Opioid-Induced Respiratory Depression Resulting from Transdermal Fentanyl-Clarithromycin Drug Interaction in a Patient with Advanced COPD

Abstract

Levomepromazine, also known as methotrimeprazine, is an antipsychotic drug. In addition to this use, it has a role in palliative care for the alleviation of nausea. It also has been used to manage terminal restlessness, although it can cause restlessness and akathisia.Drug-induced lupus is a condition that resembles a mild form of idiopathic systemic lupus erythematosus and is associated with drugs such as procainamide, hydralazine, minocycline, quinidine, chlorpromazine, isoniazide, and methyldopa. 1,2 It is a reversible condition, with the symptoms often resolving within days of stopping the offending medication. 1,3,4 Symptoms may develop up to one year after the drug is commenced. It is diagnosed when a patient has one or more symptoms of systemic lupus erythematosus, with positive ANA titer and no symptoms of lupus before starting the suspected drug. Table 1 shows the features that can be associated with drug-induced lupus. 5 Although there is no published literature directly pertaining to lupus secondary to levomepromazine, this drug has pharmacological activity similar to that of chlorpromazine, for which a published association with the onset of lupustype symptoms exists. 6 The combination of raised homogeneous ANA levels, features of lupus (Table 1), symptoms starting after months of treatment with levomepromazine and resolving within days of discontinuing it, all support the possibility of drug-induced lupus secondary to levomepromazine.Antihistone antibodies are raised in approximately 90% of cases of drug-induced lupus and would have certainly supported the

8-OH-DPAT abolishes the pulmonary C-fiber-mediated apneic response to fentanyl largely via acting on 5HT1Areceptors in the nucleus tractus solitarius

“…Opioids are the most powerful analgesics with side effects such as the risk of ventilatory depression and apnea (12,14,44,52). The latter could be lethal (16,44), especially in some patients with pulmonary diseases such as chronic obstructive pulmonary disease (4,15,18). Many studies have shown that pulmonary inflammatory mediators-hypoxemia and hypercapnia, congestion, and edema-that are common in patients with these diseases, can sensitize and/or stimulate PCFs to prolong PCFmediated apnea (8,17,41).…”

Pharmacokinetic interaction of intravenous fentanyl with ketoconazole

“…Fatal drug interactions between fentanyl and CYP3A inhibitors, eg, fluconazole, clarithromycin, diltiazem, and itraconazole have been reported in chronic pain patients treated with transdermal fentanyl resulting in opioid intoxications of these patients …”

Activation of opioid μ-receptors, but not δ- or κ-receptors, switches pulmonary C-fiber-mediated rapid shallow breathing into an apnea in anesthetized rats

“…RSB commonly occurs in patients with pulmonary inflammation (infection), congestion, and edema (Churchill & Cope, 1929; Hatridge et al , 1989; Roussos & Koutsoukou, 2003). These patients are more vulnerable to suffering from respiratory depression and even respiratory failure than normal subjects when opioids are administered as analgesics, mainly due to acting on μ-receptors, in the clinical setting (Gruber & Tschernko, 2003; Horton & Barber, 2009). However, the reason for this vulnerability is not clear.…”