Drugs for Pain (Wolff) Flashcards
What are 4 common classes of adjuvant therapy for pain (T/S/AC/TA)?
- TCAs
- SNRIs
- anticonvulsants
- topical anesthetics
Aspirin
What is its MOA, what is it used for, and what are 4 common toxicities it can cause in patients (U/B/RS/SC)?
MOA: IRREVERSIBLY inhibits COX-1 AND COX-2 (platelet inhibition lasts its lifetime)
- administered orally, rectally
- used for a variety of painful issues
T: ulcers, inc. risk of BLEEDS, Reye Syndrome (<18 yo w/chicken-pox or flu), and inc. Serum Creatinine
How does Aspirin/Salicylate lead to Metabolic Acidosis?
- salicylates uncouple the mitochondrial oxidative phosphorylation in CNS, which the respiratory center registers as HYPOXEMIA due to dec. ATP
- causes patient to HYPERVENTILATE
- hyperventilation leads to dec. CO2, causing respiratory alkalosis which causes kidney to deplete bicarbonate
- organic acids accumulate because ATP is no longer generated = inc. lactic acidosis –> life-threatening metabolic syndrome
Ibuprofen
What is its MOA, what are its 2 common uses, and what are 3 serious toxicities of use (O/MI/B)?
MOA: REVERSIBLY inhibits COX-1 AND COX-2
- administered orally
- used for reduction of fever and pain management
T: Oligohydramnios (also premature ductus arteriosus closure) in pregnant women, inc. risk of MI/stroke, GI BLEEDING
How is Naproxen different than Ibuprofen?
- naproxen has a longer half-life (t1/2 - 12-17 hrs) than ibuprofen (t1/2 - 2 hrs)
- naproxen is available for ONCE DAILY dosing
Celecoxib
What is its MOA, what is it used for, and what are 3 serious toxicities of use (O/M/GI)?
MOA: inhibits prostaglandin synthesis by COX-2 BUT NOT COX-1
- administered orally (capsule)
- prolonged absorption = low solubility
- used for acute pain management
T: Oligohydramnios/closure of ductus arteriosus, inc risk of MI/stroke, and serious GI RISKS (bleed/ulceration/perforation
Why are Thrombotic events like MI and Stroke more of a problem with COX-2 inhibitors, like Celecoxib, than with COX-1 and COX-2 inhibitors?
- COX-2 inhibitors do NOT inhibit thromboxane synthesis in platelets, meaning that thrombotic events are MORE likely to develop than if patient was using dual COX inhibiting drugs
What are two conditions that Aspirin is very useful in helping treat?
- Rheumatoid Arthritis
2. Chronic Inflammatory Conditions
What are two things that should be done to help minimize the risk of aspirin-induced ulceration in patients?
- test for/eliminate H.pylori infections BEFORE starting therapy
- give a Proton Pump Inhibitor in addition
When should non-aspirin NSAIDS, like ibuprofen and naproxen, be taken when also using aspirin and why?
- should be taken 2 hours AFTER aspirin use
- non-aspirin NSAIDS antagonize the antiplatelet actions of aspirin, thus dec. protection against MI and STROKE
non-aspirin NSAIDS should be used at LOWEST effective dosage for SHORTEST possible time possible
Which NSAID is recommended for use in patients with Cardiovascular Complications that REQUIRE therapy?
Naproxen
- has long half-life and is relatively non-selective
What are 5 common contraindications for NSAID use (C/U/C/A/A)?
- Chronic Kidney Dz (creatine clearance < 60 mL/min)
- active duodenal/gastric ULCER
- Cardiovascular Dz (heart failure, uncontrollable HTN)
- NSAID Allergy
- ongoing ANTICOAGULANT treatment (Warfarin)
Acetaminophen
What is its MOA, what is it used for, and what are 2 major toxicities of use?
MOA: not fully understood but believed activation of descending serotonergic inhibitory pathways in CNS and inhib. of hypothalamic heat-regulating center
- administered orally and parenterally
- used for temporary reduction of fever and pain, but does NOT SUPRESS INFLAMMATION
T: medication errors can lead to HEPATOTOXICITY with acute liver failure and DEATH
When does Acetaminophen become toxic and what is used as an antidote to Acetaminophen poisoning?
- becomes toxic when GLUTATHIONE is depleted
- use N-acetylcysteine as an antidote
What 3 things does Acetaminophen NOT cause?
- does NOT cause GI ulceration
- does NOT suppress platelet aggregation
- does NOT impair renal function
What drug does Acetaminophen block the metabolism of, leading to inc. risk of bleeding?
Warfarin
Morphine
What is its MOA, what is it used for, and what are two toxicities of use?
MOA: binds to opioid receptors in CNS leading to inhibition of ascending pain pathway and alters perception of pain response
- 2nd line for treatment of Nociceptive pain
- used for pain management and acute/chronic pain
T: respiratory depression and CNS depression
What drugs are used in Management of Neuropathic Pain:
- First Line (C/S/T)
- Second Line (VA/O/T)
- Third Line (N/A/T/B)
- Fourth Line - ineffective analgesia (B/Z)
- calcium channel alpha2delta ligands, SNRIs, TCAs
- valproic acid, opioids, tramadol
- NMDA antag., analgesic combos, tizanidine/baclofen
- Botulinum toxin, intrathecal ziconotide
Amitriptyline
What is its MOA, what two things is it used for, and what is a major toxicity of use (SI)?
MOA: tricyclic antidepressant (TCA) that inhibits NE/serotonin reuptake by presynaptic neuronal membrane pump (inc. synaptic concentrations)
- used for Unipolar Major Depressive Disorder and Neuropathic Pain
T: inc. risk of suicidal thinking/behavior in children, adolescents, and young adults
Duloxetine
What is its MOA, what is it used for, and what are two toxicities of use (SI/H)?
Who is this drug especially useful for?
MOA: SNRI that is potent inhibitor of serotonin/NE reuptake and is also a weak dopamine reuptake inhibitor
- used for Neuropathic Pain associated with DM
T: suicidal ideations/behaviors and hyponatremia (SIADH)
especially useful for patients with Neuropathic Pain with concurrent depression
Pregabalin (Gabapentin)
What is its MOA, what two things is it used for, and when are pain benefits usually seen?
MOA: binds to a2d subunit of voltage-gated calcium channels that does NOT bind to GABA receptors
- inhibits excitatory neurotransmitter release
- used for Neuropathic Pain and seizures
- pain benefits evident in the first week of use
do NOT discontinue abruptly due to increased risk of seizures
What are the 4 approved indications for Pregabalin use?
NP/PN/S/F
- Neuropathic pain with diabetic neuropathy
- Postherpetic neuralgia
- seizures
- fibromyalgia
FIRST DRUG approved for use with fibromyalgia
Tramadol
What is its MOA, what is it used for, and what are 4 toxicities of use (RD/A/C/WS)?
MOA: partial agonist at mu-opiate receptors in CNS and inhibits NE/serotonin reuptake
- used for altering perception of/response to pain (pain relief)
T: respiratory depression, addiction, CYP450 inducer, withdrawal syndrome
low abuse potential but used for suicide
Tapentadol
What is it and who is it reserved for?
- moderate-strong opioid agonist that also blocks NE reuptake
- reserved for patients who are not effectively treated with other non-opioids and opioids
Ketamine
What is its MOA, what is it used for, and what is a major toxicity of use?
MOA: noncompetitive NMDA receptor antagonist that causes dissociation from pts. surrounding environment
- given IV
- used for induction/maintenance of general anesthesia and sub-doses for acute/chronic pain/analgesia
T: prolonged emergence from anesthesia (carefully monitor)
helps reduce amount of morphine needed for pain control
Dexmedetomidine
What is its MOA, what is it used for, and how is it administered?
MOA: selective a2-adrenoreceptor agonist with sedative properties due to receptor activation in brainstem
- inhibits NE release; causes periph. vasoconstriction
- used for sedation of ventilator patients in the ICU and procedural sedation
- administered IV (unlike clonidine)
What is Clonidine used for (H/P) and how is it administered vs Dexmedetomidine?
- a2 adrenergic agonist used for HYPERTENSION and severe PAIN RELIEF
- administered as continuous infusion through EPIDURAL CATHETER (vs Dexmedetomidine = IV)
treats severe cancer pain in those not treated effectively with opioid alone
Ziconotide
What is its MOA, what is it used for, how is it administered, and what are two toxicities of use (PS/PH)?
MOA: selective N-type voltage-sensitive Ca channels on nociceptive afferent nerves of DORSAL HORN that blocks excitatory neurotransmitter release
- dec. painful stimuli sensitivity
- used for severe chronic pain in patients requiring INTRATHECAL THERAPY that are INTOLERANT/REFRACTORY to other therapies
T: psychiatric symptoms, inc. risk of significant patient harm when used in error
How do these Topical Anti-Pain Agents work:
- Capsaicin
- Camphor
- Menthol
- Lidocaine
- stims TRPV1 –> depletes substance P (heat from red pepper)
- stims TRPV1 –> heat similar to Capsaicin
- stims TRPM8 –> causes cooling sensation
- topical Na channel blocker in Aspercreme
Sumatriptan
What is its MOA, what is it used for, and what are 3 toxicities of use (TdP/MI/S)?
MOA: selective 5-HT1B/HT1D agonist causing vasoconstriction and dec. neurogenic inflammation
- used for migraine of moderate-severe intensity and cyclic vomiting syndrome (SubQ has most availability)
T: Torsades de Points, MI (vasospasm), stroke (HTN)
Lasmiditan
What is its MOA, what is it used for, and how is it administered?
MOA: high-affinity selective 5-HT1F agonist
- used to treat migraine WITHOUT causing vasoconstriction
- administered by PO tablets
Ubrogepant
What is its MOA, what is it used for, and how is it administered?
MOA: calcitonin gene related peptide (CGRP) receptor antagonist that inhibits pathologic dilation of intracranial arteries WITHOUT reflexive VASOCONSTRICTION
- used for migraine with/without aura in adults
- administered by PO tablets
Dihydroergotamine
What is its MOA, what is it used for, and what is its major toxicity?
MOA: ergot alkaloid binding to multiple receptors that constricts BVs and can cause behavioral disturbances and distal gangrene
- used as LATE TREATMENT for migraine, as well as cluster headaches
T: contraindicated w/inhibitors of CYP3A4 due to inc. risk of vasospasm –> cerebral ischemia and ischemia of extremities
