Pm Taylor

Effects of acepromazine, butorphanol and buprenorphine on thermal and mechanical nociceptive thresholds in horses.

REASONS FOR PERFORMING STUDY To investigate the antinociceptive effects of buprenorphine administered in combination with acepromazine in horses and to establish an effective dose for use in a clinical environment. OBJECTIVES To evaluate the responses to thermal and mechanical stimulation following administration of 3 doses of buprenorphine compared to positive (butorphanol) and negative (glucose) controls. METHODS Observer blinded, randomised, crossover design using 6 Thoroughbred geldings (3-10 years, 500-560 kg). Thermal and mechanical nociceptive thresholds were measured 3 times at 15 min intervals. Horses then received acepromazine 0.05 mg/kg bwt with one of 5 treatments i.v.: 5% glucose (Glu), butorphanol 100 µg/kg bwt (But) buprenorphine 5 µg/kg bwt (Bup5), buprenorphine 7.5 µg/kg bwt (Bup7.5) and buprenorphine 10 µg/kg bwt (Bup10). Thresholds were measured 15, 30, 45, 60, 90, 120, 150, 180, 230 min, 4, 5, 6, 7, 8, 9, 10, 11, 12 and 24 h post treatment administration. The 95% confidence intervals for threshold temperature (ΔT) for each horse were calculated and an antinociceptive effect defined as ΔT, which was higher than the upper limit of the confidence interval. Duration of thermal antinociception was analysed using a within-subjects ANOVA and peak mechanical thresholds with a general linear model with post hoc Tukey tests. Significance was set at P<0.05. RESULTS Mean (± s.d.) durations of thermal antinociception following treatment administration were: Glu 0.5 (1.1), But 2.9 (2.0), Bup5 7.4 (2.3), Bup7.5 7.8 (2.7) and Bup10 9.4 (1.1) h. B5, B7.5 and B10 were significantly different from Glu and But. No serious adverse effects occurred, although determination of mechanical thresholds was confounded by locomotor stimulation. CONCLUSIONS Administration of acepromazine and all doses of buprenorphine produced antinociception to a thermal stimulus for significantly longer than acepromazine and either butorphanol or glucose. POTENTIAL RELEVANCE This study suggests that buprenorphine has considerable potential as an analgesic in horses and should be examined further under clinical conditions and by investigation of the pharmacokinetic/pharmacodynamic profile.

Thermal antinociception after dexmedetomidine administration in cats: A comparison between intramuscular and oral transmucosal administration

Dexmedetomidine 40 μg/kg was administered either intramuscularly (IM) or oral transmucosally (OTM) to 12 cats in a randomised cross-over study. Thermal nociceptive thresholds and visual analogue scale (VAS) sedation scores were obtained before and at regular intervals up to 24 h after test drug administration. The summary measures of overall mean threshold, overall mean VAS sedation plus onset, offset and duration of analgesia were investigated using a univariate general linear model. There were no significant differences between treatment groups. Data are presented as mean±standard deviation: delta T mean increase over time (IM 6°C±3°C, OTM 6°C±2°C); overall mean VAS (IM 43±9 OTM 39±1); onset (IM 35±32 and OTM 30±40 min); offset (IM 96±56 and OTM 138±135 min); duration (IM 61±47 OTM 99±124 min). Dexmedetomidine is well absorbed through the oral mucosa in cats since OTM and IM administration of dexmedetomidine 40 μg/kg produced similar overall sedative and antinociceptive effects.

Postcastration analgesia in ponies using buprenorphine hydrochloride.

Buprenorphine has recently obtained UK Marketing Authorisation for horses. The analgesic effects are long lasting, and have considerable potential for postoperative pain relief. This observer blinded, randomised study aimed to evaluate postsurgical analgesia in ponies premedicated with buprenorphine prior to castration under intravenous anaesthesia. Ponies received either 0.01 mg/kg bodyweight (BW) buprenorphine (group B) or an equivalent volume of 5 per cent glucose (group C) given intravenously before induction of anaesthesia. Pain was assessed and recorded using dynamic interactive visual analogue scores (DIVAS 0–100) and a Simple Descriptive Scale (SDS 0–3) (high scores=most pain) before and 1, 3, 6, 9, 12 and 24 hours after anaesthesia. Rescue analgesia was given if DIVAS>40 mm. Data were analysed using the Mann-Whitney U test at P<0.05. Median (range) areas under the curve for DIVAS were 63 (0–383) mm hour in group B and 209 (0–391) mm hour in group C (P=0.0348). The SDS was lower in group B than in group C (P=0.038). Three group B and five group C animals required rescue analgesia. Buprenorphine did not produce any serious adverse effects. Buprenorphine at 0.01 mg/kg BW intravenously administered before anaesthesia provided near-comprehensive postoperative analgesia after surgical castration in ponies.

Assessment of the sedative effects of buprenorphine administered with 10 μg/kg detomidine in horses

The aim of this randomised, observer-blinded, crossover study was to compare the effects of six treatments, administered intravenously to six horses: saline and saline (S/S); detomidine and saline (D/S); detomidine and 5 µg/kg buprenorphine (D/B5); detomidine and 7.5 µg/kg buprenorphine (D/B7.5); detomidine and 10 µg/kg buprenorphine (D/B10); and detomidine and 25 µg/kg butorphanol (D/BUT). The detomidine dose was 10 µg/kg for all treatments in which it was included. Sedation was subjectively assessed and recorded on a visual analogue scale. Peak sedation, duration of sedation and the area under the curve (AUC) for sedation scores were investigated using a univariate general linear model with post-hoc Tukey tests (P<0.05). Peak sedation and duration of sedation were statistically significantly different between treatments (P<0.001). No sedation was apparent after administration of S/S. The AUC was significantly different between treatments (P=0.010), with S/S being significantly different from D/S, D/BUT, D/B5 and D/B7.5, but not D/B10 (P=0.051).

Buprenorphine in combination with naloxone at a ratio of 15:1 does not enhance antinociception from buprenorphine in healthy cats.

Naloxone can enhance the antinociceptive/analgesic effects of buprenorphine in humans and rats. The antinociceptive effects of a patented 15:1 buprenorphine:naloxone combination was investigated in cats using a thermal and mechanical nociceptive model. Twelve cats received buprenorphine 10 μg/kg, naloxone 0.67 μg/kg or a buprenorphine-naloxone combination intramuscularly in a randomised cross over study. Using thermal and mechanical analgesiometry validated in the cat, pre-treatment baselines were measured. Following test drug administration, thresholds were studied for the next 24h. Naloxone did not enhance the thermal antinociceptive effect of buprenorphine. The results from this study are in agreement with previously published work showing that naloxone antagonises the effects of clinically analgesic doses of buprenorphine. Mechanical nociceptive thresholds were not affected by buprenorphine.

Ranking the harm of non-medically used prescription opioids in the UK

A panel of nine experts applied multi-criteria decision analysis (MCDA) to determine the relative overall harm to users and harms to others of street heroin (injected and smoked) and eleven non-medically used prescription opioids. The experts assessed harm scores for each of the 13 opioids on each of 20 harm criteria, weighted the criteria and explored the resulting weighted harm scores for each opioid. Both forms of heroin scored very high: overall harm score of 99 for injected heroin and 72 for smoked heroin on a scale of 0-100. The main feature that distinguishes both forms of street heroin use is that their harm to others is more than five times that of the other eleven opioids. The overall harm score of fentanyl (including injection of fentanyl extracted from patches) and diamorphine (medically prescribed form of heroin) was 54 and 51, respectively, whereas that of orally used opioids ranged from 32 (pethidine) to 11 (codeine-containing pharmaceuticals). Injected street heroin, fentanyl and diamorphine emerged as most harmful to users, with the latter two very low in harm to others. Pethidine, methadone, morphine and oxycodone are also low in harm to others, while moderate in harm to users. We conclude that the overall harms of non-medically used prescription opioids are less than half that of injected street heroin. These data may give a basis for precautionary regulatory measures that should be considered if the rising trend in non-medical use of prescription opioids were to become evident in the UK.

Ketamine—the real perspective

We would like to highlight the medicinal value of ketamine. In November, 2015, WHO’s Expert Committee on Drug Dependence ( E C D D ) r e v i e w e d k e t a m i n e among drugs “with potential for dependence, abuse and harm to health”, to make recommendations to the UN Commission on Narcotic Drugs (CND) on the need for their international control. The ECDD recommended unequivocally that ketamine should not be placed under international control as they concluded that ketamine abuse does not pose a global public health threat and that such control would limit access for those who most need it as a life-saving anaesthetic. This month in March, the 59th CND will vote on this issue. Some disagree with ECDD’s opinion and consider that ketamine should be banned because of misuse as a recreational drug. However, there is widespread failure to appreciate that ketamine is an essential medicine—a remarkably safe anaesthetic that has been used worldwide for over 50 years. The drug does not depress respiration or the cardiovascular system, it can be used without electricity, oxygen, ventilators, and all the support systems required for other anaesthetics. Ketamine can be administered by trained non-physicians. Ketamine is an essential anaesthetic in any situation with scarce facilities. Therefore this drug is the only anaesthetic available for surgery in most low-income and middle-income countries (LMICs). Ketamine also has particular value as an emergency on-site anaesthetic for accidents, natural disasters, and war zones. In high-income countries, ketamine is increasingly used to treat depression and chronic pain. Ketamine also plays a crucial role in veterinary medicine. The drug has been extensively used since the 1970s to provide anaesthesia and pain relief in animals and is now probably the most widely used veterinary anaesthetic. As in human medicine, ketamine is essential in LMICs; in high-income countries, this drug is now virtually the only injectable anaesthetic used in horses and is widely used in small animal clinics for high-risk cases and exotic species. The side-eff ects of bladder damage from chronic ketamine misuse are horrifi c, but this aff ects only a few who take very high doses; most recreational users have few ill eff ects. Recreational use of ketamine should not prevent millions of people from surgery under the only anaesthetic in LMICs, or its use in disaster and confl ict trauma, and in veterinary medicine. Let us support WHO’s analysis that the medical benefits of ketamine far outweigh potential harm from recreational use.

A new approach to formulating and appraising drug policy: a multi-criterion decision analysis applied to alcohol and cannabis regulation.

BACKGROUND Drug policy, whether for legal or illegal substances, is a controversial field that encompasses many complex issues. Policies can have effects on a myriad of outcomes and stakeholders differ in the outcomes they consider and value, while relevant knowledge on policy effects is dispersed across multiple research disciplines making integrated judgements difficult. METHODS Experts on drug harms, addiction, criminology and drug policy were invited to a decision conference to develop a multi-criterion decision analysis (MCDA) model for appraising alternative regulatory regimes. Participants collectively defined regulatory regimes and identified outcome criteria reflecting ethical and normative concerns. For cannabis and alcohol separately, participants evaluated each regulatory regime on each criterion and weighted the criteria to provide summary scores for comparing different regimes. RESULTS Four generic regulatory regimes were defined: absolute prohibition, decriminalisation, state control and free market. Participants also identified 27 relevant criteria which were organised into seven thematically related clusters. State control was the preferred regime for both alcohol and cannabis. The ranking of the regimes was robust to variations in the criterion-specific weights. CONCLUSION The MCDA process allowed the participants to deconstruct complex drug policy issues into a set of simpler judgements that led to consensus about the results.

Analgesia protocols in donkeys

PAIN recognition in donkeys is notoriously difficult, and this can make provision of effective analgesia problematic. In order to obtain a greater insight into current analgesia protocols in donkeys, the University of Bristol veterinary school is conducting a questionnaire-based study to investigate