still looking for some explanations as why macrolids make me weak and heavy, like if I had a sudden paresis... in this article's extract, they talk about effect on intracellular calcium... "Mechanisms of Action and Clinical Application of Macrolides as Immunomodulatory Medications Effects on Cell Signaling There have been so many different reported effects of macrolides on cell signaling pathways that attempts to put these actions together as one mechanism is difficult. In fact, all macrolides seem not to have similar ranges or degrees of activity. Proposed mechanisms and their influence on cell signaling are discussed below. Intracellular calcium. Intracellular Ca2+ plays a fundamental role in signal transduction and regulates many enzymes, such as proteases, phospholipases, and endonucleases (44). Moreover, alteration of intracellular Ca2+ homeostasis is an early event in the development of irreversible cell injury (209). In airway epithelium, intracellular Ca2+ mobilization induced by proinflammatory mediators influences various cell functions, including ion transport and mucus secretion (43, 141). Experiments on epithelial cell lines suggest that Ca2+ signaling is involved in activation of the ERK1/2-NF-κB pathway and in ATP release as well as TLR-mediated responses by P. aeruginosa or flagellin (70, 184, 231, 277). Furthermore, intracellular Ca2+ agonists such as bradykinin and ATP can also increase cytokine expression and secretion in airway epithelia (199, 234, 235). We and others (126, 127, 151, 289) have shown that macrolides inhibit purinoceptor-mediated intracellular Ca2+ oscillations and Ca2+ influx in primary cultured airway epithelial cells, thereby reducing Cl secretion, perhaps through suppression of Ca2+-activated Cl channels. Similarly, Zhao et al. (346) have shown that erythromycin inhibits the ATP-mediated Ca2+ increase by suppressing Ca2+ influx from the extracellular space in A549 cells. Although molecular mechanisms of macrolide action on Ca2+ dynamics remain unclear, erythromycin does not affect verapamil-sensitive, voltage-dependent Ca2+ channels (151, 346). The effect of macrolides on the calcium response has been observed in other cells. Ca2+ influx into neutrophils and the oxidative burst were inhibited by erythromycin but not clarithromycin, suggesting that effects of macrolides on calcium mobilization are not completely homogenous (189). Recently, roxithromycin was shown to suppress histamine release and prostaglandin D2 production from human β-defensin-2-stimulated mast cells, and this was accompanied by inhibition of the intracellular Ca2+ increase (130). Calcium signaling after activation of apical G-protein-coupled receptors by proinflammatory mediators is amplified in Chronic Fibrosis airway epithelia (234, 235). Data suggest that the increased Ca2+ signal in CF cells may be due to the endoplasmic reticulum Ca2+ store increase or to inositol 1,4,5-triphosphate receptor (IP3R) dysfunction (9, 234). Macrolides may normalize Ca2+ responses and stabilize intracellular Ca2+ levels."