Opioid Analgesics

1. Analgesic Drug Classification:

There are two main categories:

• Opioid analgesics:

• These drugs have a chemical structure similar to morphine and act on opioid receptors in the brain and spinal cord, leading to strong pain relief.

• Important notes:

• Opioid drugs are highly addictive and should only be used under a doctor’s prescription.

• Never buy, sell, or use opioid drugs without a legitimate medical reason.

• Non-opioid analgesics:

• These include non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), etc.

• They offer generally milder pain relief compared to opioids, are less addictive, but may cause side effects on the stomach, liver, and kidneys.

2. Morphine’s Origin:

Morphine is extracted from the resin of the opium poppy plant (Papaver somniferum).

3. Alkaloids in Opium Resin:

Opium resin contains two main groups of alkaloids:

• Phenanthrene:

• Morphine (10%): A potent pain reliever, widely used in healthcare.

• Codeine (0.5%): A weaker pain reliever, often used in cough syrups.

• Thebaine (0.2%): Has pain-relieving properties but is rarely used due to its frequent side effects.

• Benzyl-isoquinolone:

• Papaverine (1%): A smooth muscle relaxant, commonly used to treat smooth muscle spasms in the digestive tract.

• Noscapine (6%): A cough suppressant, acting by suppressing the cough center in the medulla oblongata.

4. Key Functional Groups in Morphine’s Structure:

Two crucial functional groups influence morphine’s activity:

• C3 Phenol group: Related to pain-relieving and addictive properties.

• C6 Alcohol group: Associated with pain-relieving and toxic effects.

5. Modifications of the C3 Group:

• Alkylation:

• Example: Codeine = Methyl morphine

• Decreases pain-relieving effect, increases addictive properties.

• Esterification:

• Example: Acetyl morphine

• Enhances pain relief, increases addictive potential.

6. Modifications of the C6 Group:

• Hydrogenation: Enhances pain relief, increases toxicity.

• Esterification: Increases pain relief, shortens duration of action.

• Etherification: Increases pain relief, increases toxicity.

7. Acetylation at Both C3 and C6 Groups:

• Heroin = Diacetyl morphine:

• Increases pain relief, intensifies addictive properties, elevates the risk of death.

• Classified as an extremely dangerous opioid, prohibited for medical use.

8. Morphine and Opioid Receptors:

Morphine and opioids act on specific receptors in the central nervous system, categorized based on their effects:

• μ (mu) receptor:

• Offers pain relief in the spinal cord, causes respiratory depression, pupil constriction, reduces stomach spasms, induces euphoria, slows heart rate.

• The primary receptor responsible for morphine’s analgesic effects.

• κ (kappa) receptor:

• Provides pain relief in the spinal cord, leads to respiratory depression, pupil constriction (milder than mu), sedation.

• σ (sigma) receptor:

• Reduces pain in animals, its effects on humans are unclear.

9. Pharmacological Effects on the Central Nervous System:

• Pain relief: Strong pain relief, inhibiting all key points along the pain sensory pathway.

• Sleep induction: Reduces mental activity, induces sleep, high doses can cause anesthesia and loss of consciousness.

• Euphoria: Tranquility, relaxation, euphoria, prone to drug abuse and addiction.

• Respiratory depression:

• Decreases CO2 sensitivity in the medulla oblongata, affecting respiratory rate and amplitude.

• Dangerous for patients with COPD, asthma, pregnant women, and children under 30 months old.

• Endocrine suppression:

• Suppresses the hypothalamus, reduces body temperature, lowers GnRH and CRH secretion, leading to reduced LH, FSH, ACTH, and TSH secretion.

• Increases ADH release.

• Nausea and vomiting: Stimulates the chemoreceptor trigger zone (CTZ) in the medulla oblongata.

• Pupil constriction: Stimulates the center of the IIIrd cranial nerve, pupils constrict to a pin point size during prolonged opioid poisoning.

10. Pharmacological Effects on the Periphery:

• Smooth muscle:

• Decreases intestinal motility, increases bladder sphincter contraction, leading to urinary retention.

• Increases tone and contractions of smooth muscles in other locations.

• Skin: Vasodilation, facial flushing, neck and upper body flushing, increased histamine release causing itching, redness, and hives.

• Metabolism: Decreases oxygen levels, reduces base reserves, increases acid accumulation in the blood, leading to facial swelling and dark discoloration of fingernails and lips.

• Hypotension: Vasodilation, suppression of the cardiovascular center.

11. Description of Pain Relief Effects:

• Mechanism: Inhibits all key points along the pain sensory pathway.

• Effects: Powerful pain relief, effective for cancer pain and visceral pain (e.g., kidney stones).

12. Description of Sleep-Inducing Effects:

• Effects: Reduces mental activity, induces sleep, high doses can cause anesthesia and loss of consciousness.

13. Description of Euphoria-Inducing Effects:

• Effects: Tranquility, relaxation, euphoria, optimism, increased imagination, reduced anxiety, restlessness, and pain-induced tension.

• Risk: Prone to drug abuse and addiction due to the euphoric effect.

14. Description of Effects on the Respiratory System:

• Respiratory center suppression: Decreases CO2 sensitivity in the medulla oblongata, affecting respiratory rate and amplitude.

• Cough center suppression:

• Codeine, PHOLCODIN: Selectively suppress cough, but cause constipation.

• Noscapine, Dextromethorphan: Cough suppressants, selective cough suppression with fewer side effects.

15. Description of Effects on the Endocrine System:

• Hypothalamus suppression: Reduces body temperature, lowers GnRH and CRH secretion, leading to reduced LH, FSH, ACTH, and TSH secretion.

• Increased ADH release:

16. Description of Pupil Constriction Effects:

• Mechanism: Stimulates the center of the IIIrd cranial nerve.

• Effects: Pupils constrict to a pin point size during prolonged opioid poisoning.

17. Description of Nausea Effects:

• Mechanism: Stimulates the chemoreceptor trigger zone (CTZ) in the medulla oblongata.

• Effects: Nausea and vomiting.

18. Description of Effects on the Cardiovascular System:

• High doses: Hypotension due to cardiovascular center suppression, vasodilation caused by histamine, reflex vasodilation due to increased CO2.

19. Description of Effects on Smooth Muscle:

• Intestinal smooth muscle: Reduces intestinal motility, decreases acid, gastric juice, and intestinal juice secretion, increases water and electrolyte absorption, increases Oddi’s sphincter contraction, causing epigastric pain.

• Other smooth muscles: Increases tone, contraction, and constriction of the bladder sphincter, causing urinary retention, airway constriction, leading to asthma (in combination with histamine release).

20. Description of Effects on the Skin:

• Vasodilation: Facial flushing, neck, and upper body flushing.

• Increased histamine release: Itching, redness, hives.

21. Description of Effects on Metabolism:

• Decreased oxygen:

• Reduced base reserves: Increases acid accumulation in the blood, leading to facial swelling and dark discoloration of fingernails and lips.

22. Opioid Types:

• Full agonists: Similar to morphine, act on mu, kappa, and sigma receptors: Meperidine, Fentanyl.

• Partial agonists:

• Pentazocin: Primarily acts on kappa receptors, antagonizes mu receptors.

• Nalbuphine: Similar to pentazocin.

• Buprenorphine:

• Antagonists: Naloxone, Naltrexone.

23. Opioid Use in Surgical Pain Management / Post-Surgery Pain:

• Fentanyl: Low doses, rapid onset of action.

• Morphine: Higher doses than fentanyl, similar effects.

• Buprenorphine: Moderate doses, slower onset of action than fentanyl and morphine.

24. Examples of Strong Agonists:

• Morphine

• Hydromorphone

• Methadone

• Meperidine

• Fentanyl

25. Characteristics of Each Strong Agonist:

• Morphine: Preferred for acute and chronic pain.

• Oral administration is less effective than injection, undergoes first-pass metabolism in the liver, oral bioavailability is lower than injection (40% for injection, 25% for oral).

• Oral doses are six times higher than injection doses (standard injection dose 10mg).

• Hydromorphone:

• Less likely to cause constipation, sedation, nausea, and euphoria.

• Used as an alternative to morphine.

• Methadone:

• Long half-life (40 hours), well absorbed orally, high bioavailability.

• Used for morphine and heroin withdrawal.

• Meperidine:

• Weaker pain relief than morphine (7-10 times).

• Used in obstetrics, biliary colic, and pancreatitis.

• Fentanyl:

• Rapid onset within 2-3 minutes, powerful pain relief 80-100 times stronger than morphine.

• Combined with Droperidol for anesthesia.

26. Examples of Moderate to Weak Agonists:

• -codeine derivatives: Codeine, Oxycodone, Dihydrocodeine.

• Tramadol.

• Propoxyphene.

• Dextropropoxyphene + Paracetamol —> Diantalvic.

27. Characteristics of Moderate to Weak Agonists:

• Codeine, Oxycodone, Dihydrocodeine, Tramadol: Combined with NSAIDs, provide moderate pain relief.

• Propoxyphene: Pain relief is half that of codeine, twice to three times that of aspirin.

• Diantalvic: Pain relief and fever reduction.

28. Partial Agonists:

• Pentazocin, Nalbuphine, Buprenorphine.

• Moderate pain relief, less addictive, no euphoric effects.

• Administered intravenously (poor oral bioavailability).

29. Opioids for Cough Suppression:

• Noscapine, Pholcodine, Dextromethorphan, Levopropoxyphene (often combined with paracetamol for fever reduction).

30. Opioid Antagonists:

• Nalorphine: Partial antagonist (acts on mu receptors), not used clinically (respiratory depression, bradycardia).

• Naloxone Hydrochloride (Narcan): Antagonist at mu and kappa receptors (administered intravenously, subcutaneously, intramuscularly).

• Naltrexone:

• Longer duration of action than Naloxone.

• Not tolerated, does not cause withdrawal symptoms with long-term use.

• Indications: Treatment of acute opioid overdose, heroin withdrawal.

31. Indications for Opioid Treatment:

• Pain after injury, cancer pain, post-operative pain.

• Kidney stone pain, biliary colic (combined with antispasmodics).

• Anesthesia and pre-anesthesia (Morphine, Fentanyl).

• Acute pulmonary edema (Morphine, limits spasms, facilitates fluid and plasma passage through damaged alveolar membranes).

32. Opioid Toxicity:

• Acute toxicity:

• Hypotension, tachycardia, vomiting, pupil constriction, coma, respiratory depression, cardiovascular collapse, high risk of death.

• Other symptoms: Headache, dizziness, cyanosis.

• Antidotes: Naloxone, Naltrexone.

• Chronic toxicity:

• Constipation, anemia, loss of appetite, insomnia.

• Risk of infectious diseases like HIV (injection drug use).

• Addiction:

• Develops after treatment: 1-2 weeks, sometimes after 2-3 days.

• Withdrawal syndrome:

• Anxiety, restlessness, agitation, delirium, nausea, muscle aches, fever, sweating.

• Occurs a few hours after stopping treatment, peaks after 2-3 days.

• Tolerance:

• Requires increasing doses with prolonged use to achieve the initial effect.

• Dependence:

• Withdrawal syndrome occurs upon discontinuation (due to tolerance).

33. Drug Interactions:

• Avoid concurrent use with Monoamine Oxidase Inhibitors (MAOIs): Risk of cardiovascular collapse, hyperthermia, coma, and death.

• Phenothiazines, benzodiazepines, alcohol: Enhance the central nervous system depressant effects of morphine, causing greater sedation and sleepiness.

34. Endogenous Morphine:

• Endogenous morphine: Naturally occurring peptides produced in the body, acting like morphine (Enkephalin, Endorphin, Dynorphin).

• Role: Regulates nerve impulse transmission (brain, spinal cord).

• Release: Occurs during stress, effects decrease or disappear when exposed to opioid antagonists.

Note:

• This information is for general educational purposes only and does not substitute medical advice.

• Always consult with your doctor before using any medication.

• Never buy, sell, or use opioid drugs without a legitimate medical reason.

In addition to the information provided, it is crucial to note:

• Opioid dosage and duration of use: Opioid dosage and duration of use depend on individual cases, specific drug, medical condition, and body response.

• Side effects of opioid medications: Besides pain relief, opioids can cause dangerous side effects such as respiratory depression, seizures, overdose, and addiction.

• References: Seek further information about opioids from reputable sources like medical literature and websites of reliable healthcare organizations.

Advice:

• Always adhere to your doctor’s and pharmacist’s instructions.

• Store opioid medications securely, out of reach of children.

• If you suspect opioid overdose, seek immediate medical attention at the nearest healthcare facility.