NSAID and non-Narcotic Flashcards
what are these definition for?
- increased response to a stimulus that normally is painful
- diminished response to a normally painful stimulus
- increased sensitivity to stimulation, excluding the special senses
- diminished sensitivity to stimulation, excluding the special senses
- an unpleasant abnormal sensation, whether spontaneous or evoked
- an abnormal sensation, whether spontaneous or evoked
- pain resulting from the stimulus (such as light touch) that does not normally elicit pain
- hyperalgesia
- hypoalgesia
- hyperesthesia
- hypoesthsia
- dysesthesia
- paresthesia
- Allodynia
this pain type is the perception of input from nociceptor, a nerve fiber preferentially sensitive to a noxious stimulus
- somatic: arises from injury to body tissue; well localized but variable in description and experience
- visceral: arises from the viscera stretch receptors; poorly localized, deep, dull, and cramping
these can be subdividied as MSK pain, inflammatory pain and mechanical/compressive pain
This pain arises from abnormal neural activity secondary to disease, injury, or dysfunction of the nervous system, commonly persists without ongoing disease
- sympathetic mediated pain (SMP)-arising from peripheral nerve lesion and associated with autonomic changes (complex regional pain syndrome 1 and 2)
- peripheral neuropathic pain- is due to damage to a peripheral nerve without autonomic change (Postherapetic neuralgia)
3. central pain arises from abnormal CNS activity (phantom limb)
what is mononeuropathy, mononeuropathy multiplex, and polyneuropathy?
nociceptive pain
neuropathic pain
mononeuropathy- one nerve is affected
mononeuropathy multiplex (several nerves affected in different areas)
polyneuropathy (sx are diffuse and bilateral)
FIRST CRUCIAL FRIST STEP –> DIAGNOSIS
cell membrane contain dietary PUFA (polyunsaturated FA) in their phospholipid bilayer. arachidonic acid (AA) -eiccosatetraenoic acid is a major PUFA in cells
stumuli liberate AA- the substrate for COX
COX enzymes transform teh AA to PG ( prostaglandins), which bind receptor and signal cells
key concept:
cyclooxygenase 1 (COX-1) and Cyclooxygenase 2 (COX-2
both use the same substrate (AA)
both make the same product (PGs)
both have a role in inflammation
both have a physiological role in renal function
COX-1 expression is constitutive-expressed in all tissues all the time, prominent role responding to physiological stimuli
also contributes to response to an pathological stimuli that release AA from cells (inflammation)
1. inflammation stimulate AA release
2. COX-1 converts AA to PGE2
3. PGE2 causes symptoms (erythema, edema, pain)
COX-2 expression induced in some tisses, some times
physiological role in kidney, complements COX-1
prominent role in response to any pathological stimuli that release AA from cells (inflmmation)
indication for NSAID
MSK
osteoarthritis and other arthritides, bursitism gout flare, ankylosing spondylitis
Others
dysmenorrhea
HA
aspirin have 4 major benefits
1. suppression of inflammation
2. relief of mild to moderate pain
3. reduction of fever
- prevention of MI and stroke- due to inhibition of COX-1 in platelets, suppresses platelet aggregation
because aspirin inhibits COX-1 and COX-2, it cannot causee beneficial effects without posing a risk of gastric ulceration, bleeding, and renal impairment
irreversible inhibition of cyclooxygenase
anti-inflammatory doses of aspirin are much higher than analgesic or antipyretic doses, its very useful drug for RA and other chronic inflammatory conditions
ASA is very effective alagesic and can be as effective as opiods for post-operative pain
to minimize risk of aspirin-induced ulcers- test/eliminate H. pylori before therapy, give a proton pump inhibitor
when taken for primary prevention, ASA reduces first MI in men and first ischemic stroke in women
ibuprofen, naproxen and other non-ASA NSAIDs antagonized the antiplatelet actions of ASA
- thereby decreases protection against MI and stroke,
- miminized by taking aspirin 2 hours before other NSAID
- because of its antiplatelet effects- risk of bleeding if patient take warfarin, heparin, other anticoagulants
- impairing renal function- ASA can cause sodium and water retention, edema, and HTN with adverse effect only seen in
- advanced age
- pre-existing renal dysfunction
- hypovolemia
- HTN
- hepatic cirrhosis
- heart failure
aspirin-induced asthma- thought to be a consequence of shift in balance between PG and LT toward LT which is proinflammatory
long-term use of aspirin can lead to renal papillary necrosis and other renal injury
do not give aspirin to kids with chicken pox or influenza due to Reye syndrome risk
use of ASA during labor and delivery can suppress spontaneous uterine contractions, induce premature closure of the ductus arteriosus and intensitfy uterine bleeding
treat ASA hypersensitivity reaction (nasal polyp, asthma, rhinitis) with epinephrine
ASA toxicity
- salicylates uncouple mitochondrial oxidative phosphorylation in CNS
- respiratory center register decrease ATP as hypoxemia and response with hyperventilation
- blows off CO2, drop in PCO2 causes respiratory alkalosis-eventually prompting kidney to deplete bicarbs
- organic acids accumulate because ATP is no longer generated through kerbs cycle
5, metabolic acidosis becomes life-threatening
remember that aspirin have irrversible affects- so effect persist until cells make more COX, because platelet cannot synthesis new COX , anti-platelet effect last for the life of the platelets (8 days)
nonaspirin NSAIDs
inhibitor COX-1 and 2, suppress inflammation, pain, fever
increase risk of gastric ulceration, renal impairment and bleeding like ASA
different from ASA as it has reversible effects (so decline as blood level decline)
suppress platelet aggregation, but use actually increases risk MI and stroke, therefore use lowest effective dosage for the shortest possible time
Coxibs-second generation NSAIDs
celecoxibs- selectivley blocks COX-2 (only one of the -xibs marketed in US)
suppresses inflammation, pain and fever with less gastric ulceration than the nonselective inhibitors
does not inhibit platelet aggregation (no bleeding risk)
increase MI and stroke risk- thought to be due to blockade of prostacyclin synthesis in blood vessels (same mechanism as other NSAIDs other than ASA)
in general, all NSAIDs should be used at their lowest effective dose
all NSAIDs and paticularly COX-2 selective agents should be avoided in patient with CV risk factors (such as HTN, hypercholesterolemia, angina, edema, recent by pass surgery and abd history MI)
use only when sufficient pain relief is not achieved with other therapies and if benefit outweighs the increase CV attack
where NSAIDs is required for patients at risk of CV complication, Naproxen is recommended as the NSAID of choice
contraindication for NSAIDs
Chronic kideney disease with creatinine clearance of less than 60mL/min per 1.73m2
- patient with kidney disease or compromised renal function (as in elderly) administration of NSAIDs rapidly reduces kidney function
active duodenal or gastric ulcer
NSAID-mediated suppression of COX 1 synthesis in the gastric mucosa increases acid secretion and compromises integrity of gastric mucosa
CV disease, particularly HF or uncontrollable HTN
- COX-2 selective inhibitor are assoicated with increased risk of MI, stroke or HF
NSAID allergy
ongoing treatment with anticoagulants
what drug suppresses pain and fever, but not inflammation
MOA: inhibition of prostaglandin synthesis in the CNS, but not in periphery, consequently
- lack anti-inflammatory actions
- does NOT cause GI ulceration
- does NOT suppress platelet aggregation
- does NOT impair renal function
…perhaps due in part to peripheral inhibition by peroxide
this drug is acetaminophen
hepatic necrosis from acetaminophen overdose resulting from acculumation of a toxic metabolite that forms when glutathione is depleted
risk increased with undernourishment, alcohol and pre-existing liver dz
overdose is treated with acetylcysteine, a drug that substitutes for depleted glutathione
acetaminopehn inhibits metabolism of warfarin and therefore can increase risk bleeding associated with its use
drugs for neuropathic pain
antidepressants: tricyclic antipressants first line drugs
independent analgesic effects as well as ability to relieve the depressive symtpoms associated with chronic pain (analgesic mechanism unknown)
amitriptyline has been the most widely studied TCA in chronic pain
- doxepin, imipramine, nortriptyline, desipramine
adverse effect may diminish over time
anticholinergic- dry mouth, constipation
cardiovascular-tacycardia, palpitations
GI-N/V
neurologic- sedation, mental clouding
antidepressants: dual reuptake inhibitors of serotonin and norepinphrine (SNRI)
Venlafaxine, duloxetine are among agents used
benefical in patients with concurrent depression
known to cause Nausea, dizziness, diaphoresis, sexual dysfunction, insomina/agitation, increase in BP
weak evidence for pain relief compared to TCAs
drugs for neuropathic pain/antiepileptic first line drug
MOA: GABA analog, but ecert its effects by binding alpha2-delta subunit of voltage-agted calcium channels within the CNS
- modulates calcium influx at the nerve terminals, thereby inhibiting excitatory neurotransmitter release
4 indications
- neuropathic pain associated with diabetic neuropathy
- postherpetic neuralgia
- adjunctive therapy for partial seizures
- fibromyalgia
this is the first drug approved for fibromyalgia, but benefits are modest and fade
Schedule V
pregnancy category C
alcohol, opioids, benzodiazepines among agents that may intensify its depressant effects
pregabalin
drugs for neuropathic pain first line drugs
Gabapentin
MOA: GABA analog, but exert its effects by binding alpha2-delta subunit of voltage-agted calcium channels within the CNS
- modulates calcium influx at the nerve terminals, thereby inhibiting excitatory neurotransmitter release
broad-spectrum anti-seizure activity for partial seizures
>80% of prescriptions written for off-label uses
post-herpetic neuralgia
diabetic neuropathy
prohylaxis for migraine
treatment of fibromyalgia
restless legs syndrome
pregnancy category C
alcohol, opioids, and benzo among agent that may intensify its depressant effects
neuropathic pain-second line drug
tramadol
codeine analog, weak mu agonist, but works primarily by blocking NE and 5-HT reuptake (naloxone only partially blocks its effects, instead–> activates monoaminergic spinal inhibiton of pain
causes: sedation, dizziness, HA, dry mouth, constipation
low abuse potential, but used for suicide
tramadol
moderate to strong opioid agonist similar to oxycodone at mu receptors
also blocks re-uptake of NE
causes less constipation than tradition opioids
reserved for patients who are not effectively treated with other non-opioids
Tapentadol
neurologic pain-third line drug
NDMA- antagonist
- starting and maintaining anesthesia (notable for causing a trace-like state with sedation, analgesia and memory loss)
- post-operative pain
common side effects including psychological reactions such as agitation, confusion, hallucination as drug wears off
-nasal formulation approved for depression
can elevate BP and reduce the amount of morphine needed for pain control
katamine
neurologic pain-3rd line drug
MOA: alpha2- adrenergic agonist used for analgesic and sedation
approved for stort-term sedation in critically ill patients who were intubated and are undergoing mechanical ventilation
-sedation prior to/during surgical procedures
off-label used for sedation and analgesia in patients undergoing general anesthesia
IV for pain unlike clonidine
causes hypotension, bradycardia, nausea, dry mouth, transient HTN, agitation, constipation, respiratory depression
pregnancy category C
enhances hypotensive and bradycardia effects of other drugs
Dexmedetomidine
