Opioid Pharmacology Introduction

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Questions and Answers

What is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage?

Sedation

Euphoria

Pain (correct)

Analgesia

Which type of opioid receptor is primarily associated with euphoria and physical dependence?

Mu receptors (correct)

Delta receptors

Kappa receptors

ORL 1 receptors

Which of the following opioids is considered a strong agonist?

Oxycodone

Morphine (correct)

Propoxyphene

Codeine

What action do opioids primarily inhibit to exert their effects?

Adenylcyclase activity Signup and view all the answers

Which type of opioid is nalbuphine classified as?

Mixed agonist-antagonist Signup and view all the answers

Which effect is NOT typically associated with opioid administration?

Increased GI motility Signup and view all the answers

What is the primary reason opioids are used as antitussives?

To suppress the cough reflex Signup and view all the answers

Which of the following endogenous opioid peptides is NOT listed as a neuromodulator?

Cannabinoids Signup and view all the answers

Which conditions are indicated for the use of paracetamol?

Metastatic bone pain and postoperative pain Signup and view all the answers

What are common contraindications for the use of paracetamol?

Ulcer and chronic liver disease Signup and view all the answers

What is known about the mechanism of action of paracetamol?

It influences multiple central mechanisms and pathways Signup and view all the answers

Which drug interaction can enhance the effect of paracetamol?

Anticoagulants like warfarin Signup and view all the answers

Which of the following groups should avoid paracetamol?

Patients with nasal polyps and chronic liver disease Signup and view all the answers

Which opioid is known for causing a muscarinic blocking action that prevents miosis?

Meperidine Signup and view all the answers

What is a common acute effect of opioids on gastrointestinal function?

Constipation Signup and view all the answers

Which of the following statements about tolerance to opioid analgesics is true?

Tolerance does not develop to constipation. Signup and view all the answers

What typically characterizes opioid overdose?

Pupillary constriction and respiratory depression Signup and view all the answers

Dependence on opioids is primarily characterized by which of the following?

Compulsive craving for the drug Signup and view all the answers

What is one of the treatments for opioid overdose?

Naloxone use Signup and view all the answers

What effect do opioid analgesics have on biliary smooth muscle?

Contraction Signup and view all the answers

Which statement about the management of acute pulmonary edema involving opioids is correct?

Morphine is administered parenterally. Signup and view all the answers

What is the primary clinical use of opioid antagonists such as naloxone?

Opioid overdose management Signup and view all the answers

Which opioid antagonist is known for blocking the effects of strong agonists for at least 24 hours after oral administration?

Naltrexone Signup and view all the answers

Which class of analgesics includes both non-selective COX inhibitors and selective COX-2 inhibitors?

Non-narcotic analgesics Signup and view all the answers

Which of the following is classified as a preferential COX-2 inhibitor?

Meloxicam Signup and view all the answers

What biochemical process is COX (Cyclooxygenase) primarily responsible for?

Synthesis of prostanoids Signup and view all the answers

Which of the following drugs is classified as an analgesic with poor anti-inflammatory action?

Paracetamol Signup and view all the answers

Which two isoforms of cyclooxygenase were discovered in the 1990s?

COX-1 and COX-2 Signup and view all the answers

Which compound is NOT classified as a non-selective COX inhibitor?

Nimesulide Signup and view all the answers

What is the primary role of COX-1 in the body?

To protect the stomach lining Signup and view all the answers

What is a common adverse effect associated with long-term use of anti-inflammatory doses of NSAIDs?

Erosive gastritis Signup and view all the answers

Which of the following best describes the action of NSAIDs related to prostaglandins?

They inhibit prostaglandin synthesis Signup and view all the answers

What is a characteristic action of COX-2 that differentiates it from COX-1?

Found primarily at inflammation sites Signup and view all the answers

Which mechanism is NOT associated with the action of NSAIDs?

Activation of serotonin release Signup and view all the answers

What therapeutic effect is associated with salicylates, particularly aspirin?

Prevents heart attacks and strokes Signup and view all the answers

Which of the following conditions is NOT typically treated with NSAIDs?

Severe bacterial infections Signup and view all the answers

What is the consequence of inhibiting COX-1's action in the body?

Increased risk of gastrointestinal problems Signup and view all the answers

Study Notes

Introduction

Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage.

Narcotics (Opioids)

Includes natural opiates, semi-synthetic alkaloids derived from opium poppy, and pharmacologically similar synthetic drugs.
Interact with opioid receptors.

Opioid Receptors (O.R.) and Effects

Mu receptors: Supraspinal analgesia, respiratory depression, euphoria, and physical dependence.
Kappa receptors: Spinal analgesia, miosis, and sedation.
Delta receptors: Analgesia, respiratory depression, affective behavior, and reduction in GI motility.
ORL 1 receptors: Recently identified by cloning techniques.

Endogenous Opioid Peptides

Serve as neuromodulators produced and secreted by nerve cells.
Act in the brain and spinal cord to modulate the actions of other neurotransmitters.
Include enkephalins, endorphins, and dynorphins.

Opioids: Agonists

Strong: Morphine, Methadone, Mepridine.
Moderate: Codeine, Oxycodone.
Weak: Propoxyphene.

Opioids: Classification

Mixed agonist-antagonist: Buprenorphine, Nalbuphine.
Antagonists: Naloxone, Naltrexone.

Mechanism of Action of Opioids

O.R. are G-coupled receptors.
Stimulation inhibits adenylcyclase and decreases intracellular cAMP content.
Act through ion channels, promote K+ channel opening, causing hyperpolarization.
Inhibit voltage-gated calcium channels, leading to inhibition of transmitter release.

Acute Effects of Opioid Analgesics

Analgesia: Perception of pain and reaction to it.
Sedation: Drowsiness, higher doses produce sleep and coma.
Mood and subjective effects: Calming effect, feeling of detachment, inability to concentrate, and euphoria.
Respiratory depression: Dose-dependent depression of respiratory center.
Antitussive actions: Suppression of cough reflex by unknown mechanism.
On the smooth muscle: Opioids (except meperidine) cause contraction of biliary smooth muscle and reduction of uterine tone.
GI effects: Constipation occurs through decreased intestinal peristalsis.
Miosis: Pupillary constriction is a characteristic effect of all opioids except meperidine.

Chronic Effects of Opioid Analgesics

Tolerance: Marked tolerance can develop to most acute pharmacologic effects except constipation and miosis.
Dependence: Defined as compulsive craving resulting from repeated drug administration.
Physical dependence: Revealed on abrupt discontinuance as an abstinence syndrome (rhinorrhea, lacrimation, etc.).

Clinical Uses of Opioid Analgesics

Analgesia: Relieving traumatic, visceral, ischemic (MI), postoperative, burn, and cancer pain.
Cough suppression.
Treatment of diarrhea: Diphenoxylate, loperamide given orally.
Management of acute pulmonary edema: Morphine used parenterally.
Anesthesia.

Toxicity

Most adverse effects are predictable extensions of pharmacological effects (nausea, constipation, respiratory depression).
Overdose and drug interactions are important.

Toxicity: Overdose

Triad of pupillary constriction, comatose state, and respiratory depression is characteristic.
Respiratory depression is responsible for most fatalities.
Treatment involves antagonists (naloxone) and other therapeutic measures (ventilatory support).

Toxicity: Drug Interactions

Additive CNS depression: With ethanol, sedative-hypnotics, antipsychotics, TCADs, and anti-histamines.
Increased hyperpyrexic coma risk: With some opioids (meperidine) and MAO inhibitors.
Serotonin syndrome: Meperidine and SSRI.

Opioid Antagonists

Naloxone, nalmefene, and naltrexone.
Pure opioid receptor antagonists with few other effects.
Produce marked antagonism of agonist effects.
Greater affinity for mu receptors than other receptors.
Major clinical use is in management of acute opioid overdose.
Naloxone and nalmefene are given intravenously.
Multiple doses of naloxone are needed due to short duration of action (1-2 hours).
Naltrexone blocks strong agonist effects (heroin) for at least 24 hours after oral use.
Naltrexone decreases ethanol craving and is approved for adjunctive use in alcohol dependency programs.

Non-Narcotic Analgesics (Aspirin-like Analgesics)

Analgesic-antipyretic and anti-inflammatory agents.

Classes of Non-Narcotic Analgesics

NSAIDs (Non-Steroidal Anti-Inflammatory Drugs)
- Aspirin
- Other non-selective NSAIDs
- Cox-2 inhibitors
DMARDs (Disease-Modifying Anti-Rheumatic Drugs)

Classification: Non-Selective COX Inhibitors

Salicylates: Aspirin, Salicylamide, Benorylate, Diflunisal.
Pyrazolone derivatives: Phenylbutazone, Oxyphenylbutazone.
Propionic acid derivatives: Ibuprofen, Naproxen, Ketoprofen, Fenoprofen, Flurbiprofen, Oxaprozin.
Indole derivatives: Indomethacin, Sulindac.
Anthranilic acid derivative: Mephanimic acid, Flufenamic acid.
Aryl acetic acid derivative: Diclofenac, Tolmetin.
Oxicam derivative: Piroxicam, Tenoxicam.
Pyrrolo pyrrole derivatives: Ketorolac.

Preferential COX-2 Inhibitors

Nimesulide
Meloxicam
Nabumetone.

Selective COX-2 Inhibitors

Valdecoxib
Celecoxib
Rofecoxib

Analgesics with Poor Anti-inflammatory Action

Paraminophenol derivative: Paracetamol (Acetaminophen).
Pyrazolone derivative: Metamizol, Propiphenazone.
Benzoxazocine derivative: Nefopam.

COX (Cyclooxygenase)

Officially known as prostaglandin_x0002_endoperoxide synthase (PTGS).
Enzyme responsible for formation of prostanoids (thromboxane and prostaglandins) from arachidonic acid.
Older terms include "prostaglandin synthase (PHS)", "prostaglandin synthetase (PHS)", and "prostaglandin-endoperoxide synthetase (PES)".

COX 1 vs COX 2

COX-1: Present in most tissues, maintains the normal lining of the stomach and intestines, protects the stomach from digestive juices, involved in kidney and platelet function.
COX-2: Primarily found at sites of inflammation.

Mechanism of Action of NSAIDs

COX 1 and COX 2 pathway: Inhibition of prostaglandin synthesis.
Lipo-oxygenase pathway: Inhibition of leukotriene synthesis.
Interference with G-protein-mediated signal transduction: Possible analgesic mechanism unrelated to inhibition of prostaglandin synthesis.
Central action: Mediation through endogenous opioid peptides or blockade of serotonin release.
Inhibition of excitatory amino acids: Blockade of N-methyl-D_x0002_aspartate receptor activation.

Pharmacological Actions of NSAIDs

CNS: Depressant and stimulant action.
CVS: Vasodilation.
GIT: Constipation.
Smooth muscles: Increased ureter contraction, bronchoconstriction.
ANS: Mild hyperglycemia.

Adverse Effects of NSAIDs

Analgesic doses: Usually well tolerated.
Anti-inflammatory doses (long-term use): Associated with adverse effects.
GI tract: Epigastric distress, nausea, vomiting, erosive gastritis, peptic ulcer, increased occult blood loss in stools.
Allergic reactions: Rashes, photosensitivity.
Hemolysis.
Nephrotoxicity.
Reye’s syndrome.
Salicylism.
Acute salicylate intoxication.

Functions of NSAIDs

Reduce high temperature and fever.
Reduce inflammation.
Reduce pain.
Anti-clotting properties (aspirin).

Uses of NSAIDs

Acute or chronic conditions with pain and inflammation.
Rheumatoid arthritis.
Osteoarthritis.
Inflammatory arthropathies (ankylosing spondylitis).
Acute gout.
Dysmenorrhoea.
Metastatic bone pain.
Headache and migraine.
Postoperative pain.
Mild-to-moderate pain due to inflammation and tissue injury.
Pyrexia.
Renal colic.
Given to infants whose ductus arteriosus is not closed within 24 hours of birth.

Contraindications of NSAIDs

Ulcer.
Asthma.
Patients with nasal polyps.
Diabetes.
Gout.
Influenza (Reye’s syndrome).
Hypocoagulation state.
Chronic allergic disorders.
Chronic liver disease.
Renal failure.
Salicylate allergy.
Breastfeeding mothers.
Pregnancy.

Mechanism of Action: Paracetamol

Exact mechanism remains unclear.
Evidence for multiple central mechanisms, including effects on prostaglandin production, serotonergic, opioid, nitric oxide (NO), and cannabinoid pathways.

Drug Interactions: Paracetamol

Anticoagulants: Effect of warfarin and other coumarins may be enhanced.
Metoclopramide: May increase absorption speed.
Domperidone: May increase absorption speed.
Colestyramine: May reduce absorption if given within one hour.
Imatinib: Restriction or avoidance of concomitant regular use recommended.

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Description

This quiz explores the fundamentals of opioid pharmacology, including the classification of narcotics, their mechanisms of action, and the effects on different opioid receptors. Understand the role of endogenous opioid peptides and their impact on pain modulation and analgesia.