a-Absorption : Most opioid analgesics are well absorbed whengiven by subcutaneous, intramuscular, and oral routes. First -pass effect canaffect the opioid(morphine) and cause to give higher dose in oral more thanparentally . first-pass can predict the effect of the oral dose that given.Certain analgesics such as codeine and oxycodone are effective orally becausethey have reduced first-pass metabolism. Nasal insufflation of certain opioidscan result in rapid therapeutic blood levels by avoiding first-pass metabolism.The latter can provide delivery of potent analgesics over days. B.
Distribution Theuptake of opioids by different organs and tissues is a function of bothphysiologic and chemical factors. Although all opioids bind to plasma proteinswith varying affinity, the drugs rapidly leave the blood compartment andlocalize in highest concentrations in tissues that are highly perfused such asthe brain, lungs, liver, kidneys, and spleen. Drug concentrations in skeletalmuscle may be much lower, but this tissue serves as the main reservoir becauseof its greater bulk. C. Metabolism Theopioids are converted in large part to polar metabolites (mostly glucuronides),which are then readily excreted by the kidneys. In contrast, approximately 10%of morphine is metabolized to morphine- 6-glucuronide (M6G), an activemetabolite with analgesic potency four to six times that of its parent compound.
However, these relatively polar metabolites have limited ability to cross theblood brain barrier and probably do not contribute significantly to the usualCNS effects of morphine given acutelyD. Excretion Polarmetabolites, including glucuronide conjugates of opioid analgesics, areexcreted mainly in the urine. Small amounts of unchanged drug may also be foundin the urine. In addition, glucuronide conjugates are found in the bile, butenterohepatic circulation represents only a small portion of the excretoryprocess. Clinical Pharmacology Of The Opioids A-Analgesia Severe, constant pain is usually relievedwith opioid analgesics with high intrinsic activity, whereas sharp,intermittent pain does not appear to be as effectively controlled. Pain from cancer and sever illness must bemanage aggressively .
Such conditions may need continuous management withpotent opioid . However, this should not be used as a barrier to providingpatients with the best possible care and quality of life. Studies shows that afixed admitting doses is better to relief the pain than 1 full dose of opioid .New dosage forms of opioids that allow slower release of the drug are nowavailable, eg, sustained-release forms of morphine (MS Contin) and oxycodone(OxyContin). Their purported advantage is a longer and more stable level ofanalgesia.
B. Acute Pulmonary Edema Therelief produced by intravenous morphine in dyspnea from pulmonary edemaassociated with left ventricular heart failure is remarkable. Proposedmechanisms include reduced anxiety ( perception of shortness of breath) and reduced cardiac preload (reduced venoustone) and afterload (decreased peripheral resistance). However, if respiratorydepression is a problem, furosemide may be preferred for the treatment ofpulmonary edema. On the other hand, morphine can be particularly useful whentreating painful myocardial ischemia with pulmonary edema.C.
Cough Canobtained in lower dose than that which given for pain relief. However, in recentyears the use of opioid analgesics to allay cough has diminished largelybecause a number of effective synthetic compounds have been developed that areneither analgesic nor addictive .D. Diarrhea Diarrhea from any disease or cause can bemanaged with the opioid analgesics, only if the diarrhea is associated withinfection, such use must not substitute for appropriate chemotherapy. Crudeopium preparations (eg, paregoric) were used in the past to control diarrhea,but now synthetic surrogates with more selective gastrointestinal effects andfew or no CNS effects, eg, diphenoxylate or loperamide, are used. E.
Shivering Althoughall opioid agonists have some propensity to reduce shivering, meperidine isreported to have the most pronounced ant shivering properties. Meperidineapparently blocks shivering mainly through an action on subtypes of the ?2 adrenoceptor. Adverseeffect of opioids Nausea and vomiting: opioid will stimulate the receptor of nausea and vomiting that present in gastrointestinal tract also it will stimulate the center which present in brain stem that will produce nausea and vomiting in patient. Some opioids such as morphine and codeine cause more nausea than other opioids.
Drowsiness or sedation: Opioids, and in particular morphine, are known to cause severe sedation and drowsiness because it will affect the receptor in brain so patient who use opioids will inter in state of drowsiness while he using them. People taking opioids are thus advised to refrain from driving and operating heavy machinery in order to avoid accidents. Skin changes: urticaria may develop and cause a skin rash which characterized by red, itchy, raised bumps. Because of histamine released that stimulating by the giving of opioid. Individuals may also experience flushing or cooling of the skin. In the case of cooling, skin may appear cool and clammy and an individual may shiver or even develop hypothermia. Miosis: This describes the formation of small, constricted pupils, similar to how pupils respond to bright light. Constipation: Opioids cause sluggish peristaltic movements in the digestive tract.
This will lead to lose of intestinal movement or deacrease it that will cause a severe constipation, especially in the case of long-term use. Respiratory depression: The breathing mechanism in response to a low blood oxygen level may be suppressed. As blood oxygen falls and blood carbon dioxide rises, there is an increase in drive for respiration. However, opioids adversely affect the ventilatory response to hypoxemia, therefore increasing the risk for hypoventilation.
However, this occurs mostly in cases of opioids that are more potent and taken in higher doses Psychological effects: Opioids give rise to a sense of euphoria and may also lead to hallucinations, delirium, dizziness and confusion. There may be some amount of memory loss and headache. Changes in heart rate: Heart rate may become either rapid or very slow.
Some opioid users may also develop postural hypotension or a severe fall in blood pressure on standing up from a sitting or lying position. Spasms: Some people may develop spasms of the ureter and urinary retention or biliary colic and spasms of the biliary tree.