наркол. опий

Opioid Abuse

Opioid AbuseOpioids are the most powerful known pain relievers.

The pain relieving and euphoric effects ofopioids were known more 4000 years ago. Their use and abuse date back to antiquity.

Although the term opiate is often used as a synonym for opioid, the term opiate is properly limited to only the natural alkaloids extracted from the plant Papaver somniferum.

The main active ingredient is alkaloid morphine. Opioids, meaning opiate like, are derivatives of opium. All opioids can produce euphoria and can be used as analgesics.

Opioids can be classified as the following:

Naturally occurring opium derivatives - Morphine, odeine Partially synthetic derivatives of morphine - Heroin, xycodone, xymorphone

Synthetic compounds - Fentanyl, lfentanil, Levorphanol, Meperidine, Methadone, Propoxyphene

PathophysiologyVarious opioid receptors exist in the mammalian CNS. There are three principal classes of opioid receptors: , , (mu, kappa, and delta), although up to seventeen have been reported, and include the , , , and (epsilon, Iota, lambda and zeta) receptors.These receptors are located in the brain (mostly in the periaqueductal grey), spinal cord, peripheral nerves, adrenal medulla, ganglia and gut.Stimulation of mu receptors produces intense feelings of well being and euphoria. Kappa-receptor stimulation produces dysphoria. Antagonism at these receptors may produce dysphoria, but not consistently. Antagonists block euphoria produced by opioids.Endogenous opioid peptides produced naturally in the body, such as:

endorphins, enkephalins, dynorphinsendomorphins.Endogenous opioidsthough not highly selective, have a preference for specific receptor types. Beta-endorphin is an endogenous ligand for the -receptor; enkephalins and dynorphins have an affinity for sigma- and kappa-receptors, respectively.The dopaminergic mesolimbic system, which originates in the ventral tegmental area of the midbrain and projects to the nucleus accumbens, is crucial in the reward effects of intracranial self-stimulation, the natural rewards of water and food intake, and the action of abusive drugs, including opioids. Basal activity of this system, expressed in dopamine release in the nucleus accumbens, is under the tonic control of 2 opposing opioid systems, activation of mu- and sigma-receptors increases, while kappa-receptor activation decreases the basal activity of the mesolimbic system.Experimental evidence with laboratory animals supports the idea that manipulation of these receptors with opioids and other substances of abuse (as well as electrical stimulation) affects self-administering behavior. These reward pathways have evolved for the natural rewards such as food and water intake.

Opioids have long been used to treat acute pain (such as post-operative pain). They have also been found to be invaluable in palliative care to alleviate the severe, chronic, disabling pain of terminal conditions such as cancer, and degenerative conditions such as rheumatoid arthritis. Adverse reactions in patients taking opioids for pain relief include:dose-related respiratory depression confusion, hallucinations, delirium urticariahypothermiabradycardia / tachycardiaorthostatic hypotension dizziness, headacheurinary retentionureteric or biliary spasm, muscle rigidity, myoclonus (with high doses) flushingThe death rate of people who use opioids is disproportionately high compared with those who use other drugs such as cocaine and phencyclidine (PCP). Most people who abuse these drugs die in their third decade of life.Compared with the general population, the risk of death is 11 times higher among males who use drugs and 20 times higher among females who use drugs.The Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition (DSM-IV) defines substance abuse as a maladaptive pattern of substance use leading to clinically significant impairment or distress occurring in any of the following areas, within a 12 month period.Working, social and interpersonal problems Recurrent substance use in hazardous situations (driving or operating heavy machines)Legal problems

Most individuals who meet the criteria of substance abuse and continue to use substances eventually meet the criteria of substance dependence. At that stage, the diagnosis would be substance dependence and not substance abuse.

Tolerance is the need for increasing doses of medication to achieve the initial effect of the drug. Tolerance to the analgesic and euphoriant effects and unwanted adverse effects, such as respiratory depression, sedation, and nausea, may develop. However, little tolerance develops to constipation and meiosis.

Major clinical problems related to opioids may be divided into the following categories:

1. Dependence2. Withdrawal3. Intoxication4. AddictionDependence is a physiological, behavioral, and cognitive symptom complex. The WHO defines drug dependence as a syndrome in which the use of a drug or class of drugs takes much higher priority for a given person than behaviors that once had higher value. A decrease in volitional control over the use of opioid drugs is the central part of the behavioral symptoms observed in opioid dependence.

The DSM-IV defines substance dependence as a syndrome characterized by a maladaptive pattern of substance use, leading to clinically significant impairment as manifested by at least 3 of the following and occurring in a 12-month period. Tolerance Withdrawal Substance is taken in larger amounts or for longer periods than intended Persistent desire or unsuccessful efforts to cut down or control substance use A significant amount of time is spent in activities to obtain the substance Important social, occupational, or recreational activities are given up or reduced Continued substance use despite knowledge of having a persistent or recurrent physical or psychological problem

Physical:

DependenceMental status effects include depression with any or all of its symptoms (sleep disturbances, lack of interest, restlessness, thoughts of suicide).Physiological effects: because tolerance to many of the actions of the opioids develops, it is not likely for even a careful observer to notice the effects of opioids. Small-sized pupils may be the only observation because only very mild tolerance develops for miosis. Inflamed nasal mucosa may be seen if heroin is snorted.

WithdrawalContinuous administration of opioids leads to physical dependence, the emergence of withdrawal symptoms during abstinence. Physical dependence is expected after 2-10 days of continuous use when the drug is stopped abruptly. The onset and duration of withdrawal varies with the drug used. For example, meperidine withdrawal symptoms peak in 8-12 hours and last for 4-5 days. Heroin withdrawal symptoms usually peak within 36-72 hours and may last for 7-14 days.

Physical: withdrawalMental status effects include purposive behaviors, such as complaints and manipulations directed at getting more drug, and anxiety.Physiologic effects Autonomic signs - Tachycardia, high blood pressure, fever, piloerection (goose flesh), mydriasis, and lacrimation Central nervous system arousal - Irritability Yawning

Symptoms of opioid withdrawal include the following:

Autonomic symptoms - Diarrhea and rhinorrhea, nausea and emesis Central nervous system arousal - Sleeplessness Pain - Abdominal cramping, bone pains, and diffuse muscle aching Craving - For the medication

In milder abstinence syndrome, clinical features may be limited to

dysphoria, craving, yawning, lacrimation, rhinorrhea, restlessness.

In moderate-to-severe abstinence syndrome piloerection mydriasis increased BP and pulse GI symptoms are seen as well.

Intoxication:Mental status effects include euphoria, sedation, decreased anxiety, a sense of tranquility, and indifference to pain produced by mild-to-moderate intoxication. Severe intoxication can lead to delirium and coma. Query patient about the use of other drugs and alcohol; confirm these answers with multiple resources if possible.

Intoxication - physiological effects

Respiratory depression (may occur while the patient maintains consciousness) Alterations in temperature regulations Hypovolemia leading to hypotension Miosis Needle marks or soft tissue infection Increase sphincter tone (can lead to urinary retention)AddictionThe phenomenon of addiction is seen in a variable number of patients using drugs. Addiction is characterized as a psychological and behavioral syndrome in which the following features are observed: Drug craving Compulsive use Strong tendency to relapse after withdrawalAddiction

The physical examination provides little information to add in the diagnosis of addiction. However, symptoms of opioid withdrawal and track marks are suggestive of addiction.Constipation is a common occurrence due to almost continuous use of narcotics.

CausesOpioid dependence is considered a biopsychosocial disorder. Pharmacological (more prominent), social, genetic, and psychodynamic factors associated with drugs consumption.

Pharmacological factors: Opioids are strongly reinforcing agents because of the euphoric effects and reported ability to reduce anxiety, increase self esteem, and help coping with daily problems. Most opioids associated with abuse and dependence are mu-agonists, such as heroin, morphine, hydrocodone, oxycodone, and meperidine. Some partial mu-agonists, such as buprenorphine, or some that have no mu-agonism, such as pentazocine, also can possess reinforcing properties. Rapid development of physical dependence and a protracted abstinence syndrome are unique to opioid use and can make abstinence difficult.

Social factors: Easy drug availability make experimentation easy.

A high rate of drug use is seen in disadvantaged social groups.

Psychological factors: Ego defects in certain patients are postulated to form the basis of drug use. Opioids are theorized to help the ego in managing painful effects such as anxiety, guilt, and anger. Behavioral theory postulates that basic reward-punishment mechanisms perpetuate addictive behavior

Genetic factors: Genetically transmitted vulnerability factors may predispose individuals to become drug dependent.

Treatment

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Detoxification is based on the principle of cross-tolerance in which one opioid is replaced with another and then slowly withdrawn. Methadone is most commonly used in the detoxification of patients dependent on opioids. LAAM, a derivative of methadone, also may be used but has more complex pharmacological properties and requires more skilled physicians for use.

Antidotes for opioidsNaltrexone and Naloxone are antidotes for opioids, inhibit opioid effects.

Alpha 2 adrenergic agonists used primarily for the treatment of hypertension (Clonidine).

PrognosisOpioid treatment relapse rates vary from 25-97%. Cigarette smokers have higher rates of relapse than nonsmokers.Success is measured as improvement in following areas:Social functionsReduction of illicit drug usePerformance at work and schoolThe prognosis varies according to the type of agent abused and other variables, such as medical care, employment, legal situation, family, and psychological difficulties.