Calcium and neostigmine antagonize gentamicin, but augment clindamycin-induced tetanic fade in rat phrenic nerve-hemidiaphragm preparations

Lee, Soo-Il; Lee, Jong‐Hwan; Lee, Seung Cheol; Lee, Jung Moo; Lee, Ji Hyeon

doi:10.1007/s00540-008-0646-y

Cited by 11 publications

(15 citation statements)

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“…Clindamycin causes muscle relaxation alone [17,22], enhances the activities of d-tubocurarine and pancuronium [11] in addition to prolonging the rapacuronium-induced neuromuscular block [14]. Consistent with what has been observed for other muscle relaxants, the results of this study indicate that clindamycin augments rocuronium-induced neuromuscular block.…”

Section: Discussionsupporting

confidence: 82%

“…Van Nyhuis et al [15] observed that neostigmine augments the neuromuscular block caused by polymyxin B alone as well as in combination with pancuronium or d-tubocurarine. The antagonism by neostigmine and calcium may be incomplete at reversing the clindamycin-induced block [11] even though neostigmine augments clindamycin-induced neuromuscular block [17]. However, the results of this study indicate that neostigmine shifts the concentration-response curves of rocuronium to the right in the presence of clindamycin, which is a phenomenon that has not been observed for polymyxin B.…”

Section: Discussionmentioning

confidence: 73%

“…Single-twitch tension was calculated based on the average of three consecutive single-tension measurements. The effective concentrations (EC) of rocuronium or clindamycin for ST (percent reduction of control) and TF (tetanic fade: percent increase of TF) were determined by the probit model [17] and the concentration-response curves of rocuronium and clindamycin were obtained for each pre-treatment.…”

Section: Methodsmentioning

confidence: 99%

“…It has been demonstrated that neostigmine augments clindamycin-induced neuromuscular block [17]; however, it remains unclear whether neostigmine enhances the neuromuscular block that is caused by a combination of rocuronium and clindamycin.…”

Section: Introductionmentioning

confidence: 99%

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The antagonistic effect of neostigmine on rocuronium-, clindamycin-, or both-induced neuromuscular blocking in the rat phrenic nerve-hemidiaphragm

Kim

Lee

Chung

et al. 2011

Korean J Anesthesiol

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BackgroundNeostigmine augments clindamycin-induced neuromuscular block and antagonizes rocuronium-induced neuromuscular block; however, it remains unclear whether neostigmine enhances the neuromuscular blocking (NMB) that is caused by combinations of rocuronium and clindamycin. The intent of this study was to determine whether neostigmine potentiates the muscle relaxation that is induced by combinations of rocuronium and clindamycin and to estimate whether both clindamycin and rocuronium have synergistic actions on NMB.MethodsForty-one left phrenic nerve-hemidiaphragms (from male Sprague-Dawley rats, 150-250 g) were mounted in Krebs solution. Three consecutive single twitches (ST, 0.1 Hz) and one tetanic tension (50 Hz for 1.9 s) were obtained for each increase in concentration of rocuronium or clindamycin. The concentrations of rocuronium were cumulatively increased until an 80% to 90% reduction in ST was attained in the Krebs solutions pre-treated with 0 (n = 5), 0.1 (n = 1), 0.25 (n = 1), 0.5 (n = 4), or 1.0 (n = 1) mM clindamycin or with 0 (n = 4), 0.1 (n = 1), 0.5 (n = 5), 1.0 (n = 5), or 2.0 (n = 4) mM clindamycin in combination with 250 nM neostigmine, and so were the concentrations of clindamycin in the Krebs solutions pre-treated with 0 (n = 6) or 250 nM (n = 6) neostigmine.ResultsClindamycin increased the potency of rocuronium for ST and tetanic fade, irrespective of the presence of neostigmine. Neostigmine shifted the concentration-response curve of rocuronium to the right in the presence or absence of clindamycin. The interaction between rocuronium and clindamycin was synergistic when clindamycin concentrations were in excess of 0.5 mM, irrespective of the presence of neostigmine.ConclusionsNeostigmine may partially antagonize the neuromuscular block that is induced by a combination of clindamycin and rocuronium. Clinicians are advised to be aware that clindamycin synergistically increases the degree of rocuronium-induced neuromuscular block, even when neostigmine is present.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 73%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The antagonistic effect of neostigmine on rocuronium-, clindamycin-, or both-induced neuromuscular blocking in the rat phrenic nerve-hemidiaphragm

Kim

Lee

Chung

et al. 2011

Korean J Anesthesiol

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“…97 For example, the oxazolidinones and aminoglycosides are inhibitors of bacterial ribosomes but some of their off-target effects appear to be directly based on inhibition of human mitochondrial ribosomes. 98 The mechanism behind this is the secondary structure of the A site with the A1555G or C1494T human mitochondrial mutation mimics the analogous secondary structure of the 30S bacterial ribosome A site. 99 Similarly, ionophores have been shown to induce ion channel dysregulation in myocytes associated with adverese effects such as myopathies.…”

Section: Off-target Effects Of Antimicrobialsmentioning

confidence: 99%

A tug-of-war between the host and the pathogen generates strategic hotspots for the development of novel therapeutic interventions against infectious diseases

et al. 2015

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Adverse Effects of Antimicrobials via Predictable or Idiosyncratic Inhibition of Host Mitochondrial Components

Barnhill

Brewer

Carlson

2012

Antimicrob Agents Chemother

108

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This minireview explores mitochondria as a site for antibiotic-host interactions that lead to pathophysiologic responses manifested as nonantibacterial side effects. Mitochondrion-based side effects are possibly related to the notion that these organelles are archaic bacterial ancestors or commandeered remnants that have co-evolved in eukaryotic cells; thus, this minireview focuses on mitochondrial damage that may be analogous to the antibacterial effects of the drugs. Special attention is devoted to aminoglycosides, chloramphenicol, and fluoroquinolones and their respective single side effects related to mitochondrial disturbances. Linezolid/oxazolidinone multisystemic toxicity is also discussed. Aminoglycosides and oxazolidinones are inhibitors of bacterial ribosomes, and some of their side effects appear to be based on direct inhibition of mitochondrial ribosomes. Chloramphenicol and fluoroquinolones target bacterial ribosomes and gyrases/topoisomerases, respectively, both of which are present in mitochondria. However, the side effects of chloramphenicol and the fluoroquinolones appear to be based on idiosyncratic damage to host mitochondria. Nonetheless, it appears that mitochondrion-associated side effects are a potential aspect of antibiotics whose targets are shared by prokaryotes and mitochondria-an important consideration for future drug design. SIDE EFFECTS OF ANTIBACTERIAL DRUGST he desired activity of an antibiotic is to kill or prevent the growth of offending pathogenic bacteria, and yet these drugs may impact the host in an injurious manner. Generalized adverse events are common to most antibiotics (e.g., gastrointestinal distress with any oral antibacterial drug), but certain antibiotics are associated with specific effects (Table 1). Some adverse events are mild, e.g., yellowing of the teeth for tetracyclines (77, 79), increased intestinal peristalsis related to erythromycin therapy (7, 67), and reversible orange discoloration of skin and body fluids as observed with rifampin treatment (23, 31). Altered drug metabolism (106) is a common side effect that, in the absence of co-drug therapy, could also be considered mild. More serious side effects include photosensitivity (44) and anaphylactoid reactions (34) observed with many agents, ototoxicity (27, 83) following aminoglycoside therapy, chondrotoxicity (85, 88) and retinopathy (95) with fluoroquinolones, neuropathies associated with metronidazole (30, 107) and linezolid (15), and lactic acidosis and serotonin syndrome attributed to linezolid (21, 61). Other consequences can be severe or even devastating such as: the dermonecrolytic Stevens-Johnson syndrome associated with sulfonamide antimicrobial agents (74, 81); nephrotoxicity related to aminoglycosides (63, 73); aplastic anemia due to chloramphenicol (9, 91); hepatitis caused by many drugs, including isoniazid (72, 89); neuromuscular blockade related to aminoglycoside (64, 65) or lincosamide (4, 70) therapy; myopathies due to ionophores (5, 28, 75); and neoplasia related to metronidazole (19)....

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Calcium and neostigmine antagonize gentamicin, but augment clindamycin-induced tetanic fade in rat phrenic nerve-hemidiaphragm preparations

Abstract: Clindamycin and gentamicin interfere with neuromuscular transmission and cause tetanic fade. Neostigmine and calcium antagonized the neuromuscular blockade caused by gentamicin, but augmented that caused by clindamycin.

Cited by 11 publications

References 24 publications

The antagonistic effect of neostigmine on rocuronium-, clindamycin-, or both-induced neuromuscular blocking in the rat phrenic nerve-hemidiaphragm

The antagonistic effect of neostigmine on rocuronium-, clindamycin-, or both-induced neuromuscular blocking in the rat phrenic nerve-hemidiaphragm

A tug-of-war between the host and the pathogen generates strategic hotspots for the development of novel therapeutic interventions against infectious diseases

Adverse Effects of Antimicrobials via Predictable or Idiosyncratic Inhibition of Host Mitochondrial Components

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