Pain Medications and Mechanism of Action Thomas B. Gregory, PharmD, BCPS, DASPE, CPE
Disclosure
Nothing to disclose
Objectives List pain medications and mechanism of action according to their specific therapeutic class or family Differentiate multimodal analgesia from multiple analgesic agents alone Choose medication combinations that would be effective in multimodal management of pain
httpwww.google.comimgreshl=en&biw=1400&bih=917&tbm=isch&tbnid=8AYyu6Dd2Wy6DM&imgrefurl=httpwww.changepain-emodules.comindex%3F modulesId%3D9%26languagesId%3D1&docid=YjqjkcwIlu-aTM&imgurl=httpwww.changepain-emodules.comimgm9_4.jpg&w=.jpg. Accessed May 12, 2012
Analgesic Families Opioids –Modulation of the mu opioid receptor, altering nociceptive stimuli in the central nervous system (CNS)
Non-steroidal anti-inflammatory agents (NSAID) –Inhibition of prostaglandin synthesis, preventing part of the inflammatory response
http://journals.lww.com/ejanaesthesiology/Fulltext/1997/05001/Mechanisms_of_actions_of_opioids_and_non_steroidal.3.aspx#. Accessed on August 1, 2012
Analgesic Families (cont’d) Local Anesthetics3 – Blocking voltage-gated sodium channels in neurons
Tricyclic Antidepressants (TCA) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRI)4 – Inhibition of serotonin and norepinephrine enhances the descending inhibitory pathway in the CNS
Antiepileptic agents5 – Inhibition of sodium channels in afferent and transmission neurons in the CNS CNS; central nervous system 3. Br Journal Anaesth.89; 1: 52-61 2002 4. Current Neuropharmacology, 7 4 331-6 2009 5. Drugs 60 5 1029-52, 2000
Analgesic Families (cont’d) Glucocorticoids6
–Alteration of intracellular gene expression, inhibiting phospholipase activity and inhibition of cytokine expression
Miscellaneous –Acetaminophen7
• Exact mechanism is unknown however thought to interact with cyclooxygenase and nitric oxide pathways in the CNS
–Capsacian8
• TRPV1 agonist which leads to defunctionalization of nociceptors CNS; central nervous system 6. http://www.practicalpainmanagement.com/corticosteroid-use-pain-management. Accessed August 1, 2012 7. Pain Physician 12; 269-80 2009 8. Br Journal of Anaesth 107; 4: 490-502 2011
Rational Pharmacology Use of a single agent at the lowest effective dose Rotating to another agent in the same medication family can have a positive or negative impact depending on the reason for the rotation Other disease states often require multiple agents for maximum benefit too – Hypertension – Diabetes – Chronic pain
9 Multimodal Analgesia
Adjuvant agents in addition to opioids can lead to the same degree of pain management with lower doses of opioids Opioids are not always effective with certain painful conditions –Chronic or neuropathic pain
The use of non-pharmacologic therapy along with pharmacologic should always be considered 9. Current Opinion in Anaesthesiology 23; 6: 697–703, 2010
Rational Polypharmacy Using a single medication from multiple families to maximize efficacy and minimize side effects Using pain medications in multiple families to have synergistic effects – Each medication should have activity on different receptors within the pathway
NOT using multiple agents in the same family for additive effect – Increased risk of development of side effects
10 Opiate Sparing Effects
Combination of NSAID with opioids for severe pain due to trauma Combination of TCA or SNRI with opioids for chronic pain Combination of antiepileptics with opioids for neuropathic pain Steroids as another adjuvant for acute inflammation NSAID- Non-steroidial anti-inflammatory agents TCA- Tricyclic Antidepressants SNRI- Serotonin-Norepinephrine Reuptake Inhibitors 10. Anesth Analg 101: S5–S22 2005
Short Acting Versus Long Acting Short acting opioids for severe acute pain Short acting and long acting opioids for prolonged severe acute pain or chronic pain Rapid onset opioids with short and long acting opioids for break though pain
Summary Use of rational polypharmacy can maximize efficacy in pain management and decrease the incidence of adverse events Each medication family has its advantages and disadvantages regarding specific pain conditions Formulation of the medication has just as much to do with selection as the family the medication is in does
References 1. http:www.google.comimgreshl=en&biw=1400&bih=917&tbm=isch&tbnid=8AYyu6Dd2Wy6DM&imgrefurl=http www.changepain-emodules.comindex%3FmodulesId%3D9%26languagesId%3D1&docid=YjqjkcwIluaTM&imgurl=httpwww.changepain-emodules.comimgm9_4.jpg&w=.jpg. Accessed May 12, 2012. 2. http://journals.lww.com/ejanaesthesiology/Fulltext/1997/05001/Mechanisms_of_actions_of_opioids_and_non _steroidal.3.aspx#. Accessed on August 1, 2012. 3. Br Journal Anaesth.89; 1: 52-61 2002 4. Current Neuropharmacology, 7.4. 331-6 2009 5. Drugs 60 5 1029-52, 2000 6. http://www.practicalpainmanagement.com/corticosteroid-use-pain-management. Accessed August 1, 2012 7. Pain Physician 12; 269-80 2009 8. Br Journal of Anaesth 107; 4: 490-502 2011 9. Current Opinion in Anaesthesiology 23; 6: 697–703, 2010 10. Anesth Analg 101: S5–S22 2005