Details of Drug Interaction | MecDDI

Drug General Information (ID: DDIRYPKTA3)
Drug Name			Treprostinil		Drug Info		Penbutolol		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antihypertensive Agents				Antihypertensive Agents
Structure

Mechanism of Treprostinil-Penbutolol Interaction (Severity Level: Moderate)
Additive hypotensive effects Click to Show/Hide Mechanism Graph

Drug Name		Treprostinil				Penbutolol
Mechanism		Antihypertensive agent Prostaglandin receptor Agonist				Antihypertensive agent Beta-1 adrenergic receptor Antagonist
Key Mechanism Factor 1
		Factor Name		Prostaglandin D2 receptor				× Structure Sequence MKSPFYRCQNTTSVEKGNSAVMGGVLFSTGLLGNLLALGLLARSGLGWCSRRPLRPLPSVFYMLVCGLTVTDLLGKCLLSPVVLAAYAQNRSLRVLAPALDNSLCQAFAFFMSFFGLSSTLQLLAMALECWLSLGHPFFYRRHITLRLGALVAPVVSAFSLAFCALPFMGFGKFVQYCPGTWCFIQMVHEEGSLSVLGYSVLYSSLMALLVLATVLCNLGAMRNLYAMHRRLQRHPRSCTRDCAEPRADGREASPQPLEELDHLLLLALMTVLFTMCSLPVIYRAYYGAFKDVKEKNRTSEEAEDLRALRFLSVISIVDPWIFIIFRSPVFRIFFHKIFIRPLRYRSRCSNSTNMESSL
		Gene Name		PTGDR
		Uniprot ID		PD2R_HUMAN
		KEGG Pathway		hsa:5729
		Protein Family		G-protein coupled receptor 1 family
		Protein Function		Receptor for prostaglandin D2 (PGD2). The activity of this receptor is mainly mediated by G(s) proteins that stimulate adenylate cyclase, resulting in an elevation of intracellular cAMP. A mobilization of calcium is also observed, but without formation of inositol 1,4,5-trisphosphate (By similarity). Involved in PLA2G3-dependent maturation of mast cells. PLA2G3 is secreted by immature mast cells and acts on nearby fibroblasts upstream to PTDGS to synthesize PGD2, which in turn promotes mast cell maturation and degranulation via PTGDR (By similarity). Click to Show/Hide
Key Mechanism Factor 2
		Factor Name		Adrenergic receptor beta-1				× Structure Sequence MGAGVLVLGASEPGNLSSAAPLPDGAATAARLLVPASPPASLLPPASESPEPLSQQWTAGMGLLMALIVLLIVAGNVLVIVAIAKTPRLQTLTNLFIMSLASADLVMGLLVVPFGATIVVWGRWEYGSFFCELWTSVDVLCVTASIETLCVIALDRYLAITSPFRYQSLLTRARARGLVCTVWAISALVSFLPILMHWWRAESDEARRCYNDPKCCDFVTNRAYAIASSVVSFYVPLCIMAFVYLRVFREAQKQVKKIDSCERRFLGGPARPPSPSPSPVPAPAPPPGPPRPAAAAATAPLANGRAGKRRPSRLVALREQKALKTLGIIMGVFTLCWLPFFLANVVKAFHRELVPDRLFVFFNWLGYANSAFNPIIYCRSPDFRKAFQRLLCCARRAARRRHATHGDRPRASGCLARPGPPPSPGAASDDDDDDVVGATPPARLLEPWAGCNGGAAADSDSSLDEPCRPGFASESKV
		Gene Name		ADRB1
		Uniprot ID		ADRB1_HUMAN
		KEGG Pathway		hsa:153
		Protein Family		G-protein coupled receptor 1 family
		Protein Function		Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity. Mediates Ras activation through G(s)-alpha- and cAMP-mediated signaling. Involved in the regulation of sleep/wake behaviors (PubMed:31473062). Click to Show/Hide
Mechanism Description		Additive hypotensive effects by the combination of Treprostinil and Penbutolol

Recommended Action
Management		While therapies that target the prostacyclin pathway have been used in combination with diuretics, antihypertensives, or other vasodilators in the management of pulmonary arterial hypertension, caution is recommended if they must be administered concurrently. If these drugs are used together, it is generally recommended that blood pressure be measured more frequently until a stable blood pressure pattern is observed. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their doctor if they experience dizziness, lightheadedness, syncope, orthostatic hypotension, or tachycardia.

References
1	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
2	Product Information. Flolan (epoprostenol). Glaxo Wellcome, Research Triangle Park, NC.
3	Product Information. Remodulin (treprostinil). United Therapeutics Corp, Silver Spring, MD.