ABSTRACT
Thyroid hormone (TH) is critical in cardiac cell differentiation (regulating contractile proteins and cell geometry) and this effect could be potentially exploited therapeutically in reversing the process of de-differentiation which underlies postischemic cardiac remodeling. Acute myocardial infarction was induced in male Wistar rats by ligating left coronary artery (AMI, n=8), while sham operated animals served as control (SHAM, n=8). 13 weeks after AMI, TH was administered in a group of animals for 4 weeks (AMI-THYR, n=9). TH significantly increased beta-MHC and decreased alpha-MHC expression in the myocardium. This response was accompanied by changes in cardiac geometry: sphericity index, (SI, long to short axis ratio) was found to be 1.95 (SEM, 0.02) in SHAM, 1.51(0.03) in AMI and 1.64(0.03) in AMI-THYR, p<0.05. As a consequence, cardiac function was significantly improved: left ventricular ejection fraction (EF%) was 74.5% (SEM, 2.8) in SHAM vs 29.5% (2.1) in AMI, and 40.0% in AMI-THYR, p<0.05. Furthermore, +dp/dt and -dp/dt were 4250 (127) and 2278 (55) in SHAM vs 2737(233) and 1508 (95) in AMI vs 3866 (310) and 2137(111) in AMI -THYR, respectively, p<0.05. TH treatment partially reverses cardiac dysfunction in rats with old myocardial infarction by favorably changing cardiac chamber geometry and expression of myosin isoforms. Thyroid hormone, unlike current treatments, appears to be a paradigm of therapeutic intervention which aims at restoring cardiac geometry and may prove new effective treatment for heart failure.
Subject(s)
Myocardial Infarction/drug therapy , Myocardium/pathology , Thyroid Hormones/physiology , Thyroid Hormones/therapeutic use , Ventricular Remodeling/drug effects , Animals , Echocardiography , Heart Failure/prevention & control , Male , Myocardial Infarction/diagnostic imaging , Myocardial Infarction/physiopathology , Myocardium/metabolism , Myosin Heavy Chains/metabolism , Protein Isoforms , Rats , Rats, Wistar , Thyroid Hormones/administration & dosage , Thyroid Hormones/pharmacokinetics , Time FactorsABSTRACT
Transdermal fentanyl is an opioid analgesic that is effective on chronic pain, and which appears to be advantageous due to several factors such as ease of administration, the relatively stable serum concentration and long dose intervals. Nevertheless, the danger of abuse and dependence exists among patients who are prescribed fentanyl patches. We present a case of transdermal fentanyl abuse, where the administration route of the drug was changed. Our patient, who had no history of substance abuse and who suffered from chronic nonmalignant pain, used the fentanyl transdermal patches as oral transmucosal medication, raising the dose by ten-fold. This abuse of the drug was only for analgesic purposes without seeking anxiolysis and/or euphoria. After treatment and progressive reduction of fentanyl, the patient remains in good condition, and is currently taking the initial dose of the drug transdermally, without having experienced any withdrawal symptoms.
Subject(s)
Administration, Cutaneous , Administration, Oral , Fentanyl/adverse effects , Fentanyl/therapeutic use , Substance-Related Disorders/etiology , Adult , Chronic Disease , Depressive Disorder/complications , Depressive Disorder/diagnosis , Depressive Disorder/drug therapy , Drug Administration Schedule , Drug Therapy, Combination , Dysthymic Disorder/complications , Dysthymic Disorder/diagnosis , Female , Fentanyl/administration & dosage , Fluoxetine/therapeutic use , Greece , Humans , Mouth Mucosa/drug effects , Pain/complications , Pain/diagnosis , Pain/drug therapy , Pica/complications , Polychondritis, Relapsing/complications , Polychondritis, Relapsing/diagnosis , Polychondritis, Relapsing/drug therapy , Self Administration/methodsABSTRACT
Zolpidem is a short-acting imidazopyridine hypnotic that is an agonist at the gamma-aminobutyric acid A type (GABAA) receptor. It has been suggested that it acts selectively on alpha1 subunit-containing GABAA benzodiazepine (BZ1) receptors presenting (contrary to classic benzodiazepines) low or no affinity for other subtypes. Therefore, it has been proposed that it lacks the benzodiazepines-like side-effects, having minimal abuse and dependence potential. Nevertheless, there is a considerable number of zolpidem dependence case reports in the literature. We present eight cases of zolpidem abuse and dependence without criminal record, without history of substance abuse (except for one alcohol abuser), with minor psychiatric disorders, who took zolpidem after physicians prescription in order to deal with their insomnia. However, they became zolpidem abusers not craving its sedative, but its anxiolytic and stimulating action, which helped them to cope with everyday activities. It is possible that, in the high doses that our patients used, zolpidem abandons its selectivity for BZ1 receptors and demonstrates all the actions of classic benzodiazepines. Molecular biology, via possible mutations on GABA receptors, may provide some answers as to why our eight patients (who did not differ much from the thousands of insomniacs who use zolpidem) and other zolpidem abusers, raised the dose progressively, and sought something from the drug other than hypnotic action.
Subject(s)
GABA Agonists/adverse effects , Hypnotics and Sedatives/adverse effects , Pyridines/adverse effects , Substance-Related Disorders/etiology , Adult , Aged , Aged, 80 and over , Female , GABA Agonists/therapeutic use , Humans , Hypnotics and Sedatives/therapeutic use , Male , Middle Aged , Pyridines/therapeutic use , Receptors, GABA-A/drug effects , Sleep Initiation and Maintenance Disorders/drug therapy , Substance-Related Disorders/psychology , ZolpidemABSTRACT
A case is presented of a 30-year-old man, prescribed zolpidem for insomnia arising from cocaine abuse, who sought to use this hypnotic to reduce his craving for cocaine. However, after taking cocaine and up to 300 mg/day zolpidem, he became euphoric and hyperactive. It is suggested that at high doses, zolpidem, like cocaine, has a stimulatory effect on the brain dopaminergic reward pathway. (Int J Psych Clin Pract 2002; 6: 217-219 ).