Drugs for Pain Flashcards
What is an analgesic?
Drug that relieves pain without causing loss of consciousness
What causes signs and symptoms of inflammation?
excess of prostaglandins in inflamed tissue
-OA and other arthritis
-bursitis
-gout flare
-ankylosing spondylitis
-dysmenorrhea
-headache
are indications for what?
NSAIDS
Which COX is expressed in all tissues all the time and have a prominent role in responding to physiological stimuli and pathologic reponse that releases AA from cells
COX-1
What COX is induced in some tissues and has a physiologic role in the kidney and a prominent role in path?
COX 2
What drug irreversibly inhibits COX 2 and COX1 via acetylation?
Aspirin
What are toxicities of aspirin?
- ulcer
- increased risk for bleeding
- multiple drug interactions
- Reye syndrome
- Increased serum creatine because kidneys lose PG eff
What level of aspirin is toxic?
> 400-500 mcg/mL
-respiratory alkalosis
What drug reversible inhibits COX1 and COX2 to decrease prostaglandin synthesis?
Ibuprofen
- has antipyretic, analgesic, and anti-inflammatory properties
What are the effects of ibuprofen?
- antipyretic
- analgesic
- anti inflammatory
What are ibuprofen toxicities?
NSAID use around 20 weeks or later can cause fetal renal dysfunction leading to oligohydramnios
- at greater than 30 weeks it can cause closure of the ductus arteriosus
- increase risk of MI and stroke–contraindicatd in CABG
- can increase GI bleeding
- may compromise existing renal function
Ibuprofen is contraindicated in what patients?
CABG because of increased risk of MI and stroke
pregnant
renal issues
What NSAID inhibits COX2 but not COX1 at therapeutic concentrations?
Celecoxib
What are BBW of celecoxib?
- Pregnancy–> fetal renal dysfunction leading to oligohydramnios and closure of ductus arteriosis at 30 wks
- severe risk of thrombotic event (MI and stroke) contraindicate celecoxib in CABG
- serious GI risk (bleeding, ulcer, perforation)- less concerning with COX-2 selective
How can risk of aspirin induced ulcers be minimized?
test for/eliminate H. pylori and give PPI
Ibuprofen, naproxen, and non aspirin NSAIDs antagonize what aspirin effect?
Antic platelet actions–> decrease aspirin protection against MI and stroke
- minimize this adverse effect by takin aspirin 2hrs before other NSAIDs
Aspirin can increase bleeding risk in which patient?
Those on warfarin, heparin, or other anticoagulants
- high dose aspirin should be discontinued 1 week before elective surgery but low dose can continue
What NSAID is recommended when NSAID therapy is required but the patient is at risk for CV complications?
NAPROXEN
What are contraindications of NSAID use?
- CKD with creatinine clearance of less than 60 mL/min
- Active duodenal or gastric ulcer
- CV disease–> heart failure or uncontrolled HTN
- Anticoagulat tx (warfarin)
What analgesic is believed to be a TRPV1 and TRPA activator or central PG synthhase inhibitor due to the activation of descending serotonergic inhibitory pathways in the CNS?
acetaminophen
What are the toxicities of acetaminophen?
-risk of medication errors and overdosage–> hepatotoxicity with acute liver failure and possible death
What is antidote for acetaminophen toxicity?
Acetaminophen becomes a toxic metabolic when glutathione is depleted
N-ACETYLCYSTINE IS ANTIDOTE
Acetaminophen inhibits prostaglandin synthesis in the CNS but not the periphery, what does this mean?
acetaminophen suppresses pain and fever but NOT INFLAMMATION
- lacks anti-inflammatory actions
-does NOT cause GI ulceration
-does NOT suppress platelet aggregation
does NOT impair renal function
used for temporary relied of minor aches, pains, and headache
Hepatic necrosis from glutathione depletion and increased bleeding risk can be caused by what?
Acetaminophen
What is morphine MOA?
binds to opioid receptors in the CNS
-inhibits ascending pain pathways
- alters perception of pain and response to pain
- generalized CNS depressant
What drug has BBW for respiratory depression with to without combining other drugs
Morphine
What can create a physical dependence on opiods?
administration of opioids at high doses for > 20 days
What is Amitriptyline MOA?
- tricyclic antidepressant
- inhibition of NE and 5-HT reuptake by the presynaptic neuronal membrane pump
effect ins to increase concentration of NE and 5HT in the synaptic cleft
What are clinical applications of amitriptyline?
- unipolar major depressive disorder
- Chronic fatigue syndrome from sleep disturbances and pain
- fibromyalgia
- functional dyspepsia
- neuropathic pain (including diabetic neuropathy
What drugs have BBW of increased risk of suicidal thinking and behavior in children, adolescents, and young adults?
- amitriptyline
2. duloxetine
What is MOA of duloxetine?
- potent inhibitor of neuronal 5 HT and NE reuptake
- weak inhibitor of DA uptake
- anxiety benefits are observed within 2 weeks of tx and continue to improve through 4-6 weeks
What drugs are dual reuptake inhibitors of serotonin and NE making them beneficial in patients with concurrent depression?
- duloxetine
- venlafaxine
What is pregabalin MOA?
-Binds alpha-2-delta subunit of voltage gated calcium channels to modulate calcium influx at nerve terminals
What are clinical applications of pregabalin (Lyrica)?
- Neuropathic pain (diabetic peripheral neuropathy and spinal cord injury)
- seizures (focal and partial)
- postherpetic neuralgia
- fibromyalgia (modest benefits)
What is gabapentin MOA?
-binds to the alpha2-delta subunit of calcium gated channels to inhibit excitatory NT release (glutamate)
What drug has broad spectrum antiseizure effects?
gabapentin
What is MOA of Tramadol?
- partial agonist at mu opiate receptors in the CNS (weak action)
- schedule IV controlled substance
- inhibits reuptake of NE and 5-HT (primary mode of action )
What drug has BBW of
-risk of medication error
- addiction, abuse, and misuse
- interactions with drugs affecting cytochrome P450 isoenzymes withdrawal syndroms
- increased risk of respiratory depression from concomitant use with other benzodiazepine or other CNS depressants
Tramadol
also causes sedation, dizziness, headache, dry mouth, and constipation
What is MOA of tapentadol?
- moderate-strong opioid agonist similar to oxycodone at mu receptors
- blocks reuptake of NE
- causes less constipation than traditional opioids
Why would someone use tapentadol over other opioids?
- less constipation
- reserved for patients not effectively treated with other non-opioids and opioids
What is the MOA of ketamine?
Non-competitive NMDA receptor antagonist that blocks glutamate
KetAMiNe –> only missing the D and it tells you what it does
What is dexmedetomidine MOA?
- selective alpha2 adrenoceptor agonist
- anesthetic and sedative properties thought to be due to activation of G-proteins by alpha2a adrenoceptors in the brainstem
does ketamine elevate or lower BP?
Elevate! differs from many other anesthetics that lower it
How is dexmedetomidine administered? What is it used for?
- IV administered (unlike clonidine)
- alpha 2 adrenergic agonist used for analgesia and sedation
What is clonidine MOA? Use?
- alpha 2 adrenergic agonist for
- HTN
- relief of severe pain
What is ziconotide MOA?
- selectively binds to N-type voltage sensitive calcium channels
- located on the nociceptive afferent nerves of the dorsal horns in the spinal cord
What is BBW of ziconotide?
- severe psychiatric sx and neuro impairment
- significant pt harm if used in error
- n type voltage sensitive ca2+ channel inhibitor
What is BBW of ziconotide?
- severe psychiatric sx and neuro impairment
- significant pt harm if used in error
What is only indicated for sever pain when intrathecal (into spinal cord) administration is warranted when refractory to other treatments?
Ziconotide
What topical anti pain agent stimulate TRPV1
Camphor- in ICY hot
Capsaicin from red pepper desensitizes and depletes substance P
- moderate to poor efficiency on nociceptive and neuropathic pain
How does aspercreme work?
ir is a topical Na+ channel blocker
how does sumatriptan work?
- selective 5HT1B and 5HT1D agonist
- activates receptors on intracranial blood vessels and sensory nerves of the trigeminal
- used for migranes of moderate to severe intensities
- cluster headaches
What are clinical applications of sumatriptan and how?
Sumatriptan is used for migraines of moderate to severe intensity
- causes vasoconstriction and reduces neurogenic inflammaiton
Risk of sumatriptan?
- prolonged QT–> torsades
- MI
- stroke
- transient / permanent blindness
- serotonin syndrome
What is lasmiditan MOA?
high affinity, high selectivity 5HT1F receptor agonist
- decrease stimulation of the trigeminal system
- treat migraine pain without causing vasoconstriction
What are the effects of lasmiditan?
-decreased stimulation of the trigeminal system
–treat migraine pain without vasoconstriction
What is MOA of ubrogepant?
Calcitonin gene-related peptide receptor antagonist
- tx of migraine with or without aura
What is MOA of dihydroergotamine?
- ergot alkaloid
- binds serotonin, dopamine, and adrenergic receptors
- late tx option for migra
- cluster headahces
off label: orthostatic hypotension, pelvic congestion with pain
