Details of Drug Interaction | MecDDI

Drug General Information (ID: DDIQFH04S5)
Drug Name			Terazosin		Drug Info		Nebivolol		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antineoplastics				Antihypertensive Agents
Structure

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

Drug Name		Terazosin				Nebivolol
Mechanism		Hypotensive effects Alpha-1 adrenergic receptor Antagonist				Hypotensive effects Beta-1 adrenergic receptor Antagonist
Key Mechanism Factor 1
		Factor Name		Adrenergic receptor alpha-1				Structure Sequence
		Protein Family		G-protein coupled receptor 1 family
		Protein Function		This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes. 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 Terazosin and Nebivolol

Recommended Action
Management		Caution is advised during coadministration of these agents, particularly when initiating an alpha-blocker in the presence of a beta-blocker, including ophthalmic formulations. Small initial dosages of the alpha-blocker should be considered and gradually titrated to desired effect, while the systemic beta-blocker dosage may also need to be reduced. Hemodynamic responses should be monitored, especially during the first few weeks of therapy. Taking the alpha-blocker at bedtime may minimize the occurrence of orthostatic effects. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

References
1	Chrysant SG "Experience with terazosin administered in combination with other antihypertensive agents." Am J Med 80 (1986): 55-61. [PMID: 2872808]
2	Elliott HL, McLean K, Sumner DJ, Meredith PA, Reid JL "Immediate cardiovascular responses to oral prazosin: effects of concurrent beta-blockers." Clin Pharmacol Ther 29 (1981): 303-9. [PMID: 6110503]
3	Holtzman JL, Kaihlanen PM, Rider JA, Lewin AJ, Spindler JS, Oberlin JA "Concomitant administration of terazosin and atenolol for the treatment of essential hypertension." Arch Intern Med 148 (1988): 539-43. [PMID: 3277569]
4	Pool JL "Combination antihypertensive therapy with terazosin and other antihypertensive agents: results of clinical trials." Am Heart J 122 (1991): 926-31. [PMID: 1678924]
5	Product Information. Xatral (alfuzosin). Sanofi-Synthelabo Canada Inc, Markham, ON.
6	Rubin P, Jackson G, Blaschke T "Studies on the clinical pharmacology of prazosin II: the influence of indomethacin and of propranolol on the action and disposition of prazosin." Br J Clin Pharmacol 10 (1980): 33-9. [PMID: 7397054]
7	Seideman P, Grahnen A, Haglund K, Lindstrom B, Von Bahr C "Prazosin first dose phenomenon during combined treatment with a B-adrenoceptor blocker in hypertensive patients." Br J Clin Pharmacol 13 (1982): 865-70. [PMID: 7093116]
8	Stokes GS, Mennie BA, Gellatly R, Hill A "On the combination of alpha- and beta-adrenoceptor blockade in hypertension." Clin Pharmacol Ther 34 (1983): 576-82. [PMID: 6627819]