermediate so this
Metabolite is nothing but the sixth ionosinic acid so here a sugar moiety is attached with a phosphate group and this reaction is going to be mediated by one of the enzyme hypoxanthine guanine phosphorus riboseal transferase so this enzyme is response for the transfer of the phosphor ribosyl group that is a sugar moiety along with one phosphate group to this
Hypoxanthin and guanine moieties so hypoxanthine guanine phosphorus ribosyltransferase which is commonly known as hgprt so this enzyme converts the six mercaptopurine into the sixth ionozinic acid which acts as a false metabolite thereby inhibits the sins of pure nucleotides now let us see in detail the different steps involved in this conversion this drug is
Initially converted into six thio inosinic acid which is commonly known as 60 imp so this is the sixth thio inosin monophosphate so this reaction is going to be mediated by one of the enzyme hgprt hypoxanthine guanine phosphor ribosyltransferase then what is the role of this sixth io inosinic acid this intermediate acts as a false metabolite therefore it inhibits
The activity of the imp ionosine monophosphate normally imp can be converted into amp adrenosine monophosphate by two sequential steps and this imp can also be common to xanthan monophosphate by single step which are acting like the pure nucleotides but here this sixth ionosinic acid is going to inhibit the acute of the imp so that the purine nucleotides are
Not going to be synthesized at the same time this sixth ionosinic acid is going to be converted into enter metabolite 6 tx mp 6th thiox xanthan monophosphate by one of the enzyme inosin monophosphate dehydrogenase when two hydrogens are going to be removed imp can be current to xmp six thio inosin monophosphate is current to sixth io xanthan monophosphate which is
Not having the activity of xanthan monophosphate and finally this sixth dioxanethine monophosphate can be converted into six thio guanine monophosphate which is commonly known as six thio guanine by one of the enzyme xmp aminogens in this way six thianosinic acid can be come to six thio guanine which is responsible for the cytotoxicity now here six thio inosinic
Acid is one of the important intermediate formed from the six mercaptopurine which inhibits the biosense of pure nucleotides therefore it acts as anti-metabolite but here in all these steps we cannot observe any enzyme like xanthan oxidase so how this elephant can interact with this six mercaptopurine so yellow penal is not interacting at the activation of the
Six meg cap top urine instead it is going to interact with the metabolism of the six megapurine resulting in the accumulation of the strike now six mercaptopurine can be metabolized to six dioxanthine and this six thiojanthin can be converted into six thiouric acid in this way just like the purines this six mercaptopurine can be converted into uric acid by the
Same enzyme xanthine oxidase enzyme so here elopinol can inhibit these two steps thereby it can inhibit the conversion of the six mercaptopurine into the sixth or uric acid and when this pathway somewhat inhibited then this truck can be more converted into six thio ionosinic acid and this intermediate mainly acts as an antimatter blood thereby inhibits the pure
Instances resulting in the anti-cancer activity similarly this intermediate can also be connected to ender metabolite 6-methyl thiocenic acid which is one more active metabolite which can again shows the anti-cancer activity in this way yellow purenol can increase the acute of the six mercapta purine by inhibition of the xanthan oxidase pathway which converts this
Merceptopurine to six thiouric acid that’s why whenever this yellow pineal is given concomitantly with this six mercaptopurin the dose of this mercaptopurin should be somewhat reduced in order to prevent the toxicity so that’s about this interaction hope you have enjoyed this video if you like this video please subscribe to our channel share this video with your
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Transcribed from video
Mercaptopurine and Allopurinol drug interaction By egpat
