Opioid Pain Pathways - PDF

+-----------------------+-----------------------+-----------------------+ | **Components of | | | | Pain** | | | +=======================+=======================+=======================+ | -...

+-----------------------+-----------------------+-----------------------+ | **Components of | | | | Pain** | | | +=======================+=======================+=======================+ | - **Physical | | | | sensation** in | | | | response to | | | | nociceptive | | | | stimulus (ability | | | | to perceive pain) | | | | | | | | - **Emotional or | | | | affective | | | | response** to | | | | pain | | | +-----------------------+-----------------------+-----------------------+ | **Afferent Pain | | | | Pathways** | | | +-----------------------+-----------------------+-----------------------+ | **Receptors of Pain** | | | | | | | | **Different | | | | receptors, but same | | | | pathway to perceive | | | | pain!** | | | | | | | | ([RECEPTOR]{.underlin | | | | e}) | | | | Na+/Ca++ influx | | | | membrane | | | | depolarization Action | | | | potential PAIN | | | | | | | | - **Thermal**: | | | | | | | | - **TRP | | | | Receptors -- | | | | Temperature | | | | activated | | | | receptors** | | | | | | | | - **TRPV1 | | | | --** | | | | activated | | | | above 40C | | | | or below | | | | 10C | | | | | | | | - **TRPV2 | | | | --** | | | | activated | | | | above 50C | | | | | | | | - **Mechanical**: | | | | | | | | - **ENaC -- | | | | *Intense* | | | | mechanical | | | | force | | | | activated | | | | receptors** | | | | | | | | - **Chemical**: | | | | | | | | - **ASIC** -- | | | | acid | | | | sensitive | | | | sodium ion | | | | channels | | | | | | | | - **P2X / P2Y** | | | | -- G-coupled | | | | receptors | | | | activated by | | | | extracellular | | | | ATP | | | | | | | | - **B1 / B2 | | | | --** | | | | bradykinin | | | | and G-coupled | | | | receptors | | | | | | | | *After stimulation of | | | | pain receptors, pain | | | | project to the spinal | | | | cord* | | | | | | | | **Transmission of | | | | Pain (Primary)** | | | | | | | | - **A0 fibers:** | | | | | | | | - Rapid | | | | transmitting | | | | [SHARP]{.unde | | | | rline}, | | | | localized | | | | pain | | | | | | | | - **C fibers:** | | | | | | | | - Slow | | | | transmitter | | | | Prolonger, | | | | *BURNING* | | | | pain | | | | | | | | **Transmission of | | | | Pain (Secondary)** | | | | | | | | - **Fast Excitatory | | | | Transmission:** | | | | | | | | - Activates ion | | | | channels -- | | | | **Glutamate** | | | | | | | | - **Glutama | | | | te** | | | | stimulate | | | | s | | | | NMDA and | | | | AMPA | | | | (excitato | | | | ry | | | | receptors | | | | ) | | | | | | | | - Influ | | | | x | | | | of | | | | Ca++/ | | | | Na+ | | | | chann | | | | els | | | | Posit | | | | ive | | | | ions | | | | stimu | | | | late | | | | actio | | | | n | | | | poten | | | | tial | | | | Quick | | | | er | | | | stimu | | | | lation | | | | | | | | - **Slow Excitatory | | | | Transmission:** | | | | | | | | - Activates | | | | GPCRs -- | | | | **GABA** | | | | | | | | - Slow | | | | modulator | | | | y | | | | response | | | | Postsynap | | | | tic | | | | depolariz | | | | ation | | | | Action | | | | potential | | | +-----------------------+-----------------------+-----------------------+ | **Types of Pain** | | | +-----------------------+-----------------------+-----------------------+ | **Nociceptive Pain** | ***Opioids are VERY | | | | EFFECTIVE*** | | | | | | | | - **Somatic --** | | | | pain where the | | | | source is known | | | | (generally | | | | localized) | | | | | | | | - **Visceral --** | | | | Referred pain | | | | (pain from | | | | internal | | | | organs... not | | | | well localized) | | +-----------------------+-----------------------+-----------------------+ | **Inflammatory Pain** | ***Opioids are VERY | | | | EFFECTIVE*** | | | | | | | | - **Allodynia --** | | | | non-painful | | | | stimuli perceived | | | | as painful | | | | | | | | - **Hyperalgesia | | | | --** painful | | | | stimuli perceived | | | | as MORE painful | | | | than usual | | +-----------------------+-----------------------+-----------------------+ | | ***Peripheral | | | | Sensitization*** | | | | | | | | - Stimuli-induced | | | | changes to | | | | nociceptors that | | | | lower activation | | | | threshold of | | | | receptors | | | | | | | | - **Direct:** | | | | | | | | - Induced | | | | by | | | | repeated | | | | activatio | | | | n | | | | of | | | | nocicepto | | | | rs | | | | | | | | - **Indirect:** | | | | | | | | - Induced | | | | by | | | | inflammat | | | | ory | | | | mediators | | | | and nerve | | | | growth | | | | factor | | +-----------------------+-----------------------+-----------------------+ | **Neuropathic Pain** | ***Opioids are NOT | | | | EFFECTIVE*** | | | | | | | | - **Sustained | | | | pain** -- no | | | | tissue injury, | | | | but rather nerve | | | | damage | | +-----------------------+-----------------------+-----------------------+ | **Opioid Receptors** | | | +-----------------------+-----------------------+-----------------------+ | - **Mu, Delta, and | | | | Kappa** | | | | | | | | - Activate Gαi | | | | and Gα0 | | | | | | | | - Inhibition of | | | | Ca+ on the | | | | **presynaptic | | | | ** | | | | decrease | | | | neurotransmit | | | | ter | | | | release | | | | | | | | - Activation of | | | | K+ on the | | | | **postsynapti | | | | c** | | | | decrease in | | | | action | | | | potential | | | +-----------------------+-----------------------+-----------------------+ | **Mu Receptor | | | | Agonist** | | | +-----------------------+-----------------------+-----------------------+ | ***Effects with LESS | | | | TOLERANCE to opioids: | | | | Constipation, Miosis, | | | | Respiratory | | | | Depression*** | | | +-----------------------+-----------------------+-----------------------+ | **Short Acting** | **Long Acting** | | | | | | | - Hydromorphone | - Levorphanol | | | | | | | - Meperidine | - Methadone | | | (Demerol) | | | | | - Buprenorphine | | | - Morphine and | | | | Morphine-related | | | | | | | | - Codeine | | | | | | | | - "Codones" | | | | | | | | - Hydrocodone.. | | | |. | | | | Oxycodone... | | | +-----------------------+-----------------------+-----------------------+ | **Common ADRs** | - *Effects:* | | | | | | | | 1. *Analgesia* | | | | | | | | - *More | | | | **effecti | | | | ve** | | | | **against | | | | ** | | | | **dull** | | | | rather | | | | than | | | | sharp | | | | pain* | | | | | | | | - *Spinal | | | | analgesia | | | | via | | | | action at | | | | dorsal | | | | horn | | | | neurons* | | | | | | | | - *Supraspi | | | | nal | | | | analgesia | | | | via | | | | action at | | | | the | | | | thalamus, | | | | RVM, and | | | | PAG* | | | | | | | | 2. *Sedation* | | | | | | | | 3. *Euphoria* | | | | | | | | 4. *Pinpoint | | | | pupils | | | | (miosis)* | | | | | | | | 5. *Suppression | | | | of | | | | respiratory | | | | center* | | | | | | | | 6. *Antitussive | | | | effect* | | | | | | | | 7. *Nausea and | | | | vomiting* | | | | | | | | 8. *Constipation | | | | * | | | | | | | | 9. *Itching* | | +-----------------------+-----------------------+-----------------------+ | **Morphine** | ***Drug choice to | | | | treat myocardial | | | | infarction related | | | | pain*** | | | | | | | | - **Contraindicatio | | | | n** | | | | | | | | - Head, heart, | | | | lung, kidney, | | | | liver | | | | | | | | - Shortness | | | | of break, | | | | hypotensi | | | | on | | | | -- due to | | | | respirato | | | | ry | | | | suppressi | | | | on | | | | | | | | - **Pharmacokinetic | | | | s:** | | | | | | | | - Longer half | | | | life 3-4 | | | | hours | | +-----------------------+-----------------------+-----------------------+ | **Other** | - **Hydromorphone:* | | | | * | | | **Morphine-related** | | | | | - 2-hour half | | | **Drugs** | life | | | | | | | | - More potent | | | | -- increased | | | | bioavailabili | | | | ty | | | | | | | | - **Norco & | | | | Oxycodone & | | | | Percocet** | | | | | | | | - Tend to cause | | | | less itching, | | | | less | | | | nausea/vomiti | | | | ng | | | | than morphine | | | | | | | | - **Levorphanol** | | | | | | | | - Extended | | | | half-life | | | | (12-16 hours) | | | | | | | | - **Oxymorphone** | | | | | | | | - Not intended | | | | for | | | | opioid-naïve | | | | patients | | | | | | | | - **Apomorphine** | | | | | | | | - NOT OPIOID | | | | RECEPTOR -- | | | | D2 dopamine | | | | receptor | | | | agonist | | +-----------------------+-----------------------+-----------------------+ | **Phenylpiperidine-li | - **Meperidine** | | | ke | | | | Opioids** | - Shorter | | | | duration of | | | | action | | +-----------------------+-----------------------+-----------------------+ | | **Advantage** | **Disadvantage** | | | | | | | - Less constipation | - Toxic metabolite | | | and urinary | NORMEPERIDINE | | | retention | | | | | - Interaction with | | | | MAOI | | | | | | | | - Leads to | | | | convulsions | +-----------------------+-----------------------+-----------------------+ | | ***Drugs used as | | | | anesthetics*** | | | | | | | | **Fentanyl --** | | | | | | | | - More lipid | | | | soluble, meaning | | | | *[faster onset | | | | and shorter | | | | duration]{.underl | | | | ine}* | | | | | | | | - Less histamine | | | | release | | +-----------------------+-----------------------+-----------------------+ | | ***Drugs used as | | | | anti-diahrreal*** | | | | | | | | **Diphenoxylate, | | | | Difenoxin, Loperamide | | | | --** | | | | | | | | - Low abuse | | | | potential -- low | | | | solubility and | | | | poor BBB | | | | penetration | | | | | | | | - Less histamine | | | | release | | +-----------------------+-----------------------+-----------------------+ | **NMDA Antagonist** | **Methadone --** Long | | | | duration of action | | | | | | | | - Greater sedation | | | | and low | | | | dependence | | +-----------------------+-----------------------+-----------------------+ | **Other** | **Tramadol --** | | | | | | | | - Weak mu receptor | | | | agonist | | | | | | | | - Inhibits NE and | | | | 5-HT reuptake | | | | | | | | - Less respiratory | | | | suppression and | | | | constipation | | | | | | | | **Tapentadol** | | | | | | | | - MORE potent | | | | compared to | | | | tramadol | | | | | | | | - Tramadol \< | | | | Tapentadol \< | | | | Morphine | | +-----------------------+-----------------------+-----------------------+ | **Mixed** | **Buprenorphine** | | | | | | | | - Partial mu | | | | agonist -- | | | | | | | | - "Ceiling | | | | effect" | | | | | | | | - less | | | | respirato | | | | ry | | | | distress | | +-----------------------+-----------------------+-----------------------+ | **Opioid Antagonist** | - **Narcan** | | | | | | | | - **Naltrexone --** | | | | longer acting | | | | than naloxone | | +-----------------------+-----------------------+-----------------------+ | **Non-Opioid | | | | Analgesic** | | | +-----------------------+-----------------------+-----------------------+ | **COX** | ***COX inhibitors | | | | reduce the effects of | | | | prostaglandins*** | | +-----------------------+-----------------------+-----------------------+ | | **Non-Selective COX** | - **Salicylic --** | | | | | | | | - Irreversible | | | | serine | | | | residue | | | | Salicylate | | | | Poisoning | | | | | | | | - **NSAIDs \--** | | | | | | | | *Ibuprofen, | | | | Diclofenac, | | | | Nabumetone, | | | | Naproxen, | | | | Meloxicam* | | | | | | | | - Heart failure | | | | with chronic | | | | use | | | | | | | | - **Tylenol** | +-----------------------+-----------------------+-----------------------+ | | **Selective COX** | - **Celecoxib \--** | +-----------------------+-----------------------+-----------------------+ | **PLA2 Inhibitors** | **Steroidal** | - **Prednisone / | | | | Fluticasone** | | | **anti-inflammatory** | | | | | - Inhibits | | | | production of | | | | both PGs and | | | | LTs | +-----------------------+-----------------------+-----------------------+