Accurate measurement of blood pressure is essential to classify individuals, to ascertain blood pressure-related risk, and to guide management. The auscultatory technique with a trained observer and mercury sphygmomanometer continues to be the method of choice for measurement in the office, using the first and fifth phases of the Korotkoff sounds, including in pregnant women. The use of mercury is declining, and alternatives are needed. Aneroid devices are suitable, but they require frequent calibration. Hybrid devices that use electronic transducers instead of mercury have promise. The oscillometric method can be used for office measurement, but only devices independently validated according to standard protocols should be used, and individual calibration is recommended. They have the advantage of being able to take multiple measurements. Proper training of observers, positioning of the patient, and selection of cuff size are all essential. It is increasingly recognized that office measurements correlate poorly with blood pressure measured in other settings, and that they can be supplemented by self-measured readings taken with validated devices at home. There is increasing evidence that home readings predict cardiovascular events and are particularly useful for monitoring the effects of treatment. Twenty-four-hour ambulatory monitoring gives a better prediction of risk than office measurements and is useful for diagnosing white-coat hypertension. There is increasing evidence that a failure of blood pressure to fall during the night may be associated with increased risk. In obese patients and children, the use of an appropriate cuff size is of paramount importance.

/pdf/recommendations-for-blood-pressure-measurement-in-humans-and-19z5w6eq69.pdf

Recommendations for Blood Pressure Measurement in Humans and Experimental Animals Part 1: Blood Pressure Measurement in Humans: A Statement for Professionals From the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research

https://cyberleninka.org/article/n/148766.pdf

Cytochrome P450 enzymes in drug metabolism: Regulation of gene expression, enzyme activities, and impact of genetic variation

http://academic.oup.com/milmed/article-pdf/146/7/506/24126715/milmed-146-7-506.pdf

Goodman and Gilman's The Pharmacological Basis of Therapeutics

The self-medication hypothesis of addictive disorders derives primarily from clinical observations of patients with substance use disorders. Individuals discover that the specific actions or effects of each class of drugs relieve or change a range of painful affect states. Self-medication factors occur in a context of self-regulation vulnerabilities--primarily difficulties in regulating affects, self-esteem, relationships, and self-care. Persons with substance use disorders suffer in the extreme with their feelings, either being overwhelmed with painful affects or seeming not to feel their emotions at all. Substances of abuse help such individuals to relieve painful affects or to experience or control emotions when they are absent or confusing. Diagnostic studies provide evidence that variously supports and fails to support a self-medication hypothesis of addictive disorders. The cause-consequence controversy involving psychopathology and substance use/abuse is reviewed and critiqued. In contrast, clinical observations and empirical studies that focus on painful affects and subjective states of distress more consistently suggest that such states of suffering are important psychological determinants in using, becoming dependent upon, and relapsing to addictive substances. Subjective states of distress and suffering involved in motives to self-medicate with substances of abuse are considered with respect to nicotine dependence and to schizophrenia and posttraumatic stress disorder comorbid with a substance use disorder.

The Self-medication Hypothesis of Substance Use Disorders: A Reconsideration and Recent Applications

Medications which bind to opioid receptors are increasingly being prescribed for the treatment of multiple and diverse chronic painful conditions. Their use for acute pain or terminal pain is well accepted. Their role in the long-term treatment of chronic noncancer pain is, however, controversial for many reasons. One of the primary reasons is the well-known phenomenon of psychological addiction that can occur with the use of these medications. Abuse and diversion of these medications is a growing problem as the availability of these medications increases and this public health issue confounds their clinical utility. Also, the extent of their efficacy in the treatment of pain when utilized on a chronic basis has not been definitively proven. Lastly, the role of opioids in the treatment of chronic pain is also influenced by the fact that these potent analgesics are associated with a significant number of side effects and complications. It is these phenomena that are the focus of this review. Common side effects of opioid administration include sedation, dizziness, nausea, vomiting, constipation, physical dependence, tolerance, and respiratory depression. Physical dependence and addiction are clinical concerns that may prevent proper prescribing and in turn inadequate pain management. Less common side effects may include delayed gastric emptying, hyperalgesia, immunologic and hormonal dysfunction, muscle rigidity, and myoclonus. The most common side effects of opioid usage are constipation (which has a very high incidence) and nausea. These 2 side effects can be difficult to manage and frequently tolerance to them does not develop; this is especially true for constipation. They may be severe enough to require opioid discontinuation, and contribute to under-dosing and inadequate analgesia. Several clinical trials are underway to identify adjunct therapies that may mitigate these side effects. Switching opioids and/or routes of administration may also provide benefits for patients. Proper patient screening, education, and preemptive treatment of potential side effects may aid in maximizing effectiveness while reducing the severity of side effects and adverse events. Opioids can be considered broad spectrum analgesic agents, affecting a wide number of organ systems and influencing a large number of body functions.

/pdf/opioid-complications-and-side-effects-29996mciak.pdf

Opioid complications and side effects.

Investigating the correlation between wastewater analysis and roadside drug testing in South Australia.

Inter- and intra-subject variability in ethanol pharmacokinetic parameters: Effects of testing interval and dose

This study aimed to determine if morphine is effective in ameliorating Neonatal Abstinence Syndrome (NAS) symptoms to non-opioid-exposed control levels in methadone- and buprenorphine-exposed infants. A prospective, non-randomized comparison study with flexible dosing was undertaken in a large teaching maternity hospital in Australia. Twenty-five infants in the groups of buprenorphine-, methadone- and control non-opioid-exposed infants were compared (total n = 75 infants). Oral morphine sulphate (1 mg/ml) was administered every 4 h to opioid agonist-exposed infants. Modified Finnegan Withdrawal Scale (MFWS) scores determined dosing: score of 8-10: 0.5 mg/kg/day, 11-13: 0.7 mg/kg/day and 14+: 0.9 mg/kg/day. Withdrawal score, amount of morphine administered and length of hospital stay, were used to assess NAS over a 4-week follow-up period. No controls achieved a score higher than 7 on the MFWS. There was no significant difference in the percentage of infants requiring treatment between methadone (60%) and buprenorphine (48%) infants. For treated infants, significantly (P < 0.01) more morphine was administered to methadone (40.07 ± 3.95 mg) compared with buprenorphine infants (22.77 ± 4.29 mg) to attempt to control NAS. Following treatment initiation, significantly more (P < 0.01) methadone (87%) compared with buprenorphine infants (42%) continued to exceed scoring thresholds for morphine treatment requirement, and non-opioid-exposed control infant scores. For treated infants, there was no significant difference in length of hospital stay between methadone and buprenorphine infants. Morphine treatment was not entirely effective in ameliorating NAS to non-opioid-exposed control symptom levels in methadone or buprenorphine infants. The regimen may be less effective in methadone compared with buprenorphine infants.

Ineffective morphine treatment regimen for the control of Neonatal Abstinence Syndrome in buprenorphine- and methadone-exposed infants

Increased synaptic serotonin (5-hydroxytryptamine) levels may underlie antidepressant-like effects of 3,4-methylenedioxymethamphetamine (MDMA) that may be more prominent in subjects with mood disturbance. The Flinders Sensitive Line (FSL) strain is an important animal model of depression. These rats are more immobile in the forced swimming test (FST), and their immobility is reversed by known antidepressants after prolonged administration. The objective of this study was to determine whether MDMA administration has a dose-dependent antidepressant-like effect in this animal model of depression. The effects of MDMA at 5 and 10 mg/kg following single and repeated administration were assessed in FSL rats using the FST. Sprague-Dawley rats were used as a control. During both FST sessions, saline-treated FSL rats were significantly more immobile than Sprague-Dawley rats (P<0.001). Acute MDMA administration had a dose-dependent antidepressant-like effect in FSL rats, which was most evident after 10 mg/kg. This effect was diminished after repeated administration. Methamphetamine 2 mg/kg, which was used as a positive control for locomotor activity induction, did not affect the depressive-like state in FSL rats. There were no changes in the cortical levels of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid after treatments. It is concluded that MDMA exhibited an antidepressant-like effect in FSL rats, which was most evident following acute administration.

Antidepressant-like effects of 3,4-methylenedioxymethamphetamine in an animal model of depression.

1. 1. While GABAB antagonists have been examined in vitro, very few have been tested in vivo. A range of GABAB antagonists were tested against baclofen-induced muscle relaxation and hypothermia. 2. 2. The GABAB antagonists exhibited a range of in vivo activity profiles. 3. 3. CGP 35348 showed clear antagonist effects, while BPBA and 4-ABPA appeared to have agonist properties. 4. 4. Phaclofen, 2-hydroxysaclofen, 3-APPA and 9G seemed to have little effect in this system at the doses tested. 5. 5. Differences between in vivo and in vitro activity could be explained by differences in blood-brain barrier permeability, or possible differences in affinities for the sub-classes of GABAB receptors.

Jason M. White

Papers

Investigating the correlation between wastewater analysis and roadside drug testing in South Australia.

Inter- and intra-subject variability in ethanol pharmacokinetic parameters: Effects of testing interval and dose

Ineffective morphine treatment regimen for the control of Neonatal Abstinence Syndrome in buprenorphine- and methadone-exposed infants

Antidepressant-like effects of 3,4-methylenedioxymethamphetamine in an animal model of depression.

Characterization of GABAB ligands in vivo.