Central nervous system opiate effects

Loperamide is an opiate drug that decreases motility of the intestine. It does not cross the blood-brain barrier easily and therefore does not have the central nervous system effects (euphoria, respiratory depression, nausea and vomiting and dependence) of other opiates. Loperamide is prescribed to counteract gastrointestinal side effects (diarrhoea) of therapeutic radiography. 

Miller MW (1992) Effects of prenatal exposure to ethanol on cell proliferation and neuronal migration. In Miller MW (ed) Development of the Central Nervous System Effects of Alcohol and Opiates, Wiley-Liss, New York, pp 47-69. 

Morphine, C17H19NO3, is a complex phenolic compound whose pentacyclic structure is derived from tyrosine. It is analgesic, narcotic and a powerful respiratory depressant which was previously used iu cough elixirs. Morphine induces euphoria and dependency in some people, anxiety and nausea in others. The central nervous system effects occur through stimulation of specific receptors. Opiate receptors are widely distributed in animals they respond to both endogenous transmitters (peptides) and ingested plant alkaloids. The main receptor types are 8 emotional X. sedative x analgesic a psychotomimetic (Robinson 1986). 

P-Endorphin. A peptide corresponding to the 31 C-terminal amino acids of P-LPH was first discovered in camel pituitary tissue (10). This substance is P-endorphin, which exerts a potent analgesic effect by binding to cell surface receptors in the central nervous system. The sequence of P-endorphin is well conserved across species for the first 25 N-terminal amino acids. Opiates derived from plant sources, eg, heroin, morphine, opium, etc, exert their actions by interacting with the P-endorphin receptor. On a molar basis, this peptide has approximately five times the potency of morphine. Both P-endorphin and ACTH ate cosecreted from the pituitary gland. Whereas the physiologic importance of P-endorphin release into the systemic circulation is not certain, this molecule clearly has been shown to be an important neurotransmitter within the central nervous system. Endorphin has been invaluable as a research tool, but has not been clinically useful due to the avadabihty of plant-derived opiates. 

There is an increased central nervous system (CNS) depressant effect when the skeletal muscle relaxants are administered with other CNS depressants, such as alcohol, antihistamines, opiates, and sedatives. There is an additive anticholinergic effect when cyclobenzaprine is administered with other drugs with anticholinergic effects (eg, antihistamines, antidepressants, atropine, haloperidol). See Chapter 30 for information on diazepam. 

There is an increased risk for bone marrow suppression when levamisole or hydroxyurea are administered witii other antineoplastic dni. Use of levamisole witii phenytoin increases die risk of phenytoin toxicity. Pegaspargase may alter drug response of the anticoagulants. When procarbazine is administered with other central nervous system (CNS) depressants, such as alcohol, antidepressants, antihistamines, opiates, or the sedatives, an additive CNS effect may be seen. Procarbazine may potentiate hypoglycemia when administered witii insulin or oral antidiabetic dru . ... 

There are a number of side-effects of opiates that are due to their actions on opiate receptors outside the central nervous system. Opiates constrict the pupils by acting on the oculomotor nucleus and cause constipation by activating a maintained contraction of the smooth muscle of the gut which reduces motility. This diminished propulsion coupled with opiates reducing secretion in the gut underlie the anti-diarrhoeal effect. Opiates contract sphincters throughout the gastrointestinal tract. Although these effects are predominantly peripheral in origin there are central contributions as well. Morphine can also release histamine from mast cells and this can produce irritation and broncho-spasm in extreme cases. Opiates have minimal cardiovascular effects at therapeutic doses. 

Binds to DNA and prevents separation of the helical strands Affects neuronal transmissions Binds to opiate receptors and blocks pain pathway Acts as central nervous system depressant Inhibits Na/K/ATPase, increases intracellular calcium, and increases ventricular contractibility Blocks the actions of histamine on Hi receptor Blocks ai-adrenergic receptor, resulting in decreased blood pressure Inhibits reuptake of 5-hydroxytryptamine (serotonin) into central nervous system neurons Inhibits cyclooxygenase, inhibition of inflammatory mediators Inhibits replication of viruses or tumor cells Inhibits HIV reverse transcriptase and DNA polymerase Antagonizes histamine effects... 

Mechanism of Action An opioid agonist that binds at opiate receptor sites in central nervous system (CNS). Therapeutic Effect Reduced intensity of pain stimuli incoming from sensory nerve endings, alteringpain perception and emotional response to pain. Pharmacokinetics Rapidly absorbed. Protein binding 40%-50%. Extensively distributed. Metabolized in liver. Excreted in urine. Half-life 11 hr. 

The opium alkaloids codeine and morphine served as models for the synthesis of naloxone, an important analog used to treat and diagnose opiate addicts, and also led to the discovery of endogenous opioids (enkephalins and endorphins) (see Chapter 47). Similarly, A9-tetrahydro-cannabinol (THC), the component of Cannabis sativa responsible for the central nervous system (CNS) effect, has also been found to reduce nausea associated with cancer chemotherapy (see Chapter 18). 

Another important side effect of all opiates on the central nervous system is respiratory depression. This is caused by an inhibitory effect on the brain stem, which is the part of the brain that controls breathing and other involuntary bodily systems such as heart beat, etc. Like nausea and vomiting, people who take methadone and other opiates normally develop a tolerance to this side effect. However, even people who have taken methadone for a long period of time can develop major respiratory depression. 

The morphinomimetic peptides react with the same receptors as the opiate alkaloids and presumably represent the endogenous agonists of these receptors. /i-Endorphin, which represents the functionally active molecule, plays a role in the response of the organism to stress stimuli. The analgesic effect in the body can be traced back to the secretion of /1-endorphin. Accordingly, acupuncture, for example, activates the central nervous endorphin system and causes an increase in the endorphin concentration, leading to the elimination of sensitivity to pain. Presumably there are endorphinergic systems in the central nervous system (CNS) in which the endorphins assume a neuro-modulatory function. 

Use of the opium poppy (Papaver somniferum) to ameliorate pain dates back thousands of years, and the active metabolite morphine (2) was isolated first from its extracts in 1806 followed by codeine (53) in 1832 (27, 28). Morphine and its derivatives are agonists of opiate receptors in the central nervous system and are some of the most effective pain relievers known and prescribed for postoperative pain. Morphine and codeine differ by substitution by methyl ether. Unfortunately, addictive properties of these compounds limit their use. Efforts have been made to reduce the addictive properties of morphine, which resulted in a semisynthetic derivative buprenorphine (54) (29). This compound is 25 to 50 times more potent than morphine with lower addictive potential and has been indicated for use by morphine addicts. 

Narcotic— A group of drugs (opiates) that depress or decrease the activity of the central nervous system. Two effects of narcotics is that they give relief from pain and produce a state of euphoria. They also have a high potential for addiction. 

Heroin s primary toxic principle is its profound ability to depress the central nervous system (CNS). Opioid analgesics bind with stereospecific receptors at many sites within the CNS. Heroin, similar to other opioids, exerts its pharmacologic effect by acting at mu, kappa, and delta receptors in the brain. Although the precise sites and mechanisms of action have not been fully determined, alterations in the release of various neurotransmitters from afferent nerves sensitive to painful stimuli may be partially responsible for the analgesic effect. Activities associated with the stimulation of opiate receptors are analgesia, euphoria, respiratory depression, miosis, and reduced gastrointestinal motility. 

Morphine is the prototype for the class of natural and synthetic opioid analgesics and its toxicity stems mainly from its extensive effect on the central nervous system (CNS), principally that of a descending depression. Opioids interact with stereospecific and saturable binding sites mostly located in the CNS. Interaction with the opioid receptors mimics the actions of endogenous enkephalins and endorphins. Morphine is a pure opiate agonist and exerts its activity primarily on the mu receptor. Activity also appears to involve an alteration in the release of neurotransmitters, such as the inhibition of acetylcholine, norepinepherine, and dopamine. These actions result in the therapeutic effects of analgesia, sedation, euphoria, and decreased gastrointestinal motility however, in toxic amounts they can lead to... 

What are the major central nervous system (CNS) effects of opiates ... 

Opiates decrease intestinal motility thereby decreasing persistalsis. Constipation is a common side effect. Examples are tincture of opium, paregoric (camphorated opium tincture), and codeine. Opiates are frequently combined with other antidiar-rheal agents and can cause central nervous system (CNS) depression when taken with alcohol, sedatives, or tranquillizers. Duration of action is about 2 hours. 

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