Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2758_Библиотеки_им_академика_М_И_Перельмана

5-HT 5-Hydroxytryptophan ACE Angiotensin-converting enzyme EGFR Epidermal growth factor receptor EGFRI Epidermal growth factor receptor

from the Boston Collaborative Drug Surveillance which followed over 15,000 patients from the years 1975 to 1982, it was shown that among hos­pitalized patients, pruritus without concomitant skin lesions accounted for about 5% of adverse reactions after drug intake (Bigby etal. 1986). In 1998, a study on skin reactions secondary to anti­bacterial agents used in over 13,000 patients showed that general pruritus accounted for 13.3% of adverse events reported (Van der Linden etal.

latency, which is the time period between drug initiation to the rst symptoms of pruritus. Drugs inducing pruritus may differ in this category. For example, calcium channel blockers have been shown to induce itch within 24h of drug intake, while reports of beta-blocker-induced itch describe lag periods of up to 6months (Orme and Da Costa 1997; Hagmeyer and Stein 2001). The second parameter used to differentiate the types of drug-induced itch depends on whether the itch is localized to a specic part of the body, or whether it is generalized. For example, itch asso­ciated with cholestasis may be more prominent in the palms and soles, while opioid-induced itch can often be seen in areas of the face (Pusl and Beuers 2007; Szarvas etal. 2003). The third cat­egory involves severity of itch, a clinical term used to describe the intensity of a medical event, as in the grading “mild,” “moderate,” and “severe.” Some drugs may cause mild itch, while others may result in intractable itch that decreases quality of life and thus may induce patient non­compliance. Itch severity may also depend upon whether the pruritus is localized or generalized as well.

itch and are activated by histamine. Nonhistaminergic neurons are implicated in chronic itch and express a wide variety of recep­tors that are activated by pruritogens other than histamine (Yosipovitch etal. 2018). Histaminergic and nonhistaminergic nerve signals travel along distinct spinal tracts and activate different pro­cessing areas of the brain (Davidson etal. 2012; Papoiu et al. 2012). Supraspinal processing of itch occurs in multiple sites of the brain, most commonly the primary and secondary somato­sensory cortex (Drzezga etal. 2001; Yosipovitch etal. 2004) (see Fig.1).

their use is limited by several adverse effects, one of the most common being pruritus (Benson etal.

(See Table1).

when administered intravenously, and 30–100% after spinal or epidural administration (Szarvas et al. 2003; Swegle and Logemann 2006; Schofferman and Mazanec 2008; Gan etal. 1997;

(xerosis cutis),

unknown

Unknown N/A 9.1% (Ensslin etal.

injury (Salti etal.

injury (Skurnik etal. 2003)

Anelli etal. 1994; Boström 1999)

Woodhouse etal. 1996). Patients who experience opioid-induced itch may complain of generalized itching, or they may experience more intense itch in areas with higher concentrations of mu-opioid receptors, such as the face (Benson etal. 2015). Lag time from treatment initiation to onset of pruritus is usually within 12 h (Ganesh and Maxwell 2007; Krajnik and Zylicz 2001; Bounes etal. 2017).

pruritus as “unbearable” and 21% regarded it as “severe” (Ajayi etal. 1989). In a study in Kenya, 10% of pregnant women refused free malaria prophylaxis with chloroquine due to fear of chloroquine- induced itching (Kaseje etal. 1987). Itching has been reported to occur mainly in the hands, feet, and scalp, but there have also been reports of generalized itching as well (Ekpechi and Okoro 1964; Osifo 1984). Lag time from treatment initiation to onset of pruritus has ranged from 6 to 24h, and usually subsides within 76h after onset (Ajayi et al. 1989; Osifo 1984; Adebayo etal. 1997).

1991). Additionally, opioidergic mechanisms

may be involved in chloroquine-induced itch, as studies have shown that chloroquine-induced itch in rats may be blocked by mu-opioid receptor antagonist naltrexone and potentiated by mu­opioid receptor agonist morphine (Onigbogi etal. 2000).

As stated above, chloroquine-induced pruritus is more commonly seen in African populations, and high genetic polymorphism seen in human Mrgpr genes may provide a molecular explana­tion for this nding (Dong etal. 2001; Yang etal.