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Opioids analgesics
Pain: is 'an unpleasant sensory and emotional experience associated with actual or
potential tissue damage, or described in terms of such damage'.
This implies that the degree of pain experienced by the patient may be unrelated to the
extent or presence of underlying tissue damage and that emotional or spiritual distress can
add to the patient's experience of pain.
Nociception: physiological process by which pain is perceived.
Hyperalgesia: an increased amount of pain associated with a mild noxious stimulus.
Allodynia : pain evoked by a non-noxious stimulus or spontaneous pain without any
precipitating stimulus.
Analgesia : reduction in pain sensation.
An analgesic: defined as a drug that relieves pain.
Analgesics classified as:
1- opioids
2- non-opioids, e.g. nonsteroidal anti-inflammatory drugs (NSAIDs).
3- Co-analgesics or adjuvants : are drugs that have a primary indication other than pain
but are analgesic in some conditions. For example, antidepressants and anticonvulsants
also act to reduce nociceptive processing in neuropathic pain.
OPIOID ANALGESICS
Opioid is a generic term for natural or synthetic substances that bind to specific opioid
receptors in the CNS, producing an agonist action.
Mechanism of action
Opioids act to reduce the intensity and unpleasantness of pain. They produce their effects
by activating specific G protein-coupled receptors in the brain, spinal cord and peripheral
nervous system. There are three major classes of opioid receptor: δ-opioid, κ-opioid and μopioid, which correspond respectively to their endogenous ligands, dynorphin, enkephalin
and β-endorphin.
Agonist activity at opioid receptors acts to open potassium channels and prevent the
opening of voltage-gated calcium channels. This reduces neuronal excitability and inhibits
the release of pain neurotransmitters.
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Opioids analgesics
Morphine is the major analgesic drug contained in crude opium and is the prototype
strong μ receptor agonist. Codeine is present in crude opium in lower concentrations
and is inherently less potent, making codeine the prototype of the weak opioid agonists.
Morphine Actions:
a. Analgesia
b. Euphoria: Morphine produces a powerful sense of contentment and well-being.
c. Respiration: Morphine causes respiratory depression by reduction of the
sensitivity of respiratory center neurons to carbon dioxide.
d. Depression of cough reflex: Both morphine and codeine have antitussive
properties.
e. Miosis: The pinpoint pupil characteristic of morphine use results from stimulation
of μ and κ receptors.
f. Emesis: Morphine directly stimulates the chemoreceptor trigger zone in the area
postrema that causes vomiting.
g. GI tract: Morphine relieves diarrhea by decreasing the motility and increasing the
tone of the intestinal circular smooth muscle. Morphine also increases the tone of the
anal sphincter. Overall, morphine and other opioids produce constipation.
h. Cardiovascular: Morphine has no major effects on the blood pressure or heart rate
at lower dosages. With large doses, hypotension and bradycardia may occur.
i. Histamine release: Morphine releases histamine from mast cells causing urticaria,
sweating, and vasodilation.
Therapeutic use:
1-Analgesia: Morphine is the prototype opioid agonist. Opioids used for pain in
trauma, cancer, and other types of severe pain.
2-Treatment of diarrhea :Agents commonly used include diphenoxylate and
loperamide
3-Relief of cough: Morphine does suppress the cough reflex, but codeine and
dextromethorphan are more commonly used.
4-Anesthesia: Opioids are used as pre anesthetic medications, for systemic and spinal
anesthesia, and for postoperative analgesia.
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Adverse effects:
1- With most μ agonists, severe respiratory depression can occur and may result in
death from acute opioid overdose.
2- Elevation of intracranial pressure, particularly in head injury, can be serious.
Morphine should be used with caution in patients with asthma, liver disease, or renal
dysfunction.
3-Physical and psychological dependence can occur with morphine and with some of
the other agonists. Withdrawal produces a series of autonomic, motor, and psychological
responses that incapacitate the individual and cause serious symptoms, although it is rare
that the effects cause death.
Codeine
is a naturally occurring opioid that is a weak analgesic compared to morphine. It
should be used only for mild to moderate pain. Codeine is commonly used in
combination with acetaminophen (paracetamol) for management of pain. Codeine
exhibits good antitussive activity at doses that do not cause analgesia.
Oxycodone
is a semisynthetic derivative of morphine. It is orally active and is sometimes formulated
with aspirin or acetaminophen. Its oral analgesic effect is approximately twice that of
morphine.
Fentanyl
a synthetic opioid chemically related to meperidine, has 100-fold the analgesic potency
of morphine and is used for anesthesia. The drug is highly lipophilic and has a rapid onset
and short duration of action (15 to 30 minutes). It is usually administered IV, epidurally,
or intrathecally. Fentanyl is combined with local anesthetics to provide epidural analgesia
for labor and postoperative pain.
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Opioids analgesics
Partial Agonists and Mixed Agonist–Antagonists
Buprenorphine
is classified as a partial agonist, acting at the μ receptor. Buprenorphine tablets are
indicated for the treatment of opioid dependence and are also available in a combination
product containing buprenorphine and naloxone. Naloxone was added to prevent the
abuse of buprenorphine via IV administration.
Pentazocine
acts as an agonist on κ receptors and is a weak antagonist at μ and δ receptors.
Pentazocine promotes analgesia by activating receptors in the spinal cord, and it is used to
relieve moderate pain.
Other analgesics
Tramadol
is a centrally acting analgesic that binds to the μ opioid receptor. The drug undergoes
extensive metabolism via CYP450 2D6, leading to an active metabolite with a much
higher affinity for the μ receptor than the parent compound. In addition, it weakly inhibits
reuptake of norepinephrine and serotonin. It is used to manage moderate to moderately
severe pain. Its respiratory depressant activity is less than that of morphine.
Opioids antagonists
Naloxone
is a competitive antagonist at μ, κ, and δ receptors, with a 10-fold higher affinity for μ
than for κ receptors. Naloxone is used to reverse the coma and respiratory depression of
opioid overdose. It rapidly displaces all receptor-bound opioid molecules and, therefore, is
able to reverse the effect of a morphine overdose. Within 30 seconds of IV injection of
naloxone.
Naltrexone
has actions similar to those of naloxone. It has a longer duration of action than naloxone,
and a single oral dose of naltrexone blocks the effect of injected heroin for up to 24 hours.
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