Opioids
Opioids
Opioid is any naturally occurring, semi-synthetic or synthetic compounds that bind specifically to opioid receptors and share the properties of one or more of the naturally occurring endogenous opioids. The term opiate was originally used to refer to drugs derived from opium, including morphine. Narcotic is a term from the Greek meaning to numb or deaden. It is often used to denote an opioid but also widely used to describe drugs of addiction and hence includes non-opioid compounds. Naturally occurring opioid compounds are found in plants (e.g. morphine) and produced in the body (endogenous opioids e.g., Enkephaline, endorphine), where they are widely distributed throughout the central nervous system (CNS).
Mechanisms of Action and Use of Opioids
Opioids bind to specific receptors located throughout the central nervous system and other tissues. Although opioids provide some degree of sedation, they are most effective at producing analgesia (Table 2.3). The Pharmacodynamics properties of specific opioids depend on which receptor is bound, the binding affinity, and whether the receptor is activated. Although both opioid agonists (a substance which produces an observable physiological effect or initiate physiologic response by acting through specific receptors) and antagonists (a substance which acts through specific receptors to block the action of another substance, but which has no observable physiological effect itself) bind to opioid receptors.
Systemic Effects and Side Effects of Opioid Agonists
Central Nervous System
- Analgesia: Most effective in relieving dull, continuous and poorly localized pain arising from deeper structures, for example the gut. Less effective against superficial and sharp pain.
- Sedation: Drowsiness, feeling of heaviness and difficulty in concentrating are common. Sleep may occur with relief of pain, although they are not true hypnotics.
- Euphoria: A feeling of extreme happiness. Morphine and other opioids cause a sense of contentment and well-being (euphoria).
- Tolerance and Dependence: Tolerance is the decrease in effect seen despite maintaining a given concentration of a drug. Dependence exists when the sudden withdrawal (unpleasant physical condition which occur when someone stops an addictive medication) of an opioid, after repeated use over a prolonged period, results in various physical and psychological signs. These include; restlessness, irritability, increased salivation, lacrimation and sweating, muscle cramps, vomiting and diarrhea.
Table 2.3 Uses and Doses of Common Opioids.
| Agent | Use | Route | Dose | Onset (min) |
|---|---|---|---|---|
| Morphine | Premedication | IM | 0.05 - 0.2 mg/kg | |
| Postoperative analgesia | IM | 0.05 - 0.2 mg/kg | ||
| IV | 0.03 - 0.15 mg/kg | 15 - 30 | ||
| Meperidine | Premedication | IM | 0.5 - 1 mg/kg | |
| Postoperative analgesia | IV | 0.5 - 1 mg/kg | ||
| IV | 0.2 - 0.5 mg/kg | |||
| Fentanyl | Intraoperative anesthesia | IV | 2 - 15μ g/kg | 5 - 10 |
| Postoperative analgesia | 0.5 - 1.5μ g/kg |
Site of Clearance: Hepatic
Cardiovascular System
- Mild bradycardia is common as a result of decreased sympathetic drive and a direct effect on the sino-atrial (SA) node.
- Peripheral vasodilatation caused by histamine release and reduced sympathetic drive may result in a slight fall in blood pressure that may be significant in hypovolemic patients.
Respiratory System
- Respiratory depression is mediated via mu receptors at the respiratory centers in the brainstem. Respiratory rate falls more than the tidal volume and the sensitivity of the brain stem to carbon dioxide is reduced. Concurrent use of other CNS depressants, for example benzodiazepines or halogenated anaesthetic, may cause marked respiratory depression.
- Opioids suppress cough. Codeine suppresses cough to a degree similar to morphine but has lesser analgesic activity.
Gastrointestinal System
- Stimulation of the chemoreceptor trigger zone causes nausea and vomiting. Smooth muscle tone is increased but motility is decreased resulting in delayed absorption, increased pressure in the biliary system (spasm of sphincter of Oddi) and constipation.
Endocrine System: Secretion of antidiuretic hormone is increased. Urine output decreased
Ocular effects: Constriction of the pupils (meiosis).
Histamine release and itching: Some opioids cause histamine release from mast cells resulting in urticaria, itching, bronchospasm and hypotension. Naloxone reverses it
Muscle rigidity: Large doses of opioids may occasionally produce generalized muscle rigidity especially of thoracic wall and interfere with ventilation.
Effects on Pregnancy and Neonates
- All opioids cross the placenta and if given during labor, can cause neonatal respiratory depression.
- Chronic use by the mother may cause physical dependence in utero and lead to a withdrawal reaction in the neonate at birth that can be life threatening.
Partial Agonist and Antagonist
Tramadol: It is weak agonist at all opioid receptors with 20-fold preference for mu (μ) receptors. It inhibits neuronal reuptake of norepinephrine. Oral and parenteral dosage requirements are similar, 50-100 mg 4 hourly.
Pentazocine is partial agonist and has 25% of the analgesic potency of morphine. It is not very effective in relieving severe pain. It produces an increase in heart rate and BP. Nausea, vomiting; bizarre dreams and hallucination are more common than morphine. Dose 5-30 mg IV bolus
Opioid Antagonists: Naloxone is the drug of choice for the treatment of opioid induced respiratory depression. The usual dose is 200-400micrograms intravenously, titrated to effect. Smaller doses (0.5-1.0 microgram/kg) may be titrated to reverse undesirable effects of opioids. The duration of effective antagonism is limited to around 30 minutes and therefore longer acting agonists will outlast this effect.