At Home Drug Withdrawal

Sobriety Success

The dependence on sobriety is defined as the state of sobriety. When a person is sober, they can live on a daily basis without their thoughts and behaviors being controlled by substance dependence. They do not feel obliged to use it because they manage to live without it. They see and appreciate so much the benefits of living without substance that they do not feel they have to use drugs or alcohol. Therefore, they refrain from using it to continue enjoying this new, healthier lifestyle. The success product of sobriety is a step-by-step manual for everyone. The product has been said to be beneficial for many people around the world. The reason why the product is gaining so much popularity among individuals. They see and appreciate so much the benefits of life without substance that they do not feel they have to use drugs or alcohol. Therefore, they refrain from using it to continue enjoying this new, healthier lifestyle. This strategy encourages you to maintain the long-term vision of recovery. Recognize that this is not a one-off thing, something you try for a few weeks to several months, then return to your previous life. You will be in recovery if you decide it's the life you want to live for the rest of your life. As such, there is no immediate timeline to which you must adhere, nor should you strive to achieve goals that you are clearly not ready to face. More here...

Sobriety Success Summary


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The writer has done a thorough research even about the obscure and minor details related to the subject area. And also facts weren’t just dumped, but presented in an interesting manner.

As a whole, this book contains everything you need to know about this subject. I would recommend it as a guide for beginners as well as experts and everyone in between.

What Is The Relationship Between Stress And Illicit Drug

People take drugs for lots of reasons. People who are stressed may want to escape from reality because they cannot cope, and they may indulge in a variety of drugs. All illicit drugs are dangerous to some extent, but some are very dangerous. Cocaine may cause heart attacks and angina because it causes the heart arteries to clamp down very suddenly.

PhMRI Studies of Drug Abuse

Drugs of abuse such as nicotine, cocaine, and heroin are major problems plaguing the industrialized world. While each of the aforementioned drugs targets a different neurotransmitter system (cholinergic, dopaminergic, and opioid, respectively), there is a general consensus that much of the rewarding effects of the drugs act through the mesocortical limbic dopaminergic system including the sublenticular extended amygdala, hypothalamus, nucleus accumbens, striatum, and frontal cortex. This reward pathway is common to many other drugs of abuse, such as alcohol, as well as behaviors such as sex 144 , video games 145 , and even music 146 . Thus, there is a number of ways for investigating drugs of abuse using fMRI or phMRI. For instance, the effects of the drugs of abuse on cognitive or visual tasks targeting brain regions of interest can be studied. These effects can either be chronic or can be studied during administration of the drug of abuse 147-149 . In the latter case it is of...

Cocaine and Amphetamine Regulated Transcript

Cocaine- and amphetamine-regulated transcript (CART) encodes several putative peptide fragments, some of which decrease feeding upon central administration.36,37 (see ref 38). CART is expressed in numerous brain nuclei, and the actual site of its anorexigenic actions has not yet been fully determined. In the rat LHA, CART is detected in the lion's share of MCH neurons of the zona incerta and medial LHA, whereas most peripeduncular MCH cells do not contain CART.39-40 In contrast, no Hcrt neurons stain for CART.39-40 Notably, according to a preliminary report, some degree of Hcrt CART coexistence can be seen in the human brain.41 This would not be the first example of differential distribution of CART in primate and rodent brain the transcript displays prominent discrepancies in expression e.g. between the human and rat thalamus.42 Coexpression of orexigenic and anorexigenic neuromodulators within the same cell presents an intriguing paradox, which remains to be explained. Further...

Cocaine and Amphetamines

Cocaine is derived from the coca plant, native to South America, and is typically insufflated nasally ( snorted ), smoked (in the form of freebase or crack ), or injected intravenously. Amphetamines are analogues of naturally occurring ephedrine and have been abused in various forms since their original synthesis in 1887. Currently, -methamphetamine ( crystal meth, meth ) is the most popular form of amphetamine abused, and in some areas of the country, such as the West Coast, abuse of meth-amphetamine is more prevalent than cocaine abuse. Cocaine acts as a competitive blocker of dopamine reuptake in the synaptic cleft, which increases the concentration in the cleft, with resultant activation of dopamine type 1 and 2 receptors. In addition, cocaine increases norepinephrine and serotonin neurotransmission via reuptake inhibition, but these monoamines do not play the dominant role in its CNS effects (Jaffe 1999b). By contrast, amphetamine increases the availability of all synaptic...

Illicit drug use

Sharing occurred whether drug dependence occurred any physical, mental or social problems arising from drug misuse (as for alcohol history) any treatment interventions. Inquiries concerning illicit drug use are fraught with even greater difficulty if the patient has been indulging in other illegal activities such as theft to fund the purchase of drugs, How far questioning should be pursued depends upon the urgency of the clinical problem. Information about drug-taking by a young person brought into casualty having collapsed may prove crucial. The past medical history may also include disorders which could be due to intravenous drug misuse while the social history may include interests like attending 'raves' where the use of stimulants is common. The patient may be more forthcoming if there is an established dependence on drugs which are being medically prescribed to control dependence and to reduce harm.

Drug Enforcement Administration

The Drug Enforcement Administration (DEA) within the US Department of Justice is the chief federal agency responsible for enforcing the Controlled Substances Act. Failure to comply with the Controlled Substances Act is punishable by fine and or imprisonment. With drug abuse so prevalent, nurses must diligently adhere to the regulation imposed by the FDA and the Nurse Practice Act of their state. Any violation may result in the loss of the nurse's license to practice. Nurses must also report any misuse or abuse of these substances by other nurses to their State Board of Nursing. Most states have provisions within their Nurse Practice Act to assist nurses who have problems with drug abuse.

HIV and Rheumatological Disease

A probable role for mast cells and IgE-mediated pathology has been reported in HIV infection (130). The chemokine receptor, CCR3 is expressed on mast cells and may provide one explanation for the chemotactic effects of tat protein on mast cells (130). In one study, increased adventitial mast cell numbers were noted in the arteries of patients dying of cocaine toxicity (131,132), but the role of mast cells in HIV and cocaine-induced vascular pathology is unclear (132).

Bromide Treatment In Epilepsy

Although my work, to date, with this simplified tcchnic has not been extensive (fifty cases), I feel justified in setting rough standards as to the safety limits of bromide content in the blood serum. I feel that it is not wise to exceed a limit of 125 mg. of sodium bromide per hundred cubic centimeters of serum for the average patient. It seems likely that the bromide tolerance of patients suffering from anemia, malnutrition, cardiorenal disease, and possibly also alcoholism and drug addiction, is lower, and therefore this arbitrary standard may be a little high in these particular cases. On the other hand, in some epileptic patients it is well known that certain factors tend to increase the frequency of convulsions (such as menstruation, unavoidable periods of overwork and excitements, or dietary alterations of salt balance), and under these circumstances it will probably be wise to allow this level of blood bromides to be exceeded. When the blood bromides increase beyond 150 mg....

Colocalization Of Neurochemicals In Hcrt Neurons

Following the identification of Hcrt neurons, colocalization studies were performed to determine whether other functionally important neurotransmitters are expressed in these neurons. Substances reported to colocalize with Hcrt can be classified into three major categories neuropeptides and other neurotransmitters, receptors for neuromodulators, and other cellular factors. The neuropeptide melanin-concentrating hormone (MCH), originally isolated from the salmon pituitary, does not colocalize with Hcrt,5,18,19 although it is expressed in a large population of perifornical and LHA neurons. Broberger et al. reported that the number of Hcrt neurons was equivalent to the number of MCH neurons at the level of the LH containing the Hcrt population, but that MCH neurons were more extensive in the rostral-caudal direction. The MCH neuron population extends rostrally to the level of the caudal suprachiasmatic nucleus (SCN) and caudally to the level of the mammillary recess.18 In contrast, the...

In Agglutination Inhibition Absence of Agglutination Is Diagnostic of Antigen

Agglutination Inhibition Hcg Assay

Agglutination inhibition assays can also be used to determine whether an individual is using certain types of illegal drugs, such as cocaine or heroin. A urine or blood sample is first incubated with antibody specific for the suspected drug. Then red blood cells (or other particles) coated with the drug are added. If the red blood cells are not agglutinated by the antibody, it indicates the sample contained an antigen recognized by the antibody, suggesting that the individual was

Epidemiology and Significance of the Problem

This work was supported in part by grants R01-DA-13672, R01-DA-14039, and K12-DA-00167 to Dr. George from the National Institute on Drug Abuse (NIDA), and a Wodecroft Young Investigator Award to Dr. George from the National Alliance for Research on Schizophrenia and Depression (NARSAD).

Adjust Measures of Association for Known Sources of Non Comparability

Consider a case-control study of the role of cocaine use in relation to migraine headache, built on a case register from a regional referral hospital that specializes in the treatment of migraine headaches. If we select controls by random-digit dialing from the same geographic area as the cases, we will have to contend with the potential biases arising from differential tendency to seek medical care and particularly, medical care from this institution. Socioeconomic status is likely to be one such influence on the opportunity and ability to access care at this referral center, so that we recognize and accept that there will not be a natural balance between the social class distribution of selected controls and the true (but unknown) study base for these cases seen at this health care facility. Furthermore, social class is one predictor of cocaine use, with greater prevalence among lower social class persons. Adjusting for socioeconomic status will be beneficial to the extent that this...

Diagnostics and therapy

MS-lipidomics also offers a powerful tool for nutritional studies. For instance, the effect of caloric restriction on lipid composition of murine myocardium has been investigated by this method 148 . In another study, the effect of structure of TAGs on the chylomicron TAG composition in humans was investigated 149 . MS-lipidomics also appears to be useful in resolving the mechanisms underlying drug addiction and related issues 150 .

Side Effects of Immunosuppressants

In the first week of treatment and include pancreatitis (3.3 of patients), allergic reactions including rash, idiosyncratic hepatitis with cytonecrosis, cholestasis or insidious onset of liver dysfunction (3.3 ) and infections (7.4 ). Pancreatitis resolves upon drug withdrawal but recurs on retreatment, which precludes the use of either AZA or 6MP.

Other Cerebral Symptoms

Patients with rheumatic fever usually do not have chills. Chills are common in patients with bacterial endocarditis. Symptoms of fever, chills, or sweats in any patient with a heart murmur should lead one to suspect infective endocarditis (see Chap. 73). A history of valvular heart disease is not a prerequisite for a diagnosis of endocarditis, since previously normal valves become infected. A history of recent dental work, genitourinary surgery, or illicit drug use increases the suspicion of infective endocarditis. Fever may accompany pericarditis. Myalgia, chills, and fever on rare occasions may be related to MI, presumably because of some form of immunologic response to the necrotic myocardial tissue. An intracardiac tumor (myxoma) may produce systemic symptoms in the absence of infection. Low-grade fever in a patient with heart failure may be a sign of pulmonary emboli.2 A profuse cold sweat mediated by sympathetic discharge often accompanies early stages of acute MI. Excessive...

Mental Performance Outputoriented versus Engagementoriented

In areas other than athletics, we accept to a considerable extent that artists may use specific forms of mind altering procedures or artificial enhancers of their creativity, without in the least lowering our admiration for the works they produce. For example, the fact that Charles Baudelaire took cocaine before writing some of the poems from the Fleurs du Mal , leaving more or less obvious vestiges of this enhancing substance in the poems themselves, does not diminish their artistic value (although some people with a faint puritan inclination may find that it diminishes their respect for Baudelaire as a poet and a person). Contrasting that real-life example with our Beethoven thought experiment above, the following supposition seems fairly plausible. Artificial means intentionally applied for the purpose of enhancement in a creative process of art, would probably have to cover an overwhelming share of the entire range of preconditions of that...

Orexigenic and Anorexigenic Studies

A combination of central and peripheral mechanisms control food intake. Indeed, hypothalamic nuclei and the brainstem act as input stations for hormonal and gastrointestinal information (10,11). Furthermore, peripheral satiety factors such as cholecystokinin (CCK) activate CCK1 receptors on vagal afferents, which transmit signals to hindbrain nuclei such as the nucleus tractus soli-tarius (NTS). The NTS in turn communicates with several hypothalamic nuclei, which play critical roles in appetite regulation. In addition, adipose tissue secretes the hormone leptin, which enters the CNS and stimulates the arcuate nucleus within the hypothalamus. Leptin appears to be the main signal via which the hypothalamus senses nutritional states and modulates food intake. Leptin directly affects neurons in which either the anorexigenic (appetite-reducing) peptides proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) or the orexigenic (appetite-stimulating) peptides...

Examine Subsets of the Population with Differing Exposure Data Quality

Accuracy of exposure assignment may vary in predictable ways in relation to attributes such as gender, education, or age. Based on previously reported research or based on validation studies contained within the study of interest, groups may be defined for whom the routine exposure measure is more likely to be valid than it is for other groups in the study. Younger persons may show a greater or lesser concordance of the routine and superior exposure measures than older persons, or women may report more or less accurately than men. Often, groups expected to have superior cognitive function, e.g., younger participants versus the elderly, or those without a history of alcohol and drug abuse compared to those with such a history, are likely to provide better quality information through recall and self-report. In fact, when the disease itself is associated with cognitive decline, e.g., studies of chronic neurodegenerative disease, case-control studies are susceptible to bias because cases...

Table 151 Characteristics of different pain types

Known allergies to the materials in the implant Known allergies to the intended medication(s) Active intravenous drug abusers Psychosis or dementia Relative exclusion Emaciated patients Ongoing anticoagulation therapy Children whose epiphyses have not fused Occult infection possible Recovering drug addicts

Substance Use Screening and Treatment

More recent controlled studies of integrated dual-diagnosis treatment have demonstrated the efficacy of this approach. McHugo et al. (1999) showed that programs with high fidelity to dual-diagnosis treatment principles produced markedly greater rates of sobriety than other treatment strategies. After 36 months, patients in high-fidelity programs had a 55 rate of stable remission, whereas only about 15 of patients in low-fidelity programs were in stable remission. In Manchester, UK, Barrowclough et al. conducted a controlled 12-month study comparing outcomes in 18 patients with schizophrenia and substance use disorders employing an integrated approach of motivational interviewing, family interventions (including a family support worker), and cognitive behavior therapy, with outcomes from usual care (n 12) (Barrowclough et al. 2001). There was high retention in the integrated-care group (94 ), with significant improvements compared with usual care on the Global Assessment of Functioning...

Psychological disorders

Patients with psychological disorders need to maintain their medication however, this may interact with the anaesthesia required for the surgical procedure. Problems can also arise with patients with a drug abuse problem who may engage in non-therapeutic self-medication prior to surgery, which can give rise to pharmacological and handling problems. Full cooperation of the patient is essential, both at the time of surgery and subsequently if the outcome is to be optimum. While psychological problems are not in themselves an absolute contraindication to implant treatment, most clinicians experienced in this field have treated patients whose personality problems have subsequently given them cause to regret their original decision.

Lateral Hypothalamic Selfstimulation And The Hypocretin System

Most drugs of abuse have been shown to increase brain reward function, as measured by lowering of ICSS reward thresholds.52-54 This drug-induced lowering of ICSS thresholds, considered as an accurate measure of euphorigenic drug action,55 suggests that drugs of abuse synergize with the rewarding ICSS and that both these rewarding stimuli likely act on the same reward substrates in the brain. In contrast to this acute lowering action, chronic exposure to drugs of abuse generates adaptations in reward circuitries such that drug withdrawal significantly elevates ICSS thresholds.56-60

Hypocretin And Brain Reward Modulation

To summarize, starvation activates the hypocretin orexin system which relay these signals to the brainstem nuclei involved in the modulation of brain reward function and arousal. The concomitant brain reward function decrease, usually observed under drug withdrawal, can be considered here as a food withdrawal which will lead to food seeking and, ultimately, food taking. In this perspective, the hypocretin system could be considered as a key relay that promotes incentive motivation for food-seeking, and as such enhances wakefulness and locomotor activity.82

Evidence Supporting Alterations of DA Systems in Schizophrenia

Ellinwood (Ellinwood 1967 Ellinwood et al., 1973) provided one of the most insightful descriptions of amphetamine-induced psychosis by conceptualizing the condition as a continuum that evolves from the gradual onset of paranoid tendencies to delusional paranoia. The first step is characterized by stimulation of interpretative mental activities (great attention to details, intense feeling of curiosity, repetitive searching, and sorting behavior). Ellinwood sees in Sherlock Holmes, a regular cocaine user, a prototypical example of the endless search for meanings (my mind rebels at stagnation). With increased exposure, these paranoid tendencies and interests for the minutiae develop into an intermediate stage, which is characterized by marked enhancement of perceptual acuity, sustained ''pleasurable'' suspiciousness, and compulsive probing behavior. Finally, this inquisitive behavior is reversed and projected to others (persecution), leading to paranoia and ideas of references. The...

Hypocretin And Relapse For Drugseeking

In contrast to Hcrt-1-induced long-lasting elevations in ICSS thresholds, a single injection of Hcrt-1 was associated with a slight effect on cocaine self-administration, given that cocaine consumption remained nearly unchanged just after or 6 hours after the Hcrt-1 infusion.61 Preliminary results obtained in our lab showed that Hcrt did not induce any significant increase on heroin intake in rats either. Furthermore, despite an effect on ICSS thresholds,42 leptin does not modulate cocaine nor heroin self-administration in rats. Such a discrepancy between a marked elevation in ICSS thresholds and an absence of effect on both cocaine and heroin intake remains unclear. However, dissociation of neural systems subserving positive reinforcement and incentive motivation has been proposed previously.83-85

Imaging Techniques for Studying Neuronal Activity

The technique of functional magnetic resonance imaging (fMRI) using either relative cerebral blood volume (rCBV), blood oxygenation level dependent (BOLD) or Trbased cerebral blood flow (CBF) techniques has led to a revolution in brain mapping 1 -3 . This is largely due to the fact that the advent of a noninvasive tool with reasonable contrast to noise, spatial, and temporal resolution, allows for studies to be conducted more easily than the prior positron emission tomography (PET) studies of brain activation. Both fMRI and PET studies of brain activation are based upon the coupling between neuronal activity, metabolism, and hemodynamics (see also Chapter 11, Section 2). The possibility that fMRI may help understand the organization and flow of information in the brain has led to an explosion in the number of centers dedicated to performing the technique. In addition to the interest in fMRI by the neuroscience community, a number of clinical conditions has the potential to benefit...

Summary And Perspectives

However, Hcrt-1-induced drug seeking can not be limited to a simple stress like-reinstatement given that Hcrt-1 was shown to reinstate both drug- and food-seeking, whereas footshock stress, for example, was shown to reinstate cocaine-but not food-seeking behavior after extinction.88

Anatomical Basis Of Dopamineorexin Interactions

The dopaminergic neurons of the ventral mesencephalon are a major site of action of psychostimulants, such as amphetamine and cocaine. Lesions of the A10 DA neurons in the ventral tegmental area (VTA) or the dopaminergic axons of VTA neurons that innervate the nucleus accumbens block psychostimulant-induced hyperactivity.5 The A10 DA neurons projection widely to corticolimbic forebrain sites, including the medial and suprarhinal prefrontal cortices, the nucleus accumbens, lateral septum, bed nucleus of the stria terminalis, and central and basolateral amygdala. Because orexin-containing axons are found in the ventral mesencephalon, it follows that the orexin and dopamine systems may interact. The involvement of mesotelencephalic dopamine systems in such diverse functions as locomotor activity, cognition, and affect, and the alterations in these domains in neuropsychiatry disorders, suggests that orexin-dopamine interactions may prove to be a fruitful target for new approaches to...

Future Prospects With Promising Molecules

Leptin exerts its action through different neurot-ransmitters such as neuropeptide Y (NPY), glucagon-like peptide 1 (GLP-1), a-melanocyte-stimulating hormone (a-MSH), corticotrophin-re-leasing hormone (CRH) and cocaine and amphetamine regulated transcript (132,133). Extensive research has been done on the role of these peptides in the regulation of food intake in both animals and humans. The most recently discovered families of hy-pothalamic peptides involved in the regulation of food intake are the cocaine and amphetamine regulated transcript peptides (CART) (141) and the orexins (142) or hypocretins (143), confirming the complex neuroendocrine system of weight regulation.

Field Strength Dependencies of BOLD and IRON

An attractive feature of measurement of rCBV, as opposed to BOLD, is that rCBV changes should be independent of field strength, whereas BOLD signal changes are extremely field strength dependent. This means that drug-induced changes observed at different fields can be compared for IRON, but not for BOLD. We investigated whether or not such a contention was true, by comparing the activation due to two drugs targeting the dopamine transporter cocaine and methylphenidate. We then compared the measured rCBV changes at 2 T, 4.7 T, and 9.4 T. As expected, the interanimal variability was much larger than the variation in rCBV as a function of field strength 94 . Both experimental data and simulations showed that the CNR advantages of IRON persist even at field strengths as high as 4.7 T by a factor of 3 87,94 . At very high fields such as 9.4 T, BOLD CNR increases to the point where it is competitive with IRON. However, there are some additional considerations that render the IRON technique...

Altered States Of Consciousness Internal Influences

Both techniques produce changed states of consciousness for some users. Many meditators claim profound benefits from meditation, including increased understanding of the self and the relationship of the self to the environment. Sometimes meditation is accompanied by changes in physiological processes such as those found in biofeedback. Meditation even has been used as therapy for drug abuse.

Basic Drug Challenge Designs 1041 Acute Model

In this regard it should be kept in mind that the pharmacodynamic profile of various drugs can often be very different even when targeted towards the same receptor system. For instance, cocaine and amphetamine have very similar effects upon the synaptic dopamine concentration, however, cocaine has a much shorter time course. In addition, cocaine has effects that are extremely sensitive to the method of administration. A similar effect upon synaptic dopamine changes and hemodynamic changes that occurs for cocaine at a dose of say 1 mg kg i.v. requires about 10 mg kg i.p. or p.o. For amphetamine, the relative difference for i.p. vs. i.v. challenge is about 30 less for the i.p. administration compared with the factor of 10 for cocaine. Thus, it cannot be stressed enough, to understand as much as possible about the pharmacodynamic profile of the drug of choice before performing the experiment. On the other hand, maybe phMRI will become a useful adjunct for performing such pharmacodynamic...

Antagonism and Agonism of Acute Drug Challenges

A new compound, is the antagonism and agonism of the drug effects. Examples of this type of experiment have been the use of D1 antagonists to turn off the effects of cocaine 10 , the use of adenosine A2a antagonists to turn off the effects of amphetamine 61 , the use of D2 agonists to turn off amphetamine-induced rCBV 56 , and the use of D2 and D3 receptor antagonists to potentiate the effects of amphetamine 56,132 .

The Acute Model for Examining the Effects of Chronic Drug Administration

At first glance it may appear as if the acute drug challenge model has severe limitations for examining the effects of chronic drug changes. Such changes are of crucial importance for understanding receptor dynamics in situations often encountered clinically. Two important examples stand out. The first is the effects of chronic administration of antipsychotic medications in schizophrenic populations. Drugs such as haloperidol, olanzapine, or clozapine often require a period of time before attaining full efficacy. A second salient example comes from the study of chronic abusers of drugs such as cocaine or ecstasy. It is well known that abusers often experience a tolerance to the effects of these drugs, implying changes in receptor populations that modulate the pharmacology of the drug of abuse. Thus, it would appear as if the acute drug challenge may not provide an adequate model for examining receptor dynamics. However, there are many ways to construe the acute drug challenge model....

Altered States Of Consciousness External Influences

Psychologists make several distinctions regarding behaviors associated with drugs. First, they distinguish between drug use, where no impairment or actions harmful to others seem to occur, and drug abuse, where users' daily actions or health may be significantly impaired and harmful actions toward others may result. EXAMPLE 6.11. A casual alcoholic drink with friends at an evening party constitutes drug use but is unlikely to result in drug abuse. Repeated binge drinking that impairs health, jeopardizes others (for example, driving while intoxicated), or impairs normal functioning on the job would be classified as drug abuse. Interestingly, some forms of abuse may not be readily recognized Many people abuse the intake of caffeine, drinking coffee or soft drinks to the extent that failure to have the beverages causes various forms of impairment. Psychologists also distinguish between physiological drug dependence and psychological drug dependence. Physiological drug dependence occurs...

At the Epidermal Growth Factor Receptor Tyrosine Kinase

Abstract The epidermal growth factor receptor (EGFR) is a promising target for anti-cancer therapy because of its role in tumour growth, metastasis and angiogenesis, and tumour resistance to chemotherapy and radiotherapy. This chapter describes a low-molecular-weight EGFR tyrosine kinase inhibitor (EGFR-TKI), Iressa (gefitinib, ZD1839). Iressa is a potent EGFR-TKI which blocks EGF-stimulated EGFR autophosphorylation in tumour cells and selectively inhibits EGF-stimulated tumour cell growth. In studies with mice bearing a range of human tumour-derived xenografts, Iressa given orally, once daily, inhibited tumour growth in a dose-dependent manner. Long-term ( 3 months) Iressa treatment of xenograft-bearing mice was well tolerated, and Iressa completely inhibited the growth of xenografts derived from A431 cells which highly express EGFR, and induced regression of advanced A431-derived tumours. No Iressa-resistant tumours appeared during treatment, but some tumours regrew following drug...

In Vivo Antitumour Activity

In long-term treatment studies, Iressa provided complete control of tumour growth when drug treatment was withdrawn after 4 months, most but not all tumours resumed growth, demonstrating that Iressa has a cytostatic effect. When drug treatment was delayed until tumours were well-established, Iressa caused complete regression of all A431 tumours. Drug withdrawal again allowed tumour regrowth. No evidence for the development of drug resistance emerged during these studies with A431 tumours, since no tumour regrew during Iressa treatment (Wakeling et al. 2002). To assess the pharmacodynamic action of Iressa treatment, A431 tumours were excised 6 h after the last of four daily doses of 0, 12.5, 50 and 200 mg kg Iressa, or at 2, 4, 6, 24, 30 and 36 h after a single 50 mg kg dose. Total RNA was extracted from the tumours to quantify c-fos mRNA by RT-PCR. C-fos expression was inhibited in a dose-dependent manner at the anti-tumour ED50 dose (50 mg kg), c-fos mRNA was reduced by 94 and was...

Pyrrolidine and Tropane Alkaloids

Simple pyrrolidine-containing alkaloid structures are exemplified by hygrine and cuscohygrine, found in those plants of the Solanaceae that accumulate medicinally valuable tropane alkaloids such as hyoscyamine or cocaine (see Figure 6.3). The pyrrolidine ring system is formed initially as a A pyrrolinium cation (Figure 6.2). PLP-dependent decarboxylation (see page 20) of ornithine gives putrescine, which is then methylated to N-methylputrescine. Oxidative deamina-tion of N-methylputrescine by the action of a diamine oxidase (see page 28) gives the aldehyde, and Schiff base (imine) formation produces the N-methyl-Ax-pyrrolinium cation. Indeed, the aminoaldehyde in aqueous solution is known to exist as an equilibrium mixture with the

Kearns Sayre Syndrome

Sequelae Hypoxic Ischemia Mri

Specific chemical affinity contributes to selective vulnerability. It has been known for a long time that certain areas in the brain are especially liable to damage by certain toxic agents. Hexachloro-phene intoxication involves myelin sheaths exclusively. Hexachlorophene encephalopathy, induced in preterm neonates by washing them for antiseptic reasons with hexachlorophene-containing solutions, causes a myelinopathy with splitting of the myelin lamellae and intramyelinic vacuole formation. Vacuolating myelinopathy in the neonate always has a special distribution,irrespective of its cause, related to the distribution of myelinated versus unmyelinated areas. A clear example is found in maple syrup urine disease. Intoxication with triethyltin, cuprizone, toxic heroin, or poisoned cocaine also leads to myelin splitting and vacuolation. Furthermore, lipophilic substances

Mesolimbic Dopamine System

Twins separated at birth and reared in different environments, and other studies involving the use of rats, have implicated the gene that codes for one subtype of dopamine receptor (designated D2) in alcoholism. Other addictive drugs, including cocaine, morphine, and amphetamines, are also known to activate dopaminergic pathways. Wfr Cocaine a stimulant related to the amphetamines in its action is currently widely abused in the United Ji i i States. Although early use of this drug produces feelings of euphoria and social adroitness, continued use leads to social withdrawal, depression, dependence upon ever-higher dosages, and serious cardiovascular and renal disease that can result in heart and kidney failure. The numerous effects of cocaine on the central nervous system appear to be mediated by one primary mechanism cocaine binds to the reuptake transporters for dopamine, norepinephrine, and serotonin, and blocks their reuptake into the presynaptic axon endings. This results in...

Functions of the Autonomic Nervous System

Cocaine blocks the reuptake of dopamine and norepinephrine into the presnaptic axon terminals. This q causes an excessive amount of these neurotransmitters to remain in the synaptic cleft and stimulate their target cells. Since sympathetic nerve effects are produced mainly by the action of norepinephrine, cocaine is a sympathomimetic drug (a drug that promotes sympathetic nerve effects). This can result in vasoconstriction of coronary arteries, leading to heart damage (myocardial ischemia, myocardial infarction, and left ventricular hypertrophy). The combination of cocaine with alcohol is more deadly than either drug taken separately, and is a common cause of death from substance abuse.

Freuds Specimen Dream of the Botanical Monograph

On the night before Freud received a letter from Wilhelm Fliess I am very much preoccupied with your dream-book. I see it lying finished before me. I see myself turning over its pages. 8 That morning, preceding the dream, Freud had seen a new book on the genus Cyclamen in the window of a book shop. Freud recounts a further day residue of the dream. During the same evening he had a long conversation with his friend Konigstein regarding a Festschrift that omitted reference to Freud's contribution to the discovery of the anesthetic properties of cocaine. Freud's conversation with his friend also included an allusion to a patient of Freud's called Flora and a friend of his wife, Frau L., who had met Freud's wife Martha two days before the dream and whom he had treated some years earlier. Frau L. had been accustomed to receiving a bouquet of flowers from her husband on her birthday, and once, he forgot, causing her to burst Freud's associations to his dream also included a revealing...

Patterns of Substance Abuse Among Persons With Schizophrenia

Phrenia, and then prospectively interviewed and followed another sample of 115 first-episode patients representing 86 of consecutive admissions for admissions in the local area (Buhler et al. 2002). The investigators found that 62 of those with drug abuse and 51 with alcohol abuse began their habit before any signs of the illness were manifest, including prodromal nonpsychotic symptoms. Significantly, there was no correlation found between onset of abuse and onset of psychotic symptoms, although it was noted that the onset of abuse and the psychotic disorder occurred in the same month in 18.2 who abused alcohol and 34.6 who used drugs, implying that there may be a subset of schizophrenia patients whose development of psychotic symptoms were speeded or precipitated by substance use, particularly cannabis use. These data from the combined pools of first-episode patients are similar to those reported for the original group of 232 first-episode patients analyzed separately (Hambrecht and...

Environmental Factors

Fetal Alcohol Syndrome Vulva

Amphetamines Warfarin ACE inhibitors Cocaine One of the increasing problems in today's society is the effect of social drugs, such as LSD (lysergic acid diethylamide), PCP (phencyclidine, or angel dust ), marijuana, alcohol, and cocaine. In the case of LSD, limb abnormalities and malformations of the central nervous system have been reported. A comprehensive review of more than 100 publications, however, led to the conclusion that pure LSD used in moderate doses is not teratogenic and does not cause genetic damage. A similar lack of conclusive evidence for teratogenicity has been described for marijuana and PCP Cocaine has been reported to cause a number of birth defects, possibly due to its action as a vasoconstrictor that causes hypoxia.

Interpretation And Implications For Addiction Biology

The data discussed in this chapter is suggestive of a direct involvement of the ORX HCRT system in response to morphine. However, a number of critical questions remain with regard to the role of ORX HCRT neuropeptides in drug addiction. First, it should be emphasized that the above studies focus on morphine dependence and do not evaluate the role of ORX HCRT in the reinforcing properties of drugs of abuse. Studies using conditioned place preference, or drug self-administration are needed to garner a more complete picture of the role of ORX HCRT in addiction. Nonetheless, the development of physical dependence is an important component of drug addiction. Koob and colleagues have proposed that negative physical and emotional states are the critical components that drive addiction.45 Thus, it is essential to define the molecular adaptations that lead to dependence and the development of negative states since they represent potential targets for treatment of drug addiction. The...

Geographic Spread and Control of Epidemics

The geographic spread of epidemics is less well understood and much less well studied than the temporal development and control of diseases and epidemics. The usefulness of realistic models for the geotemporal development of epidemics be they infectious disease, drug abuse fads or rumours or misinformation, is clear. The key question is how to include and quantify spatial effects. In this chapter we describe a diffusion model for the geographic spread of a general epidemic which we then apply to a well-known historical epidemic, namely, the ever fascinating mediaeval Black Death of 1347-50. We then discuss practical models for the current rabies epidemic which has been sweeping through continental Europe and is now approaching the north coast of France. These types of models, of course, are not restricted to one disease.

Paracrine Regulation of Blood Flow

Cocaine inhibits the reuptake of norepinephrine into the adrenergic axons, resulting in enhanced sympathetic-induced vasoconstriction. Chest pain, as a result of myocardial ischemia produced in this way, is a common cocaine-related problem. The nicotine from cigarette smoke acts synergistically with cocaine to induce vasoconstriction.

The Hypothalamus And Addiction

Neuron 10x

Many levels of hypothalamic function are likely to influence addiction. While most of the previous work on the role of the hypothalamus in addiction assessed effects of the HPA (hypothalamic-pituitary-adrenal) axis and various physiological states, such as stress, on addiction,25-27 the LH-restricted expression of ORX HCRT suggests a direct role for these peptides in controlling addiction-related behaviors. Indeed, the ORX HCRT neurons project broadly to regions throughout the brain, including mesolimbic and brainstem nuclei known to be important in the development of drug addiction.15,28-30 The LH, in particular, has a history of being associated with drug addiction and drug abuse behavior. The relationship between the LH and both feeding and addiction may not be surprising since behavioral studies have shown cross-sensitization between 'natural' rewards and drugs of abuse. Both drugs of abuse and food restriction profoundly modulate LH-mediated ICSS and their effects can...

Psychiatric Disorders

Because of the recent interest in hypocretin dysfunction in neurological diseases and because of the functions of the hcrts, recent studies have evaluated whether altered hypocretin neurotransmission might be also involved in some psychiatric disorders. We will focus in the present review on depression and schizophrenia. The involvement of the hypocretins in stress and drug addiction is also today documented and we recommend to the readers to refer to the specific chapters in the book devoted to these two aspects of behavior. The hcrt system is also currently evaluated in other psychiatric disorders such as eating disorders.

Mesenteries Of The Intestinal Loops

Transverse Colon Abnormalities

Gastroschisis (Fig. 13.31 C) is a herniation of abdominal contents through the body wall directly into the amniotic cavity. It occurs lateral to the umbilicus usually on the right, through a region weakened by regression of the right umbilical vein, which normally disappears. Viscera are not covered by peritoneum or amnion, and the bowel may be damaged by exposure to amni-otic fluid. Gastroschisis occurs in 1 10,000 births but is increasing in frequency, especially among young women this increase may be related to cocaine use.

Surgical Technique

Endonasal Dcr Surgery

In approximately 8 of patients there is an agger nasi cell in this area and the light will be more diffuse. Very occasionally, the light is difficult to see and then the light on the endoscope can be turned off to help define where the bone is thinnest. If the light is diffuse and there is an agger nasi air cell, it will be necessary to open this up and go through it before going through the lateral wall and the lacrimal bone into the sac. It is best not to open the sac very high up without also opening it inferiorly, as a sump can form that collects mucus and can predispose to recurrent infection. If the procedure is done under local anesthesia, amethocaine drops are placed in the eye, followed by a nasal pack (1 cm ribbon gauze or a patte soaked in cophenylcaine or 6 cocaine) and an injection of 1 lignocaine injected through the surface of the conjunctiva around the sac. The latter may look alarming to the novice, but the conjunctiva is well anaesthetized with...

Dopamineregic Transmission and EEG Arousal

Amphetamine (which showed a potent EEG arousal property) has however, a relatively low DAT binding affinity,67 suggesting that other mechanisms, such as monoamine release (exchange diffusion through the DAT) by amphetamine, are also involved in the mechanism of EEG arousal. Amphetamine is also reported to block the vascular monoamine transporter 2 (VMAT 2) and to induce reverse-transport of monoamines into the synaptic area.68 To further assess the net effects of amphetamine on monoaminergic neurotransmission, we measured DA and NE efflux together with wake-promoting effects of amphetamine-analogs and isomers in the canine narcolepsy model.69 Polygraphic recordings demonstrated that d-amphetamine was about twice as potent as l-amphetamine, and was 6-times more potent than l-methamphetamine in increasing wakefulness, while d-amphetamine and l-amphetamine were equipotent in reducing REM sleep and cataplexy, and l-methamphetamine was about half as potent as l- and d-amphetamine.69 By...

Human And Ecological Relevance Of Leaves

Pennyroyal Mosquito Plants

Leaves are an important source of drugs used in medicine and also of narcotics and poisons. Cocaine, obtained from plants native to South America, has been used medicinally and as a local anesthetic, but its use as a narcotic has, in recent years, become a major problem in western cultures. Andean natives chew coca leaves while working and are reported capable of performing exceptional feats of labor with little or no food while under the influence of

Vasospastic claudication

Certain pharmacologic agents can cause or aggravate Raynaud's phenomenon. The most notorious for that toxicant is nicotine. Smoking can cause both coronary and peripheral vasoconstriction and has been associated with coronary spasm in men and women (61). Cocaine is another cause of both coronary and peripheral vasospasm. Ergotamine derivatives can also produce both coronary and peripheral vasospasm. Raynaud's phenomenon occurs in about 30 of cases following chemotherapy with Vinca alkaloids and bleomycin. -Blockers have also been reported to cause Raynaud's phenomenon, but very rarely as have certain sympathomimetic agents used as over-the-counter cold preparations.

Sarcoid And Maxillary Sinus

Sinonasal Wegener Granulomatosis

Destruction of central facial bone structures is the hallmark of cocaine induced midline destructive lesions. This process shows a centrifugal pattern of progression, starting from the nasal septum (eroded in 100 of patients) to involve turbinates Fig. 6.30. Cocaine induced midline destructive lesions. Gd-DTPA enhanced SE T1, axial plane. Extensive destruction of midline nasal structures with involvement of the nasal septum and both inferior turbinates. Distortion of the inferior portion of the nose is also seen Fig. 6.30. Cocaine induced midline destructive lesions. Gd-DTPA enhanced SE T1, axial plane. Extensive destruction of midline nasal structures with involvement of the nasal septum and both inferior turbinates. Distortion of the inferior portion of the nose is also seen Fig. 6.31. Cocaine induced midline destructive lesions. TSE T2, coronal plane. Bilateral meningoencephalocele (arrows) secondary to extensive destruction of all centrofacial structures Fig. 6.31. Cocaine induced...

Perioperative Anesthetic Management

Adequate vasoconstriction of the nasal mucosa is essential for providing reasonable conditions for transsphenoidal surgery. This need becomes even more important if an endoscopic technique is being used. Traditionally, mixtures of cocaine and epinephrine have been used, but the high incidence of subsequent arrhythmias has resulted in the search for safer alternatives a mixture of the sympathomimetic xylometazoline and lidocaine produces effects equivalent to those of cocaine.

Treatment And Prevention

In the event that these conditions cannot be fulfilled, and in case of homelessness, suspected or known history of noncompliance, MDR-TB, and illicit drug use, the local health department (that should be informed of all suspected or proven TB cases) facilitates methods to achieve appropriate respiratory isolation.

General Anesthetic Technique

Palatine artery this appears to reduce the amount of peroperative bleeding. Whether cophenylcaine, or 2 ml of 6 cocaine with 8 ml of saline, or Moffatt's solution (2 ml of 6 cocaine, 1 ml of 1 1000 epinephrine, 1 ml of sodium bicarbonate 8 , made up with 6 ml of saline to 10 ml overall) is used depends on the surgeon's preference. It is best left in position for at least 5 minutes to have its maximum effect (Fig. 10.2).

Viral Hepatitis 21 Hepatitis A

Infection with HBV accounts for approx 20 of cases of acute viral hepatitis in older adults (60,66). Because the primary risk group in the U.S. and Europe is intravenous drug abusers, a group not highly represented in the elderly population, acute infection is not common in this age group. Transfusion-related HBV infection from contaminated blood in the window period of detection is a now an uncommon event with risk estimated to be 1 in 63,000 transfusions (67). Long-term care facilities were at one time considered a risk area for HBV when several outbreaks occurred during the 1970s-1980s (60). However, recent surveys of geriatric hospitals indicate the prevalence of HBSAg is similar to the general geriatric population (

Norepinephrine as a Neurotransmitter

Norepinephrine, like ACh, is used as a neurotransmitter in both the PNS and the CNS. Sympathetic neurons of the PNS use nor-epinephrine as a neurotransmitter at their synapse with smooth muscles, cardiac muscle, and glands. Some neurons in the CNS also use norepinephrine as a neurotransmitter these neurons seem to be involved in general behavioral arousal. This would help to explain the mental arousal elicited by amphetamines, which stimulate pathways in which norepinephrine is used as a neurotransmitter. Such drugs also stimulate the PNS pathways that use norepinephrine, however, and this duplicates the effects of sympathetic nerve activation. A rise in blood pressure, constriction of arteries, and other effects similar to the deleterious consequences of cocaine use can thereby be produced. 4. Explain how cocaine and amphetamines produce their effects in the brain. What are the dangers of these drugs

Routine Laboratory And Neuroimaging Tests

Index of suspicion based on the clinical history. Spells thought to be related to alcohol or drug abuse can be investigated by toxic screens of blood or urine. An impression of vestibular disease can be investigated with quantitative calorics and nystagmography. No blood tests or special diagnostic studies are presently widely accepted for the diagnosis of complicated migraine, although provocative tests, such as the histamine challenge, have been advocated by some. In general, routine laboratory studies and neuroimaging should be performed selectively in diagnosis of spells, based on a suspicion for particular etiologies.

The Evaluation Of Syncope

It is imperative that the physician should explore the potential for drug use as a cause of syncope. Illicit use of recreational drugs, such as cocaine, heroin, methylam-phetamine, and alcohol may result in syncope because of heart rhythm or blood pressure disturbances (2). A number of therapeutic agents may also produce syncope, either by provocation or exacerbation of arrhythmias or by the volume depleting or vascular relaxing effects of antihypertensives.

The Poppy Family Papaveraceae

Oozing Opium

Heroin, a scourge of modern societies, is a derivative of morphine. It is from four to eight times more powerful than morphine as a painkiller, and less than 100 years ago, it was advertised and marketed in the United States as a cough suppressant. It is estimated that 75 of American drug addicts used heroin up until the early 1980s, but cocaine has now largely replaced it. The loss to society in terms of its economic,

Neurovascular Coupling Many Neurotransmitters Are Vasoactive

This fact will not necessarily generalize to the other neurotransmitter systems, such as the dopaminergic system, for the simple reason that in the case of dopamine most of the reuptake occurs on the presynaptic side of the dopamine neuron via the dopamine transporter (DAT) protein. This system is reviewed by Cooper et al. 35 . Second, dopamine synthesis and uptake are, to a large degree, controlled by presynaptic D2 autoreceptors that are more sensitive than postsynaptic dopamine receptors to the effects of dopamine or apomorphine. These data seem to suggest that the metabolic changes would be mediated via the presynaptic dopamine neurons. It was with this thought in mind that we investigated this hypothesis using unilateral lesioning of the nigrostriatal dopamine tracts using 6-hydroxydopamine 5 . These experiments showed that the hemodynamic changes induced by either amphetamine or (CFT) were ablated by the presynaptic lesioning, and this was consistent with PET data obtained in...

Specific Activities as Potential Triggers of Acute Myocardial Infarction

Trigger Worksheets For Mental Health

Cocaine use (105) Further analysis of the data from the Myocardial Infarction Onset Study has identified an increased risk of myocardial infarction following exposure to specific substances. One such analysis identified a nearly 24-fold increase in the risk of myocardial infarction in the 60 min following cocaine use (95 confidence interval 8.5-66.3) (105). Another

Rat and Monkey Models of Parkinsons Disease

We have extensively studied the 6-OHDA rat PD model using phMRI 5,8,12 . A schematic of such a model was shown in Figure 10.11. Our studies have been geared towards multiple objectives. First, we wished to show that the hemodynamic effects of amphetamine or p -CFT (a selective dopamine transporter blocker similar to cocaine or methylphenidate) were due to dopamine release itself, and not some other neurotransmitter. This aspect of the experiment was discussed above in the beginning of Section 10.5. Careful lesioning leads to selective dopamine cell loss, whereas cholinergic, serotonergic, and noradrenergic neurons are preserved. Thus, we showed that there was loss of the hemodynamic response on the lesioned side, whereas the phMRI response was preserved on the intact side 5,8 . This effect is shown in Figure 10.12. In this figure there is a loss of response to amphetamine on the lesioned side. Conversely, there is an increased response to apomorphine. Second, we showed that the...

How might intracranial vascular imaging influence clinical management

Intra Carotid Plaque

Fig. 7. a Selective intra-arterial carotid DSA (lateral projection) showing luminal irregularity with segmental narrowing and widening of branches of both the middle and anterior cerebral arteries. The patient presented with a haemorrhagic stroke after taking an unknown mixture of illicit substances, thought to include 'ecstasy'and cocaine. These peripheral arterial branches are rarely clearly visualised with current intracranial CTA or MRA imaging techniques b High power view of the same patient showing stenotic and dilated segments of the angular branch of the middle cerebral artery (arrows) c I-ADSA following a left common carotid injection shows occlusion of the cervical internal carotid artery with refilling of the cavernous and supraclinoid internal carotid artery by reversed flow in the ophthalmic artery the ophthalmic artery is supplied by branches of the external carotid artery. Large arrow, point of reconstitution of the intracranial cavernous ICA Small arrow, reversed flow...

Housing Instability and Homelessness

Comorbid substance use disorders in schizophrenia are consistently associated with increased risk for homelessness among persons with schizophrenia (Drake et al. 1991). In Caton and colleagues' (1994) case-control study comparing 100 indigent men with severe mental illness and home-lessness with 100 men with schizophrenia who were not homeless, homeless subjects had significantly higher rates of drug abuse. Studies of innovative service models for the homeless mentally ill have found that persons with substance use comorbidity do not benefit as much from these programs as do the non-substance-using severely mental ill individuals, in part due to the fact that substance-using severely mental ill patients lead a more transient lifestyle. In one study of assertive community treatment for the homeless mentally ill, homeless persons with substance use disorders had more moves during the treatment year than other severely mental ill patients (Holohan et al. 1997).

Pathogenesis And Immunologic Aspects

Containment of the TB infection results in an asymptomatic and noninfectious state with a positive tuberculin skin test reaction (TB infection) the viable tubercle bacilli remain dormant indefinitely with intact host immune integrity. Factors that compromise host immunity, e.g., HIV infection, aging, illicit drug use, alcoholism, poor nutrition, and certain chronic diseases, may result in reactivation of latent TB infection (TB disease). The increased frequency of TB seen in aging may be explained in large part by the impairment of cell-mediated immunity, which results from senescence (demonstrated in murine models) as well as age-associated diseases (diabetes mellitus, malignancy), renal impairment, malnutrition, and immunosuppressive agents (13).

Anorexigenic Peptides

Effects of Cocaine- and Amphetamine-Regulated Transcript (CART) Cocaine- and amphetamine-regulated transcript (CART) is a recently discovered hypothalamic pept-ide which is regulated by leptin and is endowed with appetite-suppressing activity (69,70). In the rat, the CART gene encodes a peptide of either 129 or 116 amino acid residues (70). In contrast, only the short form of CART exists in humans (70). The mature peptide contains several potential cleavage sites and CART may be post-transcriptionally processed into several biologically active fragments. Thus, in most tissues studied, CART peptides are short, CART (42-89) being found in the rat hypothalamus (71). This tissue processing of CART resulting in neuropeptides of different lengths may indicate that different CART peptides have different biological functions (71).

Demographics of Substance Use in Patients With Schizophrenia

The Epidemiologic Catchment Area (ECA) study revealed that 47 of all individuals in the United States with a lifetime diagnosis of schizophrenia or schizophreniform disorder met criteria for some form of substance abuse or dependence (33.7 for alcohol disorder and 27.5 for another drug abuse disorder) (Regier et al. 1990). This figure is comparable with the range of 40 -60 lifetime prevalence gleaned from an analysis of 47 published studies of schizophrenia patients with sample sizes of at least 30 in which the criteria for abuse or dependence were clearly delineated (Cantor-Graae et al. 2001). The authors of this review also found that studies in which more than one method of diagnosis was employed (e.g., chart review plus interview) yielded higher prevalence rates compared with studies that relied on a single method. Regardless of method, in community samples of patients with schizophrenia that are not composed solely of inpatient groups, a figure of approximately 50 lifetime...

Local Anesthetic Technique

Either cophenylcaine (a mixture of lignocaine and norepinephrine) or a 6-10 solution of cocaine can be placed on a patte or thin ribbon gauze in the nasal airway for several minutes before replacing it in the middle meatus and nasal airway more posteriorly (Fig. 10.1a, b). Although an initial spray of the solution can be used, much of it ends up in the oropharynx. This produces an unpleasant sensation for the patient, making them feel there is something there and that they have to continually try to swallow it away. After 5 minutes the patte can be removed and local anesthetic injected using 1-2 lignocaine with norepinephrine 1 200 000 using a dental needle. Bending the end can help to deliver it at the correct angle. We inject less than 1 ml into the lateral nasal wall just behind the anterior lacrimal crest. We do not inject the inferior turbinate.

Early Systolic Regurgitant Murmurs

The systolic murmur of organic tricuspid regurgitation is often unimpressive and presents as an early systolic murmur ending well before A2, even in the presence of severe regurgitation.296 In this condition, the RV pressure is nearly normal, and massive regurgitation may be present with only a small pressure differential between the right ventricle and the right atrium. The small pressure head results in a low-velocity flow, minimal turbulence, and a soft, abbreviated murmur. Occasionally, only minimal early systolic vibrations are heard. In most patients, large vwaves are readily apparent in the JVP. The murmur retains the characteristic inspiratory augmentation seen in right-sided regurgitant murmurs and is frequently associated with an S4 that increases in intensity with inspiration. A right-sided S4 and a prominent diastolic tricuspid flow rumble are the rule when the tricuspid regurgitation is acute, as in endocarditis of the tricuspid valve. After total excision of the...

Amino Acid Transmitters

Orexin Molecule

Schematic depiction of colocalization patterns of signalling molecules in the LHA. Hypocretin (Hcrt) and melanin-concentrating hormone (MCH)-expressing neurons form two mutually exclusive cell groups. A near total colocalisation has been reported between Hcrt and dynorphin (Dyn) and secretogranin II (Sgr II). These cells are also believed to be glutamatergic. A few Hcrt neurons contain galanin (Gal). MCH neurons, on the other hand, contain cholinergic receptors (MC 3R) as well as acetylcholine esterase (AChE). These cells also label for markers of a glutamatergic phenotype. A large subpopulation of these cells express cocaine- and amphetamine-regulated transcript (CART) and the neurokinin 3 receptors (NK 3R). Of these, a considerable proportion also contains GABAergic markers. A minor degree of MCH Substance P (SP) colocalisation has been reported. Both Hcrt and MCH overlap with the serotonin 5-HT1A receptor. There may also be additional overlap between Hcrt and MCH and...

History of Interventions in the Brain Using Psychotropic Substances

It was not before 1880 that the active ingredient Ephedrine was isolated, finally leading to its characterisation in 1920. Ephedrine was widely used in the treatment of asthma. Increased efforts to search for a synthetic substitute led to the rediscovery of amphetamine that was synthesised 40 years before. Since then, many analogues of amphetamine have been developed and characterised, including the popular street drug, Methamphetamine, which was synthesised in 1912 in Darmstadt by Merck. During World War II, amphetamines came into use in the military as a means to keep pilots awake and vigilant during long flight hours. The first condition amphetamine was clinically used for was narcolepsy. Although not curative, it revolutionised therapy for this condition by making the patients relatively symptom free. The story of the Coca plant Erythroxylon, which was used in South America 2000 years ago, seems comparable. The active ingredient Cocaine was first isolated in 1800, rapidly gaining...

Circulatory Analgesic and Cancer Fighting Drugs

Opiate alkaloids such as opium, extracted from a poppy (Papaver sonniferum), and its derivatives, such as morphine as well as cocaine, from Erythro-xylum coca and Erythroxylum truxillense, have long been known for their analgesic (pain-relieving) properties through their extremely dangerous and addictive effects on the central nervous system.

Drug Tolerance

Drug tolerance is a term used to describe a decreased response to a drug, requiring an increase in dosage to achieve the desired effect. Drug tolerance may develop when a patient takes certain drugs, such as the narcotics and tranquilizers, for a long time. The individual who takes these drugs at home increases the dose when the expected drug effect does not occur. The development of drug tolerance is a sign of drug dependence. Drug tolerance may also occur in the hospitalized patient. When the patient receives a narcotic for more than 10 to 14 days, the nurse suspects drug tolerance (and possibly drug dependence). The patient may also begin to ask for the drug at more frequent intervals.


Ergot alkaloids have a direct vasoconstrictive action on blood vessels. Methysergide may cause intimal fibrosis. Exposure to vinyl chloride and bleomycin can cause a scleroderma-like illness with RP. Beta blockers, sympathomimetics, cocaine, cyclosporine, interferon-alfa, vinblastine, and cisplatin have been all implicated in the development of RP.


Frequently the dominant symptoms are those of the underlying pathological process and lymphadenopathy is only discovered during physical examination. Where HIV infection is a possibility, the patient should be asked about possible drug abuse, sexual habits and other risk factors.

Social history

The aetiological role of smoking in coronary and other vascular disease necessitates a detailed smoking history. Consumption of alcohol is also relevant. Although possibly 'cardioprotective' in moderation, excessive alcohol consumption is associated with atrial fibrillation, hypertension and cardiomyopathy (Fig. 1.9, p. II). Enquiry should also be made into caffeine consumption which, when excessive, can cause palpitation. Some recreational drugs can occasionally be associated with cardiac symptoms (e.g. cocaine and chcst pain).

Topical Anesthesia

In most cases, the level of anesthesia achieved with a topical anesthetic will be sufficient to alleviate discomfort during the injection of dermal fillers. There are basically two groups of topical agents the ester group (cocaine, tetracaine, and benzocaine), and the amide group (lidocaine and prilocaine).


Long-term use of antianxiety drugs may result in physical drug dependence (addiction) and tolerance (increasingly larger dosages required to obtain the desired effect). Withdrawal syndrome has occurred after as little as 4 to 6 weeks of therapy with a benzodiazepine. Withdrawal syndrome is more likely to occur when the benzodi-azepine is taken for 3 months or more and is abruptly discontinued. The antianxiety drugs must never be discontinued abruptly because withdrawal symptoms, which can be extremely severe, may occur. The onset of withdrawal symptoms is usually within 1 to 10 days after discontinuing the drug, with the duration of withdrawal symptoms from 5 days to 1 month. Symptoms of withdrawal are identified in Display 30-1.

ADrug toxicity

In the rush to look for other causes of myopathy, one must remember that the use of recreational drugs is common in many persons infected with HIV. Besides ethanol, the most common offenders are cocaine, crack, and mixtures of heroin. The extent to which these drugs, even in small quantities, contribute to significant myopathy is not fully appreciated.

Laboratory studies

Creatine kinase (CK) and aldolase are the most common and sensitive indicators of muscle damage. Either may be elevated exclusively. In general, the CK level should be checked first and aldolase measured as needed if the CK level is not elevated and clinical suspicion is high. In the face of intercurrent infection, trauma, fever, or use of cocaine or alcohol, the CK level may become dramatically elevated. Typically, after the insult has been eliminated, CK will return to the normal range within a few days.

The Nun Study

David Snowdon and his colleagues had the insight to assess a large group of Catholic nuns as an epidemiologic cohort. This is about as scientifically well-controlled a group of humans as is imaginable, practically speaking. Most of them have lived their entire adult lives alongside their Sisters, eating the same foods and living in the same environment. Detailed personal histories are available, including very early records from when they joined the order in their late teens. Confounding vices, such as illicit drug use, are understandably of minimal concern with a group of this sort. A constant and comparable level of health care applies across the group as well. Comparison within this group to assess who develops AD and who doesn't allows new insights into individual attributes that correlate with a risk of AD.


Both above studies examined the question and or assumed that the BOLD response was proportional to the lifetime of the drug at its effective site (i.e., possibility (2) described above). In the first cited study, where the possibility was stated that the drug could persist in the brain for a time period longer than the hemodynamic effects. An instructive example of such a case is provided by the comparison of two different dopamine transporter blockers, cocaine and CFT. The latter has a much longer half-life at the dopamine transporter. PET imaging studies can provide excellent information on the time course for specific drug binding in the brain. Figure 10.10 shows data from PET studies on nC-CFT binding in the rat brain along with microdialysis measurements of dopamine release as well as changes in rCBV. It is clear that the specific binding in the striatum had an extremely long half-life (showing little decrease over at least) 2 h (Figure 10.10a), whereas both the rCBV changes...


The use of phMRI for investigations of conditions and systems related to drug abuse can only be described as in its infancy. Nevertheless, MRI lends itself well to multiple longitudinal studies, which will be of great value for studying the effects of withdrawal and therapy. In addition, the high temporal and spatial resolution of MRI may well allow for more fine discrimination of subtle pharmacodynamic effects than is possible with other techniques.

Male Fertility

Oligospermic Mane And Enzymes Levels

A sperm concentration below about 20 million per milliliter is termed oligospermia (oligo few) and is associated with decreased fertility. A total sperm count below about 50 million per ejaculation is clinically significant in male infertility. Oligospermia may be caused by a variety of factors, including heat from a sauna or hot tub, various pharmaceutical drugs, lead and arsenic poisoning, and such illicit drugs as marijuana, cocaine, and anabolic steroids. It may be temporary or permanent. In addition to low sperm counts as a cause of in

Stria Medullaris

Stria Terminalis And Stria Medullaris

The mesolimbic mesocortical system of dopaminergic neurons originates in the ventral tegmental area of the midbrain region of the brainstem and innervates most structures of the limbic system (olfactory tubercles, septal nuclei, amygdala, nucleus accumbens) and limbic cortex (frontal and cingulate cortices). This dopaminergic system plays an important role in motivation and drive. For example, dopaminergic sites in the limbic system, particularly the more ventral structures such as the septal nuclei and nucleus accumbens, are associated with the brain's reward system. Drugs that increase dopaminergic transmission, such as cocaine, which inhibits dopamine reuptake, and amphetamine, which promotes dopamine release and inhibits its reuptake, lead to repeated administration and abuse presumably because they stimulate the brain's reward system. The mesolimbic mesocortical dopaminergic system is also the site of action of neuroleptic drugs, which Noradrenergic neurons innervate all parts of...

Arterial Dissection

Intracranial Carotid Dissection Mri

Arterial dissection involves intimal disruption or tearing of the intima with subsequent dissection of blood into the arterial vessel wall. This intramural hemorrhage may result in luminal narrowing or total occlusion of the vessel lumen 42 . Vessel dissection can be divided into two major categories. The first is traumatic in origin usually following blunt injury to the head and neck or injury from chiropractic manipulation. The second major category is that of spontaneous vessel dissection and occurs without predisposing trauma. In the second type of dissection there is usually underlying disease involving the vessel wall that predisposes these patients to dissection. Such predisposing factors include hypertension, fibromuscular dysplasia, genetic diseases such as Marfan syndrome with cystic medial necrosis (Fig. 23), Ehlers Danlos syndrome, alpha-1 anti-trypsin deficiency, or other etiologies including drug abuse with sym-pathomimetics and infection 2,43,44 . Dissection of the...

Acupuncture needles

Ancient Japan And Medicine

A recent review on the effectiveness of acupuncture concluded that, despite the difficulties and methodological constraints in conducting high-quality acupuncture clinical trials, a general international agreement has emerged that acupuncture appears to be effective for postoperative dental pain, postoperative nausea and vomiting, and chemotherapy-related nausea and vomiting 11 . For numerous other conditions, the evidence is considered promising, but rigorous research is still needed to add to the body of evidence. For conditions such as asthma, drug addiction, and certain pain conditions, the evidence is considered inconclusive and difficult to interpret. The review also concludes that acupuncture is a relatively safe procedure, although it is not free from serious adverse events.


Olfactory Cells

Much research today is being directed toward understanding how certain animal olfactory systems can detect (as evidenced by behavior) nanomole concentrations of certain odorants. The ability of bloodhounds to track a specific person through a crowd or to follow a days-old trail when searching for lost persons or fugitives is legendary. The noses of trained dogs are also the most effective system for locating buried land mines, explosives, or drugs in luggage and automobiles. What is not known exactly is to what molecules the dogs are responding. Is it the vapor phase of the analyte (e.g., C4, TNT, cocaine, etc), or is it some less obvious scent, such as the case or envelope containing the analyte, or is it human scent, or some

The nose and sinuses

Perforation Nasal Septum

Destruction of the nasal septum may produce flattening of the bridge and a saddle-nose' appearance. This is frequently Ihe result of local trauma. Other causes include Wegener's granulomatosis, congenital syphilis or nasal sniffing of cocaine. This may also produce ulceration of the nasal mucosa. Other common mucosal abnormalities include

Hepatitis B

Concentration of HBV is very high in blood, serum, and wound exudates, and is moderate in semen, vaginal fluid, and saliva. Because of its concentration in genital fluids, HBV is classified as a sexually transmitted disease sexual transmission is highly efficient. Levels of the virus are very low in urine, stools, breast milk, tears, and sweat. The most common routes of acquisition of infection are sexual, parenteral, and vertical (perinatal from mother to child). The risk factors for acquisition of acute HBV are heterosexual activity in 41 , intravenous drug abuse in 15 , homosexual activity in 9 , household contact in 2 , health care employment in 1 , and unknown source of infection in 31 of infected subjects.

Epidural Injections

Epidural injections have been used in the management of neck and back pain for almost 100 yr, although they still remain quite controversial. The first reported epidural injection for pain management was in 1901 in Paris. M. A. Sicard injected cocaine for the treatment of sciatica (26). The description of the paramidline approach to the lumbar epidural space was proposed by Pag s in 1921 (27). Pag s' technique used the tactile feedback from the needles touching and passing through the ligamentum flavum as a means of identifying the epidural space. Confirmation of needle placement in the epidural space was based on absence of free flow of spinal fluid from the needle and the lack of resistance to injection of local anesthetic (27). This approach was technically demanding and was associated with a significant failure rate.

Anabolic Steroids

Many serious adverse drug reactions are being reported in healthy individuals using anabolic steroids. There is some indication that prolonged high-dose use has resulted in psychological and possibly physical addiction, and some individuals have required treatment in drug abuse centers. Severe mental changes, such as uncontrolled rage, severe depression, suicidal tendencies, malignant and benign liver tumors, aggressive behavior, increased risk of atherosclerosis, inability to concentrate, and personality changes are not uncommon. In addition, the incidence of the severe adverse reactions cited earlier appears to be increased in those using anabolic steroids for this purpose.

Medicinal Alkaloids

Many potentially toxic plant-derived alkaloids have medicinal properties, as long as they are administered in carefully regulated doses. Alkaloids with important medicinal uses include morphine and codeine from the opium poppy and cocaine from the coca plant. These alkaloids act on the nervous system and are used as painkillers. Atropine, from the deadly nightshade plant, also acts on the nervous system and is used in anesthesia and ophthalmology. Vincristine and vinblastine from the periwinkle plant are inhibitors of cell division and are used to treat cancers of the blood and lymphatic systems. Quinine from the bark of the cinchona tree is toxic to the Plasmodium parasite, which causes malaria, and has long been used in tropical and subtropical regions of the world. Other alkaloids are used as stimulants, including caffeine, present in coffee, tea, and cola plants (and the drinks derived from these plants), and nicotine, which is present in tobacco. Nicotine preparations are,...

Consistent Findings

Unfortunately, it is also possible for a series of studies to generate consistently incorrect findings. There are often similarities across studies in the design or methods of conduct that could yield similarly erroneous results. For example, in studies of a stigmatized behavior, such as cocaine use, in relation to pregnancy outcome, there may be such severe underreporting as to yield null results across a series of studies. On the other hand, cocaine use is strongly associated with other adverse behaviors and circumstances that could confound the results, including tobacco and alcohol use and sexually transmitted infection. These tendencies may well hold across a wide range of populations. Thus, the observation


The approaches described in the present chapter have formed the bases for our neurological and neuropsychiatric evaluation of patients who use a number of illegal drugs. As with marijuana users, we have documented the cognitive changes that are present in cocaine abusers (8,57,58). We have reported on blood flow velocity observed in cocaine and opiate abusers to determine the effects of these substances cerebrovasculature (53-55). As mentioned above, all these studies were carried out in the same populations of patients who were observed under identical conditions. It is our hope that a more widespread adaptation of these approaches will help to clarify the pathobiological substrates for the neuropsychiatric disturbances observed in a large number of patients who abuse illicit drugs.

Drugs and Toxins

Agents that mimic the action of natural transmitters are known as receptor agonists. A well-known agonist of ACh receptors in neuromuscular junction is nicotine. Nicotine binds to the ACh receptor and activates it in the same manner as ACh. However, nicotine causes persistent receptor activation because it is not degraded, as is ACh, by ACh-esterase. On the other hand, diisopropylphosphofluoridate (commonly known as nerve gas) is an example of an anticholinesterase, because it inhibits the activity of ACh-esterase, so that ACh persists in the synaptic cleft. Similarly, one effect of cocaine is to prolong the activity of dopamine, by blocking the uptake of dopamine from the synaptic cleft.

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Being addicted to drugs is a complicated matter condition that's been specified as a disorder that evidences in the obsessional thinking about and utilization of drugs. It's a matter that might continue to get worse and become disastrous and deadly if left untreated.

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