Effects of Opiates
• It has high analgesic effects and low amnesic effects.
• These drugs, especially fentanyl, sufentanil and alfentanil, cause rigidity in striated muscles, especially in the chest wall and respiratory muscles.
• They are used to provide analgesia during surgery.
• They suppress anxiety, pain sensation and respiration in CNS.
• They stimulate the vomiting center, ADH secretion and Edinger Westpal nucleus (small pupil) in CNS.
• Cerebral effects; They reduce oxygen consumption and cerebral blood flow.
• They produce only analgesic effects.
• It has no antipyretic and anti-inflammatory effect.
• All opiate receptors exert their effects on G-proteins (Gi).
• Opiates also produce analgesia via MOR receptors.
• It is effective against chronic-blunt pains rather than sharp-acute pains. It also suppresses menthol responses to pain. In people taking morphine; Although the disturbing feature of the pain has disappeared, the sensation of pain has not completely disappeared. The patient can show the location of the pain when asked.
• Respiratory effects; respiratory rate decreases and they cause respiratory depression. It creates C2O accumulation with respiratory depression (all phases of respiration). Cerebral vasodilation and an increase in CSF pressure may develop as a result of C2O accumulation.
• Antitussive effect
• The incidence of nausea and vomiting increases with stimulation of the medullary chemoreceptor trigger zone.
• Miosis with central effect (by eliminating supranuclear inhibition on µ and K receptors and Edinger-Westphal nucleus)
• This finding is the most important distinguishing feature of morphine intoxication and pons bleeding. Because in all other cases of coma and respiratory depression, mydriasis is characteristically present.
• Hypothermia
• In high doses, it inhibits the vasomotor center (and releases histamine) causing peripheral vasodilation (hypotension) and bradycardia.
• As it reduces venous return and oxygen consumption; It is useful in the treatment of acute MI, acute left heart failure and acute pulmonary edema.
• They cause bronchoconstriction as they cause the release of histamine (especially morphine and meperidine).
• Constipation (spasm and micturition difficulty in the anal canal, sphincter of Oddi and biliary tract)
• Hormonal effects; While ADH, prolactin and GH secretion increase; Gn-RH, ACTH, ᵝ-endorphin, dopamine and acetylcholine release are decreased.
• By causing catecholamine release; hyperglycemia
• They cause a decrease in renal functions. It inhibits the voiding reflex and increases bladder volume; increases ureteric contractions at therapeutic doses.
• Decrease in gastrointestinal secretions (acid, bile, etc.) and slowdown in gastric emptying
• Enlargement of cutaneous blood vessels, sweating and itching - urticaria (with histamine release)
• Its effects can be antagonized by naloxone.
Contraindications of opiates
• Head trauma
• Convulsive diseases
• COPD and cor-pulmonale
• Hypovolemia
• Adrenal insufficiency
• Pregnancy
• In prostate hypertrophy
Acute Opioid Intoxication
• Loss of consciousness, hypotension, respiratory depression, nausea-vomiting, increased intracranial pressure, severe itching around the nose, oliguria, loose muscle tone, hypothermia, noncardiogenic pulmonary edema
Advanced miosis (pinhead pupil)
• In meperidine and propoxyphene poisoning; In addition, tonic-clonic seizures are seen.
Opiate Withdrawal Syndrome
• Initially, wet symptoms such as lacrimation, rhinorrhea, sweating appear. At a more advanced stage; tremor, mydriasis, increased blood pressure and tachycardia, diarrhea and ejaculation occur. Convulsions are not observed during a withdrawal crisis.
Goose skin appearance (piloerection = gooseflesh)
• As with all withdrawal syndromes in general; Some of the findings of morphine withdrawal syndrome are sympathetic hyperactivation findings. Clonidine and lofexidine with less side effects are used in the treatment of sympathetic hyperactivity in morphine withdrawal syndrome.
Chronic Period
• Hypotension, bradycardia, hypothermia and decreased sensitivity of the respiratory center to CO2, etc.
Tolerance
• Tolerance develops most quickly with epidural application.
The most rapidly developing effects
• Analgesia
• Respiratory depression
• Euphoria
Minimal/no tolerance-developing effects
• Miotic
• Constipation
• Convulsant
• Opiates have the property of being a partial agonist (but morphine is not a partial agonist)
Morphine and Derivatives
Morphine
It is converted in the liver to morphine-3-glucuronate, which is mostly inactive metabolite.
To a lesser extent, it is converted to the active metabolite morphine-6-glucronate.
Morphine provides analgesia without CNS depression and without affecting other senses except mild vision loss due to miosis.
Codeine (Methylmorphine)
It produces only antitussive effect at low doses.
In high doses, it transforms into morphine in the liver and creates an analgesic effect.
Synthetic Agonists
meperidine
It has no antitussive effect.
Due to its anticholinergic side effects, its miotic effect is very low.
Unlike morphine, it has negative inotropic properties.
Does not prolong labor as it does not affect uterine contractions; therefore it is preferred. Like tramadol
Its structure is similar to atropine. May cause tachycardia when IV is used.
Meperidine reduces shivering after anesthesia and is used only in acute pain.
It has a very high addiction potential.
It causes less nausea, vomiting and constipation.
Sufentanil / Fentanyl / Alfentanil / Remifentanil:
Opiates with the highest analgesic effect (the strongest is sufentanil)
Analgesic Powers: Sufentanil > Remifentanil > Fentanil > Alfentanil > Morphine > Meperidine
Remifentanil; It is the shortest acting since it is broken down by pseudocholinesterases in the plasma. For this reason, it is used only by IV infusion.
They do not cause histamine release and have very little cardiac effects. Therefore, they are preferred in cardiovascular surgery.
Propoxyphene
It affects only µ receptors and is used only orally in combination with aspirin / acetaminophen as an analgesic.
IV and SC should not be used.
It should not be used with CYP inhibitors.
Agonist-Antagonist (Partial Agonist) Opiates
• When given alone, they create an agonist effect, when given together with a full agonist, they create an antagonist effect.
• Buprenorphine: It is an opiate partial agonist. It is used to prevent withdrawal symptoms in opiate addicts due to its partial agonist effect on µ receptors. Although it is a partial agonist, it produces analgesia and CNS effects as potent as morphine. The risk of respiratory depression and addiction is lower than morphine.
• Tramadol and trapentadol; They also create an analgesic effect by blocking serotonin reuptake. They are also partial agonists.
• Tramadol has a low addiction potential. Partial agonist does not cause miosis. It causes nausea and dry mouth.
Narcotic Antagonists
They are used in narcotic analgesic poisoning.
Respiratory depression is one of the first signs they correct because of their high affinity for mu receptors.
They are not addicted.
Tolerance does not develop to its effects.
naloxone (N LX)
By creating a full antagonistic effect on Mu and Kappa, it eliminates the effect of opioids (such as naltrexone).
It is not used orally because it is subject to presystemic elimination.
It is used in IV infusion because it is very short-acting.
It is used in the treatment of spinal cord and brain injuries due to ischemia and trauma.
naloxone and naltrexone; It increases the release of GnRH and PRL.
naltrexone
It is much longer acting than naloxone and can be used orally.
It is used in the treatment of alcoholism.
Naloxone and naltrexone can be used in the treatment of opiate-induced respiratory depression in the newborn.
Spinal use of opiates | |
Intrathecal uses | Epidural uses |
• Morfin and fentanil | • Morphine |
• Fentanyl | |
• Suf entanyl | |
• Alfentanil | |
• Meperidine | |
• Hydromorphone | |
Opiate | Analgesic effect duration (hours) | Analgesic potency |
Morphine | 5 | High |
hydromorphone | 5 | High |
auxomorphone | 4 | High |
Fentanyl | 1.5 | High |
Sufentanil | 1.5 | Highest |
alfentanil | 0.25 | High |
Remifentanil | 0.05 | High |
Levorphanol | 5 | High |
Codeine | 4 | Low |
hydrocodone | 6 | Middle |
oxycodone | 4 | Middle |
Propoxyphene | 5 | Very low |
nalbuphine | 6 | High |
from the meta | 5 | High |
meperidine | 4 | High |
