Drugs for Pain Flashcards
What are some nonpharmacologic therapy for pain?
- Exercise
- Physical therapy
- Heat, ice, massage
- Sleep hygiene techniques
- Behavioral/psychological therapies
- Healthy lifestyle
- Acupuncture
What are some common non-inflammatory indications for NSAIDs?
- Osteoarthritis and other arthritides
- Bursitis
- Gout ‘flare’
- Ankylosing spondylitis
- Dysmenorrhea
- Headache
Where is COX-1 expressed and what is its role?
- Expressed in “all” tissues
- Prominent role in responding to physiological stimuli
- Also contributes to response to any pathological stimuli that release AA from cells
How does COX-1 and COX-2 contribute to inflammation?
- Inflammation stimulates AA release –> COX-1 and COX-2 convert AA into PGE2 which causes symptoms
What is the MOA of aspirin?
- Irreversibly inhibits COX-1 and COX-2 enzymes
What are the clinical applications of immediate release aspirin?
- Analgesic, antipyretic, and anti-inflammatory
- Revascularization procedures
- Ischemic stroke, TIA
- STEMI or NSTEMI
What are the clinical applications of extended release aspirin?
- Ischemic stroke or TIA
- Stable ischemic heart disease
What are the toxicities seen in aspirin use?
- Ulcer
- Increased risk of bleeding
- Multiple drug interactions
- Reye syndrome in children <18
- Increased NSAIDs causes increased serum creatinine due to loss of PG effects in kidneys
What is the progression of aspirin toxicity?
- Salicylates uncouple mitochondrial oxidative phosphorylation in the CNS
- Respiratory center registers decreased ATP as hypoxemia and responds with hyperventilation
- Hyperventilation blows off CO2, drop in PCO2 causes respiratory alkalosis –> eventually prompting kidney to deplete bicarbonate
- Organic acids accumulate because ATP is no longer generated through the Krebs cycle
What are some differences between aspirin and nonaspirin NSAIDs?
- They are reversible unlike aspirin
- Suppress platelet aggregations, but use actually increases risk of MI and stroke
- Therefore use the lowest effective dosage for shortest time possible
What is the MOA of IBU? What about naproxen?
- Reversibly inhibits COX-1 and COX-2
- Naproxen has similar MOA but half life is 12-17 hours
What are some toxicities of IBU?
- NSAIDs around 20 weeks gestation or later may cause fetal renal dysfunction leading to oligohydramnios, > 30 weeks closure of ductus arteriosus
- Increased risk of MI and stroke –> contraindicated in CABG
- Increased risk of GI bleeding
What is the MOA of celecoxib?
- Inhibits PG synthesis via COX-2 but not COX-1 at therapeutic concentrations
What are the clinical applications of celecoxib?
- Acute pain
- Ankylosing spondylitis
- Juvenile idiopathic arthritis
- Osteoarthritis
- Primary dysmenorrhea
- RA
What are some toxicities of celecoxib?
- NSAIDs around 20 weeks gestation or later may cause fetal renal dysfunction leading to oligohydramnios, > 30 weeks closure of ductus arteriosus
- Serious risk of thrombotic events, including MI and stroke
- Serious GI risk but less due to being only COX-2 selective
What are some commonly used NSAIDs?
- Aspirin
- Celecoxib
- Diclofenac
- IBU
- Indomethacin
- Ketorolac
- Naproxen
When should COX-2 selective agents by avoided?
- Patients with CV risk factors
What NSAID should be used in those with CV complications?
- Naproxen
What are some contraindications for NSAID use?
- Chronic kidney disease
- Active duodenal or gastric ulcer
- Cardiovascular disease
- NSAID allergy
- Ongoing treatment with anticoagulants –> warfarin
What is the MOA of acetaminophen?
- Not fully elucidated
What are the clinical applications of acetaminophen?
- Temporary reduction of fever
- Pain, oral –> temporary relief of minor aches, pains, and headache
What are some toxicities of acetaminophen?
- Risk of medications errors –> confusing mL and mg
- Overdose –> hepatotoxicity with acute liver failure and death possible
Why does acetaminophen not suppress inflammation?
- Inhibits PG synthesis in the CNS but not periphery
What are some drug interactions of acetaminophen?
- Inhibits metabolism of warfarin and therefore can increase risk of bleeding associated with its use
What are the first line agents for neuropathic pain?
- Calcium channel alpha 2 delta ligands –> gabapentin
- SNRIs –> duloxetine
- TCAs –> amytriptyline
What is the MOA of amitriptyline?
- Inhibition of NE and 5HT reuptake by the presynaptic neuronal membrane pump
What are some toxicities of amytriptyline?
- Increased risk of suicidal thinking and behavior in children, adolescents, and young adults
- Anticholinergic effects
What is the MOA of duloxetine?
- Potent inhibitor of neuronal 5HT and NE reuptake
What are some clinical applications of duloxetine?
- Fibromyalgia
- GAD
- Major depressive disorder
- MSK pain, chronic
- Neuropathic pain associated with DM
What are some toxicities of duloxetine?
- Increased risk of suicidal thoughts and behaviors
- Activation of mania or hypomania
- Bleeding risk
- Hepatotoxicity
- Hyponatremia
- Acute angle closure glaucoma
What is the MOA of pregablin?
- Binds to CNS alpha-2-delta subunit of VGKC –> modulates calcium influx at the nerve terminals
What are some toxicities of pregabalin?
- Depression, suicidal ideation
What are the four indications of pregabalin?
- Neuropathic pain associated with DM
- Postherpetic neuralgia
- Adjunctive therapy for partial seizures
- Fibromyalgia
What is the MOA of tramadol?
- Partial agonist at mu-opiate receptors
- Also inhibits the reuptake of NE and 5HT
What are some toxicities of tramdol?
- Risk of medication errors/ingestion by children –> overdose and death
- Addiction, abuse, and misuse
- Interactions with drugs affecting cyp 450
- Withdrawal syndrome
- Increased risk of respiratory depression from concomitant use with benzos or other CNS depressants
What are some side effects of tramadol?
- Sedation
- Dizziness
- Headache
- Dry mouth
- Constipation
What is tapentadol?
- Moderate to strong opioid agonist similar to oxycodone at mu receptors
- Also blocks reuptake of NE
- Causes less constipation
What is the MOA of ketamine?
- Noncompetitive NMDA receptor antagonist
What are the toxicities of ketamine?
- Requires careful monitoring
- Could have prolonged, undesired effects
What are some main uses for ketamine?
- Complex regional pain syndrome
- Neuropathic pain
What is the MOA of dexmedetomidine?
- Selective alpha2-adrenoceptor agonist –> clonidine has similar MOA
What is the use of dexmedetomidine?
- Potent anxiolytic, part of multimodal approach to postoperative pain management
- Short term sedation in critically ill patients who were intubated and are undergoing mechanical ventilation
- Sedation prior to/during surgical procedures
What are some toxicities of dexmedetomidine?
- Bradycardia, hypotension, and sinus arrest
- Transient hypertension
What is the MOA of ziconotide?
- Selectively binds to N-type voltage sensitive calcium channels located on the nociceptive afferent nerves of the dorsal horn
What is the clinical application of ziconotide?
- Management of severe chronic pain in patients requiring intrathecal therapy
What are some toxicities of ziconotide?
- Severe psychiatric symptoms and neurological impairment may occur
- This medication among those listed for heightened risk of causing significant patient harm when used in error
What is the MOA of sumatriptan?
- Selective 5HT1B and 5HT1D agonist
What are the clinical applications of sumatriptan?
- Migraine of moderate to severe intensity
What are some toxicities of sumatriptan?
- Prolonged QT interval on ECG –> torsades, V fib
- Coronary artery vasospasm –> MI
- Hypertension –> stroke
- CNS depression –> dizziness, drowsiness
- Transient/permanent blindness or partial vision loss
- Serotonin syndrome
What is the MOA of lasmiditan?
- High affinity, highly selective 5HT1F receptor agonist
- Decreased stimulation of the trigeminal system
- Treat migraine pain without causing vasoconstriction
What are some applications for lasmiditan?
- Use if there are >3 consecutive attacks unresponsive to triptran
What are some toxicities of lasmiditan?
- Dizziness
- CNS depression
- Risk of serotonin syndrome
- P-glycoprotein interactions can potentiate toxic effects of other drugs
What is the MOA of ubrogepant?
- Calcitonin gene-related peptide receptor antagonist
What are some toxicities of ubrogepant?
- Nausea
- Somnolence
- Dry mouth
- Negligible by itself but potential for many via drug interactions
What is the MOA of dihydroergotamine?
- Ergot alkaloid
What are some clinical applications of dihydroergotamine?
- Late treatment for migraine
- Cluster headaches
What are some toxicities of dihydroergotamine?
- Ergot alkaloids are contraindicated with potent CYP3A4
- Concomitant use associated with an increased risk of vasospasm leading to cerebral ischemia and/or ischemia of the extremities
