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Antimetabolites Simplified

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In this video I will be discussing about various antimetabolites such as Sulfamethoxazole & Trimethoprim (cotrimoxazole), mechanism of action, bacterial folic acid metabolism, uses of folic acid, phenomenon of sequential blockade, dose concentration ratio of sulfamethoxazole & trimethoprim etc

And hi in this video is to get few antimetabolites so we start with the question right so which of the following drugs is often combined with sulfamethoxazole for treatment of respiratory tract and urinary tract infections and options amoxicillin ciprofloxacin clindamycin metronidazole and time with operon so we have a combination of sulfamethoxazole with

Trimethoprim it’s called as cotrimoxazole right so we just write down here code try mock the goal it’s a combination of sulfamethoxazole they sulfonamide and trimethoprim so in this video let’s discuss the important points pertaining to both sulfamethoxazole as well as trimethoprim so trimethoprim it’s basically diamino pyramidal so we just write down here this

Trimethoprim chemically it is diamino pyramidal and it is related to anti-malarial drug called pyrimethamine right so this trimethoprim has a selective affinity against dihydrofolate reductase enzyme it inhibits this enzyme present in the bacterial folate metabolism if you observe this flowchart here we have para maana benzoic acid which forms the hydra folic

Acid in terms of folic synthase and this internal presence of the hydrophilic detectives forms tetrahydrofolate acid right so this tetrahydrofolate acid it’s mainly used for production of various cofactors that are essential for synthesis of either dna rna or even proteins right so this folic acid metabolism is very much essential it happens in bacteria as well

As in humans right so the advantage of using this trimethoprim is that it has more than 50,000 times greater affinity for this dihydrofolate reductase present within the bacterial folate metabolism cycling metabolic cycle right so it has a very selective action against the bacterial the hydrophilic predictive right so that briefly about trimethoprim and also

This combination of sulfamethoxazole and trimethoprim was introduced way back in 1969 so the advantage of this combination is that as you can see here the sulfonamides usually inhibit this folate synthase enzyme whereas trimethoprim inhibits the next sequence right so there is sequential blockers of folic acid synthesis as a result these drugs are more effective

Against various bacteria which have resistance to one of the combinations either sulfonamide or trimethoprim right and most importantly the reason why we are selecting only sulfamethoxazole in combination with trimethoprim is that the half-life of both these drugs is almost the same the half-life of sulfamethoxazole as well as trimethoprim is approximately in right

And also these drugs are given in a fixed dose combination it’s a fixed dose combination in the sense the dose ratio between sulfamethoxazole and trimethoprim is approximately filed these two one so five parts of sulfamethoxazole with one part of trimethoprim and the reason why we are giving a lesser concentration let those of this time a problem is that it has

Greater distribution in the tissue greater volume of distribution and it achieves lower plasma concentration right so for this reason we are giving it in a ratio of five is to one right so this code rhyme ox is on it is a fixed combination of sulfamethoxazole and trimethoprim which has the sequential blockage in the bacterial folate metabolism and these drugs is

Selective to the bacterial folate enzyme rather than the mammalian enzyme so we have this folic acid cycle even in mammal in cell and they are relatively undisturbed so ultimately to this folic acid metabolism there is formation of tetrahydrofolate gas which is essential for formation of various cofactor which are essential for synthesis of various nucleic acids

Ultimately what’s happening when we are using these drugs they are blocking metabolite so these are considered as anti metabolize right and also remember that this sulfonamides they competitively inhibit bullets in this in the sense they structurally resemble papa and the compete with baba for folate synthase and in the process block bullets investor competitive

Inhibition whereas trimethoprim inhibits dihydrofolate reductase through competitive antagonism so these are some of the important points pertaining to ninety metabolites such as sulfonamides as well as trimethoprim you

Transcribed from video
Antimetabolites Simplified By MDS Entrance Lectures by Sai Naveen Kumar Pilli