Studies of Acute Alcohol Effects in Women and Animal Models

Alcohol Effects on Basal Hormone Levels Another approach to examination of alcohol’s toxic effects on reproductive function is to administer a single acute dose of alcohol to a normal healthy woman or experimental animal and measure the effects on pituitary and ovarian steroid hormones. Through a systematic manipulation of alcohol dose and changes in hormone levels, it should be possible to establish whether alcohol primarily disrupts hypothalamic, pituitary, or ovarian function. Surprisingly, studies of acute alcohol administration have shown that alcohol has minimal effects on basal hormone levels. Alcohol did not significantly suppress LH or estradiol in normal women or in female macaque monkeys. These data suggest that a single episode of intoxication is probably not sufficient to suppress normal basal hormone levels and that repeated episodes of intoxication are required to produce the hormonal correlates of amenorrhea, anovulation, and luteal phase dysfunction observed in clinical studies. One procedural difficulty affecting all investigations of acute alcohol effects on basal hormone levels is that studies have usually been conducted during the early follicular or luteal phase of the menstrual cycle, when basal Read more […]

Benzodiazepines in the Treatment of Alcoholism

This post comprises three sections that cover the main aspects of benzodiazepines and alcohol: (1) the basic pharmacology of benzodiazepines; (2) use of benzodiazepines in the treatment of withdrawal; and (3) the use of benzodiazepines in treating alcoholics. The basic studies suggest that a major site of action of alcohol may be the GABA/benzodiazepine receptor complex and that compensatory alterations in this complex may underly withdrawal. In the section on alcohol withdrawal, interactions between the GABA/benzodiazepine receptor complex, sympathetic nervous system, and hypothalamic-pituitary-adrenal axis are discussed. Use of benzodiazepines in the treatment of the alcohol withdrawal syndrome are reviewed, including the possibility that the benzodiazepines may prevent withdrawal-induced “kindling”. Lastly, we review indications for, and efficacy of, benzodiazepines in long-term treatment of patients with alcoholism. Benzodiazepines are not indicated for the treatment of alcoholism. Furthermore, they have very few indications in alcoholics and their dependency-producing potency has to be appreciated when they are used in patients with alcoholism. The benzodiazepines () are a group of compounds that were first Read more […]

Benzodiazepines in the Treatment of Alcoholism: Future Directions

The above treatment recommendations emphasize that minimal signs and symptoms of ethanol withdrawal can generally be treated without pharmacotherapy. The repeated experience of untreated ethanol withdrawals, however, may produce a “kindling” effect over time. Kindling is the “progressive increase in neural responsivity produced by spaced and repeated epileptogenic stimulation of certain brain structures.” The kindling hypothesis suggests that each additional episode of withdrawal will elicit increasingly severe signs and symptoms. Preclinical studies in which the severity of the ethanol withdrawal syndrome increased in rats subjected to repeated episodes of ethanol withdrawal or following kindling induced by electroshock, metrazol injections, or amygdaloid stimulation indicate that such a process may take place. In addition, a retrospective study in alcoholics reported that periods of heavy drinking and dependence on ethanol were associated with an exacerbation of agoraphobia and social phobias, and that subsequent periods of abstinence were associated with substantial improvements in these phobic anxiety states. A recent study demonstrated that patients with panic disorder and alcohol dependence do not distinguish Read more […]

Effect of marijuana the adrenal gland

Cortical Hormones Exposure to stressful situations elicits a prompt secretion of adrenocortical steriods which help the organisms to counteract the stress. The adrenal cortex responds to acute cannabinoid treatment with a prompt rise in corticosterone levels in the plasma. Exposure to a wide range of dosages of THC ranging fran 2 to 50 mg/ kg body weight produced increased corticosterone levels in the plasm of both the rat and the mouse. Dewey et al. () showed that ascorbic acid, which is inversely correlated to adrenal cortical hormne secretion, was depleted fran the adrenal cortex of laboratory rats. Maier and Maitre () demonstrated that. the increased corticosterone in plasma of rats pretreated with THC was accompanied by a decrease in adrenal cortical cholesterol, a precursor to adrenal cortical hormones, and an increase in unesterified fatty acids; however, the rabbit did not respond to THC with a similar increase in wrtisol. Birmingham and Bartova () showed that the response of elevated plasma corticosterone to THC disappeared after 8 days of treatment with a dose of 3 mg/kg body weight. Pertwee () also showed that tolerance developed to the effect of THC on corticosterone levels in muse plasm and did so without Read more […]

Drug-Drug Interactions of Cocaine

Alcohol Cocaine abusers have reported that alcohol prolongs the euphoriant properties of cocaine, while ameliorating the acutely unpleasant physical and psychological sequelae, primarily paranoia and agitation. It may also lessen the dysphoria associated with acute cocaine abstinence. It has also been proposed that concurrent alcohol abuse may be an integral part of cocaine abuse. The combination of cocaine with alcohol can cause enhanced hepatotoxicity and enhanced cardiotoxicity. Trauma in patients who use cocaine plus alcohol has been reported. Those who use cocaine plus alcohol are 3-5 times more likely to have homicidal ideation and plans; this is particularly prominent in patients with antisocial personality disorder. A large high school survey by the Centers for Disease Control and Prevention showed that illicit substance abuse, prevalence of weapon carrying, and physical fighting were higher among the adolescents who reported recent use of cocaine, marijuana, alcohol, and corticosteroids. Among 215 female homicide offenders, 70% had been regular drug users at some time before imprisonment. Alcohol, crack, and powdered cocaine were the drugs most likely to be related to these homicides. In a double-blind Read more […]

Treatment of Alcoholism: Experience with Benzodiazepines

The treatment of alcoholism depends on the phase of the disease which the physician is called on to treat: acute intoxication, acute withdrawal, or chronic alcoholism. When should anti-anxiety drugs be used? Almost never for intoxication, almost always during withdrawal, and sometimes during the treatment of chronic alcoholism. Acute intoxication First, acute intoxication, excluding pathological intoxication, but including stupor and coma, should never be treated with any depressant drug. Potentiation of the CNS depression due to the high level of blood alcohol would inevitably lead to a worsening of the condition. Alcohol plus sedative drugs are often a lethal combination. The intoxicated individual should simply be allowed to sleep it off, preferably in the protective environment of his own home. Alcoholic coma may require haemodialysis, although providing a clear airway, fluids, vasopressor drugs, steroids and meticulous nursing care usually will suffice. The one exception which requires sedative treatment is pathological intoxication. This condition of wild excitement in which the patient is a danger to himself and others probably represents an idiosyncratic reaction to a relatively small amount of alcohol. Read more […]

Amphetamines and the Law

Jimmy, 17, was riding his skateboard home on the sidewalk when suddenly, a few hundred feet ahead of him, six police cars rushed in and came to a stop surrounding a small house set back from the street. Jimmy stopped in amazement and watched as the police raced from their squad cars, banging on the door of the house and shouting at the top of their lungs. No one answered, and the police used a battering ram to break down the door and then rushed in. Jimmy and others who were passing by wanted to wait and see what happened next, but a local police officer chased everyone away, telling them to go home, the show was over. On the news that night, Jimmy heard that the house the police had raced into was a clandestine methamphetamine lab. The landlord had apparently grown suspicious and contacted the cops. Amphetamines that are abused may be diverted from legal sources, whether the drug is obtained from people with prescriptions for the drug because they have been diagnosed with attention-deficit/hyperactivity disorder or the drug is stolen from others. It may also be purchased from drug dealers or through an illicit site on the Internet. This is also the case for methylphenidate (Ritalin) that is abused. In contrast, most Read more […]

Flunitrazepam: Pharmacodynamics

Sites of Action γ-Aminobutyric acid (GABA) is the most widely distributed inhibitory neurotransmitter in the human brain. GABA owes its pharmacology to at least three receptor subtypes: GABA A-C. Whereas GABA A is coupled to a chloride channel, GABA B is coupled to cationic channels (K+, Ca2+) via G-proteins and second-messenger systems, and GABA C are chloride channels with totally different pharmacology than GABA A. A chloride channel allows negatively charged Cl- ions to enter the neurons and lower the resting membrane potential (hyperpolarization), resulting in a less excitable tissue and decreased neuronal function. The three GABA receptors have distinct structures, distinct functions, and different cellular localization and pharmacology. GABA A receptors are made of five subunits, and each subunit spans the neuronal membranes four times. This complex stoichiometry can clearly give rise to several subtypes of GABA A receptors: the most abundant human CNS receptor type is the α1β2γ2 isoform. Classically, GABA A receptors have modulatory (allosteric) sites for the binding of benzodiazepines, barbiturates, and neurosteroids. The functional response of the channel to both GABA and to its modulators is dependent Read more […]

Hallucinogens and the Law

The past fifty years have witnessed considerable debate among policy makers over the legal status of hallucinogens, although that debate has yet to reach a clear resolution. Five decades of illicit hallucinogen use by millions of Americans, coupled with legitimate scientific research, have prompted many people to challenge government claims that hallucinogens represent a serious health risk to individuals and to the nation in general. At the heart of this disagreement are the standards that since 1970 have been used to classify certain drugs as illicit while others are listed as legal. The DEA and Drug Classifications In 1970, Congress authorized the Food and Drug Administration (FDA) to study all drugs, both licit and illicit, to determine which are potentially dangerous and should be strictly regulated as controlled substances. The Controlled Substances Act, Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970, is the legal foundation of the government’s fight against the abuse of drugs and other substances. This law is a consolidation of numerous laws regulating the manufacture and distribution of narcotics, stimulants, depressants, hallucinogens, anabolic steroids, and certain chemicals Read more […]

Steroids: In the news

Steroids: Composition, Therapeutic use, Usage trends. Treatment and rehabilitation. Steroids effects. Reactions with other drugs.