OPIOIDSOPIOIDS

By: By:

Dr. safa bakrDr. safa bakrM.B.Ch.B. ,H.D.A. ,F.I.B.M S.M.B.Ch.B. ,H.D.A. ,F.I.B.M S.

General anesthesia General anesthesia is a state characterized by : is a state characterized by : unconsciousness ,analgesia, unconsciousness ,analgesia, amnesia,skeletal muscle relaxation and amnesia,skeletal muscle relaxation and loss of reflexes.loss of reflexes.

The opioid analgesics are drugs which act The opioid analgesics are drugs which act on a variety of specific receptors both on a variety of specific receptors both centrally in the C.N.S. and peripherally.centrally in the C.N.S. and peripherally.

Drugs such as morphine which bind to opioid Drugs such as morphine which bind to opioid receptors and produce dose-dependentreceptors and produce dose-dependent

agonist effects are termed opioid agonist.agonist effects are termed opioid agonist.Naloxone binds to opioid receptors also Naloxone binds to opioid receptors also antagonizing the effects of morphine and is an antagonizing the effects of morphine and is an opioid antagonist.opioid antagonist.The term opioid agonist-antagonist is applied to The term opioid agonist-antagonist is applied to drugs such as nalbuphine which possess drugs such as nalbuphine which possess agonist effects at one receptor type and agonist effects at one receptor type and antagonist effect at another.antagonist effect at another.

Endogenous opioids:Endogenous opioids:These are a series of endogenous These are a series of endogenous polypeptides(the endorphins and enkephalins).polypeptides(the endorphins and enkephalins).Possessing analgesic properties similar to those Possessing analgesic properties similar to those of exogenous opioids.of exogenous opioids.

The enkephalins: are found in high concentrations The enkephalins: are found in high concentrations in the central grey matter of the brain stem and in the central grey matter of the brain stem and the substantia gelatinosa of the spinal cord.the substantia gelatinosa of the spinal cord.

B-endorphin: is present in high concentrations in B-endorphin: is present in high concentrations in the hypothalamic-pituitary axis and regulates the hypothalamic-pituitary axis and regulates endocrine function.endocrine function.There is evidence that endogenous opioids are There is evidence that endogenous opioids are an important element in the immune system.an important element in the immune system.

Opioid receptors:Opioid receptors:Opioids act on specific receptors which are Opioids act on specific receptors which are distributed throughout the C.N.S. and are the distributed throughout the C.N.S. and are the site of action of all opioids.site of action of all opioids.

There are three classes of receptors: There are three classes of receptors: Mu,kappa,and delta.Mu,kappa,and delta.The sigma receptor is associated with dysphoria The sigma receptor is associated with dysphoria and is not a true opioid receptor because its and is not a true opioid receptor because its effects are not reversed by high concentrations effects are not reversed by high concentrations of naloxone.of naloxone.

Morphine:Morphine:

It is a tertiary amine and a weak base.It is a tertiary amine and a weak base.

It is more water soluble than most other It is more water soluble than most other opioids used in anesthetic practice.opioids used in anesthetic practice.

It is excellent analgesic.It is excellent analgesic.

Summary of actions and side effects of morphine:Summary of actions and side effects of morphine:Central:Central:Depressant:Depressant:

Analgesia.Analgesia.Sedation.Sedation.Depression of cough reflex.Depression of cough reflex.Depression of respiratory centre.Depression of respiratory centre.Depression of metabolic rate(hypothermia).Depression of metabolic rate(hypothermia).Depression of vasomotor centre.Depression of vasomotor centre.

Excitatory:Excitatory:

Euphoria,hallucinations.Euphoria,hallucinations.

Convulsions (in very high doses).Convulsions (in very high doses).

Miosis(stimulation of oculomotor centre).Miosis(stimulation of oculomotor centre).

Nausea,vomiting(stimulation of chemoreceptor Nausea,vomiting(stimulation of chemoreceptor trigger zone).trigger zone).

Bradycardia(vagal stimulation).Bradycardia(vagal stimulation).

Release of A.D.H. and other pituitary hormones. Release of A.D.H. and other pituitary hormones.

Peripheral: Peripheral:

Increase in smooth muscle tone.Increase in smooth muscle tone.

Histamine release.Histamine release.

Bronchospasm.Bronchospasm.

Hypotension.Hypotension.

Erythema.Erythema.

Sensation of warmth,flushing.Sensation of warmth,flushing.

Distribution and elimination:Distribution and elimination:

After I.V. injection 35% of morphine is After I.V. injection 35% of morphine is bound to protein,the remainder is bound to protein,the remainder is distributed with a half-life of 20-25 min.distributed with a half-life of 20-25 min.

Metabolism occurs in the liver.Metabolism occurs in the liver.

Elimination occurs through the kidney.Elimination occurs through the kidney.

Morphine crosses the placental barrier and Morphine crosses the placental barrier and may depress neonatal respiration.may depress neonatal respiration.

The duration of action after either I.V.or The duration of action after either I.V.or I.M. injection is 3-4 hr.I.M. injection is 3-4 hr.

Oral morphine is used in the treatment of Oral morphine is used in the treatment of chronic pain in the form of morphine chronic pain in the form of morphine sulphate tablet(MST).sulphate tablet(MST).

Pethidine:Pethidine:

It is a synthetic opioid with an analgesic It is a synthetic opioid with an analgesic potency approximately one-tenth that of potency approximately one-tenth that of morphine.morphine.

Actions and side effects of pethidine:Actions and side effects of pethidine:Mild cholinergic effects.Mild cholinergic effects.Smooth muscle relaxation.Smooth muscle relaxation.Sedation.Sedation.Little euphoria.Little euphoria.Respiratory depression.Respiratory depression.No specific action on the cough reflex.No specific action on the cough reflex.Reduce myocardial excitability and ventricular Reduce myocardial excitability and ventricular arrhythmias.arrhythmias.

Hypotension may occur in the hypovolemic patient as a Hypotension may occur in the hypovolemic patient as a result of venous and arterial dilatation.result of venous and arterial dilatation.Smooth muscle relaxation of the gastrointestinal and Smooth muscle relaxation of the gastrointestinal and renal tracts.renal tracts.Nausea and vomiting.Nausea and vomiting.Histamine release.Histamine release.

Its duration of action is 2-3hr.after i.v.or i.m. injection.Its duration of action is 2-3hr.after i.v.or i.m. injection.It crosses the placenta,and may cause respiratory It crosses the placenta,and may cause respiratory depression in the fetus.depression in the fetus.Its metabolites cause hyperexcitability and convulsions.Its metabolites cause hyperexcitability and convulsions.

Fentanyl:Fentanyl:

It is synthetic opioid related structurally to It is synthetic opioid related structurally to pethidine.pethidine.

Its analgesic potency is approximately 100 Its analgesic potency is approximately 100 times that of morphine.times that of morphine.

It is lipid soluble.its onset of action occurs It is lipid soluble.its onset of action occurs in 1-2 min.in 1-2 min.

Its duration of action is 20-30 min. Its duration of action is 20-30 min.

Actions and side effects of fentanyl:Actions and side effects of fentanyl:Depression of respiration.Depression of respiration.A small reduction in arterial blood pressure.A small reduction in arterial blood pressure.Heart rate may decrease because of vagal Heart rate may decrease because of vagal stimulation.stimulation.Sedation.Sedation.Nausea,vomiting.Nausea,vomiting.Histamine release.Histamine release.Spasm of sphincter of oddi Spasm of sphincter of oddi

Fentanyl is used as an analgesic during Fentanyl is used as an analgesic during anesthesia.anesthesia.

Transdermal fentanyl has been used with Transdermal fentanyl has been used with some success for post-operative analgesia some success for post-operative analgesia and the control of cancer pain. and the control of cancer pain.

Alfentanil:Alfentanil:

It is synthetic derivative of fentanyl,with It is synthetic derivative of fentanyl,with high lipid solubility,and short duration of high lipid solubility,and short duration of action. action.

Actions and side effects:Actions and side effects:

Depression of respiration.Depression of respiration.

Depression of cardiovascular system. Depression of cardiovascular system.

The duration of action is 5-10 min.The duration of action is 5-10 min.

Sufentanil:Sufentanil:

It is related to fentanyl and is 600-700 It is related to fentanyl and is 600-700 times more potent than morphine.times more potent than morphine.

It is highly lipid soluble and has rapid It is highly lipid soluble and has rapid onset and short duration of action. onset and short duration of action.

Naloxone:Naloxone:

It is opioid antagonist.It is opioid antagonist.

It acts within one minute of I.V.injection It acts within one minute of I.V.injection and has duration of action of and has duration of action of approximately 30 min.approximately 30 min.

Actions:Actions:All the C.N.S. effects of opioids administered All the C.N.S. effects of opioids administered systemically are antagonized by naloxone.systemically are antagonized by naloxone.Naloxone antagonizes opioid induced respiratory Naloxone antagonizes opioid induced respiratory depression.depression.Arterial pressure may increase after Arterial pressure may increase after administration of naloxone,due to reduction of administration of naloxone,due to reduction of sedation and emergence of pain.naloxone is sedation and emergence of pain.naloxone is effective in relieving opioid induced spasm of effective in relieving opioid induced spasm of sphincter of oddi. sphincter of oddi.