5 - Drugs Used for Pain Control Flashcards
(43 cards)
What are Analgesic drugs?
- drugs that target pain
What are the 3 types of pain?
- Nociceptive pain
→ Caused by stimulation of peripheral nerve fibres that respond to stimuli of harmful intensity
→Ex, heat/cold, irritants, force - Inflammatory pain
→ Associated with tissue damage and promotes hypersensitivity until healing occurs - Neuropathic pain
→ Caused by damage or disease that affects somatosensory system described as burning, tingling, or pins and needles
How does Pain get perceived?
- Pain is necessary to signal danger and tissue damage.
- Pain is sensed by primary sensory neurons - nociceptors
- Neurons send signals to the brain via action potentials
- Whenever a painful stimulus occurs, nociceptors create action potentials, which are passes on to the next neuron in the pain pathway via a chemical synapse
- Neurotransmitters get released and activate the next neuron, the 2ndary neuron, to cause action potential
- Secondary neurons are found in the spinal cord
- Action potential are passed to a tertiary neuron
- Tertiary neurons send signals to primary somatosensory cortex - this is where the brain deciphers what part of the body is experiencing pain
- If we can stop the action potential before it reaches the brain, we won’t feel pain
What is a drug class?
Drug class: drugs that share similar chemical structures or therapeutic effects or act through similar receptors and signalling pathways
- Analgesic drugs share the same therapeutic effect: pain relief
Drug Class: Analgesic Drugs
1. Acetaminophen
2. Opioids
3. Non-steroidal Anti-inflammatory
4. Steroidal Anti-inflammatory
5. Anesthetics
The Pain Pathway
- the pain pathway includes
1) Receptors: nociceptors
2) Synapses: spinal cord, thalamus, somatosensory cortex - Pain is sensed by nociceptors (free nerve endings)
→ They can sense different stimuli: mechanical (pinching), thermosensitive (heat/cold), polymodal (noxious chemicals can cause pain)
3 major neurons
1. Neuron/nociceptor that synapses in spinal cord
2. Spinal cord neuron travels up to thalamus
3. Neuron from thalamus to primary somatosensory cortex
2 Major Drug Classes that provide pain relief
- Opioids -Drugs that alter neural activity in pathways signalling pain
- NSAID - Drugs that sensitize pain receptors
4 Ways Opioids are used clinically
1) Opioid receptor agonist:
→ Morphine and Fentanyl: can easily cross the brain and have central effects (ie. Euphoric feelings and sedation)
→ Fentanyl is unique - can be administered via transdermal patch
→ Loperamide: does not cross the brain
→ Opioids that can cross into the brain (via BBB) can cause feelings of euphoria
→ They bind to the same receptors as endorphins (“feel good” peptides released by our body)
2) Prodrug
→ Codeine - inactive form of a drug that is converted into an active form through metabolism
3) Atypical Opioid Agonist
→Tramadol - agonist for opioid receptors but has other mechanisms of action such as: altering uptake of other neurotransmitter’s like norepinephrine
4) Competitive Antagonist
→ Naloxone - can outcompete opioid agonists for opioid receptors, block the receptors to prevent its activation, and save someone’s life when experiencing opioid overdose
2 Analgesic (pain relief) uses of opioids in practice:
- Severe, short-term pain such as major trauma or surgery when other analgesics are not effective
- Chronic pain like cancer pain in advanced stages as well as in palliative care
What is the Drug Mechanism of Action?
- describes how and where the drug acts within the body (target tissues), and its specific molecular targets or biological processes it influences (receptor, enzymes, other macromolecules, and the cellular response
Mechanism of Action of Opioid Drugs
Opioid Receptor Activation
→ Opioids act on multiple target tissues, not just pain neurons.
→They bind to G-protein coupled receptors (GPCRs).
→ Most opioids are agonists - they activate opioid receptors.
→ Activation changes cell permeability to potassium (K⁺) or calcium (Ca²⁺), reducing cell excitability.
Effects on Neurons & Action Potentials
→Opioids reduce neuron excitability, leading to fewer action potentials (APs) in pain neurons.
→Depolarization occurs when sodium (Na⁺) enters the neuron, making it more positively charged.
→If the depolarization reaches threshold, an action potential is generated.
Neuronal Communication
→Neurons communicate by releasing neurotransmitters at chemical synapses.
→ Neurotransmitters allow signals to pass between neurons.
Role of Potassium (K⁺)
→K⁺ is concentrated inside cells and leaks out down its concentration gradient.
→ Excess K⁺ leakage causes hyperpolarization, making the neuron more negative and less excitable.
Opioid Receptor
- Endorphins naturally bind to opioid receptors.
4 Classes of Opioid Receptors
1) Mu (μ) Receptor
→Endorphins bind Mu receptors, causing a feel-good response.
→ Activates G-protein 2nd messenger cascade, impacting K⁺ and Ca²⁺ channels.
→Affects permeability of K⁺ and Ca²⁺.
2) Kappa (κ) Receptor
3) Delta (δ) Receptor
4) Nociceptin (NOP) Receptor
Presynaptic VS. Postsynaptic inhibition
** GO LOOK at the slide**
Presynaptic inhibition
→ neuron before the synapse
→ Presynaptic inhibition is caused by blocking Ca from entering and allowing NT to be released
→ If we prevent channels from opening by activating opioid receptors, there will be less or NO NT release to send signal to the next pathway
→This inhibits release of NT from presynaptic neuron
Postsynaptic inhibition - in neuron after the synapse
→ Postsynaptic inhibition is caused by changes in potassium permeability
→Increase permeability of potassium out of cell causes the cell to stay (-) t does not depolarize, and you can not get an AP
Summary of Opiod Drug mechanism of action:
→Target tissues: nociceptive neurons and pain regions in the brain
→ Molecular Target: mu opioid receptor agonist
→ Biological Processes Involved: G-PCR activation triggering a second messenger cascade
→Cellular Response: decrease permeability of calcium in and increase potassium permeability out, decreasing AP generation
→ Overall Effect: decrease pain (analgesia)
Other Uses for Opioids
- Opiod drugs have other uses (other than analgesia), because opioid receptors, like the mu receptor, are not just found on nociceptive neurons and pain processing areas of the brain and spinal cord
→ They are found in many other areas of your brain, such as your brainstem, the limbic system of the brain, and in other areas of the body, such as the gastrointestinal tract
→ opioids tend to suppress neuron excitability - they are known as central nervous system (CNS) depressants
- Opioids can be prescribed for:
1. Diarrhea
→ By suppressing excitability of the GI tract, the motility (movement) slows down.
→This leads to more time for fluids to be absorbed out of the GI tract and the reduction of loose stool or diarrhea
→Loperamide is an opioid agonist used to treat diarrhea.
- Cough suppression
→ Since opioid receptors are in the brainstem, including areas controlling cough, opioids are used to treat chronic cough.
→ Codeine - opioid used to treat cough
Adverse Drug Reactions with Opioids
1) Substance use disorders
2) Constipation
3) Respiratory depression
→Effect of opioid drugs that can cross the blood-brain barrier (morphine and fentany)
→ Slows breathing, and if too high of a dose is taken, a person may stop breathing
→ due to the CNS depressant properties on the brainstem in the location of the respiratory centre
→At higher levels of drug, apnea and resp depression is still seen
→At lowest levels, there is no resp depression; exposure to opioids did develop some tolerance to resp depression effects
4) Sedation
How id Tolerance Developed?
- Tolerance is related to receptor uptake leading to fewer opioid receptors present on the cell membrane
→ Less receptors means a smaller response.
How to treat toxicity with Naloxone?
- Reverses the effects of opioids
→ Taking too many opioids causes so many receptors to fill/ activate that breathing can become slow or stop - Naloxone has strong affinity to opioid receptors
→ It is an antagonist; attaches to opioid receptors without activating them
→ It pushes the opiods off the receptor and allows breathing to be normalized - Can be administered via nasal spray or injection
→Begins working in a few minutes
→ Lasts for 30-90 minutes - Multiple doses may be needed (although 1 dose can reverse the overdose)
→Can produce withdrawal symptoms
→Has no abuse potential It is opioid specific - only works for opioid overdose
Symptoms of Opiod Withdrawal?
- A prescription opioid taken for more than a few weeks may lead to uncomfortable withdrawal symptoms if it is suddenly stopped
- occurrence and severity of these symptoms will depend on the type of opioid used, the dose, and the length of time it was taken
Symptoms include:
1. Nausea, vomiting, diarrhea
2. Feeling very anxious
3. Insomnia and yawning
4. Feeling hot and cold leading to sweating and ‘goosebumps’
Patients at Risk of More Pronounces Adverse Drug Reactions
- Older adults
→ They tend to be more sensitive to the respiratory depression
→ They tend to be on many other prescription drugs, leading to drug-drug interactions
→Decreased kidney and liver function in older adults can decrease drug metabolism, leading to higher drug levels in the blood - People with Resp diseases or sleep apnea
→ Respiratory depression associated with opioid use increases risk for patients with respiratory diseases such as asthma or emphysema, where breathing may already be compromised
→Sleep apnea is associated with breath-holding which can cause respiratory depression to be more severe - People with liver or kidney disease
→ reduced metabolism or excretion of opioid drugs can lead to higher drug levels in the blood and opioid toxicity. - Pregnant people
→Since opioids are highly addictive, exposing an unborn baby to opioids can lead to opioid withdrawal that can be life-threatening
→ These drugs can also lead to premature births and developmental issues. - Those with history of opioid abuse
How Genetics Impacts Metabolism
- Genetic polymorphisms mean that some people may metabolize drugs differently than others
- People can fall into 3 different groups or phenotypes for CYP2D6: ultra-rapid metabolizers, intermediate metabolizers, and poor metabolizers
→ A poor metabolizer would make very little active drug (morphine) from codeine, while ultra-rapid metabolizers will make a lot of morphine from codeine - Different ethic groups vary in how they metabolize drugs
→keep this in mind when caring for patients
What are Drug-drug interactions (DDI):
- occur when two or more medications affect each other in a way that changes how one or both drugs work in the body
→ This can make a drug less effective, cause unwanted side effects, or even be dangerous
How do NSAID’s Work?
- SAIDs do not work by binding to a receptor. Instead, they target enzymes known as cyclooxygenase (COX) enzymes and inhibit their activity.
- Most NSAID drugs affect COX 1 and 2, so we call them non-selective drugs, while others only affect one
→ Irreversible non-selective COX inhibitor: Acetylsalicylic acid (ASA)
→ Reversible non-selective COX inhibitor: Ibuprofen
→ Reversible selective COX-2 inhibitor: Celecoxib
What are NSAID’s Used to treat?
- NSAIDs are used to treat mild-moderate and sometimes even severe pain because of their analgesic properties and to treat inflammation
- Analgesic uses of NSAIDs in practice:
1. post-operative pain control
2. back pain, muscle pain, and joint pain (arthritis)
3. headache, menstrual pain (dysmenorrhea), and any other painful conditions
NSAID Action on COX Enzymes
- NSAIDs relieve pain and decrease inflammation by decreasing the production of an inflammatory mediator called prostaglandins.
- COX enzymes are required to make prostaglandins
→ NSAIDs inhibit these enzymes from functioning, preventing arachidonic acid’s conversion into prostaglandins. - Prostaglandins are lipid-derived mediators produced everywhere in the body from a substance called arachidonic acid.
- Prostaglandins are chemical signals that act on neighbouring cells in a tissue.
→ Because they are made locally and act locally, they are considered paracrine factors, not hormones.
→Hormones will travel in the blood to act on a distant target.
