title: Amiloride-quinidine interaction: adverse outcomes.
abstract: OBJECTIVE
  Previous studies have reported beneficial antiarrhythmic effects when selected drugs were combined. The purpose of this study was to assess whether a favorable interaction would occur with amiloride and quinidine.
  
  
  METHODS
  The antiarrhythmic and electrophysiologic effects of quinidine alone and in combination with amiloride were assessed in 10 patients with inducible sustained ventricular tachycardia. Parallel electrophysiologic studies assessed this drug combination in guinea pig papillary muscle.
  
  
  RESULTS
  None of the patients had adverse effects during quinidine monotherapy. However, seven of 10 patients had adverse responses to the combination treatment: three patients had suppression of inducible ventricular tachycardia during quinidine monotherapy but had sustained ventricular tachycardia induced during combination treatment; three other patients had somatic side effects that resulted in discontinuation of the combination therapy but were absent during quinidine monotherapy; and one patient had 12 episodes of sustained ventricular tachycardia during this combination therapy. The patient had no such response during monotherapy. Surface QRS duration was significantly more prolonged during combination therapy than during monotherapy. Parallel electrophysiologic effects assessed this drug combination in guinea pig papillary muscle. The combination of amiloride (1 mumol/L) and quinidine (10 mumol/L) synergistically decreased the maximum rate of rise of phase 0 of the action potential (Vmax) (43 +/- 12 V/sec) compared with quinidine alone (24 +/- 9 V/sec) because of a greater degree of tonic block of Vmax (14% +/- 6%) as compared to quinidine alone (3% +/- 3%) with no significant change in action potential duration.
  
  
  CONCLUSIONS
  Amiloride exaggerates the effects of quinidine on QRS duration in patients and on Vmax during in vitro study, which implies that the proarrhythmic effect of the combination of amiloride and quinidine may be associated with synergistic increase in sodium channel blockade.
authors.affiliation: Cardiovascular Research Group, University of Calgary, Alberta, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: R S
authors.initials: RS
authors.lastname: Sheldon
authors.forename: L B
authors.initials: LB
authors.lastname: Mitchell
authors.forename: D G
authors.initials: DG
authors.lastname: Wyse
authors.forename: A M
authors.initials: AM
authors.lastname: Gillis
authors.forename: N
authors.initials: N
authors.lastname: Chiamvimonvat
authors.forename: H J
authors.initials: HJ
authors.lastname: Duff
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000368:Aged; D000584:Amiloride / Q000009:adverse effects* / Q000627:therapeutic use; D000818:Animals; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D008875:Middle Aged; D010210:Papillary Muscles / Q000187:drug effects* / Q000503:physiopathology; D011802:Quinidine / Q000009:adverse effects* / Q000627:therapeutic use; D017180:Tachycardia, Ventricular / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology
chemical_list: D000584:Amiloride; D011802:Quinidine