An Assessment of the Oral Bioavailability of Three Ca-Channel Blockers Using a Cassette-Microdose Study: A New Strategy for Streamlining Oral Drug Development

2015 ◽  
Vol 104 (9) ◽  
pp. 3154-3161 ◽  
Author(s):  
Shinji Yamashita ◽  
Makoto Kataoka ◽  
Yuki Suzaki ◽  
Hiromitsu Imai ◽  
Takuya Morimoto ◽  
...  
Keyword(s):  
Drug Development ◽  
Oral Bioavailability ◽  
Oral Drug ◽  
Channel Blockers ◽  
Ca Channel ◽  
Ca Channel Blockers ◽  
New Strategy ◽  
Microdose Study

Abstract P024: Pharmacological Treatment of Hypertension and Lv Dysfunction Predictors in ESRD Patients With AV Fistula

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Sayed Tariq ◽  
James Anderson ◽  
Rohit Dhingra ◽  
Mikhail Torosoff
Keyword(s):  
Systolic Function ◽  
Beta Blockers ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Channel Blockers ◽  
Ca Channel ◽  
Av Fistula ◽  
Fistula Surgery ◽  
Lv Dysfunction ◽  
Ca Channel Blockers

Background: Effects of anti-hypertensive medications on left ventricular dimensions and systolic function in patients with arterio-venous (AV) fistulas have not been well investigated. Material and Methods: Medical charts and echocardiograms of 346 patients with AV fistula were reviewed. Of 346, 149 patients had TTE prior to the AV fistula surgery, 197 had TTE after the AV fistula surgery, and 76 patients had TTE before and after the AV fistula surgery. Data on medication use was available in 314 patients. ANOVA, chi-square, and logistic regression tests were employed. Results: In patients scheduled for AV fistula placement, 20% (31/149) patients had systolic dysfunction and 15% (22/142) had increased LV end-diastolic dimensions (LVEDD). Moderate systolic LV dysfunction was observed in 6% (9/149) and additional 8% (12/149) had severe LV dysfunction. Increased LVEDD with some LV dysfunction was noted in 27% (38/142).Following the AV fistula placement, 18% (36/197) of patients had systolic dysfunction and 12% (22/187) had increased LV end-diastolic dimensions (LVEDD). Moderate or severe systolic LV dysfunction was observed in 6% (5/197). LV systolic dysfunction or dilatation was noted in 23% (43/187). Of 314 patients, 63% were on beta-blockers (BB), 25% were on ACE inhibitor or an ARB , 43% on calcium-channel blocker , and 15% on alpha-antagonist . BB, ACEi-ARB, or AA were not associated with increased LVEDD or systolic dysfunction before or after the AV fistula placement. Prior to AV fistula, CCB treatment was not related to LV dilatation (36% in each group, p=0.981) Post AV fistula, CCB treatment was associated with increased LV dimensions (71% vs. 46%, p=0.029) but not LV systolic dysfunction (49% in LV dysfunction vs. 38% in the rest, p=0.446) . This association persisted after adjustment for co-morbidities and demographic parameters. Conclusions: LV systolic dysfunction and/or dilatation are common in patients undergoing AV fistula surgery. Despite decreased use of Ca-channel blockers in patients with LV dysfunction prior to AV fistula, Ca-channel blockers are associated with increased LV dimensions post AV fistula, and probably should be avoided in this vulnerable patient population.

Modulation of Adhesion Molecule Expression on Endothelial Cells by Verapamil and Other Ca++ Channel Blockers

Immunobiology ◽  
1994 ◽  
Vol 191 (1) ◽  
pp. 38-51 ◽  
Author(s):  
Nils P. Hailer ◽  
Roman A. Blaheta ◽  
Sebastian Harder ◽  
Martin Scholz ◽  
Albrecht Encke ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecule ◽  
Channel Blockers ◽  
Ca Channel ◽  
Adhesion Molecule Expression ◽  
Ca Channel Blockers

Effects of Ca Channel Blockers on Ca Transport and Ca ATPase in Skeletal and Cardiac Sarcoplasmic Reticulum Vesicles

1982 ◽  
Vol 4 (6) ◽  
pp. 935-941 ◽  
Author(s):  
Robert A. Colvin ◽  
Neal Pearson ◽  
Frank C. Messineo ◽  
Arnold M. Katz
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Channel Blockers ◽  
Ca Channel ◽  
Cardiac Sarcoplasmic Reticulum ◽  
Ca Transport ◽  
Ca Channel Blockers

scholarly journals The effects of adrenergic agonist and Ca channel blockers on amylase release from rat parotid glands and the role of cyclic nucleotides.

1991 ◽  
Vol 55 ◽  
pp. 217
Author(s):  
Hiroko Nomura ◽  
Rie Tokoyama ◽  
Kikuko Ukai ◽  
Masakatsu Tachibana ◽  
Tatsuro Shigei ◽  
...  
Keyword(s):  
Cyclic Nucleotides ◽  
Channel Blockers ◽  
Ca Channel ◽  
Parotid Glands ◽  
Adrenergic Agonist ◽  
Amylase Release ◽  
Ca Channel Blockers ◽  
Rat Parotid

2-Alkyl-3-Alkylamino-2H-Benzo- and Pyridothiadiazine 1,1-Dioxides: From K+ATP Channel Openers to Ca++ Channel Blockers?

2002 ◽  
Vol 383 (11) ◽  
Author(s):  
R. Ouedraogo ◽  
B. Becker ◽  
S. Boverie ◽  
F. Somers ◽  
M.-H. Antoine ◽  
...  
Keyword(s):  
Channel Blockers ◽  
Ca Channel ◽  
Ca Channel Blockers

“Ca reversal”: Inhibition by submicromolar Ca2+ concentrations of contraction of smooth muscle and its use for assay of Ca channel blockers

1989 ◽  
Vol 20 (2) ◽  
pp. 117-121 ◽  
Author(s):  
Masaatsu-Koujirou Uchida ◽  
Kiyoshi Sakai ◽  
Katsurou Matsuo
Keyword(s):  
Smooth Muscle ◽  
Channel Blockers ◽  
Ca Channel ◽  
Ca Channel Blockers

scholarly journals The Influence of Iontoforesis of Ca Channel Blockers on Pain Relief.

1992 ◽  
Vol 12 (7) ◽  
pp. 749-753
Author(s):  
Akemi MIYAGAWA ◽  
Kazuo TANIGUCHI ◽  
Akio MIZUTANI ◽  
Kazumitsu SENDAYA ◽  
Shigenori YOSHITAKE ◽  
...  
Keyword(s):  
Pain Relief ◽  
Channel Blockers ◽  
Ca Channel ◽  
Ca Channel Blockers

Graded Inhibitory Synaptic Transmission Between Leech Interneurons: Assessing the Roles of Two Kinetically Distinct Low-Threshold Ca Currents

2006 ◽  
Vol 96 (1) ◽  
pp. 218-234 ◽  
Author(s):  
Andrei I. Ivanov ◽  
Ronald L. Calabrese
Keyword(s):  
Synaptic Transmission ◽  
Synaptic Vesicles ◽  
Time Course ◽  
Channel Blockers ◽  
Ca Channel ◽  
Ca Channels ◽  
Inhibitory Synaptic Transmission ◽  
Ca Channel Blockers ◽  
Low Threshold ◽  
Ca Currents

In leeches, two pairs of reciprocally inhibitory heart interneurons that form the core oscillators of the pattern-generating network for heartbeat possess both high- and low-threshold (HVA and LVA) Ca channels. LVA Ca current has two kinetically distinct components (one rapidly activating/inactivating, ICaF, and another slowly activating/inactivating, ICaS) that mediate graded transmission, generate plateau potentials driving burst formation, and modulate spike-mediated transmission between heart interneurons. Here we used different stimulating protocols and inorganic Ca channel blockers to separate the effects of ICaF and ICaS on graded synaptic transmission and determine their interaction and relative efficacy. Ca2+ entering by ICaF channels is more efficacious in mediating release than that entering by ICaS channels. The rate of Ca2+ entry by LVA Ca channels appears to be as critical as the amount of delivered Ca2+ for synaptic transmission. LVA Ca currents and associated graded transmission were selectively blocked by 1 mM Ni2+, leaving spike-mediated transmission unaffected. Nevertheless, 1 mM Ni2+ affected homosynaptic enhancement of spike-mediated transmission that depends on background Ca2+ provided by LVA Ca channels. Ca2+ provided by both ICaF and ICaS depletes a common pool of readily releasable synaptic vesicles. The balance between availability of vesicles and Ca2+ concentration and its time course determine the strength of inhibitory transmission between heart interneurons. We argue that Ca2+ from multichannel domains arising from ICaF channels, clustered near but not directly associated with the release trigger, and Ca2+ radially diffusing from generally distributed ICaS channels interact at common release sites to mediate graded transmission.

scholarly journals The dihydropyridine-sensitive calcium channel subtype in cone photoreceptors.

1996 ◽  
Vol 107 (5) ◽  
pp. 621-630 ◽  
Author(s):  
M F Wilkinson ◽  
S Barnes
Keyword(s):  
Channel Blocker ◽  
Channel Blockers ◽  
Ca Channel ◽  
Ca Channels ◽  
Cone Photoreceptors ◽  
Channel Current ◽  
Ca Channel Blockers ◽  
Voltage Dependent ◽  
P Type ◽  
Ca Channel Current

High-voltage activated Ca channels in tiger salamander cone photoreceptors were studied with nystatin-permeabilized patch recordings in 3 mM Ca2+ and 10 mM Ba2+. The majority of Ca channel current was dihydropyridine sensitive, suggesting a preponderance of L-type Ca channels. However, voltage-dependent, incomplete block (maximum 60%) by nifedipine (0.1-100 microM) was evident in recordings of cones in tissue slice. In isolated cones, where the block was more potent, nifedipine (0.1-10 microM) or nisoldipine (0.5-5 microM) still failed to eliminate completely the Ca channel current. Nisoldipine was equally effective in blocking Ca channel current elicited in the presence of 10 mM Ba2+ (76% block) or 3 mM Ca2+ (88% block). 15% of the Ba2+ current was reversibly blocked by omega-conotoxin GVIA (1 microM). After enhancement with 1 microM Bay K 8644, omega-conotoxin GVIA blocked a greater proportion (22%) of Ba2+ current than in control. After achieving partial block of the Ba2+ current with nifedipine, concomitant application of omega-conotoxin GVIA produced no further block. The P-type Ca channel blocker, omega-agatoxin IVA (200 nM), had variable and insignificant effects. The current persisting in the presence of these blockers could be eliminated with Cd2+ (100 microM). These results indicate that photoreceptors express an L-type Ca channel having a distinguishing pharmacological profile similar to the alpha 1D Ca channel subtype. The presence of additional Ca channel subtypes, resistant to the widely used L-, N-, and P-type Ca channel blockers, cannot, however, be ruled out.

Sign in / Sign up

Export Citation Format

Share Document