Pharm approach to pain Flashcards
what are analgesics?
drugs that relieve pain without causing loss of consciousness
what is secondary hyperalgesia?
pain caused by glutamate stimulation of spinal NMDA receptors
what are the characteristics of COX1?
expressed in all tissue
responds to physiological stimuli
responds to pathological stimuli (inflammation)
what is the COX1 pain pathway?
- inflammation stimulates AA release
- COX1 converts AA to PGE2
- PGE2 causes symptoms
what are the characteristics of COX2?
expressed in some tissue
physiological role in kidney and complements COX1
response to pathological stimuli (inflammation)
what is the COX2 pain pathway?
- inflammation induces COX2 expression
- COX2 also converts AA into PGE2
- COX2 derived PGE2 amplifies symptoms
what are the NSAIDs?
ASA ibuprofen celecoxib diclofenac inomethacin ketorolac (Toradol) naproxin (Aleve)
what is the MOA of most NSAIDs?
inhibits COX1 and COX2
which NSAID only inhibits COX2?
celecoxib
what are the adverse reactions of ASA?
GI bleeding
hemostatic defects
toxicity leading to respiratory failure
what is the toxic dose of ASA?
400-500 mcg/mL
what is the dose of ASA for antiplatelet or analgesia use?
100 mcg/mL
what is the dose of ASA for anti-inflammatory use?
150-300 mcg/mL
what is the dose of ASA for the treatment of rheumatic fever?
250-400 mcg/mL
what is the progression of ASA toxicity?
- salicylates uncouple ox phos in CNS
- resp center sees decreased ATP as hypoxemia
- hyperventilation causes respiratory alkalosis
- organic acids accumulate from Krebs cycle dysfunction
- metabolic acidosis becomes life-threatening
what are the adverse reactions of ibuprofen?
fetal renal dysfunction in pregnancy
increase risk of MI and stroke
increase risk of GI bleed
what are the adverse reactions of celecoxib?
fetal renal dysfunction in pregnancy
increase risk of MI and stroke
increase risk of GI bleed
what are the 4 major actions of ASA?
anti-inflammatory
mild to moderate pain relief
fever reduction
prevention of MI or stroke (anti-platelet)
what are the differences between ASA and other NSAIDs?
other NSAIDs:
reversible
increase the risk of MI and stroke
how is celecoxib different from ASA and other NSAIDs?
less likely to cause gastric ulceration
no risk of bleeding
increases MI and stroke risk
what are the contraindications of using NSAIDs?
CKD gastric/duodenal ulcer heart failure uncontrolled HTN allergy anticoagulant use
what are the possible MOAs of acetaminophen?
TRPV1 activator
central PG synthase inhibitor
cannabinoid receptor activator
what is the major adverse reaction of acetaminophen?
hepatotoxicity due to overdose
what are the effects of acetaminophen?
suppresses pain and fever
NOT anti-inflammatory
how do you treat acetaminophen toxicity?
acetylcysteine
who should not take acetaminophen?
people with liver disease
people who take warfarin (increased risk of bleeding)
what is the MOA of opioids?
act on central and peripheral µ, ∂ and k receptors
what is the blackbox warning of morphine?
respiratory depression with/without combining with other drugs
what are the adverse reactions of opioids?
constipation
CNS depression
hypotension
when are patients at risk for physical opioid dependence?
when used at high doses for > 20 days
what are indications for opioid use?
post-op pain obstetric analgesia MI head injury chronic non-cancer pain
what are the first-line agents for neuropathic pain?
calcium channel alpha 2 delta ligands
SNRIs
TCA
what is the MOA of amitriptyline?
TCA
inhibition of NE and 5-HT reuptake
what are the adverse reactions of amitriptyline?
dry mouth constipation tachycardia nausea vomiting sedation mental clouding
what is the MOA of duloxetine?
SNRI
inhibitor of neuronal 5-HT and NE reuptake
weak inhibitor of DA reuptake
what are the adverse reactions of SNRIs?
nausea dizziness diaphoresis sexual dysfunction insomnia/agitation hypertension
what is the MOA of calcium channel alpha2-delta ligands?
modulates calcium influx at nerve terminals
GABA analog but does NOT bind to GABA receptors
what are the indications for using pregabalin?
diabetic neuropathy
postherpetic neuralgia
partial seizures
fibromyalgia
what are the calcium channel alpha2-delta ligands?
pregabalin
gabapentin
what are the indications for using gabapentin?
broad-spectrum anti-seizure activity post-herpetic neuralgia diabetic neuropathy migraine prophylaxis fibromyalgia restless leg syndrome
what is the MOA of tramadol?
partial agonist of µ-opioid receptors in CNS
inhibits reuptake of 5-HT and NE
what are the adverse reactions of tramadol?
sedation dizziness headache dry mouth constipation
what are the indications for using tramadol?
moderate pain
- stronger than ASA or acetaminophen
- weaker than morphine
what are the serious side effects of tramadol?
seizures in epileptics
hypertensive crisis if combine with MAO
serotonin syndrome if combined with SSRI, TCA, MAO
what is the MOA of tapentadol?
moderate to strong µ-opioid receptor agonist
blocks reuptake of NE
what is an indication for giving tapentadol?
patients who are not effectively treated with other non-opioids and opioids
what is the MOA of ketamine?
noncompetitive NMDA receptor antagonist
what are the indications for using ketamine?
agitation sub-anesthetic doses for analgesia depressive episode procedural sedation refractory status epilepticus
what are adverse reactions of ketamine?
psych reactions:
agitation
confusion
hallucinations
what is the MOA of dexmedetomidine?
alpha2-adrenergic agonist for analgesia and sedation
what are the indications for using dexmedetomidine?
short-term sedation in intubated patients
sedation prior to procedures
administered IV for pain
what are the adverse reactions of dexmedetomidine?
hypotension bradycardia nausea dry mouth transient HTN agitation constipation respiratory depression
what is the MOA of clonidine?
alpha2-adrenergic agonist used for HTN and relief of severe pain
blocks transmission of pain signals
what are the indications for using clonidine?
severe cancer pain in patients not treated effectively with opioid alone
what are the adverse reactions of clonidine?
hypotension
confusion
dry mouth
what is the MOA of ziconotide?
selective N-type voltage-sensitive calcium channel antagonist on nociceptive afferent neurons
prevents transmission of pain signals
what are the indications for using ziconotide?
chronic severe pain in those whom intrathecal administration is warranted and when refractory to other treatments
what are the adverse reactions of ziconotide?
cognitive impairment and psych symptoms
what drugs are contraindicated in pregnancy?
dexmedetomidine
clonidine
ziconotide
what are the topical anti-pain agents?
capsaicin camphor menthol topical NSAIDs topical Na channel blockers
what drugs can treat migraines?
sumatriptan
lasmiditan
ubrogepant
dihydroergotamine
what is the MOA of sumatriptan?
selective 5HT1B and 5-HT1D agonist
activates receptors on the intracranial blood vessels and sensory nerves of the trigeminal system
what are the adverse reactions to sumatriptan?
Torsades MI stroke CNS depression blindness or partial vision loss serotonin syndrome peripheral ischemia
what is the MOA of lasmiditan?
high-affinity highly selective 5-HT1F receptor agonist
what are the adverse reactions to lasmiditan?
CNS depression
serotonin syndrome
can potential toxic effects of other drugs
what is the MOA of ubrogepant?
calcitonin gene-related peptide receptor antagonist
what are the adverse reactions to ubrogepant?
nausea
somnolence
dry mouth
what is the MOA of dihydroergotamine?
ergot alkaloid
binds to serotonin, adrenergic and dopamine receptors
what are the adverse reactions to dihydroergotamine?
do not use with potent CYP3A4 inhibitors –> vasospasm
cardiac fibrosis
