**3.3. Pathophysiology**

The pathophysiology of delirium is still poorly understood. The risk factors described above may act by similar mechanisms, leading to a common pathway that interferes with neurotransmitter function or with the supply or use of substrates to the brain (Maldonado, 2008). Imbalance in neurotransmitter systems is the leading hypothesized mechanism for delirium (Inouye, 2006). Other hypothesized mechanisms are neural injury, inflammation, and stress response (Hshieh et al., 2008).

and captopril are among the mostly used durs that have primary or secondary anticholinergic effects contributing to risk of delirium (Burns, 2004,). Many commonly used drugs in the elderly, that are the principal treatments of clinical conditions, such as urinary incontinence and cardiovascular disease, have anticholinergic properties (Scheife & Takeda, 2005; Uusvaara et al., 2011). Older patients and those with mental illness are particularly vulnerable to the adverse neuropsychiatric effects of anticholinergics as they may already

Delirium has been reported to be associated with opioid use (Gray et al., 1999, Brouquet, 2010). The association of delirium with opioids is dose-related (Burkhart et al., 2010). Persistent delirium has been reported to be associated with use of opioids at doses greater than 54mg/day (Pisani et al., 2010). On the other hand, there are studies reporting no association between opioid use and delirium (Pandharipande et al., 2006; Pisani et al., 2007). In a systemic review which aimed to determine medications to avoid in people at risk of delirium, it was concluded that, although use of opioids should be prescribed with caution in people at risk of delirium, as untreated severe pain can itself trigger delirium, this caution

All tricyclic antidepressants have an anticholinergic effect, with amitryptiline having the strongest and nortriptyline the weakest (White et al., 2007). Delirium has been reported to develope after abrupt discontinuation of fluoxetine (Blum et al., 2008) and with concominant use of fluoxetine and lamotrigine (Chistyakova & Amos, 2008). In addition, concomitant use of low-dose bupropion sustained release and fluoxetine has been reported to be associated

Benzodiazepines (Sanders, 2011), antipsychotics with strong anticholinergic effects (e.g. clozapine) (Centorrino et al., 2003), antiparkinson medications (i.e. levodopa) (Delmas et al., 2008) are among the other drugs that were erorted to be associated with delirium. A systematic review of prospective studies that investigated the association between medications and risk of delirium reported that delirium risk appears to be increased with opioids, benzodiazepines, dihydropyridines and possibly antihistamine. The authors conluded that there appears to be no increased risk with neuroleptics or digoxin and there is uncertainty regarding H(2) antagonists, tricyclic antidepressants, antiparkinson medications, steroids, non-steroidal anti-inflammatory drugs and antimuscarinics (Clegg, A.

The pathophysiology of delirium is still poorly understood. The risk factors described above may act by similar mechanisms, leading to a common pathway that interferes with neurotransmitter function or with the supply or use of substrates to the brain (Maldonado, 2008). Imbalance in neurotransmitter systems is the leading hypothesized mechanism for delirium (Inouye, 2006). Other hypothesized mechanisms are neural injury, inflammation,

have cognitive impairment (Gerretsen & Pollock, 2011).

should be tempered (Clegg & Young, 2011).

**3.2.2.2 Opioids** 

**3.2.2.3 Antidepressants** 

**3.2.2.4. Other drugs** 

& Young, 2011).

**3.3. Pathophysiology** 

and stress response (Hshieh et al., 2008).

with delirium (Chan et al., 2006).
