Physical dependency level

Physical dependence A state of adaptation that is manifested by a drug class-specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and/or administration of an antagonist. 

Chronic excessive consumption of alcohol can result in physical dependence or alcoholism. There is often a steady progress in the need to drink, so that the person starts drinking early in the day to maintain blood alcohol levels and avoid withdrawal effects. Alcoholism often results in a variety of organ system effects, some of which are related to accompanying malnutrition. Treatment for alcoholism must address the withdrawal effects as well as associated vitamin deficiencies associated with malnutrition. 

All of the opioid agonists produce some degree of tolerance and physical dependence. The biochemical mechanisms underlying tolerance and physical dependence are unclear. It is known, however, that intracellular mechanisms of tolerance to opioids include increases in calcium levels in the cells, increased production of cAMP, decreased potassium efflux, alterations in the phosphorylation of intracellular and intranuclear proteins, and the resultant return to normal levels of release of most neurotransmitters and neuromodulators. Tolerance to the analgesic effects of opioids occurs rapidly, especially when large doses of the drugs are used at short intervals. However, tolerance to the respiratory depressant and emetic effects of the opioids occurs more slowly. The miotic and constipative effects of the opioids rarely show tolerance. 

It is important to distinguish three levels of dependency. The first level 1 call physical dependency. Very roughly, individuals are physically or chemically dependent on some substance if consuming that sub stance has made them prone to suffer withdrawal symptoms— discomfort, agitation, restlessness, illness—when deprived of the substance for a period of time and, usually, to find the ingestion of the substance highly pleasurable. 

Portenoy and Payne (1997) insist upon a distinction between physical dependence and addiction. What they mean by physical dependence is roughly what 1 mean, but they define addiction as a condition in which one is unable to abstain "Use of the term addiction to describe patients who are merely physically dependent reinforces the stigma associated with opioid therapy and should be abandoned. If the clinician wishes to describe a patient who is believed to have the capacity for abstinence, the term physical dependency must be used (564). Since my second level of dependency, which I consider to be addiction proper, need not involve this inability, Portenoy and Payne are marking a different distinction. 

Schedule II - The drugs at this level also have a high abuse potential and could cause psychic or physical dependence. They may be prescribed but are under stringent control. Schedule II drugs include opioids(morphine), amphetamines and methamphetamines used alone or in combination as well as some barbiturates. 

All drugs are toxic at some dose. Drugs of abuse, however, either have no medicinal function or are taken at dose levels higher than would be required for therapy. Although some drugs of abuse may affect only higher nervous functions—mood, reaction time, and coordination—many produce physical dependence and have serious physical effects, with fatal overdoses being a frequent occurrence. 

GHB is also addictive. Regular, daily use of GHB can cause physical dependency with harsh withdrawal symptoms. At four to six average doses per week, people report finding that they need to increase their dose to get the same level of intoxication. Many subsequently report that they need a little GHB just to feel normal. With very heavy use (one or more doses per day), many people report very serious physical addiction. Stopping cold turkey results in anxiety, inability to sleep, and feeling like the heart is arrhythmic (irregular). 

Barbiturates (a class of drugs with more effective sedative-hypnotic effects) replaced bromides in 1903. Depending on the dose, frequency, and duration of use, however, tolerance, physical dependence, and psychological dependence on barbiturates can occur relatively rapidly. With the development of tolerance, the margin of safety between the effective dose and the lethal dose becomes very narrow. That is, in order to obtain the same level of intoxication, the tolerant abuser may raise his or her dose to a level that can produce coma and death. 

A limiting factor in the clinical utilization of opioids for pain relief is that repeated administration leads to the development of tolerance to and physical dependence on opioids. At the cellular level, tolerance can be viewed as a form of persistent receptor desensitization associated with repeated drug administration. Phosphorylation of opioid receptors by protein kinases, especially PKC, is hypothesized to play a major role in this desensitization hence, opioid receptors in tolerant and dependent states are thought to be highly phosphorylated [135-140]. 

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