Biochemical and epidemiological investigations of non-steroidal anti-inflammatory drug usage and related side effects in equids

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in equine veterinary practice. These drugs exert their effect by inhibiting cyclooxygenase (COX) enzymes, which control prostaglandin production, a major regulator of tissue perfusion. Two isoforms of COX enzymes exist: COX-1 is physiologically present in tissues, while COX-2 is up-regulated during inflammation and has been indicated as responsible for the negative effects of an inflammatory response. Evidence suggests that NSAIDs that inhibit only COX-2, preserving the physiological function of COX-1 might have a safer profile. Studies that evaluate the effect of NSAIDs on COX enzymes are all performed under experimental conditions and none uses actual clinical patients. The biochemical investigations in this work focus on describing the effect on COX enzymes activity of flunixin meglumine and phenylbutazone, two non-selective COX inhibitors and firocoxib, a COX-2 selective inhibitor, in clinical patients undergoing elective surgery. A separate epidemiological investigation was aimed at describing the impact that the findings of biochemical data have on a large population of equids. Electronic medical records (EMRs) from 454,153 equids were obtained from practices in the United Kingdom, United States of America and Canada. Information on prevalence and indications for NSAIDs use was extracted from the EMRs via a text mining technique, improved from the literature and described and validated within this Thesis. Further the prevalence of a clinical sign compatible with NSAID toxicity, such as diarrhoea, is reported along with analysis evaluating NSAID administration in light of concurrent administration of other drugs and comorbidities. This work confirms findings from experimental settings that NSAIDs firocoxib is COX-2 selective and that flunixin meglumine and phenylbutazone are non-selective COX inhibitors and therefore their administration carries a greater risk of toxicity. However the impact of this finding needs to be interpreted with caution as epidemiological data suggest that the prevalence of toxicity is in fact small and the use of these drugs at the labelled dose is quite safe.

State-narco networks and the ‘War on Drugs’ in post-transition Bolivia, with special reference to 1989-1993

This thesis examines the development of state-narco networks in post-transition Bolivia. Mainstream discourses of drugs tend to undertheorise such relationships, holding illicit economies, weak states and violence as synergistic phenomena. Such assumptions fail to capture the nuanced relations that emerge between the state and the drug trade in different contexts, their underlying logics and diverse effects. As an understudied case, Bolivia offers novel insights into these dynamics. Bolivian military authoritarian governments (1964-1982), for example, integrated drug rents into clientelistic systems of governance, helping to establish factional coalitions and reinforce regime authority. Following democratic transition in 1982 and the escalation of US counterdrug efforts, these stable modes of exchange between the state and the coca-cocaine economy fragmented. Bolivia, though, continued to experience lower levels of drug-related violence than its Andean neighbours, and sustained democratisation despite being a major drug producer. Focusing on the introduction of the Andean Initiative (1989-1993), I explore state-narco interactions during this period of flux: from authoritarianism to (formal) democracy, and from Cold War to Drug War. As such, the thesis transcends the conventional analyses of the drugs literature and orthodox readings of Latin American narco-violence, providing insights into the relationship between illicit economies and democratic transition, the regional role of the US, and the (unintended) consequences of drug policy interventions. I utilise a mixed methods approach to offer discrete perspectives on the object of study. Drawing on documentary and secondary sources, I argue that state-narco networks were interwoven with Bolivia’s post-transition political settlement. Uneven democratisation ensured pockets of informalism, as clientelistic and authoritarian practices continued. This included police and military autonomy, and tolerance of drug corruption within both institutions. Non-enforcement of democratic norms of accountability and transparency was linked to the maintenance of fragile political equilibrium. Interviews with key US and Bolivian elite actors also revealed differing interpretations of state-narco interactions. These exposed competing agendas, and were folded into alternative paradigms and narratives of the ‘war on drugs’. The extension of US Drug War goals and the targeting of ‘corrupt’ local power structures, clashed with local ambivalence towards the drug trade, opposition to destabilising, ‘Colombianised’ policies and the claimed ‘democratising mission’ of the Bolivian government. In contrasting these US and Bolivian accounts, the thesis shows how real and perceived state-narco webs were understood and navigated by different actors in distinct ways. ‘Drug corruption’ held significance beyond simple economic transaction or institutional failure. Contestation around state-narco interactions was enmeshed in US-Bolivian relations of power and control.