A cryptic and intriguing connection exists between Methotrexate and Ticagrelor. It's sparkling ✨✨
Here is a short and sweet 🧵
@rabihmgeha @DxRxEdu @rav7ks @tony_breu @Sharminzi @jackpenner @DrCindyCooper @sargsyanz @SatyaPatelMD @ASanchez_PS @AaronGoodman33 #MedTwitter
Here is a short and sweet 🧵
@rabihmgeha @DxRxEdu @rav7ks @tony_breu @Sharminzi @jackpenner @DrCindyCooper @sargsyanz @SatyaPatelMD @ASanchez_PS @AaronGoodman33 #MedTwitter
Methorxate's and Ticagrelor's paths cross each other at the intersection named ADENOSINE
Let's dissect Adenosine receptors
> A1R and A3R (Gi->⬇️cAMP): ⬇️AV node conduction, Bronchoconstricition, ⬆️proinflammatory cytokines from leukocytes
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Let's dissect Adenosine receptors
> A1R and A3R (Gi->⬇️cAMP): ⬇️AV node conduction, Bronchoconstricition, ⬆️proinflammatory cytokines from leukocytes
#MedTwitter
A2A and A2B receptors (Gs- ⬆️cAMP > PKA pathway)
- Bronchodilation
- Coronary vasodilation
- ⬇️ proinflammatory cytokines from leukocytes
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- Bronchodilation
- Coronary vasodilation
- ⬇️ proinflammatory cytokines from leukocytes
#MedTwitter
Methotrexate's mechanism of action in RA:
- Inhibition of Aminoimidazole Caboxamide Ribonucleotide Transformylase (AICART) which in turn inhibits Adenosine deaminase -> ⬆️⬆️Adenosine in Extracellular space -> Activation of A2AR and A2BR on leukocytes -> ⬇️ Inflammation
- Inhibition of Aminoimidazole Caboxamide Ribonucleotide Transformylase (AICART) which in turn inhibits Adenosine deaminase -> ⬆️⬆️Adenosine in Extracellular space -> Activation of A2AR and A2BR on leukocytes -> ⬇️ Inflammation
Ticagrelor & dyspnea
Inhibits sodium-independent equilibrative nucleoside transporters->⬇️adenosine reuptake in cells-> ⬆️adenosine in ECF-> A1R on pulmonary vagal fiber and bronchi-> Bronchospasm
Blocks P2Y12 receptors on neurons and glia-> Central chemoreflex-> Cheyne-stokes
Inhibits sodium-independent equilibrative nucleoside transporters->⬇️adenosine reuptake in cells-> ⬆️adenosine in ECF-> A1R on pulmonary vagal fiber and bronchi-> Bronchospasm
Blocks P2Y12 receptors on neurons and glia-> Central chemoreflex-> Cheyne-stokes
Summary
- Methotrexate: ⬆️ Adenosine in extracellular space-> ⬇️leukocyte activity-> ⬇️inflammation
- Ticagrelor: ⬆️Adenosine in ECF-> Bronchoconstriction, ⬇️P2Y12 on neurons and glia-> Cheyne stokes like respirations-> Dyspnea
It's all an intricate interplay of receptors.
- Methotrexate: ⬆️ Adenosine in extracellular space-> ⬇️leukocyte activity-> ⬇️inflammation
- Ticagrelor: ⬆️Adenosine in ECF-> Bronchoconstriction, ⬇️P2Y12 on neurons and glia-> Cheyne stokes like respirations-> Dyspnea
It's all an intricate interplay of receptors.
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