Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIJAX8IFW)
  Drug Name Dyphylline Drug Info Nadolol Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Bronchodilators Antihypertensive Agents
  Structure

 Mechanism of Dyphylline-Nadolol Interaction (Severity Level: Major)
     Antagonize the effect of bronchodilators Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Dyphylline Nadolol
      Mechanism Bronchodilator effects
Phosphodiesterase 3A  Antagonist 		Bronchospasm effects
Beta-2 adrenergic receptor  Antagonist
      Key Mechanism Factor 1
Factor Name Phosphodiesterase 3A
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Structure Sequence
MAVPGDAARVRDKPVHSGVSQAPTAGRDCHHRADPASPRDSGCRGCWGDLVLQPLRSSRKLSSALCAGSLSFLLALLVRLVRGEVGCDLEQCKEAAAAEEEEAAPGAEGGVFPGPRGGAPGGGARLSPWLQPSALLFSLLCAFFWMGLYLLRAGVRLPLAVALLAACCGGEALVQIGLGVGEDHLLSLPAAGVVLSCLAAATWLVLRLRLGVLMIALTSAVRTVSLISLERFKVAWRPYLAYLAGVLGILLARYVEQILPQSAEAAPREHLGSQLIAGTKEDIPVFKRRRRSSSVVSAEMSGCSSKSHRRTSLPCIPREQLMGHSEWDHKRGPRGSQSSGTSITVDIAVMGEAHGLITDLLADPSLPPNVCTSLRAVSNLLSTQLTFQAIHKPRVNPVTSLSENYTCSDSEESSEKDKLAIPKRLRRSLPPGLLRRVSSTWTTTTSATGLPTLEPAPVRRDRSTSIKLQEAPSSSPDSWNNPVMMTLTKSRSFTSSYAISAANHVKAKKQSRPGALAKISPLSSPCSSPLQGTPASSLVSKISAVQFPESADTTAKQSLGSHRALTYTQSAPDLSPQILTPPVICSSCGRPYSQGNPADEPLERSGVATRTPSRTDDTAQVTSDYETNNNSDSSDIVQNEDETECLREPLRKASACSTYAPETMMFLDKPILAPEPLVMDNLDSIMEQLNTWNFPIFDLVENIGRKCGRILSQVSYRLFEDMGLFEAFKIPIREFMNYFHALEIGYRDIPYHNRIHATDVLHAVWYLTTQPIPGLSTVINDHGSTSDSDSDSGFTHGHMGYVFSKTYNVTDDKYGCLSGNIPALELMALYVAAAMHDYDHPGRTNAFLVATSAPQAVLYNDRSVLENHHAAAAWNLFMSRPEYNFLINLDHVEFKHFRFLVIEAILATDLKKHFDFVAKFNGKVNDDVGIDWTNENDRLLVCQMCIKLADINGPAKCKELHLQWTDGIVNEFYEQGDEEASLGLPISPFMDRSAPQLANLQESFISHIVGPLCNSYDSAGLMPGKWVEDSDESGDTDDPEEEEEEAPAPNEEETCENNESPKKKTFKRRKIYCQITQHLLQNHKMWKKVIEEEQRLAGIENQSLDQTPQSHSSEQIQAIKEEEEEKGKPRGEEIPTQKPDQ
Gene Name PDE3A
Uniprot ID PDE3A_HUMAN
KEGG Pathway hsa:5139
Protein Family Cyclic nucleotide phosphodiesterase family
Protein Function
Cyclic nucleotide phosphodiesterase with specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes (PubMed:1315035, PubMed:8695850, PubMed:8155697, PubMed:25961942). Has also activity toward cUMP (PubMed:27975297). Independently of its catalytic activity it is part of an E2/17beta-estradiol-induced pro-apoptotic signaling pathway. E2 stabilizes the PDE3A/SLFN12 complex in the cytosol, promoting the dephosphorylation of SLFN12 and activating its pro-apoptotic ribosomal RNA/rRNA ribonuclease activity. This apoptotic pathway might be relevant in tissues with high concentration of E2 and be for instance involved in placenta remodeling (PubMed:31420216, PubMed:34707099).
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      Key Mechanism Factor 2
Factor Name Adrenergic receptor beta-2
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Structure Sequence
MGQPGNGSAFLLAPNGSHAPDHDVTQERDEVWVVGMGIVMSLIVLAIVFGNVLVITAIAKFERLQTVTNYFITSLACADLVMGLAVVPFGAAHILMKMWTFGNFWCEFWTSIDVLCVTASIETLCVIAVDRYFAITSPFKYQSLLTKNKARVIILMVWIVSGLTSFLPIQMHWYRATHQEAINCYANETCCDFFTNQAYAIASSIVSFYVPLVIMVFVYSRVFQEAKRQLQKIDKSEGRFHVQNLSQVEQDGRTGHGLRRSSKFCLKEHKALKTLGIIMGTFTLCWLPFFIVNIVHVIQDNLIRKEVYILLNWIGYVNSGFNPLIYCRSPDFRIAFQELLCLRRSSLKAYGNGYSSNGNTGEQSGYHVEQEKENKLLCEDLPGTEDFVGHQGTVPSDNIDSQGRNCSTNDSLL
Gene Name ADRB2
Uniprot ID ADRB2_HUMAN
KEGG Pathway hsa:154
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. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-fold greater affinity than it does norepinephrine.
    Click to Show/Hide
      Mechanism Description
  • Antagonize the effect of Dyphylline when combined with Nadolol 

Recommended Action
      Management Oral and ophthalmic nonselective beta-blockers (e.g., carteolol, carvedilol, levobunolol, metipranolol, nadolol, oxprenolol, penbutolol, pindolol, propranolol, sotalol, and timolol) are considered contraindicated in patients with bronchospastic diseases. Cardioselective beta-blockers should generally be avoided, or used with extreme caution if no other alternatives are available and the benefits outweigh the risks of potentially severe bronchospasm. If patients do receive this combination, they should be closely monitored for increased serum theophylline levels but decreased bronchodilatory effectiveness.

References
1 Lombardi TP, Bertino JS, Goldberg A, Middleton E, Slaughter RL "The effects of a beta-2 selective adrenergic agonist and a beta- nonselective antagonist on theophylline clearance." J Clin Pharmacol 27 (1987): 523-9. [PMID: 2888791]
2 Mue S, Sasaki T, Shibahara S, et alT "Influence of metoprolol on hemodynamics and respiratory function in asthmatic patients." Int J Clin Pharmacol Biopharm 17 (1979): 346-50. [PMID: 489201]
3 Upton RA "Pharmacokinetic interactions between theophylline and other medication (Part II)." Clin Pharmacokinet 20 (1991): 135-50. [PMID: 1709398]