Analgesia

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Questions and Answers

What term describes pain due to a stimulus that does not normally produce pain?

Neuropathic pain

Allodynia (correct)

Hyperalgesia

Hyperaesthesia

What type of pain results from nerve injury, as seen in conditions such as diabetes mellitus and HIV infection?

Dysfunctional pain

Inflammatory pain

Neuropathic pain (correct)

Physiologic pain

Which category of pain is characterized by increased sensitivity to stimulation excluding special senses?

Inflammatory pain

Allodynia

Hyperaesthesia (correct)

Dysfunctional pain

Which mechanism initiates the generation of action potentials in pain transmission?

Voltage-gated sodium channels Signup and view all the answers

In what type of pain do patients experience severe pain in the absence of noxious stimuli, such as in fibromyalgia?

Dysfunctional pain Signup and view all the answers

Which type of pain is specifically linked to tissue injury and inflammation, causing heightened pain from noxious stimuli?

Inflammatory pain Signup and view all the answers

What is the role of N-type voltage-gated calcium channels in pain transmission?

They facilitate neurotransmitter release. Signup and view all the answers

Which of the following NSAIDs exhibits irreversible inactivation of COX-1?

Aspirin Signup and view all the answers

What is a significant adverse effect associated with selective COX-2 inhibitors?

Increased myocardial infarctions Signup and view all the answers

Which medication is primarily an analgesic and antipyretic but has little anti-inflammatory effect?

Acetaminophen Signup and view all the answers

Which of the following NSAIDs is known for having a higher potency and longer half-life compared to Ibuprofen?

Naproxen Signup and view all the answers

What is one of the risks associated with non-selective COX inhibitors?

Acute renal failure Signup and view all the answers

Which of the following statements is accurate regarding Salicylates such as Aspirin?

They can lead to gastric irritation and hemorrhage. Signup and view all the answers

What is a primary reason for prescribing Ketorolac?

Short-term pain control in place of opioids Signup and view all the answers

Which medication is least likely to cause GI adverse effects compared to others?

Celecoxib Signup and view all the answers

What is a major concern associated with the overdose of Acetaminophen?

Liver failure Signup and view all the answers

Which statement accurately describes the role of tryptans in migraine treatment?

Tryptans selectively target 5HT-1B and 5HT-1D receptors for effective pain relief. Signup and view all the answers

What is a common characteristic of the medications used for acute migraine attacks?

They include agents that can cause vasoconstriction. Signup and view all the answers

Which prophylactic treatment is NOT indicated for reducing migraine occurrence?

Opioids Signup and view all the answers

Which of the following best describes the half-life comparison between naloxone and morphine?

Naloxone has a shorter half-life than morphine. Signup and view all the answers

What therapeutic approach is commonly recommended for managing pain in clinical settings, according to recent practices?

Implementing a polypharmacy approach to enhance efficacy. Signup and view all the answers

What distinguishes NSAIDs from acetaminophen in terms of their mechanism of action?

NSAIDs act both centrally and peripherally. Signup and view all the answers

What role do inflammatory cytokines play in neuropathic pain?

They contribute to pain through positive signaling. Signup and view all the answers

Which of the following antiepileptics is NOT typically used to manage neuropathic pain?

Lamotrigine Signup and view all the answers

How do TCAs such as amitriptyline affect pain management?

They enhance antinociceptive pathways from the spinal cord. Signup and view all the answers

What is the primary mechanism by which gabapentin exerts its effects on chronic pain?

Binding to voltage-dependent calcium channels. Signup and view all the answers

Which treatment is indicated for both neuropathic pain and fibromyalgia?

Dual NE/serotonin reuptake inhibitors Signup and view all the answers

What is a key characteristic of neuropathic pain following nerve injury?

It involves both functional and structural alterations. Signup and view all the answers

Which statement regarding opioids and NSAIDs combined treatment is true?

They provide a synergistic effect for pain relief. Signup and view all the answers

What negative aspect contributes to neuropathic pain through the loss of support in nerve recovery?

Loss of peripheral support from neurotrophic factors. Signup and view all the answers

What distinguishes dual NE/serotonin reuptake inhibitors from traditional antidepressants in pain management?

They are used as adjuvants in chronic pain management. Signup and view all the answers

What is the primary mechanism of action of μ-opioid receptor agonists in the spinal cord?

Activating both presynaptic and postsynaptic μ-opioid receptors to inhibit nociceptive stimuli Signup and view all the answers

Which drug is specifically used to treat trigeminal neuralgia and acts by blocking Na+ channels?

Carbamazepine Signup and view all the answers

What are common adverse effects associated with opioids?

Respiratory suppression, bradycardia, orthostatic hypotension Signup and view all the answers

Which medication has a faster onset and more predictable bioavailability than gabapentin?

Pregabalin Signup and view all the answers

Which drug would likely cause fewer dose-related CNS adverse effects compared to gabapentin?

Pregabalin Signup and view all the answers

What is a characteristic of full agonists in the opioid category?

They primarily act on µ opioid receptors for analgesic effects. Signup and view all the answers

What distinguishes oxcarbazepine from carbamazepine?

Oxcarbazepine has altered liver metabolism and a reduced risk of aplastic anemia. Signup and view all the answers

Which option correctly describes the CNS effects of opioids?

Opioids can cause feelings of euphoria and relaxation. Signup and view all the answers

Which of the following is NOT a typical use of pregabalin?

Severe acute migraines Signup and view all the answers

Study Notes

Pharmacology of Analgesia

Analgesia is the unpleasant sensory and emotional experience associated with actual or potential tissue damage
Types of pain: Physiologic (intense/noxious stimulus), Inflammatory (tissue injury/inflammation causing heightened sensitivity, e.g., rheumatoid arthritis), Neuropathic (nerve injury, e.g., amputation or diabetes), and Dysfunctional (pain without noxious stimuli, e.g., tension-type headache or fibromyalgia).

Mechanisms of Pain

Transduction of intense/noxious stimuli depolarizes peripheral terminals of high-threshold primary sensory neurons (nociceptors), requiring a strong stimulus.
Action potentials are conducted to the CNS via peripheral nerves and dorsal roots, synapsing on neurons in the dorsal horn of the spinal cord.
Secondary projection neurons transmit information to the brainstem and thalamus, then relay signals to the cortex, hypothalamus, and limbic system.
Transmission is regulated by inhibitory and excitatory interneurons.

Neurotransmission in the Spinal Cord Dorsal Horn

Neurotransmission in the dorsal horn relays signals to CNS neurons that signal to the brain, part of a circuit also receiving descending modulatory control.

Descending and Local Inhibitory Regulation in the Spinal Cord

Spinal cord synaptic transmission is regulated by local inhibitory interneurons and descending projections from the brainstem.
These systems limit incoming sensory information, a crucial site for pharmacologic intervention.
Key inhibitory neurotransmitters include opioid peptides, norepinephrine, serotonin (5-HT), glycine, and GABA.

Pain Management

Pain treatment depends on the type (nociceptive or neuropathic) of pain.
Nociceptive pain (e.g., mild to moderate arthritic pain) can be managed with non-opioid analgesics (like NSAIDs).
Chronic inflammatory pain can be treated with NSAIDs, DMARDs , TNF-α inhibitors, immunosuppressants, and monoclonal antibodies.
Neuropathic pain can be treated with TCAs, serotonin-norepinephrine reuptake inhibitors,and anticonvulsants.
Severe acute pain and chronic pain may include opioid use.

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

NSAIDs inhibit the activity of cyclooxygenase enzymes (COX-1 and COX-2) required for prostaglandin production.
Major classes: Salicylates (e.g., aspirin), Propionic acid derivatives (e.g., ibuprofen, naproxen), Phenylacetic acid derivatives (e.g., diclofenac, ketorolac), and Selective COX-2 inhibitors (e.g., celecoxib).
NSAIDs affect pain pathways by reducing prostaglandin synthesis, decreasing leukocyte recruitment, and preventing prostaglandin generation in the spinal cord.
Adverse effects of non-selective COX inhibitors can include gastric mucosa and kidney injury.

Analgesic-Antipyretic Acetaminophen (Paracetamol)

Low anti-inflammatory effects; primarily reduces prostaglandin synthesis in the CNS.
Frequently combined with weak opioids for moderate pain.
Major concern is low therapeutic index; overdose can cause liver failure.
Works by penetrating the blood-brain barrier, blocking COX-3 in the brain, blocking PGE formation/release, and inhibiting pyrogens on heat-regulating centers of the brain, resulting in antipyretic effect.

NSAIDs and COX-2 Inhibitors

NSAIDs and COX-2 inhibitors act centrally and peripherally.
Celecoxib is a prominent COX-2 inhibitor and still in use, minimizing GI, renal, and hematological adverse effects.

Neuropathic Pain

Nerve injury involves both functional and structural alterations in the nervous system.
Peripheral and central alterations, including inflammation and loss of nerve growth factors, contribute.
Positive signals such as inflammatory cytokines (by macrophages and Schwann cells); negative signals like loss of peripheral support.
Sodium channel expression pattern changes in injured primary sensory neurons.

Treatment for Neuropathic Pain

Treatment options for neuropathic pain include tricyclic antidepressants (TCAs), dual NE/serotonin reuptake inhibitors, and antiepileptic drugs (AEDs).

Analgesic Use of Antidepressants

TCAs like amitriptyline and dual NE/serotonin reuptake inhibitors like venlafaxine are used as adjuvants in chronic pain management, to increase antinociceptive noradrenergic and serotonergic projections to the spinal cord.

Analgesic Use of Antiepileptics

Drugs like gabapentin, pregabalin, and carbamazepine are often used to reduce neuronal excitability, treating chronic pain conditions.

Gabapentin, Pregabalin and Carbamazepine (AEDs)

Gabapentin and pregabalin are structural GABA analogs with no effect on GABA receptors but bind to a2δ subunit of voltage-dependent calcium channels.
Gabapentin is useful in trigeminal neuralgia, diabetic neuropathy, and post-op pain.
Pregabalin is similar but has faster onset and more predictable bioavaibility.
Carbamazepine is a sodium channel blocker and oxcarbazepine is its derivative, useful in trigeminal neuralgia.

Severe Acute Pain or Chronic Pain

Management could utilize opioids.
Opioid receptor agonists are primary class for moderate to severe acute pain.

Opioid Receptors and Agonists

Opioids (e.g., Morphine, Hydromorphone, Codeine, Oxycodone, Methadone, Fentanyl, Meperidine).
Partial and Mixed Opioid Agonists (e.g., Buprenorphine, Butorphanol, Nalbuphine).
Opioid Receptor Antagonists (e.g., Naloxone, Naltrexone).

Opioid Receptor Agonist Mechanism

Activation of presynaptic and postsynaptic μ-opioid receptors by descending/local circuit inhibitory neurons inhibits central relaying of nociceptive stimuli.
In the presynaptic terminal, decrease in calcium influx; postsynaptic increase in K+ conductance, decreasing the postsynaptic response to excitatory neurotransmission.

Adverse Effects of Opioids

Cardiovascular (decreased sympathetic tone → hypotension, bradycardia); respiratory (suppression, apnea); gastrointestinal (constipation, nausea, vomiting); central nervous system (sedation, dizziness, confusion); and addiction potential.

Migraine Therapy

Migraine is a headache disorder characterized by headache lasting up to 3 days typically accompanied by light and sound avoidance, and nausea. In some cases, aura, transient neurological symptoms are associated with the migraine.
Tryptan serotonin receptor agonists (e.g., sumatriptan) act on 5HT-1B/1D receptors, reducing vascular and nociceptive transmission.
Other treatments with acute attacks include NSAIDs, opioids, caffeine, and antiemetics.
Prophylactic drugs may include β-blockers, valproic acid, serotonin antagonists, Ca2+ channel blockers, or TCAs.

Summary

Polypharmacy often used for effective pain management.
Analgesic targets continue to be identified for potential new therapies.
Effective pain management extends beyond pharmacology with physical therapy, etc., and, at times, surgery, needed to address multi-factorial issues.

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Description

Test your knowledge on various pain mechanisms and types. This quiz covers concepts such as neuropathic pain, allodynia, and the role of N-type voltage-gated calcium channels in pain transmission. Challenge yourself to understand the intricacies of how pain is perceived and processed in the body.