Pharm - Pain Flashcards
describe nociceptive pain
- what is somatic pain
- what is visceral pain
perception of input from a nocicpetor, a nerve fiber preferentially sensitive to noxious stimulus
somatic: arises from injury to body tissues, well localized
visceral: arises from viscera stretch receptors, poorly localized
describe neuropathic pain
- what is sympathetically mediated pain
- what is peripheral neuropathic pain
- what is central pain
arises from abnormal neural activity secondary to dz/injury/dysfunction of the nervous system
sympathetically mediated: arises from peripheral nerve lesion and associated w/ autonomic change
peripheral neuropathic: due to damage to a peripheral nerve W/O autonomic change
central pain: arises from abnormal CNS activity
compare mononeuropathy, mononeuropathy multiplex, and polyneuropathy
mononeuropathy: one nerve affected
mononeuropathy multiplex: several nerves affected in different areas
polyneuropathy: sx are diffuse and bilateral
what are the two types of pain sensation
1) tissue damage –> release of local inflammatory mediators –> hyperalgesia (exagerrated response to pain)/allodynia (pain from repeated exposure)
2) gluatamate stimulation of spinal NMDA receptors —> secondary hyperalgesia
what do these abbreviations stand for
- AA
- coxibs
- PG
- PGI2
- PUFA
- TxA2
- AA: arachidonic acid
- coxibs: selective inhibitors of cox-2
- PG: prostaglandin
- PGI2: prostacylin
- PUFA: polyunsaturated fatty acid
- TxA2: thromboxane A2
describe the arachidonic acid pathway
arachidonic acid –> COX –> PGI2, TXA2, PGD2, PGE2
what are the effects of thromboxane A2 (produced in the arachidonic acid pathway)
vasoconstriction
increased platelet aggregation (thrombotic)
what are the effects of prostacyclin (produced in the arachidonic acid pathway)
vasodilation
decreased platelet aggregation (anti-thrombotic)
what are the effects of PGE2 (produced in the arachidonic acid pathway)
joints: swelling, pain, edema
gastric mucosa: gastric protection
compare COX 1 and 2
both use AA, both make PGs, both have physiological role in renal function
COX1:
constitutive expression, all tissue all the time, responds to PHYSIOLOGICAL stimuli, contributes to response to pathological stimuli that release AA
COX2:
some tissues some times, prominent role in response to PATHOLOGICAL stimuli that release AA
when NSAID therapy is required for a patient at risk of CV complications, _______ is recommended as the NSAID of choice
naproxen
what are come contraindications for NSAID use
1) chronic kidney disease w/ creatinine clearance <60
2) active duodenal or gastric ulcer
3) CV dz
4) NSAID allergy
5) ongoing tx with anticoags (warfarin)
4 major actions of aspirin
1) suppression of inflammation
2) relief of mild–>moderate pain
3) reduction of fever
4) prevention of MI and stroke
MOA aspirin
irreversible Inhibition of COX
common indications for aspirin
- rheumatoid arthritis
- chronic inflammatory conditions
- post-operative pain
adverse effects of aspirin can occur in what patients
- advanced age
- pre-existing renal function
- hypovolemia
- HTN
- hepatic cirrhosis
long-term aspirin use may lead to ______ and other forms of renal injury
renal papillary necrosis
why should aspirin not be used in children with chicken pox or influenza?
due to reye syndrome
effect of using aspirin during labor and elivery
- can suppress spontaneous uterine contractions
- can induce premature closure of ductus arteriosus
- can intensity uterine bleeding
compare non-aspirin NSAIDs vs aspirin
both:
- inhibit COX 1 and COX2
- suppress inflammation, pain, and fever
- increase risk of
non-aspirin NSAIDs:
- reversible
- suppress platelet aggregation but increase risk of MI and stroke
indications ketorolac
who cannot take it
short term (<5 days) management of moderately severe acute pain that requires analgesia at the opioid level
- usually post-operative state
NOT indicated in peds patients, or for minor or chronic conditions
warnings for ketorolac
can cause peptic ulcers,GIbleeding and/or perforation of the stomach or intestines, which can be fatal
- risk of bleeding
- CV thrombotic events
- renal risk
indications for indomethacin
- Moderate to severe rheumatoid arthritis including acute flares of chronic disease
- Moderate to severe ankylosing spondylitis
- Moderate to severe osteoarthritis
- Acute painful shoulder (bursitis and/or tendinitis)
- Acute gouty arthritis
indomethacin is contraindicated in the treatment of _____
peri-operative pain in the setting of CABG surgery
contraindications ibuprofen
- Active gastric or duodenal ulcer, a history of recurrent ulceration, gastrointestinal bleeding, or active inflammatory disease of the gastrointestinal system
- Significant hepatic impairment or active liver disease
- Severely impaired or deteriorating renal function
warning and precautions ibuprofen (what pts should not take it)
- Patients with heart disease and high blood pressure
- patients with heart failure, hypertension or other conditions predisposing to fluid retention
- patients w/ gastrointestinal tract irritation, history of peptic ulcer, diverticulosis or other inflammatory disease of the gastrointestinal tract such as ulcerative colitis and Crohn’s disease
- Increased risk of renal toxicity
adverse effects ibuprofen
- decreased appetite
- edema
- fluid retention
indications flurbiprofen
sterile, topical produce for ophthalmic use for inhibition of intraoperative miosis
MOA flurbiprofen
COX inhibition
precautions flurbiprofen
may slow or delay healing
indications meloxicam
- Osteoarthritis
- Rheumatoid Arthritis
- Juvenile Rheumatoid Arthritis (JRA) in patients 2 years of age or older
contraindications meloxicam
- History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs
- In the setting of CABG surgery
warnings and precautions meloxicam
- Hepatotoxicity
- HTN
- HF, Edema
- Renal Toxicity
adverse reactions meloxicam
- diarrhea
- upper respiratory tract infections
- dyspepsia
- influenza-like symptoms
indications naproxen
- RA
- osteoarthritis
- ankylosing spondylitis
- polyarticular juvenile idiopathic arthritis
- tendonitis, bursitis
- acute gout
contraindications naproxen
- History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs
• In the setting of CABG surgery
warnings/precautions naproxen
- Hepatotoxicity
- CVR effects, HF, Thrombotic effects (BBW) and Edema
- Can significantly compromise renal function in geriatric patients
black box warning for naproxen
thrombotic effects can occur with use
adverse rxn naproxen
- Dyspepsia, abdominal pain, nausea
- headache
- rash, ecchymosis, and edema
indications diclofenac
- Ankylosing spondylitis
- Dysmenorrhea
- Migraine
- Osteoarthritis Pain
- Rheumatoid arthritis
contraindications diclofenac
- CABG surgery
- pts w/ moderate to severe renal impairment
warnings/precautions diclofenac
increased risk of serious cardiovascular thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal
this risk may occur early in treatment and may increase with duration of use. (BBW)
adverse effects diclofenac
- CV: edema, CV accident, HTN, MI
- CNS: HA, dizziness
- skin: pruritis, rash, stevens-johnson syndrome, toxic epidermal necrolysis
- endocrine/metabolic: fluid retention
- GI: constipation, abd pain, dairrhea
MOA celecoxib
selectively blocks COX-2
compare risks between celecoxib (selective COX2 inhibitor) and the non-selective cox inhibitors (COX 1 and 2)
celecoxib:
- causes less gastric ulceration
- does not inhibit platelet aggregation (no risk of bleeding)
- increased risk of MI and stroke
indications acetominophen
inhibition of prostaglandin synthesis in CNS
suppressed pain and fever but NOT inflammation
compare adverse effects b/w acetominophen and NSAIDs
- does NOT cause GI ulceration
- does NOT suppress platelet aggregation
- does NOT impair renal function
acetominophen overdose is treated with _______
acetylcysteine
why is using acetominophen with warfarin contraindicated
acetominophen inhibits metabolism of warfarin and can increase the risk of bleeding with its use
why are antidepressants (TCAs) used to treat pain
they have independent analgesic effects as well as an ability to relieve the depressive sx associated with chronic pain
what is the most widely studied TCA for chronic pain
amitriptyline
what anti-depressants are used to treat neuropathic pain
- duloxetine
- venlafaxine
(both SNRIs)
indications duloxetine (in terms of pain management)
- chronic MSK pain
- fibromyalgia
- diabetic peripheral neuropathic pain
contraindications duloxetine
- Use of a MOAI concomitantly or in close temporal proximity
- Not used in patients with uncontrolled narrow-angle glaucoma
warning duloxetine
- Suicidality: Monitor for clinical worsening and suicide risk
- Hepatotoxicity: Hepatic failure, sometimes fatal, has been reported in patients.
indications pregabalin
1) Neuropathic pain associated with diabetic neuropathy
2) Postherpetic neuralgia
3) Adjunctive therapy for partial seizures
4) Fibromyalgia
pregabalin is a schedule V drug and a pregnancy category C
remember that
indications gabapentin
mostly anti-seizure med, but for pain:
1) post-herpetic neuralgia
2) diabetic neuropathy
3) prophylaxis for migraine
4) treatment of fibromyalgia
5) restless legs syndrome
gabapentin is a pregnancy category C
remember that
MOA tramadol
codeine analog
weak mu agonist
works primarily by blocking NE and 5-HT reuptake
indications tramadol
moderate to moderately severe pain
more effective than codeine, less effective than morphine
side effects tramadol
sedation, dizziness, headache, dry mouth, constipation
Serious side effects:
1) can cause seizures in epileptics
2) can precipitate hypertensive crisis if combined with MAO
3) serotonin syndrome if combined with SSRI, TCA, triptans, MAO, etc
MOA tapentadol
moderate to strong opioid agonist
similar to oxycodone at mu receptors
blocks re-uptake of NE
compare adverse effects of tapentadol w/ traditional opioids
tapentadol causes less constipation
indications tapentadol
reserved for patients who are not effectively treated with other non-opioids and opioids
MOA ketamine
NDMA antagonist
indications ketamine
- starting and maintaining anesthesia
- post-operative pain
side effects ketamine
- psychological reactions (agitation, confusion, hallucinations)
- elevates blood pressure
MOA dexmedetomidine
alpha 2 adrenergic agonist
indications dexmedetomine
analgesia and sedation
- Short-term sedation in critically ill patients who were intubated and are undergoing mechanical ventilation
- Sedation prior to/during surgical procedures
how is dexmedetomine administered
IV
adverse effects dexmedetomidine
- hypotension, bradycardia
- nausea
- dry mouth
- transient
- hypertension
- agitation
- constipation
- respiratory depression
dexmedetomidine is a pregnancy category C
remember that
MOA clonidine
alpha 2 adrenergic agonist
blocks transmission of pain signals from periphery to brain
indications clonidine
1) used for HTN
2) relief of severe pain
3) treating severe cancer pain in those not treated effectively by an opioid alone
how is clonidine administered
continuous infusion through epidural catheter
adverse effects clonidine
enhances hypotensive and depressant effects of other drugs
MOA ziconotide
selective antagonist at N-type voltage sensitive calcium channels on nociceptive afferent neurons in dorsal horn of spinal cord
blocks transmission of pain signals from periphery to brain
indications ziconotide
only for chronic severe pain in those for whom intrathecal administration is warranted and when refractory to other treatments
adverse effects ziconotide
Confusion, memory impairment, speech impairment, hallucinations, etc.
also causes muscle injury (from elevated serum creatinine kinase levels)
**enhances depressant effects of other drugs
*generally resolve within 2 weeks of drug discontinuation
ziconotide is a pregnancy category C
remember that
MOA and indications capsaicin
stimulation of TRPV1 (heat reeptor) and desensitizes and/or depletes substance P
nociceptive and neuropathic pain
MOA camphor and menthol (ICY HOT)
camphor: TRPV1 receptors
menthol: stimulates TRPM8 (cold)
MOA pentazocine
prototype for the agonist-antagonist opioids used to treat mild to moderate pain
kappa opioid receptor agonist and mu opioid receptor antagonist
indications pentazocine
analgesia and sedation
MOA butorphanol
prototype for the agonist-antagonist opioids used to treat mild to moderate pain
contraindications butorphanol
pts w/ history of MI
b/c it increases cardiac work
how is butorphanol administered
usually given IM or IV, but nasal spray is opioid tx of choice for migraine
indications buprenorphine
used primarily to treat addicts, but also to treat mild to moderate pain
adverse effects buprenorphine
prolongs QT interval
can cause spasm of sphincter of oddi –> poses risk for pts w/ pancreatitis or biliary dz
indications ergotamine
drug of choice for terminating ongoing migraine attack
MOA ergotamine
blocks inflammation associated w/ trigeminal vascular system and suppresses release of CGRP
adverse effects ergotamine
- nausea vomiting
- weakness in legs, myalgia, numbness and tingling of fingers and toes
- angina-like pain and tachycardia or bradycardia
overdose of ergotamine causes _____
ergotism
- constriction of peripheral arteries cause extremities to become cold, pale and numb with gangrene a possibility
ergotamine is a pregnancy category X
remember that
indications dihydroergotamine
drug of choice for terminating ongoing migraine attack
MOA dihydroergotamine
blocks inflammation associated w/ trigeminal vascular system and suppresses release of CGRP
compare ergotamine and dihydroergotamine
both drug of choice for terminating ongoing migraine attack
dihydroergotamine does not cause N/V, has no physical dependence, and minimal peripheral vasoconstriction, BUT diarrhea is prominent
MOA sumatriptan
5-HT agonist
indications sumatripan
first line drug for terminating migraine attacks
constricts intracranial blood vessels and suppresses release of CGRP
relieves HA and nausea, neck pain, photophobia, and phonophobia
sumatriptan should not be combined with what other drugs
ergot alkaloids, MAOIs, SSRIs, SNRIs
