Untitled Quiz

Direct Presynaptic Inhibition: Opioids bind to mu-opioid receptors (MOR), a Gi protein-coupled receptor (GPCR), which inhibits adenylyl cyclase (AC) and reduces cAMP levels. This leads to a decrease in calcium influx by closing calcium channels, ultimately reducing excitatory neurotransmitter (glutamate and substance P) release in ascending pain pathways.
Direct Postsynaptic Inhibition: Opioid binding to MOR also increases potassium efflux by opening potassium channels, causing neuronal membrane hyperpolarization and reducing the generation of action potentials in postsynaptic fibers.
Facilitating Descending Pain Inhibitory Modulation: Opioids activate MOR receptors, leading to the inhibition of GABAergic release in the periaqueductal gray (PAG) region. This inhibition facilitates the descending inhibitory pathways originating in PAG to the rostral ventromedial medulla (RVM) and locus coeruleus (LC). These pathways indirectly activate inhibitory MOR interneurons in the dorsal horn, ultimately suppressing pain signaling.

Euphoria Induction: Opioids activate the reward pathway, primarily through dopamine release. Normally, GABAergic neurons in the frontal lobe regulate dopamine release to maintain a balanced mood. However, opioids disinhibit these GABAergic signals, leading to uninhibited dopamine release and intense feelings of pleasure, excitement, and euphoria.
Withdrawal Manifestations: Chronic opioid use leads to a compensatory increase in adenylyl cyclase (AC) synthesis. This is an adaptive mechanism to counteract the continuous suppression of AC activity by opioids. When opioids are withdrawn, AC activity surges, resulting in a rapid increase in cAMP levels. This cAMP surge is responsible for withdrawal symptoms, which peak immediately upon withdrawal and gradually subside over several days.

Route of Administration: Typically administered intramuscularly (IM) every 4 hours, but can be given subcutaneously or intravenously (IV) with dose adjustments to prevent adverse effects.
Clinical Indications:
- Controlling pain after trauma, severe burns, cancer, and visceral pain (excluding renal/biliary colic and acute pancreatitis).
- Managing distressful conditions, even without pain, such as acute pulmonary edema, acute myocardial infarction (AMI), and acute heart failure (HF).
- Pre-anesthetic medication and postoperative pain control.
Adverse Drug Reactions (ADRs):
- Pupillary constriction.
- Nausea and vomiting due to activation of the chemoreceptor trigger zone (CRTZ).
- Constipation and gallbladder contraction.
- Itching due to histamine release.
- Sedation and respiratory depression, particularly with renal impairment.
- Tolerance and physical/psychological dependence with chronic use.
Contraindications:
- Head injuries: Morphine constricts pupils, masking signs of head injury and potentially increasing intracranial pressure.
- Pregnancy and labor: Morphine can induce respiratory depression in newborns.
- Neonates and infants: Morphine toxicity can develop due to immature metabolism.
- Elderly individuals: They are more sensitive due to reduced metabolism and overall body function.
- Asthmatics: Histamine release can trigger asthma attacks.
- Renal and biliary colic: Morphine constricts sphincters, worsening these conditions.

Abuse Potential: Highly addictive, used illicitly and not in medical practice due to its rapid action and high lipid solubility.
Routes of Administration: Injected, insufflated (snorted), or smoked.

Potency: 50-100 times more potent than morphine.
Duration: Short-acting (2 hours), but highly lipophilic, allowing for transdermal patch administration for sustained release (72 hours).
Clinical Uses:
- IV injection for anesthesia induction and maintenance.
- Intrathecal administration during surgery.
- Management of severe breakthrough cancer pain and postoperative pain.

Potency: Tenth the potency of morphine.
Onset and Duration: Rapid onset and short duration.
Clinical Uses:
- Obstetric analgesia (safer on respiration).
- Severe visceral pain, including renal and biliary colic (atropine-like effects).
- Pre-anesthetic medication.

Opioid Receptor Subtypes: The most important opioid receptor subtype for analgesia is the mu-opioid receptor (MOR).
Opioid Classification:
- Endogenous Opioids: Naturally produced in the body (endorphins, dynorphins, enkephalins).
- Exogenous Opioids: Derived from external sources.
  - Natural: Extracted from the opium poppy plant (morphine, heroin).
  - Semisynthetic: Chemically modified from natural opioids (codeine).
  - Synthetic: Manufactured synthetically (meperidine, methadone, fentanyl, tramadol).
Opioid Action:
- Agonists: Bind to opioid receptors and activate them, producing analgesic effects (morphine, meperidine, methadone, fentanyl, tramadol).
- Agonist/Antagonists: Exhibit both agonist and antagonist properties in their effects on opioid receptors (buprenorphine).
- Antagonists: Block opioid receptors, counteracting the effects of agonists. They are used as antidotes in opioid overdose (naloxone).