Analgesics and Pain Management Overview

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

What is the primary function of analgesics?

To reduce inflammation

To enhance mood

To relieve pain (correct)

To improve digestion

Which of the following is NOT a type of analgesic?

Opiates

Non-steroidal anti-inflammatory drugs (NSAIDs)

Antibiotics (correct)

Acetaminophen

Which of the following statements about analgesics is true?

They can interact with other medications. (correct)

They are only effective for chronic pain.

They can only be obtained with a prescription.

They do not have any side effects.

What should be monitored when using analgesics?

Pain levels and side effects Signup and view all the answers

Which of the following is a common side effect of analgesic use?

Drowsiness Signup and view all the answers

What is the primary focus of pharmaceutical chemistry?

Design and development of drugs Signup and view all the answers

Which of the following is NOT a characteristic of pharmaceutical chemistry?

Studies the effects of climate change Signup and view all the answers

Which area is least likely associated with pharmaceutical chemistry?

Nutritional science Signup and view all the answers

What aspect of pharmaceutical chemistry deals with the safety of drugs?

Toxicology Signup and view all the answers

Which of the following processes is essential in the development of pharmaceuticals?

Compounding medications Signup and view all the answers

What is the first endogenous peptide identified related to opioid receptors?

Enkephalin Signup and view all the answers

Which two forms of enkephalin differ only by their terminal amino acid?

Met-enkephalin and Leu-enkephalin Signup and view all the answers

What type of pain relief do opioids provide?

Various types of pain including chronic and inflammatory Signup and view all the answers

What does the term 'endogenous ligands' refer to in relation to opioids?

Chemicals secreted by neurons that reduce pain perception Signup and view all the answers

What are the potential causes of pain mentioned?

Chronic nerve damage and viral infections Signup and view all the answers

What is the first amino acid in the enkephalin pentapeptide that shows a distinct preference?

Tyrosine Signup and view all the answers

What occurs when the first amino acid of the pentapeptide, Tyrosine, is substituted by other amino acids?

Inactive or weakly active peptide Signup and view all the answers

Which modification to Tyrosine in the enkephalin structure leads to reduced activity?

Masking of the phenolic hydroxyl Signup and view all the answers

What is the nature of the relationship between enkephalins and aminopeptidases?

Enkephalins are rapidly degraded by aminopeptidases Signup and view all the answers

What type of peptide is produced when the structure of enkephalins is altered significantly?

Inactive or weakly active peptide Signup and view all the answers

What is the reason for the transient nature of enkephalins' actions?

The rapid degradation of the Tyr-Gly bond Signup and view all the answers

What type of enzyme is responsible for the degradation of the enkephalin Tyr-Gly bond?

Aminopeptidases Signup and view all the answers

Which part of the enkephalin molecule is rapidly degraded?

The Tyr-Gly bond Signup and view all the answers

How does the rapid degradation of enkephalins affect their function?

It results in short-lived actions Signup and view all the answers

What is the significance of the Tyr-Gly bond in enkephalins?

It allows for enzymatic degradation Signup and view all the answers

Study Notes

Analgesics

Analgesics are compounds with varied mechanisms, relieving a wide range of pain causes.
They're categorized based on therapeutic use:
- Opioids (narcotic analgesics) play a key role in managing acute and moderate-to-severe chronic pain.
- NSAIDs and acetaminophen are commonly used to relieve mild-to-moderate pain and reduce fever.
- Other classes include triptans (antimigraine), analgesic adjuvants (tricyclic antidepressants, anticonvulsants, topical analgesics).

Pain

Pain is a frequent medical complaint with diverse underlying causes, symptoms, and neurobiological mechanisms.
- Physiological (nociceptive) pain, the most common type, often originates from injuries to body organs or tissues. It's further classified into cutaneous, somatic, and visceral pain.
- Inflammatory pain results from infection or tissue damage.
- Neuropathic pain is complex and chronic, often stemming from nervous system injury (e.g., limb amputation, spinal surgery, shingles).

Opioid Receptor Discovery and Endogenous Ligands

Enkephalin, the first endogenous peptide, is a mixture of Met-enkephalin and Leu-enkephalin, differing only in their terminal amino acids.
The actions of enkephalins are transient, correlating with rapid degradation of the Tyr-Gly bond by aminopeptidases.

SARs of Enkephalins

The first amino acid, tyrosine (Tyr¹), shows preference for this residue.
Changes in this residue, whether by substitution or masking of hydroxyl, often result in inactive or weakly active peptides.

GLY2

Replacing naturally occurring L-glycine with various D-amino acids leads to peptides resistant to aminopeptidase cleavage.
This substitution is the most effective replacement, while L-amino acid analogs show limited activity.

MET5/LEU5

Position 5 tolerates more residue changes compared to other positions.
Many amino acid substitutions at this position retain peptide activity.

Opioid Receptors

Opioid receptors are widely distributed throughout the brain, spinal cord, and peripheral tissues (μ, δ, and κ).
Activation triggers inhibition of adenylate cyclase, decreasing cAMP production and affecting various cellular processes, including nociceptive C-fiber calcium influx.
Endogenous opioid peptides for the μ-receptor include endomorphin-1, endomorphin-2, and β-endorphin.
Exogenous agonists bind to the μ-receptor, producing analgesia, respiratory depression, decreased gastrointestinal motility, and euphoria, contributing to opioid addiction.

8-Receptor

Endogenous opioid peptides for the δ-receptor include Met-enkephalin and Leu-enkephalin, and some synthetic peptides have high receptor affinity, although low bioavailability.

κ-Receptor

Kappa receptors are primarily found in the limbic system, brainstem, and spinal cord.
TRK-820 exhibits substantial selectivity for κ-receptors, compared to μ-receptors.
Methyl-substituted nitrogen amides, with a methylene spacer, are crucial for κ-receptor activity.

Other Analgesics (Examples)

Morphine: Prototype μ-receptor ligand, commonly used for severe and postoperative pain, however, it has many side effects.
Codeine: Morphine derivative metabolized to morphine, acting as a cough suppressant, with some analgesic properties.
Heroin: Morphine derivative exhibiting quicker blood-brain barrier penetration & higher potency, but also significantly increased toxicity & addiction potential.
Hydromorphone: Morphine derivative with slightly enhanced binding and potency.
Hydrocodone: Morphine derivative with better brain penetration & increased κ-receptor binding.
Oxycodone: Hydrocodone derivative, exhibiting greater potency and receptor affinity.
Oxymorphone: Hydromorphone derivative with increased receptor binding affinity, but lower bioavailability.
Dextromethorphan: Two-ring morphinan; OTC cough/cold preparation used to treat symptoms, but potentially abused.
Pentazocine: Benzomorphan acting as a partial agonist/antagonist at μ-receptors; also an agonist at κ-receptors.
Meperidine: μ-receptor agonist with some potency gains by structural changes like m-hydroxyl addition on the phenyl ring; metabolized to normeperidine.
Diphenoxylate: Weak opioid agonist, combined with atropine in OTC antidiarrheal preparations.
Loperamide: 4-phenylpiperidine used as an antidiarrheal, showing increased potency after substituting the 4-phenyl group with a 4-anilide.
Fentanyl: High lipophilicity and rapid metabolism contribute to rapid onset & short duration of action; highly potent derivative.
Remifentanil: Designed for rapid metabolism; ester group is metabolized by esterases, resulting in a very short duration of action.
Methadone: Synthetic opioid for analgesic therapy and opioid addiction maintenance; a μ-receptor agonist.
Tramadol: Weak μ-agonist with analgesic effects, somewhat antagonized by naloxone.
Naltrexone: Pure opioid antagonist at all opioid subtypes acting as a treatment of opioid dependence.
Naloxone: Pure opioid antagonist reversing opioid-induced respiratory depression from overdose

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Description

This quiz covers the various types of analgesics, including opioids, NSAIDs, and their uses in pain management. It also examines different types of pain, such as nociceptive, inflammatory, and neuropathic pain, providing insights into their causes and treatment options.