IntroductionAlthough combination therapies are generally used to achieve better therapeutic results, drug-drug interactions (DDIs) can lead to life-threatening adverse reactions (ADRs) or therapeutic failure by changing the therapeutic efficacy of drugs. DDIs have been reported to cause 4% of drug-related emergency visits (1). Changes in the pharmacokinetic properties of drugs may produce adverse drug reactions or therapeutic failure. The pharmacodynamics of DDIs can produce additive, synergistic, or antagonistic pharmacological effects (2).ADRs can be considered an important public health problem, particularly in the elderly patients (3). Polypharmacy and DDIs play critical roles in the production of ADRs and are related to an increased risk of mortality (4,5). Among identified adverse drug events, preventable adverse drug events have been reported to be 27% in primary care and 42% in long-term care, where prescribing and monitoring stages of pharmaceutical care were emphasized for prevention of adverse drug events (6,7). Potentially inappropriate medications have been identified in Beers Criteria (8), which aimed to prevent poor outcomes in elderly patients such as ADRs, hospitalization, morbidity, or mortality (8). In the elderly population DDIs can be diagnosed as severe adverse outcomes (9). Increased sensitivity to DDIs in elderly patients and the most frequent ADRs experienced by this age group have been shown in many studies (10-12). Elderly patients exposed to polypharmacy are at high risk of DDIs that depend on agerelated changes in pharmacokinetics or pharmacodynamics of drugs, and multiple co-morbidities.Another important factor for the increased vulnerability of elderly patients to DDIs can be poor compliance, underuse, overuse, or misuse of the medications (13). Moreover, elderly patients who will undergo surgical treatment or treatment in an intensive care unit have been reported to have a high risk for the occurrence of DDIs ( 14). Although there are publications investigating the use of inappropriate drugs in Turkish elderly patients (15,16), there are no data evaluating potential DDIs in Turkish elderly patients.Background/aim: Elderly patients are at high risk from drug-drug interactions (DDIs). This study evaluates the potential DDIs in Turkish elderly patients at a primary health care outpatient clinic. Materials and methods:Online database systems were used to examine DDIs on the prescriptions of patients (n = 1206). The clinical severity of DDIs was classified by the Lexi-Interact Online database.Results: Of the 5059 prescriptions, 33% were found to have DDIs. We detected 29 (0.9%) A, 380 (11.8%) B, 2494 (77.7%) C, 289 (9%) D, and 18 (0.6%) X risk rating category DDIs among the prescriptions. Prescriptions of female patients and patients aged between 65 and 72 years showed significantly higher number of DDIs. The frequency of DDIs increased both with the number of drugs and combined preparations per prescription. Acetylsalicylic acid and salbutamol were the most frequently prescribed drugs ...

Aims: This study was to investigate the effects of local administration of gamma-aminobutyric acid (GABA) agonists into the nucleus accumbens (NAc) on naloxone-induced morphine withdrawal symptoms. Methods: Bilateral guide cannulas were stereotaxically implanted in the shell or core regions of the NAc of Sprague-Dawley rats. After a recovery period, 3 morphine pellets, each consisting of 75 mg morphine base, were placed subcutaneously on the first and third days of the study with the rats under mild ether anaesthesia. The GABA agonists, baclofen hydrochloride or muscimol hydrobromide, were injected into the NAc, and morphine withdrawal was induced by naloxone on the fifth day. Results: Administration of baclofen to the shell or core regions of the NAc of Sprague-Dawley rats led to statistically significant decreases in both behavioural and locomotor activity parameters during the morphine withdrawal period, compared to the control group. However, there were no statistically significant changes in locomotor activity or withdrawal behavioural parameters, with the exception of wet dog shakes, between control and muscimol-treated groups. Conclusion: These findings show that GABAergic conduction in the NAc is effective on the morphine withdrawal symptoms, and that both the shell and core regions of the NAc are associated with this effect.

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Opium alkaloids, derived from crude Papaver somniferum L. plant, are potent analgesic drugs, but their use is limited because of dependence and withdrawal. Opium alkaloids activate the mesocorticolimbic dopaminergic system, which project from the ventral tegmental area to the nucleus accumbens and medial prefrontal cortex, and dopamine is critically important in opioid consumption and sustaining. The reward effect resulting from the activation of the dopaminergic system leads to continued opioid consumption and occurs opioid dependence. After the development of opioid dependence, consumption continues to avoid withdrawal syndrome. Opioid dependence is accompanied with tolerance, which requires the use of high doses to achieve the same effect. When tolerance develops, the chronic consumer continues to use opioid above known toxic doses to produce the same effect, which can result in death regardless of the type of opioid used. Raw Papaver somniferum L. has five high-density main opium alkaloids including morphine, noscapine, codeine, thebaine, and papaverine. Some of these alkaloids bind to classical opioid receptors to produce an opioid-like effect, while the other part mediates non-opioid effects. This chapter reviews the opiod history, receptors, mechanism of action, dependence, withdrawal. In addition, general information about five main opium alkaloids, their effects, uses, routes of administration, pharmacokinetics, adverse reactions, contraindications; effects on reproduction, pregnancy, and lactation were compiled.

Opioids are effective analgaesic agents, but serious adverse effects such as tolerance and withdrawal contribute to opioid dependence and limit their use. Opioid withdrawal is a common occurrence in human opiate addicts that is not life‐threatening. Studies have shown that the mesocorticolimbic system, especially the nucleus accumbens, is an important region in drug addiction and adenosine receptors play a modulatory role in the mechanism of action of drug dependence and withdrawal. The aim of this study was to investigate the effects of the selective A1 receptor agonist CPA (N6‐cyclopentyladenosine) on withdrawal symptoms, and the concentration of dopamine and noradrenaline in the nucleus accumbens and locomotor activity behaviour during naloxone‐precipitated withdrawal in morphine‐dependent rats. The local administration of CPA (1.5, 3.0, and 6.0 mmol/L bilateral 250 nL) into the nucleus accumbens decreased the Gellert–Holtzman withdrawal scale, and increased concentrations of dopamine and noradrenaline in the same region during naloxone‐induced withdrawal. Our findings suggest that administration of the A1 receptor agonist significantly decreased withdrawal behaviours and increased dopamine and noradrenaline concentrations in opioid withdrawal in a dose‐dependent manner. These results demonstrate that adenosine receptors should be examined as a potential mechanism that could be exploited for the treatment of morphine withdrawal.