Opioid drug action

Mechanism of Action An opioid agonist that binds with opioid receptors in the CNS. Therapeutic Effect Alters the perception of and emotional response to pain reduces withdrawal symptoms from other opioid drugs. 

Antimotility drugs are opioid drugs. They increase small bowel smooth muscle tone and segmentation activity. They also reduce propulsive movements and decrease intestinal secretions while increasing absorption. They mediate these actions through p receptors. 

For a patient in severe pain, the administration of an opioid analgesic is usually considered a primary part of the overall management plan. Determining the route of administration (oral, parenteral, neuraxial), duration of drug action, ceiling effect (maximal intrinsic activity), duration of therapy, potential for adverse effects, and the patient s past experience with opioids all should be addressed. One of the principal errors made by physicians in this setting is failure to adequately assess a patient s pain and to match its severity with an appropriate level of therapy. Just as important is the principle that following delivery of the therapeutic plan, its effectiveness must be reevaluated and the plan modified, if necessary, if the response was excessive or inadequate. 

Care should be taken not to administer any partial agonist or drug with mixed opioid receptor actions to patients receiving pure agonist drugs because of the unpredictability of both drugs effects reduction of analgesia or precipitation of an explosive abstinence syndrome may result. 

I o find new and more effective medicines, chemists use various models that J. describe how drugs work. By far, one of the most useful models of drug action is the lock-and-key model. The basis of this model is the connection between a drugs chemical structure and its biological effect. For example, morphine and all related pain-relieving opioids, such as codeine and heroin, have the T-shaped structure shown in Figure 14.1. 

To understand the benefits and drawbacks of opioid drugs, one needs to understand their primary effects on the body specifically, how they function as pain relievers. In the broadest sense, there are two types of pain— physical and emotional. Physical pain, while unpleasant, is necessary for survival. It serves as notification of the presence of injury or disease, which in turn prompts a person to take appropriate, possibly even life-saving action. Half of all individuals who seek medical attention report pain as their primary complaint. 

Drugs and chemicals are known to cause activated interaction. The depressant action of opioid drugs is enhanced by drugs acting on the central nervous system (CNS) such as alcohol, anesthetics, anxiolytics, hypnotics, tricyclic antidepressants, and antipsychotics. Concomitant administration of opioid analgesics and monoamine oxidase inhibitors (MAOIs) should be avoided, or extra care should be taken if such a therapy is inevitable. Fatal reactions are reported when treated along with selegiline. Interactions also are reported with cyclizine, cimetidine, mexiletine, cisapride, metoclopramide, or domperidone. 

Recent investigations have revealed that the delta opioid receptor also is involved in the modulation of gastrointestinal functions, particularly in mammals other than the guinea pig. In this chapter, we will discuss the presence and roles of this opioid receptor type in mediating the actions of opioid drugs and their endogenous counterparts in the digestive tract. 

Two drugs widely used to control diarrhea are diphenoxylate [di PHEN ox a late and loperamide [loe PER a mide]. Both are analogues of meperidine (see p. 138) and have opioid-like actions on the gut, activating presynaptic opioid receptors in the enteric nervous system to inhibit acetylcholine release and decrease peristalsis. Side effects include drowsiness, abdominal cramps and dizziness. Since these drugs can cause toxic megacolon, they should not be used in young children or patients with severe colitis. 

Pharmacokinetic/pharmacodynamic modeling can also assist in identification of the appropriate animal model in which to evaluate the mechanism of action. " Cox and his colleagues have developed a tooth pulp evoked potential (TPEP) rat model in order to investigate the analgesic effects of opioid drugs. The authors utilized a population sigmoidal pharmacody-... 

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