Medical and social problems of the use of psychoactive substances .

1. Medical and social problems of the use of psychoactive substances. Olena Smashna

2. Alcohol action • Alcohol affects virtually every organ system in the body and, in high doses, can cause coma and death. It affects several neurotransmitter systems in the brain, including opiates, GABA, glutamate, serotonin, and dopamine. Increased opiate levels help explain the euphoric effect of alcohol, while its effects on GABA cause anxiolytic and sedative effects.

3. Alcohol action • Alcohol inhibits the receptor for glutamate. Long-term ingestion results in the synthesis of more glutamate receptors. When alcohol is withdrawn, the central nervous system experiences increased excitability. Persons who abuse alcohol over the long term are more prone to alcohol withdrawal syndrome than persons who have been drinking for only short periods. Brain excitability caused by long-term alcohol ingestion can lead to cell death and cerebellar degeneration, Wernicke-Korsakoff syndrome, tremors, alcoholic hallucinosis, delirium tremens, and withdrawal seizures. Opiate receptors are increased in the brains of recently abstinent alcoholic patients, and the number of receptors correlates with cravings for alcohol.

5. Alcoholism • also known as alcohol dependence, is a common disorder. At all ages alcoholism is more common among males than females; however, given the somewhat later age of onset in females, the ratio tends to decrease in higher age groups. Overall the ratio is probably 3:1. Alcoholics and alcohol abusers are recurrently and persistently beset with an urge to drink, an urge that is of sufficient compellingness for them to continue to drink despite the fact that because of their drinking they sustain substantial damage to their health and personal or business affairs.

7. ONSET • The onset of alcoholism or alcohol abuse is generally insidious and spans many years. For men, onset is generally dated to the late teens ; or the early twenties; however, most alcoholics are not recognized as such until their late twenties or early thirties, and many more years may pass before the alcoholic or someone else recognizes the need for treatment. Although some otherwise typical onsets have been described in patients over 60, it is rare for the onset to occur past the age of 45.

8. CLINICAL FEATURES • the urge to drink may be experienced as a craving, an imperious need, or a compulsion; • almost all alcoholics deny they have a problem with drinking or rationalize it one way or another. • they are often quick to lay blame for their drinking on situations or other people; • stressful events may be followed by increased alcohol consumption, the alcoholic is also intoxicated during the good times, or simply the neutral times of life.

9. CLINICAL FEATURES • Most alcoholics make attempts to control their drinking, and although they may have some successes, these are generally short-lived. This "loss of control" was at one point considered the hallmark of the alcoholic. However, it may be just as fair to say that the hallmark is rather a sense of a need to control. Normal people do not experience a need to control their drinking; they simply stop, without giving it a second thought. • When alcoholics do drink, most eventually become intoxicated, and this recurrent intoxication eventually brings their lives down in ruins.

10. CLINICAL FEATURES • Friends are lost, health deteriorates, marriages are broken, children are abused, and jobs terminated. Yet despite these consequences the alcoholic continues to drink Many undergo a "change in personality." Previously upstanding individuals may find themselves lying, cheating, stealing, and engaging in all manner of deceit to protect or cover up their drinking. Shame and remorse the morning after may be intense; many alcoholics progressively isolate themselves to drink undisturbed. An alcoholic may hole up in a motel for days or a week, drinking continuously. Most alcoholics become more irritable; they have a heightened sensitivity to anything vaguely critical. Many alcoholics appear quite grandiose, yet on closer inspection one sees that their self-esteem has slipped away from them.

11. CLINICAL FEATURES • Most alcoholics also display an alcohol withdrawal syndrome when they either reduce or temporarily cease consumption. Awakening with the "shakes" and with the strong urge for relief drinking is a common occurrence; many alcoholics eventually succumb to the "morning drink" to reduce their withdrawal symptoms. • Some degree of tolerance occurs in all alcoholics. Here the alcoholic finds that progressively larger amounts must be consumed to get the desired degree of intoxication; if the amount is not increased, the alcoholic finds that the degree of intoxication becomes less and less.

12. Alcohol intoxication. • The intoxicated patient is a familiar sight in any emergency room, and the determination of a blood alcohol level (BAL) is a commonplace procedure. • BAL by convention may be expressed as milligrams per deciliter, or, as it is often charted, milligrams percent (mg%). Roughly speaking, in a 70 kg person BAL rises anywhere from 15 to 25 mg/dl with every 15 ml of rapidly ingested pure ethyl alcohol. This amount of ethanol is found in 1 ounce of 100 proof liquor, one 12-ounce bottle of beer, or about one glass (6 ounces) of wine. Given that most "social drinkers," or alcohol-naive persons, become intoxicated at a BAL of 100 mg/dl, simple arithmetic shows that for such a person only about four drinks, or beers, or glasses of wine are required to produce intoxication.

13. Alcohol intoxication. • In mild intoxication most individuals feel somewhat euphoric, they talk more and tend to shed their inhibitions. Reckless behavior may be seen; sexual indiscretion may be evident; irritability may occur. Some individuals, however, may not so well. A suspicious person, if intoxicated, may develop ideas of persecution; a mildly depressed person may become tearful and morose. • In moderate intoxication behavior tends to become coarse; improprieties are commonplace. Thinking is slow; inattentiveness occurs, and the person is slow in responding to anything, even dangerous situations. The face is flushed, the conjunctivae reddened, and the pupils dilated. Slurred speech, nystagmus, ataxia, and generalized incoordination are present.

14. Alcohol intoxication. • In severe intoxication stupor may occur. Ataxia is so severe that Standing is impossible. Vertigo is common, and persistent vomiting may occur. • Eventually if the BAL continues to rise, coma will supervene. Respiratory depression may occur, and death may ensue from respiratory arrest. • If sleep should come to the intoxicated person, it tends to be heavy and dreamless. As the BAL falls the person often wakes up and has trouble falling back asleep. • After the intoxication has passed most experience a "hangover." Headache is common, as is a pervasive dysphoria . Mild tremulousness and diaphoresis may occur; nausea is common, and the person may vomit. Depending on the degree of intoxication, a hangover may last anywhere from several hours up to almost the entire day.

15. Blackouts(palimpsests). • Blackouts are characterized by a dense anterograde amnesia. During the blackout intoxicated individuals appear outwardly unchanged; however, for the duration of the blackout, events fail to enter their memory. After "coming to" these individuals have no recollection of what was said or done during the blackout. Although the vast majority of blackouts occur during alcohol intoxication, they may also occasionally be seen in intoxication with other sedative-hypnotics, in particular high-potency benzodiazepines. Importantly, although most patients with blackouts are alcoholics, this is not always the case, as blackouts may also occur in social drinkers who simply consume more than is typical for them.

16. Blackouts(palimpsests). • Upon recovery from a blackout, drinkers often recount that they remember everything up to a certain time and then "went blank." Some patients go to sleep during a blackout, and when they awaken wonder how they got home or got to bed. • Upon recovery from a blackout, most patients are worried about what they did during the blackout. The car may be checked for evidence of an accident; indirect questions may be put to others in a discreet effort to find out if anything untoward happened.

17. Pathological intoxication. • |Classically, pathological intoxication is said to occur when, consuming a relatively small amount of alcohol, drinkers undergo a marked change in behavior, often becoming agitated or violent, afterwards having at best a spotty memory for the event. • Occurring after as little as one or two drinks, the change in behavior may be dramatic. A polite and unassuming person may start a fist fight; a well-mannered person may suddenly take offense if a date happens to look at someone else, flying into a jealous rage. This change may persist for only a few minutes, or up to hours. Upon recovery the drinker typically has difficulty in recalling everything that happened, and occasionally may report complete amnesia for the event.

18. Alcohol withdrawal. • Alcohol withdrawal, commonly known as "the shakes," may occur in anyone after excessive, prolonged use of alcohol. • In full-blown alcohol withdrawal, drinkers are apprehensive, anxious, and easily startled; they may pace agitatedly up and down the hall. Depressed mood and irritability are common. The tremor is quite characteristic; it tends to be coarse and is evident not only in the hands but also in the lips, tongue, and eyelids. In severe cases drinkers may literally "shake like a leaf" and be unable to hold things or even at times to stand up. Diaphoresis, at times profuse, is often present.

19. Alcohol withdrawal. • Most have trouble concentrating and thinking clearly; memory tends to be poor. Although fatigue is prominent, most are also unable to sleep. • Headache, dry mouth, anorexia, nausea, and vomiting are common; diarrhea may occur. • On examination the temperature, pulse, respirations, and systolic blood pressure may all be elevated. The pupils are dilated, and the deep tendon reflexes are hyperactive. Rarely, one may see transient myoclonus, choreiform movements or parkinsonism. • Occasionally patients may have isolated, brief, vague, visual hallucinations or illusions, or rarely a few auditory hallucinations. If these do occur they tend to appear as the withdrawal symptoms reach their height.

20. Alcohol withdrawal seizures. • Alcohol withdrawal seizures, also known as "rum fits," are a rare accompaniment of the alcohol withdrawal syndrome. They generally occur only after many years of heavy drinking and repeated episodes of withdrawal and are seen in from 1% to 3% of patients withdrawing from alcohol. • For the most part, alcohol withdrawal seizures present as otherwise unremarkable generalized tonic-clonic seizures. In about a quarter of the cases, however, the seizures have a focal onset. • Most patients have just one seizure; occasionally, however, patients have a cluster of two or three and rarely as many as six. Rarely, status epilepticus occurs.

21. Delirium tremens. • Delirium tremens, also known as alcohol withdrawal delirium and more commonly as "DTs," develops in the setting of the alcohol withdrawal syndrome, and is seen in about 5% of hospitalized alcoholics. It is characterized by gross accentuation of the tremor and autonomic signs and by the development of confusion, disorientation, and hallucinations. • the patient is generally agitated, markedly tremulous, and very easily startled; mydriasis and generalized hyperreflexia are prominent, as are such autonomic signs as diaphoresis, tachycardia, elevated blood pressure, and increased respirations.

22. Delirium tremens. • Visual hallucinations are very common; they tend to be extremely vivid and complex. Often the patient sees insects or animals: dogs circle the bed; rats eat at the toes; bugs crawl on the arms and face. They may cringe in fear or try to swat them away. At times the patient may see simply a benign procession of animals, which he may watch from the bed as if it were an amusing procession. Curiously one also often sees a predilection for hallucinating strings or threads; the patient may pick them out of the air or warn the physician to avoid running into one stretched across the hospital room. Often the visual hallucinations may be provoked by suggestion. In the classic "string test" the examiner holds her hands about a foot and a half apart, the thumbs and index fingers apposed, several feet in front of the patient and asks if the patient sees anything. After the patient reports seeing nothing, the examiner asks "Don't you see the string?," whereupon the patient does indeed see a string stretched between the examiner's hands.

23. Delirium tremens. • Tactile hallucinations may accompany the visual ones: the skin is ripped by teeth; spiders bite; bugs are felt crawling all over. The patient may complain of electric shocks or of pins being stuck into the toes. • Auditory hallucinations are common. Patients may hear bells, whistles, or alarms. If voices are heard, they tend to be critical, persecutory, or warning of dire events. Patients hear accusations of neglecting their children; the children are starving because the patients spent their paychecks on drink. The death sentence is pronounced; the physician is revealed as the executioner.

24. Delirium tremens. • Delusions are common and tend to be persecutory. Murderers are outside the door; the nurse is bringing poison to the patient; other patients talk about and conspire against the patient. • Disorientation always occurs, often to both time and place. At times this disorientation is intensified by hallucinations. The patient refuses the bedtime medicine offered by the nurse and announces that it must be morning as the birds are chirping; if questioned as to orientation to place, the patient, seeing the clouds out the window, may report being in an airplane or perhaps an air ambulance.

25. Delirium tremens. • Memory tends to be severely disturbed. The patient is unable to recall the name of the physician or of the hospital. Recall of events before admission is also often quite spotty. • The behavior of these patients is commensurate with their symptoms. Some may sit tremulously on the bed, picking at the bed sheets or brushing away insects. They may grasp at strings in the air and mumble agitatedly about events occurring outside the window. Others may strike out at their "persecutors"; they may attempt to escape through the door or jump out the window. • In contrast one may occasionally encounter a "quiet" delirium tremens. Here the tremor and autonomic signs and symptoms are minimal, and the patient, all the while experiencing sometimes fantastic visual hallucinations, may lie relatively quietly in bed.

26. Korsakoff’s syndrome • Korsakoff's syndrome, also known as Korsakoff's psychosis, is characterized by a striking inability to form new memories, with the subsequent "blank spots" often filled in with confabulations. • The memory loss is of the short-term variety; the patient's ability to recall anything after a few minutes (such as the physician's name) is grossly impaired. Long-term memory is relatively spared, wherein events of the distant past are better recalled than those that occurred more recently. Remarkably patients are generally unconcerned with this inability to remember things.Confabulations are typically present and may at times be quite fabulous.

27. Korsakoff’s syndrome • During casual questioning, these patients may not appear ill.They may talk appropriately about their surroundings, comment on the weather as they look out the window, or compliment the physician's taste in clothing. Some may be mildly euphoric, others bland and apathetic. A few direct questions, however, disclose the memory defect and the tendency to confabulate

28. Alcoholic dementia • Alcoholic dementia often presents with a personality change. Patients become coarse and heedless of social convention; they may become apathetic, and judgment is poor. Cognitive deficits eventually appear; short-term memory fails, and patients gradually have increasing difficulty in recalling events of the distant past. Thinking becomes concrete. With continued drinking the dementia may become profound. At times, minor "cortical" signs are seen such as apraxia, agnosia, and aphasia; however, these are not a prominent part of the clinical picture. • CT or MRI studies generally demonstrate both cortical atrophy and ventricular dilitation.

30. Alcohol hallucinosis • Alcohol hallucinosis, also known as alcohol-induced psychotic disorder with hallucinations, is seen only in alcoholics, and then only after one or more decades of heavy alcohol consumption. Hallucinations, generally auditory, are often accompanied by delusions of reference and persecution and appear relatively suddenly, persisting for variable periods of time. • Auditory hallucinations constitute the principal symptom of alcohol hallucinosis. These are often extremely vivid and clear; the patient has no doubt as to their reality and does not believe that the physician does not hear them. For the most part they are critical and often persecutory. Generally more than one voice is heard, and curiously the voices often talk among themselves - about the patient. At times one may observe patients straining to overhear what the voices are saying.

31. Alcohol hallucinosis • What the patients hear, or overhear, is often quite distressing or frightening. They are accused of murder; the food will be poisoned; their relatives are selling all their goods and will leave them destitute and in the street. • Delusions of persecution and reference often accompany the auditory hallucinations and are generally congruent with them. ; Family members talk about the patient; they conspire against the patient to force her to sign documents, but she knows the documents are in fact cleverly worded confessions and refuses to sign them. Police follow the patient; they await any excuse to arrest her. Such patients are often constrained and very watchful. They tend to be irritable. Should they feel too threatened, they may turn on their supposed persecutors. Occasionally, visual hallucinations occur, but these are far less prominent than the auditory ones.

32. Alcoholic paranoia • Is characterized by delusions of jealousy. The spouse is suspected of infidelity; absences from the house are seen as proof of it; the spouse's desire to keep apart from the patient during the patient's intoxicated rages is seen as a mere excuse. Rules are laid down; the spouse is neither allowed outside the house alone nor allowed to speak in private on the telephone. When drunk the patient may turn on the spouse, sometimes in a murderous fashion. In other cases the illness may be characterized by persecutory delusions: the police have begun to hound the patient. Yet another charge of driving under the influence of alcohol is trumped up; unmarked police cars cruise down the streets. The neighbors have been recruited to spy on the patient from behind their shades.

33. Alcoholic paranoia • Occasionally hallucinations may occur, but they play only a minor role. Footsteps and sirens are heard at night; something moves in the attic. The food tastes spoiled, rotten, perhaps even poisoned. Strange people approach the house in the dead of night.

34. Alcoholic polyneuropathy • Paresthesias begin distally, first in the feet and calves, later in the hands. Associated lancinating pains may occur. Hyperesthesia may also be present, and even the touch of a bed sheet on the soles of the feet may be more than the patient can tolerate. On examination vibratory sense is lost first, followed by other modalities; the ankle jerks are diminished or lost and the Romberg test is positive. • With continued drinking, patients develop motor weakness; this may be seen in as few as several weeks after sensory symptoms appear. Distal musculature is affected first, the lower extremities before the upper. Foot drop with a steppage gait is common; wrist drop may also occur. Atrophy of the calves and forearms may be seen. Although motor signs are bilateral, their severity is often asymmetric.

35. Treatment • Use explicit evidence; emphasize the consequences endured by the patient as a result of alcohol abuse. • Be empathic and nonjudgmental. • Avoid arguments about the diagnosis. • Avoid use of the word alcoholic.

36. Treatment • Treatment of alcohol withdrawal is best accomplished with benzodiazepines. Avoid fixed-dose therapy, and treat patients for symptoms. This results in use of lower doses of benzodiazepines, less patient sedation, and earlier patient discharge. • Other agents that have been used with some success in the treatment of withdrawal include beta-blockers, phenothiazines, and anticonvulsants. All can be used with benzodiazepines, but none has been proven to be adequate as monotherapy. A number of medications have been tried in the treatment of alcoholism.

38. Treatment • Disulfiram (Antabuse) has been used as an adjunct to counseling. Patients are reminded of the risks of adverse effects when tempted to drink. Disulfiram causes nausea, vomiting, and dysphoria with coincident alcohol use. In a large trial, disulfiram did not increase abstinence. If a patient asks for disulfiram and thinks it will help, it might be worth considering. • Naltrexone blocks opiate receptors and works by decreasing the craving for alcohol, resulting in fewer relapses. A recent positron emission tomography study demonstrated that alcoholic persons have increased opiate receptors in the nucleus accumbens of the brain and that the number of receptors correlates with craving.

40. Treatment • Opiate antagonists -- Alcohol has been shown to bind to opiate receptors in the brain. Studies show that blocking opiate receptors decreases cravings for alcohol. • Naltrexone (ReVia) -- Patients must be abstinent for 5-7 d before beginning therapy. Monitor liver function during treatment. • Contraindications Documented hypersensitivity, acute hepatitis, liver failure • Precautions Nausea/vomiting, abdominal pain, daytime sleepiness, and nasal congestion were more common vs placebo in largest randomized trial to date; discontinuation due to adverse effects was uncommon in most clinical trials

41. Treatment • Aldehyde dehydrogenase inhibitors -- Disulfiram inhibits aldehyde dehydrogenase, and, as a result, acetaldehyde accumulates. This leads to nausea, hypotension, and flushing if a person drinks alcohol while taking disulfiram. • Disulfiram (Antabuse) -- Decreases number of drinking days but does not increase abstinence. Directly observed therapy might be more beneficial but has not been studied in a good randomized trial. • Contraindications Documented hypersensitivity, severe myocardial disease, coronary occlusion • Precautions Adverse effects are uncommon, but hepatitis, optic neuritis, neuropathy, and skin rash reported

42. Treatment of DT • Benzodiazepines -- By acting on the GABA receptor, benzodiazepines produce a cross-tolerance to alcohol, thus reducing the hemodynamic and peripheral symptoms of alcohol withdrawal. The dose of benzodiazepine used should be based on the patient's symptoms and signs of alcohol withdrawal, including vital signs and amount of agitation. The longer-acting agents appear to be superior compared to the short-acting agents and may result in a smoother withdrawal course with less breakthrough and rebound symptoms, although a risk of excessive sedation exists in certain patient groups (elderly patients, patients with liver failure) with the longer-acting agents.

43. Treatment of DT • For the treatment of minor or moderate alcohol withdrawal (patient able to take oral therapy), symptom-triggered therapy has been shown in prospective, randomized, controlled trials to be superior to fixed-dose drug therapy, with less medication use and a shorter duration of therapy. • For patients with severe withdrawal symptoms, including DTs, the benzodiazepine dose should be front-loaded. That is, large doses should be administered intravenously at short intervals until the patient is calm but easily aroused. Then additional doses are administered only as needed. Most authorities recommend intravenous diazepam as the first choice for front-loading treatment of severe alcohol withdrawal. Because of its long serum half-life, and the even longer half-life of its active metabolite (desmethyldiazepam), additional doses may not be required once the patient is calm.

44. Treatment of DT • Diazepam (Valium, Diazemuls, Diastat) -- Depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA.Individualize dosage and increase cautiously to avoid adverse effects. • Anesthetic agents -- Propofol, an intravenous anesthetic agent, is active on both the glutamate and GABA-A receptors, similar to the alcohol itself, whereas benzodiazepines are active only against the GABA receptors. It may be effective for patients with DTs refractory to benzodiazepines. Due to its rapid onset of hypnosis and anticonvulsant properties, propofol is an alternative treatment for intubated patients with DTs refractory to high-dose benzodiazepines. Advantages to its use are that it is easily titratable with predictable effects and has a rapid metabolic clearance

45. Treatment of DT • Propofol (Diprivan) -- Phenolic compound unrelated to other types of anticonvulsants. Has general anesthetic properties when administered IV. Propofol IV produces rapid hypnosis, usually within 40 s. Effects are reversed within 30 min following discontinuation of infusion.

48. Disorders of personality and behavior due to drug abuse.

49. Introduction • People take various substances because they like the effects. In some, such use stays at a "recreational" or "social" level; in others, abusive use occurs; and in still others, addiction, or compulsive use, occurs. Differentiating among these three forms of use is important not only with regard to prognosis but also with regard to treatment. • Most of these substances have the capacity to produce tolerance and withdrawal, whereas others generally do not. Those that routinely produce tolerance and withdrawal include the following: caffeine, cannabis, inhalants, nicotine, amphetamines, cocaine, opioids, sedative-hypnotics, and alcohol. Those that lack substantial capacity to produce tolerance and withdrawal include hallucinogens and phencyclidine.

50. Tolerance and withdrawal • Tolerance is said to occur when the patient has to take ever increasing amounts of the substance to get the desired effect. Tolerance may also be inferred when, over time, even though the patient continues to use the same amount, the effect becomes progressively less. • Withdrawal symptoms occurring after use is discontinued often constitute a "rebound" from the effects of intoxication. • for example, a patient who had taken a benzodiazepine exactly as prescribed for years, without ever exceeding the dose but who accidentally left the medicine at home while going on vacation. After a sleepless night and experiencing tremulousness the next day, the patient calls the physician who explains to the patient that these constitute withdrawal symptoms. Such a patient, though desperate for relief, may nevertheless decide that "it isn't worth it," and because she has no craving may simply not take anymore, "tough out" the withdrawal, and then get on with life.