Central Nervous System - Analgesics

Central Nervous System - Analgesics

• Analgesics are medications used to relieve pain.
• Opioid analgesics are further categorized into strong and weak opioids.
  • Strong opioids include morphine, fentanyl, and methadone.
  • Weak opioids include codeine.
• Opioid mechanism:
  • Stimulate postsynaptic opioid receptors, leading to mainly inhibitory actions on the CNS by opening potassium channels.
  • Stimulate presynaptic receptors to prevent neurotransmitter release (e.g., Substance P) by blocking calcium channels.
• Therapeutic uses of opioid analgesics:
  • Analgesic for severe pain (e.g., post-operative, fracture, acute MI, cancer pain); meperidine (pethidine) preferred for biliary colic due to atropine-like action.
  • Acute pulmonary edema treatment (sedative, vasodilator, decrease pulmonary pressure).
  • Anaesthesia (fentanyl is more potent).
  • Cough suppressant (codeine, dextromethorphan).
  • Anti-diarrheal (loperamide & diphenoxylate).
• Adverse effects of opioid analgesics:
  • Respiratory depression (most critical; treated with naloxone).
  • Bronchospasm, biliary spasm, urine retention, delayed labor, vomiting, constipation, ileus, truncal rigidity, hypotension, and bradycardia.
  • Addiction and withdrawal syndrome (major concern with chronic use).
• Contraindications and precautions:
  • Hypovolemia (to prevent hypotension).
  • Head injury (risk of increased intracranial pressure).
  • Acute abdominal pain (potentially masking diagnosis).
  • Respiratory/liver disease (e.g., asthma, COPD).
  • Late-stage labor (to prevent neonatal asphyxia).
• Morphine substitute (Meperidine Hydrochloride/Pethidine):
  • No antitussive action.
  • Has atropine-like action.
  • Shorted duration of action than opium.
  • Uses: biliary colic, obstetric anesthesia, post-operative pain, minor surgeries.
• Tramadol:
  • Inhibits norepinephrine and serotonin reuptake.
  • Atropine-like effects.
  • Uses: moderate pain (oral, parenteral, rectal).
• Opioid antagonists:
  • Naloxone (IV, short-acting): used to treat respiratory depression from opioid overdose (toxicity) and neonatal asphyxia.
  • Naltrexone (oral, long-acting): used to prevent opioid addiction.
• Acute opioid toxicity:
  • Respiratory depression, deep sleep, stupor, coma, pinpoint pupil, reduced respiratory rate, cyanosis, hypotension, decreased urine output, decreased temperature, clammy skin, and death (from respiratory failure).
• Treatment of acute opioid overdose:
  • Induce vomiting or gastric lavage.
  • Artificial respiration.
  • Administer naloxone (2-4 hours).
• Chronic opioid toxicity:
  • Constricted pupils, constipation, skin infections, needle-scar abscesses, itching.
  • Withdrawal symptoms (intense craving, insomnia, yawning, sneezing, vomiting, diarrhea, tremors, sweating, mental depression, muscle aches, pain, chills, and anxiety).
• Non-Opioid Analgesics:

Non-Steroidal Anti-inflammatory Drugs (NSAIDs)

• Types:
  • Acetylsalicylic acid (aspirin, salicylates).
  • Enolic acid (novalgina, phenylbutazone).
  • Oxicams (piroxicam).
  • Propionic acid (ibuprofen, naproxen).
  • Acetic acid (indomethacin, diclofenac).
  • Coxibs (celecoxib).
• Mechanism of action of salicylates (e.g., aspirin):
  • Antithrombotic (antiplatelet): low doses (75-150 mg/day) irreversibly inhibit cyclooxygenase enzyme (COX-1), thereby preventing thromboxane A2 production & platelet aggregation(affect for 4 days).
  • Analgesic and antipyretic: higher doses (300 mg tds) inhibit COX-2 and prostaglandin formation.
  • Anti-inflammatory: even higher doses (500 mg qid or more) have anti-inflammatory effects.
• Indications of salicylates:
  • Antithrombotic: angina, myocardial infarction, transient ischemic attacks, cerebral infarction.
  • Analgesic: mild and moderate pain (headache, dental, muscle, gynecological).
  • Antipyretic: fever.
  • Anti-inflammatory: rheumatic fever and arthritis.
  • Recent treatment - for pregnancy-induced hypertension.
• Adverse effects of salicylates:
  • GIT upset (heartburn, peptic ulcers, hematemesis).
  • Increased bleeding tendency (especially with warfarin).
  • Hepatic enzyme increases (SGOT and SGPT).
  • Hypersensitivity reactions (skin rash, bronchospasm).
  • Renal effects (salt and water retention, hypertension, edema).
  • Acute interstitial nephritis, acute renal failure.
  • Reye's syndrome (fatal liver failure and encephalopathy in children with flu).
  • Hyperuricemia (with moderate doses).
  • Acute salicylate toxicity (salicylism).

Paracetamol (Acetaminophen)

• Mechanism: analgesic & antipyretic effects by inhibiting CNS prostaglandin synthesis (hypothalamus).
• No antithrombotic or anti-inflammatory actions.
• Safe drug, no GIT problems.
• Uses: substitute for aspirin (when contraindicated), analgesic for headache, dysmenorrhea, arthralgia, myalgia, teething, post-tonsillectomy, and antipyretic for bacterial/viral infections.
• Overdose symptoms:
  • Hepatic toxicity (general malaise, delirium, seizures, coma, death, nausea, vomiting, fever, vascular collapse).
  • Nephrotoxicity (when used with aspirin long term).
• Treatment of paracetamol overdose:
  • Induce vomiting or gastric lavage; activated charcoal.
  • Oral N-acetylcysteine (mucomyst) inactivates acetaminophen metabolites.

Sedative Hypnotics, Anxiolytics - Benzodiazepines

• Mechanism: Enhance GABA-induced opening of chloride channels by binding to the GABA A receptor's gamma subunit; leads to hyperpolarization and neuronal inhibition.
• Classification:
  • Short-acting: triazolam.
  • Intermediate-acting: alprazolam.
  • Long-acting: diazepam.
• Uses: Anxiety disorders, sedation in agitation (e.g., alcohol withdrawal), hypnotics for insomnia and parasomnia (e.g., sleepwalking), anesthesia for minor procedures and pre-anesthetic medication, muscle relaxant (for spastic states), and seizures (IV diazepam for status epilepticus).
• Adverse effects:
  • Anterograde amnesia (inability to remember recent events).
  • Learning difficulties (in children).
  • Motor coordination problems.
  • Hangover effect (residual sleep and next-day impairment).
  • Decreased lag period.
  • Increased NREM sleep.
  • Decreased REM sleep.
  • Benzodiazepine dependence (tolerance, withdrawal syndrome –rebound insomnia, increased nightmares).
  • Acute toxicity (CVS & respiratory depression). Treatment: flumazenil (competitive benzodiazepine antagonist).

This quiz covers the crucial aspects of analgesics used in pain relief, focusing on opioid analgesics and their classifications. Learn about the mechanisms of opioids, therapeutic uses in various medical conditions, and potential adverse effects. Test your knowledge on strong and weak opioids and their applications in clinical settings.